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The next issue of IPI will be published in Spring 2025. ISSN No.International Pharmaceutical Industry ISSN 1755-4578.
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06 Our Long-term View Allows us to Nurture Talent and Expertise and Build a Solid Track Record
With rising global demand for self-injection devices due to increasing chronic conditions, Ypsomed’s autoinjectors and pens offer simple, safe solutions. Ulrike Bauer at Ypsomed, highlights Ypsomed’s strong partnerships and patient-focused innovation.
REGULATORY AND MARKETPLACE
10 Enabling a Sustainable and Mutually Beneficial CDMO Partnership Contract Development Manufacturing Organisations (CDMOs) have become essential in the pharmaceutical supply chain, offering cost-effective, compliant solutions with speed to market. Annette Boland of Pharmalex a Cencora Company explains how success depends on selecting CDMOs that meet critical regulatory standards.
14 CMO Quality Management Insights
The pharmaceutical industry’s growth has increased reliance on contract manufacturing organisations (CMOs), which offer expertise, reduce costs, and accelerate drug development. Londa Ritchey at Pharmalex a Cencora Company describes how robust oversight includes initial facility audits, ongoing quality management, and clear agreements outlining expectations.
16 Assessing the Impact of EU Pharma Reform on Healthcare Resilience and Medicine Shortages
Recent medicine shortages in Europe have exposed vulnerabilities in healthcare systems, prompting the European Commission to propose sweeping pharmaceutical reforms. Bram Lardée of ProPharma highlights key measures which include fostering innovation, decentralising manufacturing, and leveraging new technologies to reduce costs and waste.
DRUG DISCOVERY, DEVELOPMENT & DELIVERY
18 How Lyophilisation Can Overcome mRNA Stability Changes
The growth of mRNA therapeutics is projected to reach $40 billion by 2033. Vincenza Pironti at Recipharm discusses challenges in development, particularly the need for lyophilisation to improve stability in storage and transport.
20 Advances in Imaging Biomarkers: Estimating Drug Efficacy with Tumour Growth Rate Modelling
Oncology drug development faces high costs and low success rates, with a 95% attrition rate. ICON’s Ramkumar Krishnamurthy, delves into the limitations of RECIST 1.1 imaging criteria and highlights tumour growth rate (TGR) modelling as a promising alternative.
22 Advancing IBD Management with Targeted Therapies and Innovative Oral Drug Delivery
Inflammatory bowel disease (IBD), which includes Crohn's Disease and Ulcerative Colitis, affects up to 10 million people worldwide. David Templeton of N4 Pharma touches on how current treatments are untargeted and challenging, but new nucleic acid-based therapies are offering hope.
27 HPAPI for Drug Development and Delivery
The rise of highly potent active pharmaceutical ingredients (HPAPIs) offers targeted therapies for cancer, minimising side effects. Lucas SauerJones of Veranova explores the crucial role of contract development and manufacturing organisations (CDMOs) in ensuring safety and innovation.
30 The Use of Autoinjectors for Autoimmune Diseases: Advancements, Benefits, and Considerations
The global market for autoimmune therapeutics is growing steadily, driven by diseases like Rheumatoid Arthritis and Multiple Sclerosis. Autoinjectors are playing a key role in managing these conditions, improving patient independence, dosing precision, and overall outcomes. Justin Schroeder at
PCI discusses how despite challenges such as cost and device malfunctions, autoinjectors' future in autoimmune care is promising.
CLINICAL & MEDICAL RESEARCH
34 Striving for Clinical Trial Success? It Starts with One Crucial Choice
As drug developers face challenges in clinical trials, partnering with a reliable Contract Development and Manufacturing Organisation (CDMO) is crucial. Mark Rauckhorst at Vetter emphasises the importance of strategic planning and expert support to navigate the complexities of early clinical phases.
MANUFACTURING
36 Dry Granulation: Efficient Production of Oral Solids for Industrial Applications
Continuous dry granulation (roller compaction) has advantages over traditional wet granulation for tablet production. These highlights include lower costs, reduced energy consumption, and scalability. Tobias Borgers of L.B. Bohle addresses the importance of containment in handling high-potency ingredients (HPAPIs).
40 From Fossil Fuels to Sustainability: Advancing Plastics Production with Mass Balance and Alternative Feedstocks
There is an urgent need for sustainable feedstock alternatives to fossil fuels in plastic and energy production due to global warming and resource depletion. Luca Chiochia of Elix Polymers explains the role of advanced recycling and biobased feedstocks, such as pyrolysis oils and used cooking oil. He also emphasises on the flexibility of dry granulators in continuous manufacturing and their importance in ensuring safety and containment for handling potent substances.
42 Innovations in ATMP Manufacturing: Preparing for the ATMP Revolution with Innovative Cleanroom Design
This article explores the critical role of cleanrooms in the development and manufacturing of advanced therapy medicinal products (ATMPs). Matthew Dean at Process Architecture highlights that modular cleanroom solutions are essential for ensuring safety and accelerating the delivery of life-saving treatments.
46 Depot Injection Formulation and Modelling (Part A)
Oil-based long-acting injectable formulations (LAIFs) dissolve or suspend drugs in an oil medium, allowing for sustained release over time, often for chronic conditions. Travis Webb at Pii, emphasises how mathematical models help optimise release mechanisms.
HEALTH OUTCOMES
50 The Use of Antimicrobial Effectiveness Testing in Pharmaceutical Biology
Antimicrobial preservatives are added to aqueous pharmaceutical products to prevent microorganism growth during production and from repeated use in multi-dose products. Antoinae Wood of Wickham Micro – A Cormica® Lab explores how these preservatives try to ensure products like hand creams and medications remain safe and effective, preventing bacterial contamination and infections.
TECHNOLOGY
54 Navigating Digital Transformation Fatigue: The Strategy for Success in Regulated Industries
There is digital transformation fatigue in regulated industries, where managing new digital tools and meeting strict regulations can overwhelm businesses. Max Kelleher at Generis, stresses the importance of digital adoption to maximise software investments, enhance employee experience, and reduce inefficiencies.
56 Connected technologies: Optimising Data Management in the Era of Wearable Technology
There are challenges posed by the increasing volume of data in clinical trials, particularly with the use of wearable devices and apps. Philip Räth of Palleos Healthcare and Paul MacDonald of Veeva Systems, discuss how data workbenches are essential tools for managing and integrating diverse data
into a cohesive dataset, to ultimately enable researchers to deliver faster and safer therapies.
58 Getting Lab Data Closer to the Decision Point Keeps Product Release on Track
The article discusses the importance of digital transformation in manufacturing labs, particularly in maintaining compliance and improving efficiency. With over 600 FDA warning letters issued since 2022, labs must streamline operations to reduce risks. Ashley McMillan, explains how adopting advanced LIMS systems can help labs enhance compliance, productivity, and speed up time-to-market for products.
LOGISTICS & SUPPLY CHAIN MANAGEMENT
60 Harnessing AI Pharmaceutical Supply Chains: A Strategic Imperative
There is a transformative role of AI and machine learning in reshaping pharmaceutical supply chains. These technologies are helping address challenges like fluctuating demand and product integrity, particularly for temperature-sensitive goods. Will Robinson of LogiPharma explores AI-driven innovations in inventory management, forecasting and order automation are positioning AI as a strategic imperative for the industry's future success.
64 AI in the Pharma Cold Chain
While AI can optimise temperature-sensitive shipments and improve patient care, its adoption faces obstacles like data inconsistencies, varying digital maturity, and security concerns. Envirotainer’s Otto Dyberg, highlights how achieving successful AI integration requires standardising data, gradual implementation, and robust privacy safeguards to protect sensitive information and ensure patient access to vital medications.
SUBSECTION: PHARMAPACK
69 Bio-based Plastics: A Bridge to Sustainable Devices
There is widespread use of plastics in the pharmaceutical industry, particularly in combination products like inhalers. While essential for safety and efficiency, managing plastic waste is challenging, with most ending up in landfills or incineration. Philip Smith at Vectura Limited, delves into how adopting biobased plastics and circular design principles can reduce environmental impact.
72 Stoelzle Glass Group: Advancing Sustainability in Glass Packaging for Pharma and Healthcare
Stoelzle Glass Group leads in sustainable glass packaging for healthcare and other industries. With EcoVadis gold status and SBTi-backed goals, they target 50% CO₂ reduction by 2030 and net zero by 2050.
74 Celebrating 10 years of VarioSys: An Unforeseeable Success Story
VarioSys, introduced a decade ago, has transformed pharmaceutical production by offering a versatile system for syringes, cartridges, and vials within a single isolator. Bernd Wieland at Bausch + Ströbel and Dr. Friedrich Haefele' of Biopharma Fill & Finish Boehringer Ingelheim, explain how VarioSys combines flexibility, compact design, and high efficiency.
76 Bag-on-Valve: An Attractive Airless Packaging
Bag-on-Valve (BoV) technology is an innovative airless packaging system that isolates products from air, ensuring integrity, longevity, and contamination-free dispensing. Magnus Hedman of Aurena Laboratories AB adds how BoV offers nearly 100% product evacuation, prolonged shelf life, and user-friendly, precise dispensing, making it ideal for preserving liquid products.
78 German Manufacturer Showcases High-performance Lubricants at Pharmapack 2025
The producer of ELKALUB high-performance lubricants, Chemie-Technik will make an appearance at Pharmapack 2025 to present its solutions tailored to meet the safety, efficiency, and regulatory demands of pharmaceutical production.
79 Driving Sustainability in Pharma: Pharmapack’s Vision for Change
Pharmapack Europe 2025 aims to drive systemic change in sustainability. Informa Market’s Silvia Forroova, explains how this can be done by uniting industry leaders through initiatives like the Sustainability Collective.
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Editor's Letter
As we draw an end to 2024, I invite you to take a moment to explore this engaging winter issue of IPI. It is overflowing with some of my favourite topics within the pharmaceutical industry, such as an article on fossil fuels to sustainability by Luca Chiochia of ELIX Polymers. As the world continues to face environmental challenges, sustainability has become a critical focus for industries across the globe, and the pharmaceutical sector is no exception.
In 2024, the pharmaceutical industry has made significant strides in adopting more sustainable practices, driven by the need to reduce environmental impact while maintaining high standards of healthcare and product quality. I have had the privilege to witness some of the forward-thinking and creative ways in which companies in the industry have made efforts to adopt greener practices across their operations.
As we look ahead to 2025, sustainability in the pharmaceutical sector is no longer a peripheral concern but a central strategy for companies looking to maintain a competitive edge while addressing global environmental challenges. As the industry continues to evolve, expect further innovations in green chemistry, supply chain transparency, and
circular economy models. The commitment to sustainability will play a crucial role in the future of healthcare, ensuring that the industry remains responsive to both the needs of patients and the planet.
We open with a piece from Ypsomed, a leader in self-care solutions for chronic conditions. Renowned for driving innovation in self-injection devices and enabling safe user-friendly treatments. Ypsomed addresses the diverse needs of the pharmaceutical industry through strategic partnerships and a strong platform-driven approach. With a forward-looking emphasis on sustainable growth, they are aligning their efforts with the pressing environmental and industry demands of today.
A key challenge for the industry is addressing medicine shortages through the EU's pharmaceutical reform, focusing on strengthening supply chain resilience, improving crisis preparedness, and increasing local production of essential medicines. Bram Lardée of Propharma discusses the challenges of harmonising regulations, enhancing local manufacturing, and managing costs.
In the Drug Discovery, Development & Delivery section, we explore advancements in imaging biomarkers. ICON’s Ramkumar Krishnamurthy explains how Tumour Growth Rate (TGR) modelling can offer complementary
Editorial Advisory Board
Bakhyt Sarymsakova, Head of Department of International Cooperation, National Research, Center of MCH, Astana, Kazakhstan
Catherine Lund, Vice Chairman, OnQ Consulting
Deborah A. Komlos, Principal STEM Content Analyst, Clarivate
Diana L. Anderson, Ph.D president and CEO of D. Anderson & Company
Franz Buchholzer, Director Regulatory Operations worldwide, PharmaNet development Group
Francis Crawley. Executive Director of the Good Clinical Practice Alliance – Europe (GCPA) and a World Health Organisation (WHO) Expert in ethics
Rick Turner, Senior Scientific Director, Quintiles Cardiac Safety Services & Affiliate Clinical Associate Professor, University of Florida College of Pharmacy
Jagdish Unni, Vice President – Beroe Risk and Industry Delivery Lead – Healthcare, Beroe Inc.
Jeffrey W. Sherman, Chief Medical Officer and Senior Vice President, IDM Pharma
Jim James DeSantihas, Chief Executive Officer, PharmaVigilant
Mark Goldberg, Chief Operating Officer, PAREXEL International Corporation
Maha Al-Farhan, Chair of the GCC Chapter of the ACRP
methods for assessing tumour response. This innovative approach could enhance precision and reduce trial costs, whilst bettering the field of oncology.
We conclude our journal Pharmapack 2025 subsection. Next year’s Pharmapack is set to be the biggest yet, bringing together industry leaders from over 70 different countries. This event offers an exciting opportunity to learn about advanced technologies while connecting with like-minded professionals from across the globe.
One of the highlights of the subsection is a feature on Stoelzle, a leading manufacturer of high-quality primary packaging glass. Known for its unwavering commitment to precision and sustainability, Stoelzle continues to lead the way in shaping the future of pharmaceutical packaging with its robust and eco-friendly solutions.
In addition, we’re thrilled to present a fascinating piece from Magnus Hedman of Aurena Laboratories AB. He delves into the groundbreaking Bag-on-Valve (BOV) technology – a pioneering packaging solution that enhances the functionality and convenience of pharmaceutical and cosmetic products.
Join us at Pharmapack 2025 to explore these exciting solutions and much more!
As 2025 dawns, let us move forward inspired by the creativity, responsibility, and determination of those in the pharmaceutical field. Together, we can continue to pave the way for a healthier, more sustainable world. I sincerely hope you enjoy this edition of IPI!
Kelly Woods, Editorial & Production Coordinator
Steve Heath, Head of EMEA – Medidata Solutions, Inc
Patrice Hugo, Chief Scientific Officer, Clearstone Central Laboratories
Heinrich Klech, Professor of Medicine, CEO and Executive Vice President, Vienna School of Clinical Research
Robert Reekie, Snr. Executive Vice President Operations, Europe, Asia-Pacific at PharmaNet Development Group
Stefan Astrom, Founder and CEO of Astrom Research International HB
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Talking Point
Our Long-term View Allows us to Nurture Talent and Expertise and Build a Solid Track Record
About
Ulrike Bauer
Ulrike Bauer has been with Ypsomed (previously Disetronic) since 2001 in various commercial roles. Since 2014, she is a member of the Executive Board and responsible for the Delivery Systems Business unit. Ulrike Bauer, Chief Business Officer Delivery Systems at Ypsomed.
The number of people with chronic conditions is increasing worldwide. In this context, the demand for Ypsomed’s autoinjectors and pens is growing rapidly, as they enable simple and safe selfadministration of liquid medication. In conversation with Susanne Köhler, Head of Public Relations, Ulrike Bauer, Chief Business Officer Delivery Systems at Ypsomed, talks about current trends and how the company’s commitment to strong partnerships, scalable business models, and strategic market positioning makes Ypsomed an ideal partner for meeting the growing demand and driving sustainable innovation.
Q: Ypsomed’s annual figures show that the company is on a steep path of success and growth. What factors are driving this growth?
A: Injectables are alongside orals the dominant category of drugs in the development pipelines of pharma and biotech. The benefits for patients and for the healthcare systems of at-home treatment are increasingly recognised. That is why there is a growing demand for innovative, user-friendly, and reliable devices that enable quick market access. Ypsomed is well positioned to serve these needs due to a comprehensive device portfolio and its established platform approach that was introduced more than ten years ago.
We have trustworthy and longstanding relationships with a huge number of both
big and small pharma and biotech customers, which provide the basis for two thirds of every new project that we work on. One third of new projects are started with new customers, so our customer base is steadily increasing.
Q: How does Ypsomed contribute to building and strengthening relationships with customers?
A: We prioritise transparency, trust, and continuous collaboration. We build joint governance structures and maintain open communication to ensure our customers’ needs are consistently met throughout all project phases and the full life cycle. Our platform approach allows us to tailor selfinjection devices to specific pharmaceutical requirements in a short time, thereby reliably supporting successful product launches. Additionally, our proactive risk management practices help sustain longterm, mutually beneficial relationships with both existing and new pharmaceutical and biotech customers.
Q: Who does Ypsomed partner with and why?
A: At Ypsomed, we partner with a broad network of global industry leaders across the pharmaceutical supply chain, including equipment suppliers, contract manufacturing organisations (CDMO/CMOs), and primary container manufacturers.
Our partnerships span the entire development process and commercial life of combination products – from ensuring primary container compatibility to collaborating on fill-finish operations, final product assembly, and packaging. Our Industry Collaboration department, staffed with subject matter experts, has a deep understanding of our partners’ capabilities, and confidently recommends the best options when it comes to equipment selection and manufacturing processes, whether customers choose to manage processes in-house or work with trusted service providers. Our partnerships
offer turnkey solutions that are easy to access and ready to order. By nurturing these strategic partnerships, pharma customers benefit from best-in-class systems that reduce costs and shorten timelines during the clinical, approval, and commercial phases for each drug product. Through this extensive network of collaborations, Ypsomed effectively supports customers and maintains the quality and safety they expect.
Q: Customers have very diverse needs and different business cases. How does Ypsomed handle these requirements?
A: Ypsomed employs a range of business models to meet the diverse needs of large, medium, and small pharmaceutical and biotech customers, whether they are in commercial production or clinical study phase. For very large quantities, we offer models that allow customers to have dedicated production lines or even license the production of the device, providing a second source of supply and enhancing supply chain resilience. In any case, Ypsomed maintains responsibility for product design during the full life cycle. Another advantage of our platform approach is that at the same time it allows us to serve also smaller and medium-sized demands, as well as clinical trial phases, ensuring consistent quality, flexibility, and efficiency. This variety of business models enables us to support a wide range of projects, from early-stage clinical studies to full-scale commercial production, allowing a balanced and sustainable growth of our diverse customer base.
Q: In which countries is Ypsomed expanding its capacities, and why at these locations in particular?
A: To continue upholding our commitment to quality and reliability, we are also expanding our production capabilities globally. Our headquarters are located in Switzerland, in the heart of Europe, where the history of Ypsomed began 40 years ago. This is where we conduct our research, development,
and production with sites in Burgdorf and Solothurn. In Schwerin, northern Germany, we have a new, state-of-the-art production facility established in 2019, which is currently undergoing further expansion. In October, we inaugurated a large extension, and we plan to more than double the size of the plant by 2027. Additionally, we are building our own plant in China, which will soon be ready for production. In North America, we are currently seeking a suitable location.
Up until now, we have supplied worldwide markets from Switzerland and Germany. However, we aim to be closer to our target markets and establish production capacities where the products are needed. Our customers appreciate this approach. The geographical proximity also supports our efforts for sustainability. We are taking one step at a time, ensuring that everything fits together seamlessly.
Q: Which indications are treated with pens and autoinjectors, and for which indications will Ypsomed's products be used in the future?
A: We began 40 years ago with insulin and peptide hormones. Then followed the complex biological molecules that must be administered subcutaneously as well. The range of acute and chronic conditions that can be treated with our pens and autoinjectors broadens each year. Currently, we have more than 70 launched combination products targeting 15 different therapeutic areas, thus improving the lives of more than eight million patients worldwide.
One significant future application for our autoinjectors could be in cancer treatments. Currently, cancer therapies are predominantly administered intravenously in hospitals, but there is a shift towards subcutaneous formulations, which opens the way to self-administration.
Drugs from the GLP-1 class are a new treatment approach for obesity management. Initially employed in the treatment of Type 2 diabetes, it was observed that patients experienced weight loss as a side effect.
With obesity and diabetes on the rise globally, weight reduction will play a crucial role in public health by helping to prevent related secondary conditions. As a number of these new drugs can also come as preserved formulations in cartridges, our portfolio of
autoinjectors and pens meets the needs in this therapeutic area.
Q: Ypsomed's products are also used to treat rare diseases. Are these cases a less interesting opportunity for the company?
A: It does not matter to us whether an indication is very common and involves high or der volumes or a rare condition with lower volumes, both are interesting opportunities for us. Thanks to our platform approach, we operate very efficiently and can quickly adapt our products to meet customer needs. As a result, even customers with smaller volumes benefit from the experience and economies of scale provided by our established platforms.
Q: In recent years, the product portfolio has been expanded to include large volume autoinjectors that cover volumes of 2.25 mL to 10 mL and different viscosities. What are they used for and what does this mean for the treatment of chronic conditions?
A: More and more therapies are being offered for self-treatment, and there are new formulations with higher concentrated
ingredients. The frequency of self-administration is decreasing, requiring higher doses of medication per injection. Overall, the increasing volume and viscosity of drugs require more powerful devices for injection. For example, new drugs for diseases such as Alzheimer’s are administered in larger volumes to effectively deliver the medication.
Currently, there is significant demand for 2.25 mL handheld injections, and the next step is handheld delivery of volumes up to 5.5 mL. Our YpsoDose patch injector is the convenient solution for even higher volumes up to 10 mL, which is sufficient for the majority of drugs in development that require higher volumes.
Q: Digital health solutions have recently been added to the portfolio. What incentives do pharmaceutical companies have to offer this additional service?
A: The trend towards selfcare necessitates more guidance for patients. Pharmaceutical companies need to ensure that medications are administered correctly and can provide this information to payers as proof of adherence. This is particularly important for remote clinical trials, where maintaining data quality and ensuring proper administration are critical for approval.
Talking Point
During treatment, it is also crucial to provide doctors with certainty about correct medication administration and the monitoring of side effects. We can ensure this effectively with digital health applications and connected devices. By also offering patients additional benefits, such as reminders, guidance during injections, information about the condition, and lifestyle support, we can improve treatment experiences and outcomes.
Q: The majority of Ypsomed’s autoinjectors are designed for single use. Why is that?
A: Patient safety and comfort are our top priorities. As already mentioned, the trend in the treatment of chronic conditions is to reduce the frequency of injections. If you only inject a medication quarterly, it is challenging to establish a routine, as is the case with weekly or even daily injections. The use of reusable devices is not ideal for infrequent treatments because the patient must go through additional handling steps for each injection e.g. re-setting the device and changing the needle and/or syringe compared to a single-use device. In many cases, a disposable solution makes more sense. Autoinjectors are designed for single use in most cases as they offer simplicity, convenience and safety, thereby simplifying drug administration and packaging while ensuring product integrity. We also offer reusable options, but their complexity and additional supply chain requirements necessitate a careful balance between sustainability and usability.
Q: What measures are taken to address sustainability?
A: We have been committed to sustainability for many years, and it is integrated in the four pillars of our corporate strategy. For us, sustainability means commitment to the environment and society. We attach great importance to acting responsibly towards employees, partners, and society and we expect the same from our partners throughout our value chain. Sustainable practices permeate our entire organisation. We recently launched the NetZero Program, which is our roadmap to achieve net zero emissions along the entire value chain by 2040. The first products from this program are already available to our customers. We
are committed to meeting the sciencebased emission reduction targets of the Science Based Targets initiative (SBTi). We minimise our environmental impact selecting raw materials with lower CO2 emissions and apply eco-design principles in the development of our new innovations. Today we already use only renewable energy for all our operations.
Q: Ypsomed is celebrating its 40th anniversary this year. After more than 20 years with the company, how do you assess the current situation and what are your expectations for the future?
A: What I have always appreciated is Ypsomed’s long-term focus and the patience which comes with it. This is
mainly because the Michel family, as the majority shareholder, understands the business very well and has always believed in steady success. Our long-term mindset has also helped us to retain and continuously develop talent and expertise. When I started at the predecessor company Disetronic more than 20 years ago, we experienced similar growth to what we see today. We understand what is essential for managing growth. We are one of the strongest manufacturers of self-injection devices, having built up economies of scale. We are in a good position with a broad customer base and a resilient foundation supported by the growth drivers of our business. Additionally, we have many bright minds at Ypsomed who work every day to make selfcare simpler and easier. My expectations for the future are therefore consistently positive.
More than 70 combination products in 15 therapeutic areas, covering both originators and biosimilars. Improving the quality of life of over 8 million people around the globe.
Over 130 large, medium and small biopharma and biotech customers worldwide.
Scalable business models for clinical trials and full-scale production.
100 % electricity from renewable sources since 2021.
www.international-pharma.com 40 years of expertise dedicated to making selfcare simpler and easier.
For more information visit www.ypsomed.com/yds or scan the QR code
Enabling a Sustainable and Mutually Beneficial CDMO Partnership
Use of Contract Development Manufacturing Organisations (CDMOs) is now the established norm in the pharmaceutical and medical technology supply chain.1 The CDMO model has been shown to provide cost-effective, reliable and compliant solutions with speed to market for critical healthcare products.
This is achieved by leveraging the core competencies and experience of the contract giver (e.g. brand development, marketing etc), and contract acceptor (e.g. manufacturing excellence, quality operations, etc.) to allow for targeted focus on key operational pillars to drive overall programme success and synergies.2 However, with many CDMO options available, all providing specialised expertise and solutions for diverse and complex activities, it can be difficult to know where to start with the selection process in a way that balances the fundamentals and aspirational goals.
Starting with the non-negotiables, companies must make sure that any partnership adheres to requirements laid out in current Good Manufacturing Practice regulations (cGMP)3 by the US Food and Drug Administration and the European Medicines Agency (EMA).4 The FDA sets out the minimum cGMP to assure that safety requirements are adhered to across the lifecycle of a drug and that it “Meets the quality and purity characteristics that it purports or is represented to possess.”5
Beyond these critical requirements, there are several key considerations we recommend before engaging a potential CDMO.
Understand the Project Status and Objectives
Make sure you understand the exact capabilities that you require from a CDMO, including both the essentials and the niceto-haves. This will vary, depending on what phase your project is at and the current timelines. Be clear about the known current risks that may impact on project timelines, such as raw material supply, testing queues if using external laboratories, regulatory
approval, etc. Have mitigation actions for each of these risks been identified and assessed? Consider your forecast and strategy for when you expect to go to market. What funding is available and is this sufficient to accelerate the timeline if needed?
Research the CDMOs Identified
Next, do some basic research to differentiate between the selected CDMOs. Key factors to consider as part of your criteria for the selection of a CDMO include technical knowhow and other key skill sets, quality and compliance, and approach to risk.
Technical Knowledge and Experience
Consider how long the CDMO has been in operation and if they have a proven track record in your niche technology. Review their case studies, success stories, and client reviews. Balance technical know-how with ability to deliver a quality product on time and within budget. That will mean weighing cost, speed, and quality in your decision-making. Sometimes speed incurs an additional upfront cost but can pay significant dividends in the long term with gaining market share. Ask whether the CDMO can support your forecast commercial ramp-up plans. Do they have the expertise in technology transfer and ability to scale-up? And can they offer an end-to-end finished product solution – from packaging to distribution to postmarket surveillance?
Quality and Compliance
Regulatory compliance is a non-negotiable, so be sure the CDMO has a proven track record. Do they understand the FDA’s definition of adulterated product i.e. “If it fails to conform to compendial standards of quality, strength or purity”6 and the consequence of such a violation. Ask which regulatory authorities have audited them, when, what the outcome was and how robust their responses to regulatory findings were. Quality considerations are equally important. Make sure their quality management system (QMS) is suitable for you. Thoroughly critique the CAPA system, change control, deviation management, self-inspection programmes. Ask key questions about the CDMO’s quality processes, including:
• Are internal issues identified and resolved in a sustainable and robust manner?
• How does the CDMO address issues that could impact product quality?
• From an infrastructure perspective, is the facility clean and well-maintained and does it meet all regulatory expectations? Is the facility equipped with the right technology and sufficient equipment capacity to handle your project needs? Is there an active contamination control strategy?
Align on Risk Attitude
Risk management is clearly defined in regulatory guidances, with ICH Q9 outlining that “effective and proactive quality risk management can enable better, more informed and timely decisions throughout the lifecycle”.7 Determine how well the CDMO can meet both regulatory and organisational requirements, including:
• Does the CDMO have a structured and documented approach to risk management?
• Does the CDMO develop defendable risk rationales and use their experience with other clients to determine how your project might be impacted?
• How does the CDMO adapt to change in a compliant way when things don’t go as expected?
The technical skillset of the manufacturing team is a priority; however, as part of the selection of the CDMO, it is important to review the skill set of the wider team, including quality assurance, quality control, supply chain, facilities, project management, regulatory and others.
• Does the CDMO have a strong quality culture in which those who have responsibility for oversight and control over manufacturing take ownership for quality, with patient safety at the centre?
• How does the CDMO’s senior leadership demonstrate their commitment to quality and continuous improvement?
• Does the CDMO invest in training, mentorship programmes, professional
development and does it set high standards for excellence?
• Is there an active succession planning programme in place and are there retention measures to retain key skill sets?
• Does the CDMO drive a continuous improvement mindset and invest in electronic systems that provide realtime metrics and analytics?
• Do the values and core operating principles of the CDMO align with your company values and is there a symbiotic relationship between business and quality objectives? In simple terms, will the CDMO become an extension of your business?
• Are quality assurance personnel just problem finders or are they also solution providers?
Building and Maintaining the CDMO Relationship
Once you have selected a CDMO, be proactive and operate with a “one-entity” mind-set. That means being prepared to manage the unexpected and adopt contingency planning to deal with the “what ifs” of supply chain disruptions. You need to be clear and realistic with your project’s goals,
Regulatory & Marketplace
milestones and budget. In addition, develop targeted and customised scenario plans, such as best-case scenarios, assuming no project delays, as well as realistic planning, which assumes delays with regulatory approvals and possible repeat testing. In the same vein, identify risks early on and develop mitigation solutions, such as dual sourcing of critical components, targeted training programmes, regular audits, enhanced testing during the project phase and targeted updates on project status with the regulatory authorities.
Use standard templates for documentation consistency and have sufficient safety stocks in place. It’s also crucial to develop a strong, transparent and honest communication plan, since a strong partnership is anchored in mutual trust and respect. Be clear what success looks like to you, for example, through agreed-on key performance indicators (KPIs) during product transfer and into commercialisation. And, crucially, ensure you not only have a Quality Technical Agreement, but maintain it as a living document.8,9 Both parties need to be aligned on responsibilities, including “the who” and “the what” in the event of “the what if” scenarios happening.
The Right Model in an Evolving Landscape
The CDMO operating model is rapidly growing and adapting as agility and speed to market in a cost effective, sustainable and compliant manner become increasingly important. At the same time, companies must be assured that cGxP are met. In recent warning letters on the use of contract manufacturers, the FDA has made clear that contractors are regarded as extensions of the manufacturer and that it is the manufacturer’s responsibility to ensure the quality of their drugs in keeping with current Good Manufacturing Practices (cGMP), regardless of agreements in place with contract facilities. “You are required to ensure that drugs you deliver into interstate commerce are not adulterated,” the FDA stated, noting that, where products are considered “adulterated” under the FD&C act, both the Contract Giver and Contract acceptor should consider these words as an indication that a recall is warranted.10,11
The requirements of the European Medicines Agency (EMA) are similar to those of the FDA. They state that “a direct written contract should also be in place between the Manufacturing/Importers Authourisation (MIA) holder responsible
Regulatory & Marketplace
for Qualified Person (QP) certification of the product and sites involved in the various stages of manufacture, importation, testing and storage of a batch before it undergoes certification (hereafter: contract manufacturers).”12
With these considerations in mind, a partnership is best realised when the CDMO is seamlessly embedded as an extension to your existing business, rather than just being perceived as a third party. Such partnerships enable a win-win scenario with alignment on the technical non-negotiables whilst simultaneously ensuring shared operating values. To achieve this, the contract giver and contract acceptor must work collaboratively together as a single entity to achieve common goals – sharing a commitment to patient safety, quality, regulatory compliance, continuous improvement and underpinning that commitment through constant colla-boration and communication.
REFERENCES
1. Current trends and strategic options in the pharma CDMO market, PwC. https://www.pwc. de/de/gesundheitswesen-und-pharma/studiepharma-cdmo-market.pdf
2. 2022 Global CDMO Study of Pharmaceutical Operations, PwC. https://www.strategyand. pwc.com/de/en/industries/pharma-lifesciences/2022-global-cdmo-study/strategyand2022-global-cdmo-study.pdf
3. Current Good Manufacturing Practice (CGMP) Regulations, FDA. https://www.fda.gov/drugs/
4. Good manufacturing practice, EMA. https:// www.ema.europa.eu/en/human-regulatoryoverview/research-development/complianceresearch-development/good-manufacturingpractice
5. Current Good Manufacturing Practice in Manufacturing, Processing, Packing or Holding of Drugs, 2. FDA 21 CFR Part 210. https://www. accessdata.fda.gov/scripts/cdrh/cfdocs/ cfcfr/CFRSearch.cfm?CFRPart=210&showFR=1#:~: text=(a)%20The%20regulations%20set%20 forth%20in%20this%20part%20and%20in
6. Adulteration of Drugs Under Section 501(b) and 501(c) of the Act, Compliance Policy Guide, FDA. https://www.fda.gov/regulatory-information/ search-fda-guidance-documents/cpg-sec420100-adulteration-drugs-under-section-501band-501c-act-direct-reference-seizure-authority
7. ICH guideline Q9 (R1) on quality risk management. https://www.ema.europa.eu/en/ documents/scientific-guideline/internationalconference-harmonisation-technicalrequirements-registration-pharmaceuticalshuman-use-ich-guideline-q9-r1-quality-riskmanagement-step-5-revision-1_en.pdf
11. Warning Letter Velocity Pharma LLC, FDA. https://www.fda.gov/inspections-complianceenforcement-and-criminal-investigations/ warning-letters/velocity-pharma-llc-67643407172024
12. Guidance on Good Manufacturing Practice and good Distribution Practice: Questions and answers | European Medicines Agency. https://www.ema. europa.eu/en/human-regulatory-overview/ research-development/compliance-researchdevelopment/good-manufacturing-practice/ guidance-good-manufacturing-practice-gooddistribution-practice-questions-answers
Annette Boland is a consultant at PharmaLex a Cencora Company, Ireland, focused on quality operations. She is an experience quality assurance professional with 30 years of experience in pharmaceutical, biologics, and medical devices having worked in both generic and branded multinational companies. Annette has a BSc (Hons) in Analytical Science & a Post Graduate Diploma in Pharmaceutical Manufacturing Technology (Qualified Person status).
Email: annette.boland@pharmalex.com
Annette Boland
Aptar Pharma – your go-to drug delivery partner, from formulation to patient
When pharmaceutical companies around the world want to develop safe, efficient and compliant medicines, they turn to Aptar Pharma for proven drug delivery solutions.
Leveraging our therapeutic insights, over 30 years of regulatory expertise and the widest portfolio of solutions and services in the industry, we accelerate and derisk our customers’ drug development process, helping them transform bright ideas into new market opportunities to improve and save patient lives.
Let’s partner together on your next bright idea. Visit www.aptar.com/pharmaceutical to get started.
From formulation to patient.
CMO Quality Management Insights
The pharmaceutical industry and the creation of new drugs is expected to continue growing at a steady rate over the next decade.1 To keep up with this growth, many companies are turning to contract manufacturing organisations (CMOs) to assist with product manufacturing. A key benefit CMOs provide is to maintain a manufacturing footprint, and the skilled talent needed to support product manufacturing. This reduces the need for the product owners to carry these costs or delay progress of their drug development until these resources are directly available. Often CMOs can also assist in bringing products to market more quickly by providing assistance on process and analytical development aspects as well. However, as with most things, the benefits of CMO use also come with some risks.
A CMO can be an important party in the product supply channel. The product sponsor is expected to ensure the CMO is part of a robust supply channel that minimises the risk to patient safety and product supply.2 To meet this requirement the product sponsor establishes and maintains a diligent quality management strategy for oversight of the CMO. Outsourcing the manufacturing activity does not alleviate the product sponsor from responsibility for the quality and safety of the drug product. This holds true for product manufacturing whenever the product is intended to be consumed by a patient; clinical trials or post-market approval. As outsourcing has become a more common practice, regulatory authorities have evolved their expectations for contract manufacturing oversight.
Regulatory Expectations
Regulatory authorities worldwide understand the need for use of contract manufacturers. This is evident in the guidelines and directives that directly address the expectations for quality oversight of a CMO. For example, the European Commission devotes the entire GMP Chapter 7 to Outsourced Activities and outlines the activities of Contract Giver (Product Sponsor) and Contract Acceptor
(CMO)3. ICH Q10, contains expectations for oversight of outsourced activities.4 Additionally, the ICH Q9 (R1) updates include the expectation for integrating quality risk management activities into industry operations. That includes the application of QRM to oversight of outsourced activities.5
The regulatory authorities have also reiterated that outsourcing does not mean the product sponsor can outsource responsibility for the quality and safety of the drug. Here are two examples of statements the USFDA has made in warning letters related to use of contract manufacturing and responsibilities:
• Responsibilities as a Contractor
FDA is aware that many drug manufacturers use independent contractors such as production facilities,... FDA regards contractors as extensions of the manufacturer. You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners.”2
• Use of Contract Manufacturers
FDA is aware that many drug manufacturers use independent contractors such as production facilities,... FDA regards contractors as extensions of the manufacturer…
You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities.”6
More recently a warning letter was issued to a sponsor company utilising a CMO that received a warning letter. The company continued to distribute drug products from their CMO after the CMO received the warning Letter. Specifically, the warning letter captures the following points:
• “You also failed to have adequate supplier qualification procedures to ensure that the drug products received… were manufactured in compliance with CGMP prior to being distributed.”7
• “You received and delivered into interstate commerce… products that were found to be adulterated…”7
These statements represent the current thinking of regulators as regards the responsibility for ensuring the quality of the drug products manufactured at CMOs on behalf of product sponsors. It is clear that this is a shared responsibility and both parties are responsible for ensuring drug products are produced under cGMP. Both parties must have a focus on patient safety.
Importance of Proper Qualification and Oversight
The key to avoiding negative regulatory actions when utilising a CMO is in the initial qualification activities and ongoing quality management engagement with the CMO. Here are some recommendations based on best practices encountered over years of personal experience. The CMO should be qualified through an onsite audit to ensure the facility and staff are capable of manufacturing, testing, storing, and distributing product in a manner consistent with cGMP. This initial qualification should also consider the capabilities of the CMO to control contamination, including crosscontamination from the other products being manufactured in this the same facility. The initial qualification activity completed prior to agreements to initiate work with the CMO.
The initial qualification audit is based on a sample of activities available for review during the agreed time. This may not allow enough time to capture all aspects of the controls needed for ongoing compliance. Therefore, it is also important to have ongoing quality management engagement with the CMO. The expectations for quality performance, responsibilities and communications should be captured in a quality agreement between the CMO and product sponsor. It is essential that each party conduct a comprehensive review to ensure the agreement captures the specifics needed for the product under consideration. Once the agreement is in place, ongoing engagement with the CMO is needed to ensure the product sponsor’s requirements are fulfilled as expected. The expected communication plan and governance should be outlined and agreed in the quality agreement.
It is common for commercial product sponsors to have formal qualification and
Regulatory & Marketplace
quality oversight plans with CMOs already in place prior to commercialisation. It is less common for those product sponsors entering clinical trials. According to FDA’s guideline for cGMP for Phase 1 investigational drugs and EC GMP Annex 13 covering investigational drugs, even at the clinical phase 1 stage these products must be produced under a state of control that ensures these products meet the safety, purity, identity requirements needed for use in patients.8,9
Even in the early phases of clinical trials, it is important that product sponsor must have qualify and maintain quality oversight engagement with the CMO. Unfortunately, failure in this area could result in the product application not being approved due to the CMO site failing the GMP inspection.10
This is not something to be learned at the application stage. Starting early with qualification of any facilities performing manufacturing on behalf of the product sponsor is essential along with continued oversight to stay on track.
Disclaimer
The information provided in this article does not constitute legal advice. PharmaLex and Cencora, Inc., strongly encourage readers to review available information related to the topics discussed herein and to rely on their own experience and expertise in making decisions related thereto.
REFERENCES
1. Precedence Research.com (2024). Retrieved from Pharmaceutical Contract Manufacturing
6. FDA Warning Letters. (2021). Warning LetterSircle Laboratories, LLC. Retrieved from https://www.fda.gov/inspections-complianceenforcement-and-criminal-investigations/ warning-letters/sircle-laboratories-llc-61509809212021
7. FDA warning Letter. (2024). Warning LetterVelocity Pharma LLC. Retrieved from https://www. fda.gov/inspections-compliance-enforcementand-criminal-investigations/warning-letters/ velocity-pharma-llc-676434-07172024
8. FDA.gov (2008). Guidance for Industry CGMP for Phase 1 Investigational Drugs. Retrieved from https://www.fda.gov/media/70975/download
9. EC.gov(2010). Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use Annex 13 Investigational Medicinal Products. Retrieved from https:// health.ec.europa.eu/document/download/ eb43a2ab-4691-4cab-938e-874f2307dca3_ en?filename=2009_06_annex13.pdf
10. Cancer Network.com (2023). Retrieved from FDA Issues Complete Response Letter for Cosibelimab in Squamous Cell Carcinoma (cancernetwork.com)
Ritchey
Londa Ritchey is currently a Quality Director at PharmaLex a Cencora Company with 30 years of experience in pharma/biopharma/ATMP quality assurance emphasising sterile drug substance and drug product operations. Londa's experience includes quality risk management, aseptic quality operations, quality systems design and implementation, contamination risk management, supplier quality management, training programme design and inspection readiness. Her educational background includes degrees in Microbiology, Biostatistics, and an MBA.
Londa
Assessing the Impact of EU Pharma Reform on Healthcare Resilience and Medicine Shortages
microbial resistance and rare diseases).
Recent medicine shortages across Europe have highlighted critical gaps in the resilience and security of our healthcare systems, prompting decisive action from the European Commission. Through an ambitious overhaul of pharmaceutical legislation, the Commission aims to strengthen supply chains, ensure reliable access to essential medicines, and foster sustainable innovation. But will these measures go far enough to secure Europe’s health future? How will they impact other aspects of the pharmaceutical sector, from cost and production to job availability? This article explores the key pillars of the proposed Directive and Regulation, examining the far-reaching implications of these changes and addressing pressing questions on the path to a more resilient and responsive healthcare framework for the EU.
On 26 April 2023, the European Commission adopted a proposal for a new Directive and a new Regulation that revise and replace the existing general pharmaceutical legislation, under the following documentation:
• Proposal for a Directive of the European Parliament and the Council of the Union code relating to medicinal products for human use, repealing Directive 2001/83/ EC and Directive 2009/35/EC.
• Proposal for a Regulation of The European Parliament and of the Council laying down Union procedures for the authorisation and supervision of medicinal products for human use, establishing rules governing the European Medicines Agency, and amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014, and repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006
The new proposed Directive is based on four pillars, which include legislative and nonlegislative elements:
1. Ensuring access to affordable medicines for patients and addressing unmet medical needs (in areas such as anti-
2. Supporting competitiveness, innovation, and sustainability of the EU’s pharmaceutical industry, and the development of high-quality, safe, effective, and greener medicines.
3. Enhancing crisis preparedness and response mechanisms, securing diversified and resilient supply chains, and addressing medicine shortages.
4. Ensuring a strong EU voice in the world, by promoting a high standard of quality, efficacy, and safety.
In this article, we will focus mainly on the third pillar ‘Enhancing crisis preparedness and response mechanisms, diversified and secure supply chains, and addressing medicine shortages’; at the same time, we will discuss the common elements across all four pillars and how they relate to each other. For instance, developing high-quality, safe, effective, and greener medicines inevitably impacts the robustness and sustainability of the supply chain, awareness of utilisation, and medicine shortages.
As stipulated in the new proposed Directive, a Marketing Authorisation Holder must ensure the appropriate and continuous supply of a medicinal product throughout its lifecycle, regardless of whether it is covered by a supply incentive.
This is further defined as ‘Crisis Preparedness and Response Planning’:
1. Better availability of medicines, particularly critical medicines, to EU citizens will need to be guaranteed by setting up earlier warnings from pharmaceutical companies regarding shortages and withdrawals of medicines, including the establishment of prevention plans. Additionally, a list of medicines critical for the EU health systems will need to be drawn up by the Competent Authorities to identify supply chain vulnerabilities and improve the security of such critical supplies. Lastly, there will need to be better monitoring and mitigation of shortages, at both national and EU levels, and a stronger guiding role for the European Medicines Agency and the European Commission
on security of supply. The main players mentioned here – pharmaceutical companies, national EU governments, the European Medicines Agency, and the European Commission – will play a crucial role in ensuring access to equitable medicines across the EU and coordinate the efforts across the various stakeholders.
2. To enforce compliance strongly with the new proposed Directive, a marketing Authorisation Holder who fails to comply with the regulations on a stable supply of products may face a fine of up to 5% of the previous year’s turnover. Upon repetition, they can be fined daily up to 2.5% of each day’s turnover.
There is broad consensus among the various stakeholders on guaranteeing a continuous supply of medicines, as shortages are widely acknowledged as a concerning reality. Especially following the Covid pandemic, which highlighted the need to prevent shortages. The main question remains on whether those measures will be sufficient, assuming seamless implementation, which we know is far from straightforward. Furthermore, what will be the impact of the measures taken on other aspects of the pharmaceutical sector?
In October 2023, the European Federation of Pharmaceutical Industries and Associations (EFPIA) assessed the main provisions of the revision of the pharmaceutical package.1 The key recommendations on medicines shortage, in summary, were:
1. The creation of a harmonised EU prevention and mitigation system.
2. Increased transparency and understanding of demand, through timely (current and forward-looking) epidemiological data.
3. Use of the European Medicines Verification System (EMVS) for medicine shortage prevention and monitoring of Marketing Authorisation Holder’s supplies to wholesalers and pharmacies, i.e. intelligence of the supply chain.
4. Adoption of a risk-based approach focused on critical products/critical shortages, leading to the implementation of targeted Shortage Prevention
Plans (SPPs) for critical products through a collaborative process across the various players. A clear, harmonised definition and list of critical products are needed to ensure a consistent approach at EU level.
It’s obvious that harmonisation, as widespread as possible, is an essential yet challenging goal for the EU’s general approach. Improved transparency across the supply chain has the potential to increase resilience and prevent shortages, but it’s indeed questionable whether this can be achieved at the desired level for all types of treatment. At a minimum, it would certainly be desirable for critical treatments, defined as those with high potential medical impact and a risk of shortage – a classification that should, however, be coordinated at the European level.
However, if we want diversified, secure, and robust supply chains for critical treatments, especially in light of enhanced crisis response capabilities and improved response mechanisms, we must address the elephant in the room and talk about production at local EU level of both Active Pharmaceutical Ingredients (APIs) and Drug Products (DPs) versus production in distant countries with lower labour costs.
So how does a more influenceable and local production of APIs and DPs relate to the total costs associated to crisis response? And how is the European Commission influencing these dynamics? This discussion on the proposed EU pharma legislation reform aspects aimed at strengthening supply chain resilience, poses a few further questions:
• How is the EU parliament prioritising secure patient access, and are cost savings still a major force?
• How might shifting labour costs back to the EU/UK affect job availability, especially given the recent wave of industry layoffs?
The pharmaceutical industry has always recognised the need for dual supply of APIs and DPs and an intention to have a geographical spread. However, with today’s global instabilities, the need for crisis preparedness will only strengthen and, in that respect, local production is potentially crucial. Established supply chain models must be re-assessed to avoid shortages of critical medicines.
One element to consider is that a large proportion of critical medicines available
Regulatory & Marketplace
What Activities Should be Initiated by Pharmaceutical Companies to Leverage Crisis Preparedness and Response Planning?
Short-term
• Start writing procedures that meet each country’s specific requirements on behalf of the Marketing Authorisation Holders to support continuous supply of product throughout its lifetime as per Directive 53.
• Start writing country specific procedures for notifying the competent authority of any plans to cease marketing of a product 12 months before last supply, or proposal to withdraw or temporarily suspend a Marketing Authorisation or any temporary disruption to supply as per Article 116.
• Writing of country specific product shortage prevention plans as per Article 117.
• Writing of country specific product shortage mitigation plans and risk assessments for suspension, cessation, or withdrawal of product from the market as per Article 119.
Long-term
• Development of new ideas and strategies for more cost-effective local production, via simplification, smart downscaling, innovative engineering, or shelf-life extensions.
• In alignment with antimicrobial awareness, development of plans on most efficient offering and usage of medicines.
• Development of plans to avoid over-production and reduce the environmental impact, pollution, etc.
today are generics, for which the API and DP manufacturing processes were in many cases developed over twenty years ago. It should be possible to simplify those legacy processes with the help of modern technologies, thereby lowering manufacturing costs, even while downscaling. Why downscaling? To bring added, practical value, for instance with ‘make to order’ decentralised production, reducing carbon footprint and waste.
Local production could be stimulated by fast-track procedures for assessing variations to achieve this objective. With local production as a potential contributor to solving the
puzzle, re-assessing infrastructure capacity is essential. This may, in turn, positively impact job availability, another key issue given recent industry layoffs.
Above all, there is a clear need for innovation: more efficient, more specialised engineering, automation, and robotisation. If ever there was a critical moment in our era for this paradigm shift, it is now. We must focus on this without delay, as innovation takes time, staff training takes time, and development of facilities takes time.
But if we are prepared to look at the bigger picture, we surely can be successful.
REFERENCES
1. https://www.efpia.eu/media/gy5j1nkt/efpiarecommendations-on-the-revision-of-thepharmaceutical-package.pdf, downloaded Nov 2024
Bram Lardée started his career as an Analytical Chemist in vitamins and pharmaceuticals at Solvay-Duphar (NL), and developed into an Analytical Expert. After performing this role for several years, he made a career switch to Pharmaceutical Technology, developing all types of dosage forms through toxicology and clinical phases up to market. Through his broad hands-on experience and ability to translate knowledge into overall Project Management, Bram received a position as Global CMC Project Lead in support of multiple clinical programmes and lifecycle management of Marketed Products at Solvay Pharmaceuticals, and later Abbott Healthcare Products. Before joining ProPharma Group, he held the position of R&D Director at Centrient Pharmaceuticals. He was technically accountable for setting-up the Finished Dosage Forms franchise. Bram has over 35 years of experience in the Pharmaceutical Industry.
Bram Lardée
How Lyophilisation Can Overcome mRNA Stability Challenges
In this article, Vincenza Pironti, Head of Business Development at Recipharm, explores the latest trends in messenger RNA (mRNA) drug development, dives into the development challenges this modality poses, and explains how lyophilisation can hold the key to optimising stability in storage and transit.
The mRNA therapeutics market was estimated to be worth $18.7 billion in 2023, and is forecast to grow to $40 billion by 2033, expanding at a compound annual growth rate (CAGR) of 8.2% throughout the forecast period.1
Stability is a Hurdle
While mRNA therapeutics offer a number of benefits for pharmaceutical companies seeking novel solutions for currently untreatable diseases, they do present challenges in development and manufacturing. These need to be addressed to deliver an effective and commercially viable end product.
A particular problem for mRNA-based therapeutics is their inherent instability. The mRNA molecule is naturally both physically and chemically unstable:
• Physical instability concerns include the loss of secondary or tertiary structure, as well as aggregation and precipitation, which affect the translation of mRNA molecules.
• Chemical instability issues include potential degradation due to hydrolysis and oxidation.2
Failure to address these issues in development can lead to a product with a short shelf life, or one that requires frozen or ultra-frozen storage and transport – as we saw with COVID-19 vaccines, some of which required storage at -70°C.3 These storage and shelf-life challenges can have implications for global accessibility of novel therapeutics – it may be difficult to transport doses long distances overseas, and emerging markets, where there is limited cold-chain infrastructure, may end up being underserved.
Lyophilisation Presents a Potential Solution
One possible answer to this issue for future mRNA-based vaccines, cancer treatments and other therapies is the use of lyophilisation in the formulation process. Lyophilisation or freeze-drying is a process in which water is removed from a product after it is frozen and placed under a vacuum, allowing the sublimation of water. The process consists of three separate, unique, and interdependent processes; freezing, primary drying (sublimation), and secondary drying (desorption).
The advantages of lyophilisation include:
• Enhancing the stability of highly sensitive products
• Gentle removal of water from the formulated mRNA
• Rapid and easy dissolution of reconstituted product
• Lyophilisation Challenges to be Overcome
To harness the benefits of lyophilisation in overcoming mRNA instability, pharmaceutical companies do need to answer a number of questions.
1. Does the Lyophilisation Process Effectively Optimise Stability of the Product in Question?
For successful drug administration, the vial must contain a high-quality final cake that can be easily reconstituted when it is time
to inject the dose without compromising the formulation's integrity. This is a particular issue for low-dosage products like mRNAbased therapies due to the disproportionate ratio of ingredients-to-dose-volume. In such cases, the incorporation of suitable cryoprotectants or bulking agents is crucial. These additives must be compatible with the formulation and the vial and ensure the stability of the final drug product. Extensive analytical testing of the formulation well before commercialisation can help determine the appropriate lyophilisation methods to preserve product stability and extend shelf-life once the therapy enters commercial use.
2. How to Maintain the Integrity of Lipid Nanoparticle Formulations (LNPs)?
Many mRNA-based therapies use LNP technology, where the active substance is encapsulated within lipids to enhance its bioavailability and stabilise it. In such cases, the lyophilisation process must be carefully designed to minimise potential damage to the LNP envelope and preserve the viability of the drug product (DP) upon reconstitution. It is essential to employ prolonged freeze-drying cycles to prevent harm to the LNPs within the formulation, which could compromise their performance and stability.
Strategies to Harness Lyophilisation
To address potential challenges with mRNA
Regulatory & Marketplace Drug Discovery, Development & Delivery
therapeutics lyophilisation, alternative approaches can be explored.
One approach is to optimise the process by ensuring it is as gentle as possible. A thorough study of each freeze-drying phase is required, rather than opting for an accelerated method that may save time but risk damaging the formulated mRNA.
Another approach is to modify the formulation. Factors such as different ionic strengths within the buffer can significantly impact the resulting cake post-lyophilisation, potentially improving stability and facilitating reconstitution. Adjusting the mRNA concentration prelyophilisation can also influence the freezedrying process and should be addressed to ensure effectiveness. For LNPs, selecting an appropriate surfactant is crucial to address aggregation challenges.
A number of technological advancements in lyophilisation in recent years have the potential to further overcome challenges when harnessing the process for mRNA products. Controlled temperature automated loading and unloading of freeze-dried products, for instance, have significantly improved the overall manufacturing and filling processes of mRNA products, ensuring optimal product stability. mRNA formulations remain sensitive to temperature even after lyophilisation, so automating and accelerating unloading minimises the risk of exposure to impactful temperatures on final stability.
The Value of Seeking Lyophilisation Guidance Early
The lyophilisation process is timeconsuming, especially for mRNA candidates. For pharmaceutical companies with a limited timeframe to move mRNA candidates from early development to clinical trials, bypassing lyophilisation during clinical manufacturing may be necessary to expedite the process. Nonetheless, the earlier lyophilisation is incorporated into the formulation development journey, the more straightforward it is to establish an effective process. This ensures the final mRNA treatment benefits from enhanced stability and simplified storage capabilities provided by lyophilisation.
The mRNA technology is frequently approached as a platform. Developing an effective process for lyophilisationalso known as a lyocycle - and selecting an appropriate formulation require a
comprehensive understanding of the technology.
With this in mind, more and more pharmaceutical companies are seeking expert external advice on lyophilisation feasibility from contract development and manufacturing organisations (CDMOs). The rapid increase in the number of mRNA treatments under development in recent years has seen such partners gain significant experience in this field, so CDMOs are well placed to assist pharmaceutical companies in accessing lyophilisation advances. This enables pharmaceutical companies to effectively leverage these advancements in a structured manner, supporting the efficient commercialisation of their mRNA products when they reach the commercialisation stage.
Learning Lessons from the Past
Due to the speed with which companies needed to develop and commercialise the vaccines, lyophilisation was not taken into account during the first COVID-19 pandemic. This meant it was necessary to have frozen and ultra-frozen transport and storage in place for the first wave of vaccines, which hindered the global vaccination process, especially in emerging markets, which lacked the necessary infrastructure. This presents clear lessons for the industry to learn from for the next outbreak.
Lyophilisation – and the stability at ambient temperatures it confers – presents significant advantages for mRNA vaccines developed to combat future pandemics, and the logistical requirements for any vaccination programme. A lyophilised product can greatly simplify logistics when vast quantities of vaccine doses need to be manufactured and distributed worldwide. This eliminates the requirement for specialised cold-chain transportation and storage, making the process more manageable and cost-effective. Lyophilisation also offers plenty of potential for mRNA therapeutics targeting cancers and other conditions, simplifying handling during manufacturing, and supply chain needs, making it easier for treatments to reach patients all over the world.
To harness the technology, it is important for pharmaceutical companies to work with a CDMO with specialist experience and infrastructure for lyophilisation and subsequent sterile fill and finish of mRNA treatments. By leveraging existing knowledge of successful strategies, it is possible to
streamline the development process. This eliminates the need for redundant efforts, as companies can build upon proven methodologies rather than starting from scratch.
Vincenza Pironti is the current Head of Business Development at Recipharm, having joined the company in 2023 as Strategic Marketing Director for Sterile fill & finish. She supports the design of strategies for the global sales and business development teams, and the analysis of new business opportunities for Recipharm's commercial business. With almost 20 years in the pharmaceutical industry and consolidated experience in business development, product development, aseptic manufacturing, and filling, Vicenza brings valuable expertise to Recipharm. She comes to the business with extensive knowledge of all phases of product development, from formulation screenings to sterile product commercial manufacturing, with expertise in small molecules and biologics in sterile formulation. Previously, Vincenza worked as Business Development Manager in Pharmatex and CordenPharma, managing multiple projects in sterile fields.
Vincenza Pironti
Drug Discovery, Development & Delivery
Advances in Imaging Biomarkers:
Estimating Drug Efficacy with Tumour Growth Rate Modelling
Even after decades of research and everincreasing R&D spending, the overall success rate of oncology programmes remains low.1,2 At an industry level, over $50bn is spent annually on failed oncology trials,3 leading to a 95% attrition rate.1 The expected cost to develop a new drug can be anywhere up to $2bn, including the expenses associated with drugs that fail to reach the market.
Research has shown that trials using biomarkers for patient selection had almost twice the probability of success compared to trials that do not use biomarkers (10.3% vs 5.5%).1 Imaging biomarkers are an essential part of oncology trials, tracking the efficacy of the new treatment and comparing it to the existing gold standard therapies. The insights gleaned from imaging biomarkers steer the course of oncology clinical trials, informing decisionmaking and endpoints. While RECIST/RECIST 1.1 is the most widely used imaging criteria, it has certain limitations. In recent years researchers have debated whether RECIST is still “the sharpest tool in the oncology clinical trials toolbox”.4
In this article we look at some of the limitations of conventional oncology imaging biomarkers (e.g. RECIST 1.1), comparing them with the advantages gained by adopting newer methods such as tumour growth rate (TGR) modelling.
Limitations of Conventional Imaging Biomarkers
Require Large Patient Cohort
Oncology studies using RECIST 1.1 require a comparative arm to derive robust statistical conclusions. More patients must be enrolled which can make clinical trials more expensive. For rarer forms of cancer, larger patient populations are not available, making developing treatments more challenging.
Inefficient Endpoints in Non-curative Trials
Statistically proving equivalence (or superiority) of the treatment arm compared to the control arm in trials with variability in end-
point assessment requires large numbers of patients. This means that conventional imaging biomarkers are not fully suitable for non-curative trials that may need a longer follow up time.5 For metastatic solid tumours there is a need for newer biomarkers to capture longer survival and correlate with developing biomarkers.5
Do Not Effectively Capture Whole Body Tumour Burden
A number of studies have shown that the drugs designed to treat primary tumour may not be as effective in treating distant metastasis.6 There are different escape mechanisms for tumours and heterogeneity between primary tumours and metastasies. Conventional imaging biomarkers do not always capture the heterogeneity and whole-body tumour burden accurately. As more specialised and targeted therapies are developed to treat one portion of a tumour over another, the RECIST protocols cannot efficiently capture tumour heterogeneity.
Lack of Tailored, Patient Specific Treatments / Patient Selection for Trial Participants
Biomarkers should be able to inform patient decisions about their treatment. More effective imaging biomarkers could be used to select patients for whom the trial treatment is most likely to prove effective.
Lack of Flexibility in Trials
Patients participating in oncology treatment studies need to have their tumours measured at timed intervals with little room for flexibility. However, there are many reasons why a patient may miss an appointment for a scan. Patients dealing with a serious illness, its associated financial and psychological burdens, and treatment side effects require more flexibility than RECIST-based biomarker studies offer.
Tumour Growth Rate (TGR) Modelling
TGR modelling provides growth/decay rate imaging biomarkers that can predict patient survival and drug responses potentially from a limited number of patients.
TGR modelling uses regression (decay) or growth models with the assumption that tumour burden change during treatment
has both an exponential growth (‘g’) and an exponential decay (‘d’) rate. The growth and decay rates are continuous variables that correspond to drug response.
Advantages of TGR Modelling
While ‘g’ does provide for a different metric to better predict patient survival,7,8 it has certain advantages over conventional radiographic tumour burden/response assessment.
Robust Estimation of "g" from Real World Data
Given the nature of modelling involved, estimation of ‘g’ is not significantly perturbed by small variations in acquisition interval or minor measurement errors. Unlike RECIST, a missed or delayed biomarker measurement will not significantly affect the study. TGR modelling can define localised tumour growth characteristics and potentially these can be robustly calculated using real world data and evidence.9 The Food and Drug Administration (FDA) announced acceptance of real-world evidence in 2021.10 This expands the possibility of using data from ongoing or past studies for future studies’ control arms.
Localised Estimation of ‘g’
While a patient’s global tumour burden can be modelled to derive a global ‘g’, TGR modelling can be used at an individual tumour level and to obtain information on location-based growth rate.
Reduced Sample Size Need
Perhaps the biggest potential benefit of TGR modelling is the possibility of a reduced sample size to understand differences between the control arm versus the treatment arm.9 Higher accuracy of volumetric estimation of tumour burden, and the fact that ‘g’ of the control arm can be derived from historical data, suggests TGR modelling’s potential to understand drug efficacy earlier in the drug development process.
Works With Existing Measurements
A number of studies showcase TGR modelling’s ability to derive tumour growth rates from RECIST-based line measurements. While volumetric assessment of tumour burden does have significant benefits in effectively capturing overall tumour burden,11 even the simpler line measurements that are
Regulatory & Marketplace Drug Discovery, Development & Delivery
conventionally used can still be utilised to assess ‘g’ accurately.
Considerations for TGR Modelling
To understand drug efficacy at an earlier stage in their trials, pharmaceutical companies should consider adopting TGR modelling and growth rate estimation. When adopting a new methodology there are certain factors to take into account, and TGR modelling is no exception. The following guidance should be considered:
Obtain Multiple Follow Up Imaging Time Points
While TGR modelling would require at least four time points (including baseline) to estimate g, obtaining as many follow up time points as possible would strengthen modelling accuracy.
Acquire More Images Where Pseudoprogression is Expected
In studies where pseudo-progression of tumour burden may be expected, it may be necessary to acquire images for more timepoints to compute tumour growth rate appropriately.
Capture as Much of the Tumour Burden as Possible
Capturing as much of the tumour burden
as possible, beyond the five-lesion limit of RECIST 1.1, may be beneficial. Similarly, volumetric estimation of tumour burden would help to more accurately capture tumour burden.
Use Standardised Imaging Acquisition
Standardise early phase imaging acquisitions with stringent quality control so that tumour burden estimates can be performed accurately.
Conclusion
There has been interest in improving imaging biomarker methodologies for many decades. While RECIST 1.1 is widely used to image biomarkers, it is important to consider new and complementary ways of measuring tumour responses in drug development. Novel TGR modelling methods address some of the shortcomings of existing conventional oncological imaging biomarkers and may help understand drug efficacy earlier. Another significant potential future benefit for drug developers is that TGR modelling has the potential to remove the need for a control arm – which can reduce the cost of developing better treatments.
REFERENCES
1. Wong CH, Siah KW, Lo AW. Estimation of clinical
trial success rates and related parameters. Biostatistics. 2019;20(2):273-286.
2. Research and development in the pharmaceutical industry. In: Office CB, ed. Washington D.C.: Congressional Budget Office.
3. Jentzsch V, Osipenko L, Scannell JW, Hickman JA. Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors. JAMA Netw Open. 2023;6(7):e2324977.
4. Sharma MR, Maitland ML, Ratain MJ. RECIST: No Longer the Sharpest Tool in the Oncology Clinical Trials Toolbox—Point. Cancer Research. 2012;72(20):5145-5149.
5. Stein WD, Gulley JL, Schlom J, et al. Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin Cancer Res. 2011;17(4):907-917.
6. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA: A Cancer Journal for Clinicians. 2016;66(4):271-289.
7. Yeh C, Zhou M, Sigel K, et al. Tumor Growth Rate Informs Treatment Efficacy in Metastatic Pancreatic Adenocarcinoma: Application of a Growth and Regression Model to Pivotal Trial and Real-World Data. Oncologist. 2023;28(2):139148.
8. Maniar A, Wei AZ, Dercle L, et al. Assessing Outcomes in NSCLC: Radiomic analysis, kinetic analysis and circulating tumor DNA. Paper presented at: Seminars in Oncology2022.
9. Wilkerson J, Abdallah K, Hugh-Jones C, et al. Estimation of tumour regression and growth rates during treatment in patients with advanced prostate cancer: a retrospective analysis. The Lancet Oncology. 2017;18(1):143-154.
10. Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making for Drug and Biological Products. U.S. Department of Health and Human Services Food and Drug Administration. https://www.fda.gov/ media/152503/download. Published 2024. Accessed.
11. Maitland ML, Wilkerson J, Karovic S, et al. Enhanced detection of treatment effects on metastatic colorectal cancer with volumetric CT measurements for tumor burden growth rate evaluation. Clinical Cancer Research. 2020;26(24):6464-6474.
Ramkumar is a medical imaging scientist and MRI physicist at ICON with over 15 years' clinical imaging experience, including body and cardiovascular imaging. He was also the technical manager for the advanced imaging clinical lab for many years, working with advanced processing of imaging data, including tumour imaging metrics.
Ramkumar Krishnamurthy
Advancing IBD Management with Targeted Therapies and Innovative Oral Drug Delivery
Inflammatory bowel disease (IBD) is a term for two conditions (Crohn's Disease and Ulcerative Colitis) that are characterised by chronic inflammation of the gastrointestinal (GI) tract. According to the European Federation of Crohn’s & Ulcerative Colitis Associations (EFCCA), there may be as many as 10 million people worldwide living with these conditions.1
While the cause of the disease is not fully understood, studies indicate that the inflammation involves a complex interaction of factors, including the genes the person has inherited and the presence of foreign substances (antigens) in the immune system. These antigens may be the direct cause of the inflammation, or they may stimulate the body's defences to produce and sustain an inflammatory response.
This response is characterised by hyperactive macrophages, white blood cells that act as the gatekeepers of balanced gut immunity. In IBD, macrophages secrete cytokines with numerous damaging effects on tissue and other cells around them. Some of the key cytokines in IBD are TNF alpha, IL-6, IL-17, IL-23.
In a healthy person, the production of these pro-inflammatory cytokines is controlled, in IBD patients it is unbalanced and leads to persistent inflammation that causes tissue damage. In addition, antiinflammatory cytokines, such as IL-10, are actively suppressed, leading to a further immune imbalance in the gut.
Scientific Knowledge Gaps
To better understand and treat IBD, genomewide association studies (GWAS) have identified segments of DNA associated with the disease at 215 different chromosomal sites,2 yet scientists have only been able to pinpoint the exact mechanisms involved for four of them.3
In a recently published paper in Nature,4 James Lee, a clinician-scientist who runs a research group at the Francis Crick Institute in London, and colleagues, used functional
genomics to investigate an intergenic haplotype on a ‘gene desert’ (swathes of the genome that initially appeared to contain nothing of relevance) known as chr21q22, which has been linked to IBD and other inflammatory diseases. They identified that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and their inflammatory cytokine status and may therefore be an appropriate target for future IBD treatment, with its inhibition potentially being clinically superior to the inhibition of single cytokine targets.
Given that the complexity of IBD is nowhere near fully understood, there is also a lack of appropriate biomarkers, which hampers treatment possibilities. Diagnosis and monitoring of the disease relies heavily on invasive and expensive endoscopy and imaging techniques. Several serum biomarkers have been established as reliable measures for disease activity in IBD,5,6 however, many of them have limitations in terms of their specificity, sensitivity, responsiveness, and/ or other desirable attributes.5 Because of this, there is a growing interest in switching from a single biomarker to a multiple panel approach specific to IBD and that can enable differential diagnosis and treatment of Crohn's disease versus ulcerative colitis.7
The identification and effective use of new biomarkers would improve diagnosis and help to predict treatment success. It would also ensure that treatment could begin before the clinical manifestation of symptoms, which could significantly improve the quality of life of patients living with this chronic disease.
Current Treatment Options
The IBD treatment market globally was worth $20.4bn in 2023 and is expected to grow by a CAGR of 3.9% to over $27.6bn by 2030,8 driven by both increased incidences of the disease and development of new treatments.
Original treatment of IBD was dominated by aminosalicylates, corticosteroids, and immunosuppressive agents, although they produce side effects that can include depression, osteoporosis, and susceptibility to infection due to the non-specificity of drug action.9,10,11 This brings further limitations, such
as non-target site toxicity and limited efficacy in the complete remission of the severe last stages of IBD.12
Targeted therapeutics, especially antibody therapeutics, directed to a more specific mechanism of action have led to reduced side effects as well as improved therapeutic efficacy.13 These drugs, known as TNF inhibitors, accounted in 2002 for 45% of the overall market8 and include Infliximab, Adalimumab and Certolizumab. However, these biologics are large molecules and are susceptible to rapid elimination by the body’s systems if administered unprotected. Furthermore, these antibodies are administered systematically as they cannot be taken orally, meaning they lack localised delivery. So far, the only formulations approved by regulators are for injectables, which require intravenous administration at regular intervals under expert supervision and therefore lack patient compliance.
siRNA-based Treatments Emerge
As an alternative to systemic antibody therapeutics, small interfering RNAs (siRNAs) directed at silencing proinflammatory cytokines have gained great attention from many research groups.14 However, systemic treatment with injectable siRNA-based therapeutics also results in non-compliance and causes unwanted side-effects caused by the systemic depletion of cytokines.
Specific delivery of siRNA to the desired inflamed site of the GI tract is needed and thus the most efficient route of administration would be oral, as the treatment would be released where it is needed most: the gut. However, there is a lack of oral drug delivery systems that have a demonstrated ability to protect siRNA from the harsh environment of the GI tract and selectively deliver siRNA to desired target sites.
Due to the attractiveness of oral treatments, both for patient compliance and comfort, as well as their obvious suitability for a disease of the GI tract, the oral IBD treatment segment is expected to be worth $7bn by 20302 – 25% of the total market.
Orally delivered, small molecule janus kinase (JAK) inhibitors have recently
Regulatory & Marketplace Drug Discovery, Development & Delivery
generated interest, with The European Medical Agency having approved three of them for treating adults with moderate to severe Ulcerative Colitis.15 However, their lack of tissue selectivity causes safety issues in other organs.16
Novel Delivery Systems for Oral IBD Treatment
Efficient siRNA delivery into the target cells is a key challenge that’s currently hampering its potential in IBD drug development. Nanoparticle-based delivery systems may hold the key to better treatment for sufferers of IBD.
Nanocarriers composed of lipid nanoparticles – which are often the first port of call – are generally biodegradable, biocompatible, with low or no immunogenicity and toxicity. However, in some cases, these nanocarriers are not completely inert, because some cationic lipids can reduce mitosis in cells, form vacuoles in the cytoplasm, and cause detrimental effects on key cellular proteins such as protein kinase C. Other notable disadvantages include their limited stability, their relatively low capacity to load siRNA, and, occasionally, the possible interaction and breakdown of pay-loaded nucleic acids.17
Alternative nanoparticles that aim to address the drawbacks of lipid-based systems include Nuvec® (N4 Pharma): a non-lipid, non-viral, silica-based nanoparticle with targeting capability and nucleic acid payload protection.
Nuvec nanoparticles are hollow silica spheres covered in thin silica structures that are functionalised with polyethyleneimine (PEI) to enhance binding of macromolecules. Their unique irregular surface structure effectively traps and protects siRNA as it migrates to the target cells (Figure 1).
A series of pre-clinical studies have shown that Nuvec’s surface structure protects the siRNA (within the spikes on the particles) from enzyme attack.
At the site of action, the particle enters the target cell where the siRNA is released in the cytosol the siRNAs action results in degradation of a homologous mRNA sequence in the cell, resulting in reduction of the relevant protein and consequent inhibition of cell growth. This mode of action allows for precise targeting and the inhibition of identified signalling pathways with reduced: toxicity; immune system response; and potential side effects.
In proof of concept studies in vivo, the successful oral administration of Nuvec loaded with a deoxyribonucleic acid (DNA) plasmid for ovalbumin has been confirmed. The Nuvec was administered by enteric coated capsule and the contents, having been released in the intestinal lumen, were taken up by intestinal cells, with successful transfection and release of the newly synthesised ovalbumin. This work together with studies demonstrating that Nuvec resists chemical and enzymatic degradation affirms the potential of Nuvec as means of oral delivery of oligonucleotides including SiRNA and MRNA.
The next evolution of siRNA therapies is likely to be solutions that deliver more than one molecule intracellularly, rather than using a formulation containing a mixture of two different siRNA, with each one being singularly delivered to a different cell.
In IBD treatment, suppressing the production of the pro-inflammatory cytokines and increasing the presence of the antiinflammatory cytokines should improve the condition significantly. N4 Pharma has shown via in-vitro experiments that it’s possible to load multiple siRNAs onto the same Nuvec nanoparticle for combination therapies.
Conclusion
Sufferers of IBD currently have no option other than to make do with current untargeted
treatments that are difficult to take and carry risks. With the increased investment and development into nucleic acid-based drugs, there is now hope that future treatment will be safer and easier to administer.
The next generation of IBD treatments will focus on achieving effective oral delivery of inflammation inhibitors – whose success depends on improved delivery technologies. If, at the same time, treatment can help promote the body’s own anti-inflammatory immune response, IBD sufferers should benefit from more effective and specific management of this chronic condition.
As research continues into the causes of IBD and more biomarkers are discovered, these targeted treatments provide the opportunity for early intervention, prior to symptoms occurring, enhancing quality of life for IBD sufferers.
REFERENCES
1. What is IBD? | efcca.org
2. de Lange, K., Moutsianas, L., Lee, J. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 49, 256–261 (2017). https://doi.org/10.1038/ng.3760
3. The 'gene deserts' unravelling the mysteries of disease - BBC Future
4. Stankey, C.T., Bourges, C., Haag, L.M. et al. A disease-associated gene desert directs
Figure 1. Graphic of Nuvec particle
Drug Discovery, Development & Delivery
macrophage inflammation through ETS2. Nature 630, 447–456 (2024). https://doi. org/10.1038/s41586-024-07501-1
5. Sands B.E. Biomarkers of Inflammation in Inflammatory Bowel Disease. Gastroenterology. 2015;149:1275–1285.e1272. doi: 10.1053/j. gastro.2015.07.003.
6. Viennois E., Zhao Y., Merlin D. Biomarkers of Inflammatory Bowel Disease: From Classical Laboratory Tools to Personalized Medicine. Inflamm. Bowel Dis. 2015;21:2467–2474.
7. Alghoul Z, Yang C, Merlin D. The Current Status of Molecular Biomarkers for Inflammatory Bowel Disease. Biomedicines. 2022 Jun 24;10(7):1492. doi: 10.3390/biomedicines10071492. PMID: 35884797; PMCID: PMC9312796.
8. 2023 Grand View Research, Inc. Inflammatory Bowel Disease Treatment. MARKET ANALYSIS, 2018–2030 | BASE YEAR - 2022
9. Cunliffe R.N., Scott B.B. Review article: Monitoring for drug side-effects in inflammatory bowel disease. Aliment. Pharm. Ther. 2002;16:647–662. doi: 10.1046/j.13652036.2002.01216.x.
10. Mason M., Siegel C.A. Do Inflammatory Bowel Disease Therapies Cause Cancer? Inflamm. Bowel. Dis. 2013;19:1306–1321. doi: 10.1097/ MIB.0b013e3182807618.
11. Kurosawa M., Nakagawa S., Mizuashi M., Sasaki Y., Kawamura M., Saito M., Aiba S. A comparison of the efficacy, relapse rate and side effects among three modalities of
systemic corticosteroid therapy for alopecia areata. Dermatology. 2006;212:361–365. doi: 10.1159/000092287.
12. Lee Y., Kamada N., Moon J.J. Oral nanomedicine for modulating immunity, intestinal barrier functions, and gut microbiome. Adv. Drug Deliver Rev. 2021;179:114021. doi: 10.1016/j. addr.2021.114021.
13. Atreya R., Neurath M.F., Siegmund B. Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF? Front. Med.-Lausanne. 2020;7:517. doi: 10.3389/ fmed.2020.00517.
14. Shinn J, Lee J, Lee SA, Lee SJ, Choi AH, Kim JS, Kim SJ, Kim HJ, Lee C, Kim Y, Kim J, Choi J, Jung B, Kim T, Nam H, Kim H, Lee Y. Oral Nanomedicines for siRNA Delivery to Treat Inflammatory Bowel Disease. Pharmaceutics. 2022 Sep 19;14(9):1969. doi: 10.3390/pharmaceutics14091969. PMID: 36145716; PMCID: PMC9503894.
15. Herrera-deGuise C, Serra-Ruiz X, Lastiri E, Borruel N. JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases. Front Med (Lausanne). 2023 Mar 2;10:1089099. doi: 10.3389/fmed.2023.1089099. PMID: 36936239; PMCID: PMC10017532.
16. Herrera-deGuise C, Serra-Ruiz X, Lastiri E, Borruel N. JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases. Front Med (Lausanne). 2023;10:1089099. doi: 10.3389/fmed.2023.1089099.
17. Morales-Becerril A, Aranda-Lara L, IsaacOlivé K, Ocampo-García BE, Morales-Ávila E. Nanocarriers for delivery of siRNA as gene silencing mediator. EXCLI J. 2022 Aug 1;21:10281052. doi: 10.17179/excli2022-4975. PMID: 36110562; PMCID: PMC9441682
David Templeton, Technical Director at N4 Pharma, is an experienced R&D manager who has worked in the pharmaceutical and biotechnology industries. He has specific expertise in early clinical development and translational biology, toxicology and safety pharmacology, lead selection, candidate characterisation, PK/ PD analysis and bioanalysis. David has also worked in various pharmacology and pre-clinical drug discovery roles for Pfizer, Xenova, Smithkline Beecham and GSK. He was the head of non-clinical development at Celltech Limited from 2003 to 2004 before moving to Merck Generics UK as head of biometrics. David was appointed as Director of clinical pharmacology of Eisai Limited in 2007. In 2010, he set up his own consulting business offering drug discovery and early development advice to several pharmaceutical companies.
Dr. David Templeton
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Regulatory & Marketplace Drug Discovery, Development & Delivery
HPAPI for Drug Development and Delivery
The increasing global incidence of cancer underscores the urgent need for more effective and targeted treatments. Highly potent active pharmaceutical ingredients (HPAPIs) offer significant potential, providing therapies that specifically target cancer cells while minimising side effects. This article explores the advantages and challenges associated with HPAPIs, including their precise targeting capabilities and reduced toxicity. Here, Lucas SauerJones, Vice President and General Manager at Veranova, discusses the role of contract development and manufacturing organisations (CDMOs) in addressing production challenges, emphasising the importance of advanced analytical techniques, regulatory compliance, and safety measures.
Potency and Processing: How CDMOs Can Rise to the Challenge of HPAPI Development
Highly potent APIs (HPAPIs) have grown in popularity over the last decade and are increasingly enabling innovators to develop targeted, low-dose therapies for patients who need them the most.
These compounds, known for their significant biological effects at very low concentrations, offer immense potential for treating various diseases, including cancer, autoimmune disorders, diabetes and more conditions. However, the journey from molecule to market for an HPAPI is complex, requiring specialised expertise and infrastructure. Therefore, it is crucial to explore how the industry can navigate these challenges to effectively scale up the development and manufacture of these vital therapeutics.
Highly
Potent
and Highly Valuable
Today, nearly 60% of approved oncology drugs involve HPAPIs.1 Their success lies in their ability to kill cells at low doses, reducing side effects and maintaining efficacy over longer durations, which decreases the need for frequent administration. HPAPIs are valuable not only as standalone therapies but also as components in advanced
treatments like antibody-drug conjugates (ADCs). These ADCs target tumor cells precisely and are sometimes described as “silver bullets” due to their ability to minimise damage to healthy cells. This precision has enabled the use of more toxic payloads that were previously deemed too dangerous, offering breakthrough therapies for cancer patients.
What is a HPAPI?
While there is no universal definition for an HPAPI, these molecules are commonly categorised based on control banding strategies, particularly occupational exposure limits (OELs). OELs represent the upper limit on the acceptable concentration of an API in workplace air. Thus, the lower the OEL limit, the higher the potency, which demands rigorous containment and controls. Typically, compounds with OELs less than 10 μg/m³ are classed as highly potent.2
When working with highly potent molecules, ensuring the safety of workers and the environment is the primary challenge. Handling these potent compounds requires substantial planning and expertise. Even minute quantities can pose significant health risks, necessitating effective containment strategies such as closed systems, isolators, and high-efficiency particulate air (HEPA) filtration.
Production line design must minimise operator exposure and ensure safe handling throughout development.
Classifying HPAPIs
To address these demands, the initial step for developers is to classify the API using all necessary data for the OEL. Toxicologists typically set this limit, incorporating data from literature, preclinical and clinical studies, and similar compounds – especially for new chemical entities (NCEs) – to determine the OEL.
Once the OEL is established, the API is assigned to the appropriate Occupational Exposure Band (OEB). This classification determines the risk level of the compound and provides guidance on necessary handling requirements. Most CDMOs utilise either a four- or five-band system to classify APIs.
In the four-band system, compounds falling under bands 3 and 4 (OEL < 10 µg/ m3) are generally considered highly potent and require special handling measures (as shown in Table 1).
For NCEs without an established OEL, the risk assessment process and strategy should be collaboratively developed between the CDMO and its client biotech companies. This
Suggested Design Controls Properties
1 > 500 µg/m3 General room ventilation. Conventional open equipment with local exhaust ventilation (LEV).
2 10–500 µg/m3 Semi-closed to closed material transfer; laminar flow/ directionalised laminar flow, engineered LEV.
3 0.03–10 µg/m3 Transfer using direct coupling and closed systems. Selected use of unidirectional air flow booths.
Compounds that are not harmful and/or have low pharmacological activity.
Compounds that are moderately toxic and/ or have moderate pharmacological activity.
Compounds that are toxic and/or have high pharmacological activity.
Compounds that are extremely toxic and/ or have very high pharmacological activity.
Table 1: Four Band Occupational Exposure Band Control Table
OEB OEL
Drug Discovery, Development & Delivery
involves reviewing preclinical study results, third-party toxicology and EHS assessments, literature searches, and Ames tests and Genotoxicity assessments.
Meeting the Demand
As of 2019, more than 1,000 small molecule highly potent drug products were in development.3 Despite the growing need for HPAPIs, analytical expertise and manufacturing capacity remains limited. The inherent potency and toxicity of HPAPIs require specialised technology and equipment for safe production, making the process both costly and complex.
Furthermore, due to the inherent complexity, developing the necessary human resources and expertise can also be timeconsuming and challenging.
Failure to manage factors like these can result in harm to production employees and the environment, as well as significant
legal and financial repercussions, including substantial fines and long-term reputational damage.
To address these challenges, many pharmaceutical companies are turning to contract development and manufacturing organisations (CDMOs). CDMOs offer tailored expertise and facilities, mitigating risks and providing a competitive edge. But when the cost of failure is so high – how can pharma companies ensure they are working with a CDMO that has the right expertise and capabilities to handle their important molecules?
Overcoming Development Hurdles
Innovators must manage these complex factors while meeting rapid development timelines and complying with regulatory requirements. Flexibility is essential to adapt to emerging issues, ensuring cost efficiency and resolving potential supply chain disruptions.
At Veranova, in response to the increasing demand for highly potent compounds and ADCs in today’s pharmaceutical landscape, we are planning to invest $30 million in our antibody-drug conjugates (ADCs) and highly potent compound manufacturing capabilities at our Devens, MA facility.
This includes a new process-development laboratory and two new cGMP suites designed to handle potent compounds with OELs of less than 0.01 µg/m³. These facilities, equipped to manage high potency compounds, ADC linkerpayloads, and other complex molecules, will feature dedicated air handling systems, airlocks for clean-in-place operations, isolator technology, and a comprehensive range of processing capabilities, including synthesis reactors, chromatography, thin-film evaporators, and lyophilisation equipment.
This substantial investment builds upon the site’s existing development and manufacturing capabilities to increase capacity and support
Regulatory & Marketplace Drug Discovery, Development & Delivery
the delivery of tailor-made solutions to the biopharma market.
Analytical and Process Development
As mentioned, the highly toxic nature and containment requirements of HPAPIs add additional analytical challenges. From accurate quantification to impurity profiling and stability testing, analytical methods are critical to ensuring the efficacy and safety of final drug products.
Managing these challenges is crucial to ensuring HPAPI therapies make it to market without delays or increased costs. Especially, as innovators are increasingly looking to apply HPAPIs in innovative delivery routes and novel modalities. When working with ADCs for example, the inherent complexity of their nature necessitates sophisticated analytical methods for their thorough characterisation, such as high-resolution mass spectrometry, ion mobility-mass spectrometry, and various chromatographic techniques.
However, characterising these biologically engineered molecules can be even more challenging. With the rapid development speeds and scales required, accelerating an innovative ADC design necessitates distinct purification processes and a profound understanding of biologics processing. Collaborating with seasoned CDMO experts, who have access to multiple process characterisation ventures, is key. This partnership provides a resilient framework to guide an ADC molecule from its earliest stages through to market approval.
Regulatory Compliance
Navigating the regulatory landscape for HPAPIs is challenging due to stringent handling and manufacturing requirements. However, the growing need for HPAPI handling has sparked a global trend towards revising the regulatory environment around highly potent compounds and creating a more appealing development and manufacturing pathway for these drug products.
Regulatory agencies such as the FDA and EMA have implemented specific guidelines for HPAPI development, production, and testing. Today, many new chemical entities are approved as "breakthrough therapies." For developers looking to leverage such fasttrack designations, flexibility in development and manufacturing is essential to meet the accelerated demands that result.
Yet, the strict processing protocols and containment processes of HPAPI drug
development can limit how a production line responds to those requests – unless flexibility is built in from the start. Collaborating with the right CDMO can ensure an HPAPI programme is ready to adapt throughout the approval process.
Building a team with strong regulatory expertise is crucial for navigating the complex regulatory landscape. Hiring professionals with experience in HPAPI development and maintaining open communication with regulatory bodies ensures compliance. Staying updated on regulatory changes helps preemptively address potential compliance issues.
Meeting Highly Potent Complexity with Confidence
The rise of HPAPIs represents a significant advancement in targeted therapy, with the potential to revolutionise treatments for cancer and other serious diseases. However, their development and manufacturing presents unique challenges that require specialised expertise, advanced infrastructure, and stringent regulatory compliance.
As the demand for these potent compounds grows, collaboration with specialised CDMOs provides drug developers with a tool to meet the dual requirements of safety and innovation.
Ultimately, strategic partnerships between pharmaceutical companies and CDMOs will be key to meeting the increasing need for targeted, effective treatments, driving forward
the next generation of medical breakthroughs, and improving patient outcomes worldwide.
2. Mahdi, M 2020, Getting a Handle on High Potency: Panel Discussion, The Medicine Maker, viewed January 2023,
3. HPAPI Panel Discussion 2022, Chemistry Today, viewed January 2023.
Lucas Sauer-Jones, Vice President & General Manger, New England , has over 10 years of experience in the medical and pharmaceutical industry. He joined Veranova in 2023 as Vice President and General Manager, New England, where his extensive experience establishing high-performing teams helps to drive operational excellence. Prior to joining Veranova, Lucas held the position of General Manager at Curia, a global CDMO, and Operations Director at AngioDynamics, a cardiology/radiology medical device manufacturer. Lucas previously served as a sergeant in the United States Marine Corps and holds a B.A. in Business Economics from the University of Albany.
Lucas Sauer-Jones
The Use of Autoinjectors for Autoimmune Diseases: Advancements,
Benefits, and Considerations
With autoimmune diseases cumulatively affecting 5 to 10% of the industrial world population, the global market for autoimmune therapeutics is set to grow at a CAGR of 3.7% between 2024 and 2031 and is anticipated to reach $200 billion by 2031.1
Autoimmune diseases, such as Rheumatoid Arthritis, Multiple Sclerosis, Lupus, and Crohn’s disease, involve the immune system mistakenly attacking the body’s own tissues. Treatments for these conditions typically aim to regulate immune responses, reduce inflammation, and alleviate symptoms.
Autoinjectors have emerged as a valuable tool for administering medication to help in the management of these chronic illnesses, providing a practical solution that enhances the effectiveness of treatments. This article explores the role of autoinjectors in treating autoimmune diseases, their benefits and impact on patient care and outcomes, together with best practice guidance on developing an autoinjector drug device combination product for autoimmune diseases.
Understanding Autoimmune Diseases and Treatment Needs
Autoimmune diseases are a family of more than 80 chronic and often disabling disorders in which the immune system becomes hyperactive and attacks the body's own cells, mistaking them as foreign invaders. This immune dysfunction leads to chronic inflammation, tissue damage, and a wide range of symptoms depending on the affected organs or systems.
• Multiple Sclerosis (MS): Damages nerve cells and the central nervous system, impairing movement and cognition.
• Lupus (Systemic Lupus Erythematosus): Causes widespread inflammation affecting the skin, kidneys, brain, and other organs.
• Crohn’s Disease: Involves chronic inflammation in the digestive tract.
Management of these diseases often includes immunosuppressive and antiinflammatory medications, such as corticosteroids, biologics, and diseasemodifying anti-rheumatic drugs (DMARDs). These medications require precise, consistent dosing to be effective and avoid adverse effects, which presents challenges, especially for patients requiring frequent injections and who often have dexterity challenges.
What are Autoinjectors?
Autoinjectors are medical devices designed to simplify the administration of injectable therapies. They are typically prefilled, singleuse syringes with a spring-loaded mechanism that delivers a set single dose of medication. Autoinjectors are designed for ease of use, with as few as two steps, making them accessible for self-administration without the need for healthcare provider assistance. The device is activated by pressing it against the skin, which triggers the needle to penetrate and deliver the medication.
Common features of autoinjectors include:
• Prefilled and premeasured dosages: autoinjectors are designed to administer precise doses of drug products, ensuring accurate and consistent delivery. By automating the injection process, autoinjectors minimise the risk of human error, providing a level of accuracy that is paramount in the treatment of complex conditions such as autoimmune and chronic diseases.
• Automatic needle retraction: The automated injection process reduces the likelihood of accidental needle stick injuries, enhancing safety for both patients and healthcare providers.
• Compact, portable and user-friendly design: These devices empower patients to self-administer medications in the comfort of their homes or on-the-go for those with active lifestyles, eliminating the need for frequent hospital visits. The user-friendly design of autoinjectors, often featuring intuitive interfaces and
ergonomic grips, enhances patient compliance and reduces anxiety associated with traditional injection methods. This change towards at-home administration not only improves patients' quality of life but also reduces the burden on healthcare infrastructure.
Due to their user-friendly design, autoinjectors are widely used for conditions like severe allergies (epinephrine for anaphylaxis) and hormone therapy (insulin for diabetes). However, their utility has expanded significantly over recent years to treat autoimmune diseases, driven by advancements in both biologic treatments and patient-centred drug delivery technologies.
Benefits of Autoinjectors in Autoimmune Disease Management
Autoinjectors have made a notable impact on the treatment of autoimmune diseases by addressing common challenges in injectable therapies and making self-administration easier and more convenient for patients managing chronic conditions. Key benefits driving the growing adoption of autoinjector usage include:
a. Improved Patient Compliance and Convenience
Administering injections for autoimmune diseases can be a challenging, unpleasant, or even a painful task, especially for patients with limited dexterity or fear of needles. Autoinjectors reduce the complexity and discomfort of injections, enabling patients to administer medications with minimal effort. This simplicity encourages better adherence to prescribed treatment regimens, which is essential for disease management and symptom relief.
b. Consistent
and Precise Dosing
For biologic drugs, which are often delicate and expensive, consistent dosing is vital to maintain therapeutic levels in the bloodstream. Autoinjectors provide premeasured doses, ensuring each injection is accurate and reducing the margin for user error. Precision is particularly important in autoimmune therapies, where under- or overdosing
Regulatory & Marketplace Drug Discovery, Development & Delivery
can lead to suboptimal results or increased side effects.
c. Reduced Dependency on Healthcare Facilities
Autoinjectors allow patients to administer their own medications at home, reducing the need for frequent hospital or clinic visits. This shift to home-based care reduces healthcare costs and alleviates the burden on healthcare systems. It also offers patients more flexibility and control over their treatment schedules, which can improve their quality of life.
d. Enhanced Safety and Hygiene
Autoinjectors are designed to minimise the risk of needle stick injuries and contamination. Many autoinjectors retract the needle after use, preventing accidental needle stick injury and facilitating safe disposal. By providing a sterile, single-use device, autoinjectors reduce infection risks, which is especially important for immunocompromised patients.
The
Future of Autoinjectors in Autoimmune
Disease Treatment
Ongoing advancements in technology are likely to not only enhance the efficacy and user experience of autoinjectors, but also advance the prospects of both higher volume and higher viscosity deliveries. Innovations in smart autoinjectors equipped with Bluetooth and digital interfaces may allow patients to
track dosage history, receive reminders, and share information with healthcare providers in real-time. These connected devices could further improve adherence, especially for patients who require regular, long-term treatment.
Moreover, continuous investment in R&D is driving improvements in drug formulations which enables smaller dosages with extended effects, reducing the need for frequent injections. For example, “microneedles” that painlessly penetrate the skin or nanoparticle-based drug delivery systems could offer alternatives for patients who struggle with traditional injections.
Best Practices and Strategies for Developing an Autoinjector for Autoimmune Therapies
Along the journey to commercialisation of autoinjectors for your autoimmune therapy, there are several key considerations and best practices to help ensure a smooth and efficient process, including:
• Human Factors Engineering (HFE): Is critical in autoinjector design, ensuring regulatory compliance and provides valuable patient feedback. With a patientcentric focus, interaction between users and the product as-received is paramount. Understanding how patients interact with the packaging, IFU, and device itself is vital for optimising usability, minimising user errors, and enhancing overall
safety, efficacy, and adherence to gain improved outcomes. Conducting usability studies and incorporating human factors considerations early in the design process can help identify potential issues and inform design modifications. Human factors and usability engineering is an integral component of regulatory submissions and is essential for demonstrating the product's usability and user comprehension.
• Device strategy:
From phase IIb clinical trials seek to make decisions on the therapy’s drugdevice strategy. By considering the Target Product Profile (TPP) / Quality Target Product Profile (QTPP) earlier in the clinical development cycle, decisions can be made if there is a unique need for device innovation for specific patient populations or if traditional, readily available platforms would be suitable. Established platforms may lower risk and speed market entry, enhancing firstto-market advantage. For innovative devices, securing intellectual property (IP) rights is essential to protect drugdevice combinations and maintain competitive positioning.
• Early collaboration:
Establish cross-functional teams of all internal and external stakeholders involved in the development process, including CMC scientists, packaging
Drug Discovery, Development & Delivery
engineers, process and testing engineers, regulatory experts, quality assurance professionals and patient focus groups. Fostering collaboration and open communication ensures alignment of goals, troubleshooting and efficient execution pathways from the outset.
• Risk management:
Proactively identifying and addressing potential risks, such as technical challenges or regulatory hurdles, helps mitigate delays and ensure project success. At the earliest stages, stakeholders should collaborate on control plans and mitigations with the commitment to regularly re-evaluate key aspects such as FMEA, evaluation of real-time data, and impacts to future plans.
• Iterative development:
Embracing an iterative approach allows for continuous refinement and optimisation based on feedback from patients themselves through user testing, regulatory feedback, and market insights.
• Regulatory compliance:
Ensure compliance with regulatory requirements for your drug-device in the target markets. This includes adherence to relevant guidelines for drug product packaging, device design, quality control, and documentation. Drug-device combination filings have very defined and elevated requirements, and stakeholders need to understand these requirements from the onset of their programme.
• Flexibility and Adaptability:
Maintain flexibility and adaptability throughout the development process to accommodate any unforeseen challenges
or changes in project requirements. Be prepared to adjust timelines, resources, and strategies as needed to optimise your autoinjector to meet the needs of your patients.
Conclusion
Autoinjectors represent a significant advancement in the treatment of autoimmune diseases, enabling patients to manage their conditions more independently and effectively. By improving convenience, ensuring precise dosing, and reducing dependency on healthcare facilities, autoinjectors enhance patient outcomes and quality of life. Despite some challenges, such as cost and the potential for device malfunction, the benefits of autoinjectors are substantial. With continued innovations, autoinjectors hold the potential to further transform autoimmune disease treatment, making it more accessible, user-friendly, and adaptable to individual patient needs.
The future of autoinjectors in autoimmune care looks promising, with the potential for
more sophisticated devices and formulations that empower patients to live healthier, more autonomous lives. As these technologies evolve, they will likely play an even more prominent role in managing autoimmune diseases, reshaping the landscape of chronic disease management.
Justin Schroeder is responsible for ensuring PCI’s global clients realise seamless lifecycle management and successful commercialisation of their therapies. Across 25 years of experience in outsourced pharmaceutical services, he has held leadership roles in various functional disciplines in global roles including Package Engineering and Design Development, Project and Programme Management, Marketing, Business Development, and progressive roles in senior executive leadership. In his current role he leads various functional disciplines in the creation and application of innovation solutions for clients with a focus on optimised drug delivery systems for patients, adaptive supply chain architecture, and strategies for short and long term lifecycle management.
Justin Schroeder
Striving for Clinical Trial Success? It Starts
with One Crucial Choice
Complex drug formulations, stringent regulatory standards, and a tough capital landscape are creating pressure for drug developers as they approach clinical trials. At this stage, a wrong decision could mean significant delays to a product’s timeline, increased costs, and even jeopardise the success of years of research.
More than ever, drug developers need strategic thinking and expert support to begin their in-human trials. During this critical early development stage, the right Contract Development and Manufacturing Organisation (CDMO) can be more than a valuable service provider—they can be a vital partner.
As Director Supply Chain and Project Management at Vetter, my colleagues and I have successfully partnered with various customers from large pharma to start-ups to bring their new molecules through the process of clinical manufacturing for their in-human trials. Up to this point, Vetter has successfully conducted over 1,000 batch fills at its two clinical sites in the U.S. and Austria. In this article, I will outline how drug developers can focus on their key competencies but also what they have to consider to start the challenging path through early clinical phases.
Begin by Finding the Right Outsourcing Partner
Most pharmaceutical and biotechnology firms have expertise in drug development but may lack the necessary infrastructure, specialised knowledge, experience, or resources to manufacture clinical trial materials (CTM) at scale. This critical step of drug product development requires precise formulation, packaging know-how, and regulatory documentation, all of which are essential to manage the integrity of the in-human trial.
Fill and finish CDMOs focus on providing the CTM, such as filled vials or syringes, in accordance with regulatory standards. The drug products and accompanying documentation are then provided to the drug developers, who use them in their clinical studies. The global clinical trial supplies market size was estimated at USD 2.58 billion in 2023 and is
anticipated to grow at a compound annual growth rate (CAGR) of 6.5% from 2024 to 2030.1 As this market grows, selecting the right filling CDMO becomes even more critical for supporting a successful clinical trial. Here are some steps drug developers can take to evaluate and select the best partner for their unique molecule:
Step 1: Conduct Comprehensive Research
Before starting the search for an outsourcing partner, it’s critical to thoroughly research potential partners that align with your criteria. Leverage resources such as online databases, industry publications, peer recommendations, and testimonials to gather insights. Check for important credentials like regulatory compliance. Gain an understanding of the different niches of potential partners, as some may have specific core competencies.
Step 2: Set Clear Objectives and Expectations
Having a solid understanding of your needs will help streamline the selection process and effectively communicate key requirements. Knowing your objective ahead of time will allow a potential partner to understand your needs.
Additionally, consider critical expectations regarding quality, timelines, budget, and deliverables. The ability of a manufacturing partner to meet the quality and scale requirements of a project is paramount. Biopharma companies benefit from working with experienced service providers who are familiar with a variety of molecules. This expertise enables the effective handling and manufacture of a wide range of compounds.
Step 3: Assess Fit and Compatibility
After narrowing down your options, evaluate the compatibility of potential partners with your needs. This can be achieved through consultants, interviews, site visits, reference checks or even audits. It's important to confirm that the partner’s culture, values, and vision align with your own.
Long-term partnerships are built on early alignment and strong relationships. We currently work with a wide range of customers from over 20 different countries. These include the global big pharma and biotech
companies, as well as start-ups developing their first compound. Looking more closely at our early clinical business, around 70% of our clients have less than 200 employees. Each customer and their molecule require a different approach, making each project unique.
Pay attention to their communication style, transparency, and how they manage feedback and change. Trust, respect, and collaboration should also be key factors in your decision-making process. Even if they are a top-performing service provider, they may not be the right fit for every drug development company. There is no harm in passing on a five-star partner if they’re not suited for your specific needs. When exploring partnership options, remember to think beyond current requirements. Look for a CDMO that can help meet the immediate milestones and support throughout the entire product life cycle. Even better, look for a partner that is making investments in capacity now to allow room for expansion in the future.
Next, Build a Plan with Your Selected Partner
Once the right partner is in place, it’s time to focus on execution. For injectable drug products, the transition from preclinical to clinical manufacturing is a vital development step – and one that involves much more than simply scaling production of an active pharmaceutical ingredient. The planning process should carefully consider timelines, batch sizes, packaging material, testing protocols, and supply chain. Think of this as a detailed onboarding process. The more that both partners can share openly at the onset, the better suited the CDMO will be to develop a filling process to get the first clinical trial batch right.
Successfully navigating the process takes experience and careful planning. Here are some of the key ways a CDMO for clinical development can help support that success through a comprehensive partnership strategy:
Identifying Development Needs
The right CDMO for your clinical trials will assess the progress made so far, identify the next necessary steps, and establish realistic timelines for CTM that meet the
stringent requirements for human use. They provide essential expertise in scaling up production, interpreting analytical methods, and maintaining regulatory compliance for injectable drugs. For example, if the primary packaging will play a role in the injectables' efficacy, a strong partner will address the time and supply chain considerations at the onset to proactively address potential hurdles before a timeline is agreed upon.
Mapping the Regulatory Pathway
CDMOs with experience manufacturing CTM possess a deep understanding of regulatory expectations for different drug substances, delivery formats, and more. A knowledgeable partner can offer valuable insights that help maintain proactive compliance with evolving regulatory standards, like the most recent revisions to Annex 1. Annex 1, which governs the manufacture of sterile products in Europe, has introduced stricter guidelines on aseptic processing, environmental monitoring, and contamination control.
Proper interpretation of these standards is critical, as missteps in compliance can lead to costly delays or, worse, failures in regulatory approval. A CDMO with engrained expertise in interpreting and implementing these updates helps maintain that the first clinical batch adheres to all the necessary protocols, minimising risks and positioning your drug for successful regulatory review.
Evaluating the API
CDMOs evaluate the API to determine its suitability for CTM production, including formulation support, handling requirements, and sourcing. They maintain that the compound is processed correctly to manage product integrity. Service providers with specialised experience developing CTM can accurately determine the required amount of API for the target quantity of CTM, while also checking that the API is properly handled, stored, and protected during clinical
Clinical and Medical Research
manufacturing based on detailed information provided by the customer.
Selecting an Optimal Container
A CDMO helps choose the right container for your drug product, considering factors like patient needs, product efficacy and market trends. They guide decisions on whether to use vials or syringes and plan for future responsibilities and licensing requirements. An understanding that clinical trial packaging may have different requirements than commercial packaging is important to get the first CTM batch right and achieve the desired outcome.
Transferring and Adapting Analytical Methods
CDMOs support the evaluation of methods and adoption of Standard Operating Procedures (SOPs) for clinical scale production. They maintain that quality attributes and process parameters are aligned with regulatory standards and that testing methods are effective.
In the pharmaceutical industry, method transfer is a critical element of quality control in the drug development process. Close collaboration with our customers is essential to transfer their product-specific and with phase appropriate qualification to our manufacturing environment. With a wide range of services and methods, our analytical experts have the flexibility to perform transfers of a variety of analytical methods.”
Building a Project Timeline
Collaborating with an experienced manufacturing partner allows drug developers to create a well-informed, strategic and realistic timeline for their CTM project, which is essential for accurate scheduling and budgeting.
Thorough planning often can make all the difference as the decisions you make early in
the process can have a significant downstream impact on your product’s development. It is also important to have all the necessary information about your drug substance and address potential logistic, technical and regulatory hurdles proactively.
Finish With Clinical Trial Success
Outsourcing clinical trial material manufacturing is a complex decision with longlasting implications on the path to clinical development. Be sure to select a CDMO partner that prioritises quality, has the necessary experience, demonstrates flexibility, and understands the urgency of your timeline.
A successful partnership with the right CDMO could mean the difference between a smooth transition from preclinical to clinical and successful path through early-stage development and costly delays, so make sure to evaluate all potential partners carefully and with the above considerations top of mind.
Mark Rauckhorst, Director Supply Chain & Project Management, Vetter, joined Vetter Development Services USA in 2013 as a Project Manager, focusing on early phase clinical projects at Vetter’s first U.S. site in Chicago. In 2022, he was promoted to Director Supply Chain and Project Management. Prior to joining Vetter, Mark was a Project Manager at Regis Technologies where he managed custom synthesis manufacturing projects with the focus on process research development, non-cGMP manufacturing, and cGMP production of Phase I & II clinical trial materials.
Mark Rauckhorst
Dry Granulation: Efficient Production of Oral Solids for Industrial Applications
When developing a tablet, three widely used technologies are often considered to produce solid dosage forms: direct compression, wet granulation and dry granulation. Wet granulation remains the most widely used method, but it has got limitations regarding moisture and heat-sensitive drugs, coupled with costly, labour intensive, and timeconsuming processes.
Continuous dry granulation or roller compaction has been a well-established method in the pharmaceutical business for decades, and it is used for more than just moisture and temperature-sensitive products. It offers several advantages to manufacturers such as overall cost-of-goods, energy consumption and/or environmental impact, as well as the potential to scaleup from development to full-scale cGMP commercial production using the same equipment.
Dry Granulation in Different Industries
In the pharmaceutical industry, the dry granulation process is essential for the production of tablets, capsules, pills and effervescent dosage forms. In recent years,
dry granulation applications have gained more attention due to their efficiency and the push toward continuous manufacturing.
Dry granulation is used in the food industry to produce a wide variety of products, including: nutritional supplements, vitamins, spices, additives, flavours, soups and sauces.
In recent years, the nutraceutical industry has become increasingly important. In the nutraceutical industry, dry granulation is used to produce dietary supplements, including: multivitamin supplements, herbal extracts, or protein powders. The resulting granules are then compressed into tablets or capsules.
Dry granulation also plays a key role in the chemical industry by improving handling and storage properties, making it the perfect approach for producing non-clumping anticaking agents, food additives and catalysts. It also improves the cleaning performance of detergent powders.
Fertilisers, pesticides and other insecticide powders are routinely processed for agricultural purposes. Thus, dry granulation process is a common practice in
agricultural industry. It also improves agricultural powder properties and reduces quality variations.
How Does the Machine Work?
During roller compaction, a blend of the API and intragranular excipients is passed between two counter-rotating rollers to generate ribbons. In the roller compactor, the blend experiences increasing pressure, reaching a peak before ribbon release.
The goal of granulation is to take fine, non-compactable powders and turn them into coarser agglomerates that can be pressed into tablets. Agglomerates can be composed of dry, solid granules, where each granule represents an agglomerate of primary particles with sufficient solidity.
In the dry granulation process, agglomerates are created through mechanical pressure alone.
Dry granulators differ in their roller arrangement: there are systems with horizontal, vertical and inclined rollers.
Horizontal rollers have the advantage that the screws are better ventilated and the flakes are discharged over a short distance.
The space between the rollers is divided into three zones. In the sliding zone, the particles are pre-compacted. In the compaction zone, the main compaction of the particles is achieved by deformation or particle breakage (depending on the material). The third zone is the material discharge.
Another difference is whether the gap is variable or not. In variable gap dry granulators, continuous measurements ensure that the gap between the rollers is always parallel. In addition, the screw speed and gap adjustment are linked so that when the gap opens, the screw transports less material into the gap and the gap closes again. This automatic control produces flakes of defined thickness and porosity across the entire width of the roll.
The powder is compacted between two rollers with specified gap widths. The impact on the rollers, as well as the gap width, is monitored via sensors and there is also the option to install process analytical technology (PAT). All data are integrated into a control circuit to ensure continuous process quality, while an electromechanical drive provides precise and fast control. The chopper unit below the compacting rollers processes flakes into a granule at a defined
granular size, and the unit is equipped with a conical sieve with replaceable inserts for different particle sizes. Even at high material throughputs, the cone-shaped sieve and its inserts gently crush the ribbons into granules with the desired particle size distribution.
The milling step has a substantial impact on the particle size of the granule. L.B. Bohle (Ennigerloh, Germany) offers a variable sieve setup for their BRC dry granulators. Milling the flakes into a granule with the desired range of particle dimensions is performed by the conical Bohle Turbo Sieve Mill (BTS) and sieve inserts with very little waste – even at a high throughput rate. Every BRC can be re-fitted in a matter of minutes to serve as an alternative oscillating sieve and adapted flexibly to the process and flake conditions.
Electro-mechanical Drive Instead of Hydraulic Systems
Similar to the automotive industry, manufacturers of pharmaceutical machinery are turning to alternative drives instead hydraulic systems. L.B. Bohle relies on electromechanical drive systems for its BRC series dry granulators. This is a sustainable and resource-conserving approach, as there is no need for regular oil changes. In addition,
the properties of the oil change over time: the aging of the oil and the control valves can have a negative effect on the compressibility and therefore the precision of the system. Eliminating oil drives is also less energy intensive because they do not need to be cooled during the process. Oil leaks in the cleanroom are also eliminated.
Hygienic Design, Operator-friendliness and Ease of Use
L.B. Bohle´s BRC 25 and BRC 100 are flexible and mobile plug & play machines. All components are integrated in the system and an external control cabinet is not required. Due to the low height, the machines do not require a ladder or step which is needed by some other machines found on the market.
The hygienic design strategy from concept to implementation guarantees optimised accessibility to all process relevant parts regarding cleaning, assembly and disassembly. Virtually tool-less assembly/ disassembly can be done in less than 10 minutes.
The machines are built in 100 % stainless steel with no use of plastic parts. Easy, fast and effective cleaning is realised by a WIP
(Washing in place) cleaning as standard. Simple cleaning from the outside is also guaranteed.
The large front door enables convenient access and an opening in seconds. Due to a tongue and groove connection, the rolls can be positioned easily. For roll positioning a cost-intensive handling aid is not needed.
High Flexibility in Throughput and Integration
Dry granulators are suitable for both large and small batch sizes. The BRC granulators enable a product capacity, capable of handling a production range of less than 1 to 400 kg/h.
Although roller compaction is a continuous manufacturing process, all machines can
be used as a stand-alone machine that produces a wide range of tablets in a batch format.
Beside the use as a stand-alone unit, the BRC roller compactor can be easily integrated into other (interlinked) systems, such as continuous manufacturing systems that produces from powder to the coated tablet.
Containment applications? No problem
Containment is an increasingly important term in the pharmaceutical industry. It describes the process of enclosing a substance in a defined space, a method of product handling suitable for protecting operators and the environment when products are highly toxic and reactive.
At the same time, containment prevents the release of dust, gases or vapours into the environment and contamination of the product.
More than 60 percent of pharmaceutical products are manufactured in the form of tablets, capsules, dragees, or the like. For newer products in particular, the active pharmaceutical ingredients (APIs) are becoming increasingly important to their efficacy. In some markets, the High Potency Active Pharmaceutical Ingredients (HPAPI) market segment is growing at doubledigit rates, driven primarily by oncology drugs.
In addition to the technical production requirements, the safety of the product for the machine operator, and of course for the patient, is essential. As a result, machine manufacturers such as L.B. Bohle are constantly faced with new challenges in all toxicity classes in which customers want to use systems and processes.
Containment versions are developed to individual customer specifications with a focus on compliance up to containment level OEB 5, convenient access and easy product handling. This has necessitated many special features such as an integrated isolator unit in the compaction unit, a glove box for scab removal, and additional containment ports. In the end, suppliers offer user-friendly and low-maintenance dry granulators with very short set-up times for fully contained operation without the need to clarify and implement interfaces between system components.
Tobias
Borgers
Tobias Borgers is a professional in Marketing, with a wide experience of multi-channel marketing initiatives. He has proven abilities in creating successful exhibitions, integrated digital and traditional marketing campaigns, social media marketing, content management, lead generation, event and project management. Tobias holds a B.A. from University of Duisburg-Essen and joined L.B. Bohle in 2012.
Email: t.borgers@lbbohle.de
PYROSTAR™ Neo+
Recombinant Endotoxin Detection Reagent Plus...
PYROSTARTM Neo+ is based on a genetically engineered approach to produce reactive factors required for endotoxin detection at pharmaceutical and medical equipment manufacturing sites. With greater stability of the negative control and better endotoxin recovery in heparin and heparin-based compounds, Neo+ facilitates the same sensitivity of endotoxin detection as our traditional limulus amebocyte lysate (LAL) reagent, through a more sustainable and environmentally friendly method.
Plastics Production with Mass Balance and Alternative Feedstocks
Global warming is a critical consequence of using fossil feedstocks to produce plastics and energy. In addition, the reserves of fossil feedstocks are going to run out in the next decades considering the actual depletion rates. These, among other considerations, highlight the urgency for a quick transition towards more sustainable feedstocks alternatives, with the need of combining different complementary solutions, from biobased feedstocks to circular feedstocks.
The quickest way to scale up this transition can be reached by feeding the petrochemical cracking units with sustainable alternative feedstocks instead of fossil feedstocks. Such new feedstocks can come from advanced recycling routes from waste of different types (bio-based (e.g. organic waste, used cooking oil), circular (e.g. plastics waste) or mixed (e.g. used tyres with biogenic certified content) and can be added to the crackers in form of pyrolysis oil, hydrotreated vegetable oils, etc. substituting fossil oil in a certain percentage).
As first ABS plastic manufacturer to get the ISCC+ certification, ELIX Polymers includes in its polymerisation process input monomers with certified origin from pyrolysis oils (chemical recycled waste) or bio-based feedstocks. The types of waste and bio-based sources are the ones described above. The implemented ISCC+ traceability certification system guarantees the circular or bio-circular loop and the inclusion of waste as feedstock alternative. ABS with ISCC+ certified recycled or bio-attributed content has the exact chemical composition as virgin ABS from fossil feedstocks. For this reason, a medical ABS ISCC+ certified from recycled and bio-attributed feedstocks maintains biocompatibility properties according to ISO10993 and is fully compatible with all stringent regulatory requirements of the medical device sector. The adopted ISCC+ certification follows a mass balance approach.
In this article, we explain the importance of a mass balance approach for plastics
production (note: not for fuel production), making specifical reference to ABS plastics production as example. This topic, called mass balance fuel-use exempt, has been already recognised by many associations in the plastics supply chain and exposed to the European Commission to take quick actions. With such approach, the recycled or bio-attributed content is formally assigned from raw materials to production lots that correspond to the orders of specific OEM customers and moulders.
These customers are only the ones who contribute to the switch from fossil feedstocks to sustainable feedstocks, including biobased feedstocks and chemical recycled waste. Because it is a pure accounting method, the sustainable feedstocks are physically distributed in all the material batches produced, including the ones that are supposed to contain only fossil feedstocks. Nevertheless, it would be an injustice to recognise the choice of sustainable alternatives also to those customer OEMs who are not making any effort for it. For this reason, the concept of sustainability credits is introduced, to grant only the OEM or moulder who specifically purchase them to get the sustainability benefits of ABS material in terms of CO2 emissions reduction, reduction of fossil depletion rate and chemical recycled waste content or bio-attributed content.
The mass balance approach exists because we are living a transition period from fossil to sustainable feedstocks. This transition would take too many years and much heavier investments to reach the scale of volumes required to make the difference. There is not enough time, since it is estimated that fossil feedstocks will run out in few decades counting from today. As previously mentioned, the sustainable feedstocks in form of oil (e.g. pyrolysis oil or hydro-treated vegetable oils) ISCC+ certified can directly substitute fossil oil. These oils are used to feed the petrochemical crackers, to produce the basic molecules (e.g. ethylene, benzene) that are used in the plastics supply chain, including ABS materials.
The substitution process needs a mighty scale-up in volume of sustainable feedstocks, that should be able in the future
to fully substitute fossil oils extracted from the ground. We are talking about hundreds of millions of metric tons of oil used annually to produce plastics, a very much higher order of magnitude than the total volume in tons of mechanically recycled plastics worldwide. Much powerful and complementary recycling technologies are needed, for both synthetic and bio-based waste feedstocks. Out of the approximately 4.5 billion metric tons of global fossil crude oil produced in 2023,1 629 million tonnes have been used to produce plastics. This is approx. 14% of global fossil oil production, one in seven barrels of all fossil oil produced worldwide.2
The 629 million tonnes produced annually, a figure that is expected to increase in the coming years, represent the volume of fossil feedstocks that needs to be substituted with sustainable feedstocks (bio, circular, or bio-circular). The great challenge is in identifying enough volume of sustainable sources to be able to generate the hundreds of millions of tonnes of oil replacement. Sustainable sources are limited and compete in other markets (e.g. fuel market), so the priority should be identifying them as soon as possible, and promote investment in the optimisation of conversion rates. When the shift from fossil to sustainable feedstocks will be completed (even if we start from now, it will take many years if not decades), the mass balance approach will have accomplished this key task of progressive substitution and investment push into sustainable alternatives and solutions. All the plastics down-streams, including ABS manufacturers and plastics OEMs and converters, will buy only sustainable feedstocks for their existing plants, with no fossil content anymore.
Let’s take a closer look at chemical plants for plastic production. They require a significant amount of money to be kept in operation and for relevant lead times to be built. They cannot be easily duplicated to keep the fossil and the sustainable raw materials in separate production process flows. They cannot start buying only sustainable feedstocks, since there isn’t enough existing demand that has been generated yet, and they would not be competitive in their respective market anymore. The fixed costs
of chemical plants are only covered if the volume of production represents a relevant percentage of the total annual production capacity. Consequently, if production capacity cannot be reasonably covered by market demand volumes, there is a clear risk of shut down for the chemical production plants.
On the other hand, chemical plastic plants (and plastic moulders and OEMs along with them) can start to move away from fossil feedstocks from now, creating the demand for bio-based and advanced recycled sources at the upstream level of the supply chain. This stimulates other types of massive investments that are required now, and with higher urgency. For example, the basic research to increase efficiency levels of waste recycling, the construction of advanced recycling plants, and the scale up in volume of recycled waste oils as new alternative feedstocks. Finally, immediate attention should be given by petrochemical companies for the optimisation of their cracking processes, to focus their efficiency and cost reduction on sustainable oils instead of fossil oils.
Regarding the investment in research to increase waste recycling efficiency, it is a key point considering how limited mechanical recycled feedstocks are. The limitations are in terms of achievable recycled volumes, which are related to their waste conversion rates and to the quality of the resulting material when compared to virgin material. According to estimations, mechanical recycling output will surpass 54 million tonnes by 2030,3 nevertheless, this will not be enough to consider it as standalone sustainable solution.
The presence of impurities and contaminants in the mechanical recycled material is also a key concern factor. This explains the need of a clear traceability certification system for mechanical recycling processes, to identify potential associated risks of the resulting material and its aptitude to fit certain final applications. There are clear application limitations according to the recycled quality level that can be achieved.
As previously mentioned, nowadays, only a low percentage of waste intended for recycling can be mechanically recycled and reintegrated in the supply chain of plastic production. Consequently, the nonmechanical recyclable material is sent to incineration along with the rest of waste, which leads to very high CO2 emissions in the environment. In the worst case, it would
be sent to landfills, which results in an even greater negative environmental impact.
Chemical recycling, also called advanced recycling, can treat the waste feedstocks that cannot be handled through mechanical recycling. This means that advanced recycling is complementary to mechanical recycling as it addresses the different types of waste feedstocks. The percentage of waste recyclability is increased, the emissions of incineration are avoided and sustainable feedstocks that can feed the petrochemical crackers are provided, which reduces and progressively substitutes the need of fossil feedstocks. Additionally, high-end applications can be covered, even the ones with the most stringent requirements, like in the case of medical devices.
The carbon footprint emissions associated with advance recycling are improving thanks to research in existing types of waste that can be more efficiently collected, sorted and chemically recycled. Heavier investments in recycling technologies and processes are needed to optimise conversion rates and volume scale up. This is another important reason why the mass balance approach is now essential and plays a crucial role in supporting these efforts. Carbon footprint calculations include three types of emission contributions: direct emissions from production facilities (scope 1), indirect emissions from energy purchased (scope 2), and other indirect emissions from purchased raw materials and logistics upstream and downstream (scope 3). Among them, purchased raw materials (part of scope 3) represent by far the highest impact on CO2 emissions.4
In the case of ABS material production (which includes polymerisation and compounding activities), the purchased monomers provide the most important contribution in the total ABS CO2 emissions (measured in Kg of CO2 emission per Kg of ABS). By producing monomers starting from advanced recycled or bio-based feedstocks, the CO2 emissions associated with these raw materials can be considerably reduced, with a clear positive impact in the carbon footprint of the final ABS material.
In conclusion, a mass balance approach along with an efficient traceability certification system (e.g. ISCC+ certification) represent a key route to scale up volumes in the urgency of replacing fossil feedstocks with sustainable feedstocks for plastics production. Chemical recycling from waste
Manufacturing
feedstocks and bio-based feedstocks will be needed, and mechanical recycling will be required to grow too. Even counting on all that together, it will be challenging to substitute fossil oils with sustainable oils completely. The reasons for this are the limited availability of sustainable sources, their competitive use in alternative market (e.g. fuels) and the need of stronger investment in recycling technologies. The most crucial factor is to get a legislative push from governments to get the key supply chain players onboard as soon as possible, and willing to adopt such solutions, including chemical and mechanical recyclers and investors, petrochemical companies, plastics manufacturers, plastics converters, OEM manufacturers, and final consumers.
Luca Chiochia, Business Development Manager, ELIX Polymers, graduated in management engineering at the "Politecnico di Milano" University (Milan, Italy). He has 20 years’ experience in the fields of plastics, composites and OEMs devices. Luca joined ELIX Polymers in 2017 as a Business Development Manager for the healthcare strategic sector. Since 2020, he is actively involved in the development of ELIX E-LOOP sustainable solutions and circular innovations. This includes a new and developing sustainable ABS and blends material portfolio, with chemically recycled, bio-attributed, bio-based and mechanically recycled content.
Email: luca.chiochia@elix-polymers.com
Luca Chiochia
Innovations in ATMP Manufacturing: Preparing for the ATMP Revolution with Innovative Cleanroom Design
The rise of advanced therapy medicinal products (ATMPs) marks a new era in medicine, offering unprecedented possibilities for treating previously intractable diseases. These cuttingedge therapies are transforming the healthcare landscape, bringing hope to patients and driving innovation across the life science industry as personalised treatments.
However, the growth of the ATMP platform also presents unique challenges for developing and manufacturing these complex therapies, including the need for meticulously designed and controlled environments to ensure the safety and quality of the product. Consequently, carefully planned cleanrooms play a vital part in meeting these stringent requirements.
In this article, Matthew Dean, Director of Process Architecture at AES Clean Technology, explores the critical role of cleanrooms in ATMP development and manufacturing, examining the specific challenges these innovative therapies pose throughout cleanroom design. Leveraging his unique insight, Matt highlights the advantages of modular cleanroom solutions and outlines key considerations for ATMP developers embarking on cleanroom projects.
The Rapid Rise of ATMPs ATMPs are revolutionising the way to treat diseases. These cutting-edge therapies, including gene, cell and tissue-engineered therapies, hold immense promise for treating a wide range of diseases, rare genetic disorders, various forms of cancer, neurological conditions and metabolic disorders.1
The global ATMP market is experiencing remarkable growth, fuelled by advancements in methodologies and technologies with an expanded understanding of molecular and cellular biology. In 2023 alone, the market was valued at USD 11.99 billion and projected to reach USD 35.59 billion by 2032, reflecting the rapidly rising demand for these innovative treatments.2
This surge in ATMP development brings new hope for patients and healthcare providers alike. With thousands of therapies in various stages of development, targeting diverse therapeutic areas, ATMPs are poised to revolutionise how we approach disease treatment and prevention.1
However, realising the potential of ATMPs and supporting their rising demand necessitates the development of highly specialised and controlled facilities capable of supporting the complex manufacturing processes and stringent quality standards. Cleanrooms play a key role in ensuring operator and product safety with the adaptability required for these advanced therapies as a core component of these technical facilities.
The Unique Challenges of ATMP Cleanrooms
ATMPs present specific challenges for cleanroom design and operations. As ATMP manufacturing operations often involve intricate processes (often manual steps), sensitive materials and the handling of patient-derived cells or tissues, they demand stringent control over contamination with a focus on containment strategies and room environment conditions. The operational challenges and potential manual processing involved in both autologous and allogeneic cell and gene therapy (C>) production platforms, in particular, introduce special cleanroom design requirements.
• Autologous Therapies
As autologous C> treatments are highly personalised, their production relies on harvesting the cells of individual patients for modification and reintroduction. With autologous C> development and manufacturing processes beginning and ending with the patient, ideally, these procedures would take place in a cleanroom environment logistically closer to medical centres, significantly improving the speedto-patient and product quality. The layouts for these cleanrooms must support patient-specific workflows while minimising the risk of crosscontamination or mix-ups. This requires meticulous segregation of materials, personnel, processing with rigorous
adherence to aseptic techniques and robust quality control measures.
• Allogeneic Therapies
Allogeneic therapies, while also developed from human cells, are donorderived and manipulated to treat groups of patients, subsequently presenting a different set of challenges. The cleanroom infrastructure must enable efficient plus scalable processing and segregation of donor-derived materials, ensuring the safety and integrity of the final product. This necessitates careful integration of the process workflow, proper segregation of flows, alignment on process automation and contamination prevention strategies into the cleanroom design.
In response to these unique challenges posed by ATMP operations, with their intricate processes, vulnerable materials and patientspecific considerations, developers and manufacturers are under rising pressure to ensure their cleanroom facility meets their complex needs.
Cleanroom Design to Meet the Needs of ATMPs
As the field of ATMPs continues to advance, the need for specialised cleanroom facilities is expanding in parallel. However, traditional stick-built cleanrooms, while functional, can present significant drawbacks in the fast-paced and demanding world of ATMP development.
Stick-build cleanroom construction projects can be time-consuming, requiring extensive on-site labour and intricate coordination of various trades (including electricians, HVAC and plumbing contractors) all while needing to ensure meticulous attention to detail. This complexity increases the likelihood of unforeseen delays, cost overruns, potential disruptions to ongoing operations with a stalled product launch.
As a result, modular cleanrooms have been proven as a game-changing solution to address the specific needs of ATMP development and manufacturing while addressing the demand for speed-to-patient. Unlike traditional stick-built construction,
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Less interactions of drug molecules and formulations with the inner glass surface
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Manufacturing
modular cleanrooms utilise prefabricated components manufactured in a controlled environment and assembled on-site. This modular approach delivers several key advantages for ATMPs:
• Speed and Efficiency
Speed is crucial in the fast-paced world of ATMP development, where getting treatments to patients quickly can significantly improve health outcomes and even save lives. Modular cleanrooms can be constructed and deployed rapidly, accelerating time-tomarket for these critical therapies. This streamlined approach eliminates the need to coordinate multiple contractors and trades, significantly reducing complexities and potential delays associated with traditional construction.
By providing a single-source solution for cleanroom design, manufacturing and installation, modular construction allows ATMP developers to focus on their core competencies while ensuring their facilities are delivered with speed and efficiency.
• Flexibility and Adaptability
The modular approach can accommodate various facility layouts and configurations, addressing challenges posed by different host building types. This adaptability is particularly crucial for ATMPs, which are often developed in diverse settings, ranging from academic scale research labs in conjunction with hospitals to industrial manufacturing facilities. Whether integrating cleanrooms into existing infrastructure or constructing new purpose-built facilities, the modular approach ensures that cleanrooms can be seamlessly incorporated, minimising disruption and maximising efficiency.
The modular nature of these cleanrooms also allows for efficient reconfiguration and expansion of rooms as processes evolve or new therapies emerge. This adaptability to process operations is essential in the rapidly evolving and dynamic ATMP landscape and the flexibility is key to accommodating future needs and advancements in technology.
• Compliance and Safety
Modular cleanrooms are designed and constructed to meet or exceed stringent regulatory requirements, ensuring the safety and quality of ATMPs. They
also promote standardisation and consistency across facilities, ensuring the seamless tech transfer across different facilities and teams. This is especially beneficial for organisations with multiple locations or those collaborating with partners or contract manufacturers. By utilising standardised modular components and designs, companies can ensure consistency in their ATMP production processes, regardless of location, contributing to greater efficiency, reduced risk and improved product quality.
• Cost-effectiveness and Operational Efficiency
Modular cleanrooms offer significant capital expense control and ongoing operational benefits, contributing to the long-term financial sustainability of ATMP development and manufacturing. By streamlining the construction process and minimising on-site complexities, modular cleanrooms also reduce the operational risks associated with ATMP manufacturing, contributing to improved commercial viability and scalability.
Preparing for ATMP Cleanroom Project Success
Realising the benefits that modular cleanrooms can provide for the expanding ATMP market relies on developers and manufacturers having a project plan that carefully considers the technical and regulatory aspects of cleanroom design. This plan must also encompass the logistical, operational and compliance aspects of ATMP manufacturing, ensuring that the facility supports the unique needs of these advanced therapies. There are a number of key steps that ATMP producers must follow when developing this plan to ensure project success and the timely delivery of these lifesaving treatments to patients:
1. Forecast Product Supply and Demand
A crucial first step is to thoroughly assess the anticipated demand for the ATMP and align the cleanroom facility's capacity accordingly. This involves understanding the current market size and forecasting future needs, considering factors such as patient population, clinical trial outcomes and potential market expansion. Accurately forecasting demand ensures that the cleanroom facility can accommodate both current and future production needs, avoiding costly bottlenecks or delays in getting therapies to patients.
2. Determine Make vs. Buy
ATMP developers and manufacturers must carefully evaluate whether to produce the product in-house, outsource production or consider dividing operations to a contract manufacturing organisation (CMO). Inhouse cleanroom facilities enable drug developers to cultivate internal process knowledge and more effectively protect intellectual property. ATMPs generally require smaller production footprints than other sterile drug manufacturing, meaning building these facilities inhouse could be within reach even for developers in early lifecycle capital investment
3. Know the Process
Developing a comprehensive understanding of the intricacies of the process and how they translate to cleanroom requirements is essential. This includes mapping out the process and ensuring a thorough understanding of the parameters and restrictions of each component. This detailed assessment will help ATMP developers and manufacturers identify the most suitable approach for their specific needs.
4. Strategise a Commercialisation Plan
The route from bench to patient might be longer if drug developers and manufacturers do not plan ahead. Minimally, a commercialisation plan will guide them from Phase 2 through product launch. Ideally, a robust plan will include the ongoing support of clinical pipeline drug product candidates. They should define their regulatory strategy from the outset and tie their product vision with flexible planning to be sure they can supply their product to market.
5. Select a Host Facility Carefully
Pharmaceutical developers and manufacturers must dream big while practicing effective due diligence, considering the practical concerns of host facility candidates, including utilities, infrastructure and patient supply distribution proximity. ATMP producers should know their footprint needs and potential to expand or scale their facilities.
6. Expect Growth
Change is inevitable in the dynamic ATMP landscape. Designing a cleanroom with flexibility in mind is essential to accommodate potential future
expansions and maintain adaptability as needs evolve.
7. Anticipate Advancements
ATMP technologies and treatments are constantly evolving. Future-proofing the facility by planning for adaptability ensures the cleanroom can keep pace with advancements in technology and treatment modalities.
By carefully considering these factors, ATMP developers can lay the foundation for a successful cleanroom project that meets their specific needs now and in the future, accelerating the delivery of these life-saving therapies to patients.
Powering the Future of ATMPs with the Right Cleanroom Design
As the field of ATMPs continues its rapid evolution, modular cleanrooms have emerged as a critical enabler of innovation and progress. By providing a flexible, efficient and compliant solution for the development and manufacture of these advanced therapies, modular cleanrooms are accelerating the delivery of life-saving treatments to patients in need.
Looking ahead, the role of modular cleanrooms in the ATMP space is only set to expand. As the industry continues to innovate and push the boundaries of personalised medicine, modular cleanrooms will remain an integral aspect of this journey, providing the infrastructure and flexibility needed to bring these transformative therapies to market. By partnering with a cleanroom vendor embracing modular solutions, ATMP developers and manufacturers can confidently navigate the challenges of this rapidly evolving field and accelerate the delivery of life-saving treatments.
REFERENCES
1. American Society of Gene & Cell Therapy. (2024). Gene, Cell, and RNA Therapy Landscape Q3 2024 Report. https://www.asgct.org/publications/ landscape-report
Matthew Dean, Director of Process Architecture. With nearly two decades of experience, Matthew is a highly specialised Process Architect focusing on cGMP design strategies and implementing regulatory guidance practices into the design of research, clinical trial, pilot and commercial scale manufacturing pharmaceutical facilities. Matthew leads the Compass Conceptual Design programme by bringing a broad breadth of knowledge of vaccine production, fillfinish, OSD, bulk bio-tech, Cell and Gene Therapeutics and compounding process technologies to clients to define end user requirements. Encompassing detailed knowledge of viral vector processes, biosafety containment and occupational exposure bands enables Matthew to deliver compliant design strategies to clients.
Depot Injection Formulation and Modelling (Part A)
The development of oil-based longacting injectable formulations (LAIF) involves creating a formulation where an active drug is dissolved or suspended in an oil-based medium, allowing for a sustained release of the drug over an extended period. These formulations are generally administered intramuscularly or subcutaneously and are designed to provide long-lasting therapeutic effects, reducing the frequency of administration compared to immediate-release formulations. They are particularly desirable in chronic conditions requiring steady medication levels, enhancing patient compliance, and improving treatment outcomes. Oil-based depot injections can also provide localised delivery of drugs, minimising systemic side effects.1 Although typically used for controlled release, in some cases, the choice of an oil-based formulation may also be driven by the poor solubility of the drug in aqueous solutions, even when a faster release is the target.
Understanding the principles of diffusion is essential for optimising the performance of oil-based injectable formulations. The diffusion process governs how the drug moves from the oil phase into the surrounding aqueous environment of the body, influencing the release rate and overall efficacy of the formulation. By applying mathematical models of diffusion and the oil-water partition coefficient (Kow), formulators can make informed decisions regarding excipient selection and formulation design, ensuring that the drug is released in a controlled and predictable manner to achieve the desired therapeutic effect.
Background
When an oil-based solution is injected into the body, typically intramuscularly, it forms a depot or reservoir at the injection site. This depot releases the drug at a slower rate due to the oil-based nature of the solution. The release process involves diffusion, which is the movement of molecules from an area of higher concentration (the depot) to an area of lower concentration (the surrounding tissues).
This process is driven by the concentration gradient and influenced by the oil-water partition coefficient (Kow) of the drug.
The diffusion coefficient (-D) plays a crucial role in determining the rate at which drug molecules move through the medium. Factors affecting the diffusion coefficient include the size and shape of the drug molecules, the viscosity of the oil, and the temperature. There are two primary mechanisms for drug release from an oil-based depot: passive diffusion and partitioning/redistribution. Passive diffusion, driven by the concentration gradient, is the main mechanism, while partitioning between the oil phase and the aqueous environment of the body tissues also occurs. Once the drug diffuses into the aqueous phase, it can be taken up by surrounding tissues or enter the bloodstream.
The diffusion process can be described mathematically according to Fick’s first law of diffusion which describes steady-state diffusion, where the flux (amount of free/ dissolved drug per unit area per unit time) is proportional to the concentration gradient.2
Fick's First Law (Steady-State Diffusion)
Where:
• J is the diffusion flux (amount of substance per unit area per unit time) – µg/min*cm2
• D is the diffusion coefficient of the drug in the specified matrix.
• dC/dx is the instantaneous concentration gradient.
It is important to note that the concentration gradient described the concentration gradient of the free/dissolved drug. The system becomes more complicated if the drug is micelle or colloid bound, or is in solid state (suspension). In these cases, the equilibrium constant for the bound drug vs free drug and/ or the dissolution rate for the suspended drug must be considered as this impacts the effective concentration gradient. While this topic is not discussed in detail here, I have provided some references for further reading.3,4
Fick’s second law allows for evaluation of diffusive properties in a more real-world
situation as it pertains to drug release because the drug concentration changes over time. But this is a much more complicated analysis compared to steady state diffusion and involves a number of steps and use of differential equations. For practical purposes formulations can be effectively evaluated and compared using steady state diffusion.
Fick's Second Law (Non-Steady-State Diffusion)
Fick’s second law allows for evaluation of diffusive properties in a more real-world situation as it pertains to drug release because the drug concentration changes over time. But this is a much more complicated analysis compared to steady state diffusion and involves a number of steps and use of differential equations. Fick’s second law is better suited to describe drug release over longer periods because as more of the drug is released from the depot an internal concentration gradient will form within the oily phase as the dose is depleted. But for practical purposes formulations can be effectively evaluated and compared using steady state diffusion.
• ∂C/∂t is the change in concentration over time, where t is time.
• ∂2C)/∂x2 is the spatial change in concentration, where x is the spatial coordinate.
Oil and Water Partition Coefficient
The oil-water partition coefficient is a measure of how a compound distributes itself between a hydrophobic (oil) phase and a hydrophilic (water) phase at equilibrium.
Where:
• K ow is the oil-water partition coefficient.
• Coil is the concentration of the drug in the oil phase at equilibrium.
• Cwater is the concentration of the drug in the aqueous phase at equilibrium.
In the context of an oil-based depot injection, the partition coefficient plays a crucial role in determining how the drug will
release from the oil phase into the aqueous phase in the tissue. A higher Kow indicates the drug is more lipophilic (oil-loving) and will tend to stay longer in the oil phase, resulting in a slower release. Conversely, a lower Kow indicates the drug is more hydrophilic (waterloving) and will diffuse more readily into the aqueous phase, leading to a faster release.
Biological Factors
Several biological factors significantly influence the diffusion process, including blood flow, tissue permeability, and enzymatic activity. Increased blood flow around the injection site can enhance the rate of drug removal from the depot, speeding up diffusion, while low blood flow can slow it down. The permeability of surrounding tissues affects how easily the drug can move through them, with higher permeability allowing faster diffusion. Additionally, enzymatic activity at the injection site or in surrounding tissues can metabolise the drug, impacting the overall diffusion and release rate.
The rate of drug diffusion from a depot injection can also vary based on whether it is delivered subcutaneously (SC) or intramuscularly (IM). Generally, intramuscular injections allow for quicker delivery and distribution of the drug compared to subcutaneous injections. This is because muscles are highly vascular structures, and IM absorption occurs by drug diffusion from interstitial fluid and capillary membranes into plasma. On the other hand, drugs injected subcutaneously must diffuse through the subcutaneous tissue to reach capillaries and then be absorbed into the systemic circulation. Consequently, the onset of action is longer with subcutaneous administration than with IM administration. Additionally, if the subcutaneous tissue is rich in adipose, drug absorption can be further prolonged, especially with repetitive dosing.
While biological factors may not be easily accounted for, especially when developing a formulation for a new drug that may have limited in vivo permeability data, controlling the formulation parameters can still provide invaluable information for selecting the appropriate formulation.
Mathematical Model in the Context of Drug Release
To model the release of a drug from an oilbased depot, the following factors need to be considered:
1. Diffusion from the oil phase to the aqueous phase.
2. Partitioning between phases.
3. Movement through the aqueous environment
The release rate of the drug can be described using a combination of diffusion equations and partitioning relationships. Where the diffusion of the drug from the oil depot to the surrounding tissues is described by Fick’s first law of diffusion such that:
At the interface between the oil and aqueous phases, the partition coefficient determines the equilibrium concentrations, or in essence, the tendency of the drug to partition from one phase to the other. This relationship can be used to link the concentrations in the two phases. Once the drug has partitioned into the aqueous matrix of the surrounding tissues it creates an area of higher concentration immediately around the margins of depot. This can saturate the surrounding fluids and the drug must diffuse away from the oil phase before more drug can partition out of the depot. This can also be described according to Fick’s first law.
The combined mathematical model for the release rate (R) of the drug from the oil-based depot can be described as:
The graph (Figure 1) provides a visual example of kinetics as it is related to drug diffusion and partitioning between two immiscible phases. For a period after injection relatively steady state diffusion is dominant and the concentration throughout the depot
is roughly uniform. At some distance from the boundary layer there will be a concentration gradient that forms due to the drug partitioning into the surrounding tissues. The magnitude of the gradient will be impacted by both constants, the oil/water partition coefficient, and the rate clearance from the surrounding tissues. As drug release continues non-steady state kinetics will begin to dominate as the drug is in the depot is depleted. At this point, the drug release will slow exponentially in correlation with time. The results in a pK profile similar to Figure 2.
Figure 1: A simple illustration of steady state vs non-steady state diffusion between two phases
Figure 2: Typical pk profile for a long-acting injectable formulation5
Manufacturing
To describe the change in drug concentrations and release from the drug product over longer periods of time, we can use differential equations:
Where:
• krelease is the rate constant for release from the oil phase.
• kclearance is the rate constant for clearance from the aqueous phase.
The corresponding pk profile (Figure 2) can be modelled as per.
To be continued in the Spring Issue 2025
REFERENCES
1. Janine Wilkinson, Damilola Ajulo, Valeria Tamburrini, Gwenaelle Le Gall, Kristof Kimpe, Rene Holm, Peter Belton, Sheng Qi, Lipid based intramuscular long-acting injectables: Current state of the art, European Journal of Pharmaceutical Sciences, Volume 178, 2022.
2. (2024). Fick’s Law of Diffusion. In: Dictionary of Toxicology. Springer, Singapore. https://doi.
4. Bao Q, Zou Y, Wang Y, Choi S, Burgess DJ. Impact of Formulation Parameters on In Vitro Release from Long-Acting Injectable Suspensions. AAPS J. 2021 Mar 11;23(2):42.
5. Correll CU, Kim E, Sliwa JK, Hamm W, Gopal S, Mathews M, Venkatasubramanian R, Saklad SR. Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview. CNS Drugs. 2021 Jan;35(1):39-59.
Travis Webb, M.S. Pharm, Chief Science Officer, brings to Pii over 17 years of experience in both analytical and formulation contract development across multiple dosage forms including injectables, liquid pulmonary, oral solids and liquids, and topical drug products. During his career he has developed over 20 approved drug generic and NDA drug products and helped bring numerous INDs to various clinical stages. Travis also has extensive experience with QBD and pediatric drug product development for both the U.S. and Europe, supporting IND/NDA filings and communicating with regulatory agencies.
Travis Webb
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Health Outcomes
The Use of Antimicrobial Effectiveness Testing in Pharmaceutical Microbiology
It’s August of 1970 and you have discovered a mysterious rash on your arm after applying a copious amount of your favourite moisturising cream. Being that this is your favourite cream, you only apply it on special occasions. The container has been sitting in your bathroom’s vanity cupboard for about 3 months. You noticed that the smell had soured slightly, but that didn’t deter you. Hospital testing has confirmed that you have a skin infection likely caused by a Staphylococcus spp. One month later, antimicrobial effectiveness testing first appears as a General Chapter in the United States Pharmacopoeia, 18th Edition. This testing could have prevented you from the agony experienced one month prior.
Antimicrobial preservatives can be added to aqueous pharmaceutical products during the manufacturing process to inhibit any growth from organisms that may have been introduced during production. They can also be added to multiple-dose products to inhibit growth from organisms introduced through repeated usage. There is always one or more antimicrobial preservative(s) in all sterile multiple-dose products. Without the addition of preservatives, bacterial proliferation can run rampant. Bacteria are able to grow rapidly with a high efficiency/ low failure rate due to their robust cell cycle. Contamination from microorganisms can cause skin irritation (if in contact with skin; especially sensitive skin or open wounds) and other types of infection.
There are two types of preservatives that can be added to pharmaceutical products to inhibit microbial growth; antimicrobials and antioxidants. Both are used to extend the shelf life and facilitate the stability of pharmaceutical and cosmetic products, but they have distinct purposes and differences.
Antimicrobial preservatives are essential for preventing the growth of microorganisms in pharmaceutical products. Contamination during manufacturing or patient use can not only spoil the product but also pose significant health risks. These preservatives
are particularly important in liquid (aqueous) formulations, such as eye drops, topical creams, and other water-containing products, which are more susceptible to microbial contamination. Common examples include benzalkonium chloride, widely used in eye drops; methylparaben and propylparaben, often found in topical and oral formulations; and phenol and chlorocresol, which are used in injectable medications.
Antioxidant preservatives are crucial for preventing or slowing down the oxidation of active ingredients and excipients in pharmaceuticals. Oxidation can degrade these components, reducing the product's effectiveness and potentially producing harmful by-products. The harmful byproducts of every antibiotic’s degradation (in relation to the product in which it is used) is, largely, not studied. Therefore, the toxicity of the degradation’s by-products may not be known. Antioxidants are particularly important in products containing oils, fats, and active pharmaceutical ingredients (APIs). Common examples include ascorbic acid (Vitamin C), frequently used in aqueous and oil-based solutions; butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), typically found in lipid-based formulations like oil-based skincare, for example; and sodium metabisulfite, which is often used in injectable medications.
The key differences between antimicrobial and antioxidant preservatives lie in their functions, targets, and applications. Anti-
microbial preservatives are designed to prevent microbial contamination, while antioxidant preservatives protect against chemical degradation caused by oxidation. Antimicrobial preservatives specifically target microorganisms, whereas antioxidants combat oxidising agents and oxidative reactions. Antimicrobial preservatives are essential in water-based formulations, which are more prone to microbial growth, while antioxidant preservatives are critical in products containing ingredients susceptible to oxidation. Both types of preservatives play a vital role in ensuring the safety and effectiveness of pharmaceutical products, each addressing different degradation processes.
The purpose of Preservative Efficacy Testing (often referred to as Antimicrobial Effectiveness Testing) is to ensure that antimicrobial/antioxidant preservatives are effective in their applications. This is done by challenging the formulation with a range of bacterial and fungal species that are commonly found in the environment. Samples are taken at individual timepoints; after which, the surviving organisms are enumerated and the values obtained are compared to a system control. A log reduction factor of the results of each enumeration is produced and analysed against the pass/fail criteria stated in the appropriate pharmacopoeia.
Pharmacopoeia are responsible for determining which organisms are required for each formulation. For example, the European
Category Product Description
1 • Parenteral (injections and emulsions)
• Optic, ophthalmic, and sterile nasal products in aqueous base
2 • Topical products in aqueous base
• Nonsterile emulsions
• Products for mucosal application
3 Oral products in aqueous base (excluding antacids)
4 Antacids in aqueous base
Health Outcomes
• ≥1.0 log reductions at day 7 relative to initial count
• No increase at day 28 relative to day 14 count
• ≥2.0 log reduction at day 14 relative to initial count
• No increase at day 28 relative to day 14 count
• ≥1.0 log reduction at day 14 relative to initial count
• No increase at day 28 relative to day 14 count
No increase at days 7,14, and 28 relative to initial count
No increase at days 7,14, and 28 relative to initial count
No increase at days 7,14, and 28 relative to initial count
No increase at days 7,14, and 28 relative to initial count Table 1. Four Categories of Drug Products and Specifications for Antimicrobial Efficacy
Pharmacopoeia (Ph. Eur) states that Parenteral & Topical formulations must be challenged with Aspergilus brasiliensis (mould), Candida albicans (yeast), Staphylococcus aureus (Gram positive cocci), and Pseudomonas aeruginosa (Gram negative rod). Whereas, the United States Pharmacopoeia (USP) includes the addition of Escherichia coli (Gram negative rod) in most formulations. E. coli is, however, recommended by the Ph. Eur for liquid oral formulations. The pharmacopoeia also decides the time points which must be performed, depending on the sample formulation.
Timepoints are the days that sampling is performed on a predetermined volume of inoculated product to analyse how much organism is remaining in the aliquots. They were designed to simulate use of the product. This type of sampling can be compared to a shelf-life study. For example, Ph. Eur have instructed that a 6-hour, 24-hour, 7-day, 14-day and 28day time point be taken for Parenteral & Topical formulations. The theory behind this type of repeated sampling is that a qualitative result is produced which is used to analyse the effectiveness of the
Cetrimide (quaternary ammonium compound used in ophthalmic and topical products)
Propylparaben (“widely used” antimicrobial preservative in injectable, topical, and oral products)
Benzyl alcohol (commonly used in injectable products)
sample's preservative system over a 28-day incubation period at 20–25 degrees Celsius (or room temperature). Pharmacopoeia also provide the accepted log reductions for each formulation. Standard Operating Procedures (SOPs) are created using the instructions provided. A formulation can be considered as “passed” if it shows an acceptable log reduction.
Pharmacopoeias categorise products based on their preparation method. each category dictates the required log reduction at specified timepoints. Category 1 products are sterile parenteral products in an aqueous (liquid) form, such as injectables, eye drops, and nasal sprays. These products have stricter log reduction requirements and shorter time intervals. A 1-log reduction in microbial count must be achieved by the 7-day timepoint, with a 3-log reduction by day 14, based on initial control counts taken at day 0. Additionally, by day 28, counts must not increase from those at the 14-day timepoint.
Category 2 products, which include nonsterile topical and nasal products, require a minimum 2-log reduction by day
14, with no increase in bacterial counts at day 28. Category 3 products, consisting of oral aqueous-based products (excluding antacids), have the same requirements as Category 2, mandating a 2-log reduction by day 14 and no increase in counts comparative to day 14 by day 28. Category 4 products, specifically aqueous-based antacids, have the least stringent requirements, needing only stability with no increase in microbial or mold counts at both 14 and 28 days.
The preparation of the organisms, used during testing, is one of the more important aspects. Laboratories must consider organism subculturing and the number of passages when preparing organisms to be used during effectiveness testing. Continuous cell propagation can lead to altering the organism’s antimicrobial susceptibility. USP recommends using cells that are no more than five passages from the freeze-dried stock culture. Although the Ph. Eur doesn’t give a specified number of passages, it states to keep the number to a minimum. A passage is when an organism that has been cultured onto one growth medium is transferred onto another for the purpose of harvesting prior to use.
“…good bactericidal activity against Gram-positive species but is less active against Gram-negative species. Pseudomonas species, particularly Pseudomonas aeruginosa, may exhibit resistance.”
“…more active against yeasts and moulds than against bacteria. They are also more active against Gram-positive than against Gram-negative bacteria.”
Prevents the growth of bacteria without killing them.
“…used as an antimicrobial preservative against Gram-positive bacteria, moulds, fungi, and yeasts, although it possesses only modest bactericidal properties.”
Table 2. Antimicrobial Properties of Commonly used Antimicrobial Preservatives As described The Handbook of Pharmaceutical Excipients
Health Outcomes
Category 1 Products
Bacteria NLT 1.0 log reduction from the initial calculated count at 7 days, NLT 3.0 log reduction from the initial count at 14 days, and no increase from the 14 days’ count at 28 days
Yeast and moulds No increase from the initial calculated count at 7, 14 and 28 days
Category 2 Products
Bacteria NLT 2.0 log reduction from the initial count at 14 days, and no increase from the 14 days’ count at 28 days
Yeast and moulds No increase from the initial calculated count at 14 and 28 days
Category 3 Products
Bacteria NLT 1.0 log reduction from the initial count at 14 days, and no increase from the 14 days’ count at 28 days
Yeast and moulds No increase from the initial calculated count at 14 and 28 days
Category 4 Products
Bacteria No increase from the initial calculated count at 14 and 28 days
Yeast and moulds No increase from the initial calculated count at 14 and 28 days
Both pharmacopoeia also dictate the incubation conditions, respective to the organism type. Bacteria are to be grown at 30–35 degrees Celsius for 18–24 hours on a Soybean-Casein Agar, like Tryptone-Soya Agar (TSA). This is so that the organisms are harvested while in the log phase; the nutrients in the agar are preferable to bacteria. This ensures that the most viable cells are harvested and used during testing as possible. Although harvesting equipment like the spectrophotometer are used, these tend to measure an approximate suspension concentration through light absorption. It is not possible to determine the viability of the cells using these methods. Yeasts and moulds are both grown on Sabouraud Dextrose Agar (SDA) and incubated at 20–25 degrees Celsius. Antibiotics like chloramphenicol are used in SDA to limit the growth of bacterial species. 20–25 degrees is a suboptimal temperature for the growth of yeasts so the incubation is typically 40–48 hours; and should not
exceed 52 hours. Mould spores are used during effectiveness testing so Aspergillus brasiliensis is given 6–10 days of incubation so that a prolific lawn of black spores are visible and harvested.
The Handbook of Pharmaceutical Excipients details a large variety of excipients used in pharmaceutical products including antimicrobial preservatives. See table 2 for a short synopsis of the typical properties of some commonly used antimicrobial preservatives.
Without the introduction of this testing, there would be no way to ensure that the preservatives used are effective at inhibiting the growth of contaminating organisms. Each time you open your favourite container of hand cream or your bottle of cold and flu medicine, be confident that the antimicrobial preservative testing that was performed has ensured that the product has an appropriate
shelf life for its intended use. Note that this test does not guarantee that a product is completely safe from antibiotic resistant organism strains, as these are not commonly tested.
Antoinae Wood, mRSB, is a Lead Senior Scientist at Wickham Micro – A Cormica® Lab, where she brings over 6 years of experience in various forms of microbiological testing. Beginning her career as an apprentice, Antoinae has advanced to lead bespoke client projects, specialising in preservative efficacy testing, antibiotic testing, and other critical analyses.
Antoinae Wood
Table 3. Criteria for Tested Microorganisms
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Navigating Digital Transformation Fatigue: The Strategy for Success in Regulated Industries
Beneath the surface of the digital transformation revolution lies a growing concern: digital transformation fatigue. This phenomenon, particularly in highly regulated industries, threatens to undermine the very initiatives designed to propel businesses forward. As companies grapple with a constantly expanding array of digital tools, stringent regulatory requirements, and a constant pressure to innovate, they find themselves at a critical juncture. How can they overcome the complexities of digital transformation while avoiding the pitfalls of employee burnout and resistance to change?
Understanding Digital Transformation Fatigue
It is no wonder businesses are prioritising digital transformation, as it promises increased efficiency, productivity, and profitability. However, digital transformation initiatives are often complex endeavours that can significantly impact the way organisations operate. This complexity gives rise to a new phenomenon known as digital transformation fatigue.
So, what exactly is digital transformation fatigue? According to KPMG, this growing trend has its roots in constant modernising initiatives, often with competing timelines and priorities. In short, companies face unprecedented technological change, which is reflected in employees' workloads, leading to frustration. What’s more, digital transformation fatigue affects productivity and thus negatively impacts profitability and return on investment.
Indeed, the sheer volume of software applications used across an organisation has surged due to the rapid adoption of new technologies. According to a 2023 Salesforce survey of IT leaders, companies now use an average of 1,061 different applications, a 10% increase from the 976 recorded in 2022. This relentless pace of change leaves employees with little time to adapt, contributing to cognitive overload and low productivity.
When employees are overwhelmed and resistant to change, transformation
initiatives fail to deliver the anticipated benefits. Estimates from McKinsey show that up to 70% of digital transformation efforts do not meet their intended goals, which implies a large potential for waste. These setbacks drain resources and hinder organisations from achieving the competitive advantages they seek through innovation. And innovation is a central topic for companies in highly regulated industries, which are looking for ways to drive growth while dealing with increasingly strict regulatory requirements.
The Challenges Faced by Regulated Enterprises
Highly regulated industries often modernise at a glacial pace, and face particularly unique hurdles in their digital transformation journeys. These sectors, as we know, must manage stringent regulatory requirements, which often create a very careful and tentative approach to the implementation of new technologies.
In many enterprises, legacy systems are so deeply entrenched in daily operations that it proves a significant challenge to attempt to replace or integrate them with more modern solutions. To add to the hesitancy, heightened concerns about data security and privacy are complicating the adoption of these cloud-based and AIdriven technologies, which are often at the forefront of digital transformation efforts.
It’s the high stakes of non-compliance in these industries that fosters such a
conservative approach to change. Not only that, but traditional organisational cultures within sectors like pharma and financial services often differ to the agile, ‘fail-fast’ approach demanded by digital transformation.
The culmination of these challenges can easily lead to digital transformation fatigue. Projects become prolonged and complex, putting a strain on resources and morale. Frequent adaptation to regulatory updates such as the multi-year implementation of IDMP within the pharmaceutical industry, means constant revisions to strategies. And, with such high implementation costs for new systems, the return on investment for these transformation efforts may be delayed or difficult to measure.
Quite simply, it can feel like ‘fatigue-bya-thousand-cuts’ – the cumulative effect of these factors creates an environment ripe for change fatigue. So how can highly regulated organisations ensure digital transformation initiatives are not only successful, but also avoid the detrimental impact of change fatigue on both the business and its employees?
Preventing Fatigue by Streamlining Complex Business Processes, Data, and Content Management – A Unified Approach Complexity is the enemy of sustainable transformation. In regulated industries, where compliance requirements add layers of intricacy to every process, simplification is not just beneficial, but essential. By streamlining
complex business processes, companies can reduce the load on their workforce, allowing employees to focus on value-adding tasks rather than getting bogged down in overcomplicated workflows.
An effort to streamline extends beyond just process optimisation, it requires a holistic view of how data and content are managed across the organisation. In many industries, information silos and a network of disparate IT systems have long been the norm, slowly causing inefficiency and employee frustration. A unified approach to data and content management with a system like the CARA Platform breaks down these barriers, ensuring that information flows seamlessly across departments, and the organisation as a whole. In a pharma company, this might look like the regulatory and clinical domains accessing the same data to compile a submission. In financial services; loan officers and underwriters simultaneously accessing updated customer financial data for faster approvals.
Streamlining business processes, data, and content in tandem creates an alignment that can dramatically reduce transformation fatigue. Employees no longer need to navigate multiple systems or reconcile conflicting information sources. Instead, they can work within a single, unified system where processes are intuitive, data is readily available, and content is managed and reused efficiently from a single source of truth. This unified strategy also enables a more gradual and coherent implementation of change; rather than overwhelming employees with a barrage of new systems and processes, organisations can roll out improvements in a more integrated and logical manner. This approach helps prevent the sense of constant, disjointed change that often leads to fatigue and resistance.
The benefits of this approach extend to most senior stakeholders within the organisation too. With streamlined and standardised processes, and centralised data and content, leadership gains a holistic picture of operations, enabling more informed decision-making. This transparency helps in demonstrating the tangible benefits of digital initiatives, maintaining stakeholder support and employee buy-in – both crucial factors in combating transformation fatigue.
Improved software adoption is a critical component of this unified strategy. Even the most well-designed processes and systems can fall short if employees struggle to use
the tools provided. By focusing on providing comprehensive and varied training, and offering ongoing support, organisations can ensure that their workforce is comfortable and proficient with new technologies. This is where Digital Adoption Solutions such as Userlane’s Platform come in.
How Digital Adoption Helps Overcome Digital Transformation Fatigue
What is digital adoption? According to Forbes, digital adoption refers to achieving a state within your company where all of your digital tools and assets are leveraged to the fullest extent.
Successful digital adoption has become critical to digital transformation and change management strategies. It aims to maximise software investments, reduce the time wasted on maintaining underused applications, and enhance employee experience.
Enterprises in highly regulated industries face unique challenges in digital adoption due to their scale, diversity of tools, and variety of user roles and responsibilities. Without proper guidance, the risk of digital transformation fatigue rises again – this can then lead to decreased productivity, resistance to digital transformation initiatives, and a less-than-optimal return on investment (ROI) on software expenditures.
Undoubtedly, successful digital transformation hinges on the seamless integration of new digital tools with existing systems and processes. Effective digital adoption ensures that these tools complement and enhance workflows rather than disrupt them. In addition, a higher level of digital adoption enables companies in highly regulated industries to remain responsive to changing regulatory demands. With the rapid pace of technological advancements and
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evolving regulations, organisations must be able to adapt quickly to maintain compliance and capitalise on new opportunities.
All in all, digital transformation and the unique context of highly regulated industries require a thoughtful approach to align technological advancements with strict compliance needs. Organisations that recognise the risk of digital transformation fatigue and prioritise digital adoption are better positioned to leverage technology for a competitive advantage, ultimately driving their initiatives toward successful outcomes.
Max Kelleher is Chief Executive Officer at Generis. Max started in Business Development, progressing to Head of European Sales, and then onto the COO position, before moving into the CEO role in early 2024. He is passionate about providing a viable, pragmatic path for modernising enterprise information management in regulated industries. His close work with pharma companies and specialist solution partners, has afforded him deep insight into the critical modern-day challenges, that traditional approaches to business processes and information use in industries like life sciences fail to meet.
Hartmut Hahn is Userlane's Chief Executive Officer (CEO). Hartmut began his career as an analyst in Management Consulting & Ventures Investments, followed by a position as a Senior Management Consultant for the consulting firm Mücke, Sturm & Company. Before co-founding Userlane, Hartmut worked for Hubert Burda Media in Business & Corporate Development. In this role, Hartmut was responsible for corporate strategy and mergers and acquisitions (M&A). Hartmut holds two Master's degrees in Business Administration and Management from the University of Regensburg and Copenhagen Business School.
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Connected Technologies: Optimising Data Management in the Era of Wearable Technology
On average, a clinical trial generates up to three million data points. These data points provide extensive insights into the health status of study participants – they can highlight their health status, responses and potential risks, enabling researchers to monitor patient safety and efficacy continuously, as well as enable the successful advancement of therapies.
At the same time, the increasing use of mobile devices (wearables) and apps to collect patient data is leading to the data becoming more and more heterogeneous. The influx of data from multiple devices, each with different formats, frequencies and parameters, presents challenges for researchers as it can be more difficult to standardise and integrate these inputs into one cohesive dataset. This is leading to challenges with creating consistent and complete data sets.
In the UK, the government plans to introduce more wearable health technology in a bid to reform and digitise the NHS. It means more people will soon be able to monitor their blood pressure, glucose levels, and cancer treatment responses from the comfort of their own home. It also highlights
that this challenge with data is only set to become more complex.
Many biopharmaceutical companies are faced with the challenge of addressing this situation in order to create a complete data set. With it, effective data management is becoming critical to the success of research, and ensuring data quality and consistency is integral.
Data workbenches play a key role here as they enable access, control, transmission, monitoring and presentation of data in dashboards. In clinical trials, a data workbench serves as a central platform that enables researchers to manage, standardise, and analyse vast amounts of data collected from multiple sources. Working as a single source of truth, it allows researchers to seamlessly merge data from diverse sources, providing a unified source for monitoring study progress, enhancing patient safety and optimising efficiency.
To realise the possibilities of a unified data foundation, the heterogeneous data sets must first be structured and standardised. The background to this is the unification of data structures in a standardised format to facilitate comprehensive analyses including new data points. Only with the help of these
analyses is it possible to draw comprehensive and evidence-based conclusions regarding the potential of therapeutic innovations.
Here, we explore the challenges that biopharmaceutical companies face in today’s increasingly digitised world, and the vital role that data workbenches play in supporting them.
Removing Barriers with a Unified Data Foundation
In practice, clinical data is collected in both structured and unstructured formats. This presents two key challenges for data controllers in clinical trials. On one hand, they must ensure that wearables and apps for collecting patient data meet the requirements of clinical research.
On the other hand, the data from these sources must be merged for further processing. This requires standardised application programming interfaces (APIs) to transfer the data between the different systems and to ensure a uniform standard of data.
While compliance with guidelines is primarily the responsibility of the wearables' manufacturers and app providers, integration into clinical databases is the responsibility of the data controllers. Data workbenches enable them to combine and process data from electronic data capture (EDC) systems and external data from apps and wearables. Data aggregation systems combine them in a database.
This means that all data is available to the study managers in a single database, the data workbench, and can be accessed and processed. This creates a central, unified data source and allows managers to monitor data quality, identify trends as well as improve trial efficacy and patient safety.
For those involved in research and development (R&D), the focus is now more than ever on increasing efficiency and costeffectiveness while improving the patient experience.
Clinical data workbenches can overcome some of the obstacles and enable a reduction
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in costs and administrative burdens for contract research organisations (CROs) and trial sites. For example, study workflows and data collection technologies can be linked, accelerating the time to market for therapies across a range of indications. Patients can share information directly through apps while participating in the study, meaning a timely analysis of information and more robust results overall.
Single Source of Truth: More Efficient Studies
By combining clinical data from diverse sources – such as electronic health records, wearable devices, mobile health apps, and lab results – into a central database, contract research organisations gain a comprehensive and real-time view of study progress. This approach enables them to monitor data trends across multiple sites, track patient engagement, and detect inconsistencies or anomalies early on. With all data consolidated, they can better evaluate the accuracy and quality of findings, streamline reporting processes, and make any adjustments as needed. This ultimately supports more effective studies.
Monitoring data quality in near real time helps to ensure data quality and provides an opportunity to identify potential risks at participating investigative sites and among other study stakeholders. Other aspects include gaining comprehensive insights into data patterns, reducing response times and enabling a more transparent exchange of information between study sponsors, contract research organisations, study sites and investigators. This allows adverse developments that could potentially jeopardise patient safety or data integrity to be detected early on and appropriate measures to be taken.
Clinical Data Workbench: The Key to Efficiency
Starting a clinical trial still requires a significant investment of resources, especially when sponsors manage and share data in traditional spreadsheets, emails, or other forms of storage that are not designed
with structured data requirements in mind.
Our experience shows that sponsors can achieve greater efficiency in their studies by optimising their data management in the following phases of the study lifecycle:
1. Preparation:
A clinical data workbench can be used to merge data from different sources more quickly. Data managers can use proven industry and technology standards, APIs and procedures such as the Study Data Tabulation Model (STDM). Standardisation makes it possible to build the entire data infrastructure faster, implement interface programmes more easily and exchange data between different databases. The one-time integration at the beginning of the project saves resources.
2. Implementation:
The uniform formatting of the data and standardised databases makes it easier to create and review reports and to carry out interim analyses quicker and more efficiently.
3. Completion:
A standardised, STDM-compatible database significantly increases the efficiency of the analysis and/or the provision of data for the sponsor, since the data is already available in a predefined structure. This makes it easier to transfer the metadata (including audit trails) to study sponsors and to subsequently archive the data structures in the standardised format.
The following applies throughout: Ensuring the security and integrity of study data is a joint task for study sponsors, trial centres, and clinical research organisations (CROs). To comply with the risk-based approach according to Good Clinical Practice GCP E6(R2), a clinical database including the workbench must meet all data protection and security requirements. One of its essential functions is therefore to create study-specific reports that can be used for quality management monitoring and compliance.
Conclusion
The constant increase in data volumes in the context of global, multi-site studies with new digital tools requires the development of methods for effective data management.
Only in this way can the necessary quality, compliance with requirements and informative analysis of study data be guaranteed in equal measure.
The growing importance of apps and wearables for collecting patient data presents CROs with data management challenges. Clinical data workbenches have proven to be an effective tool for managing the increasing volume of heterogeneous and isolated digital data, working as a single source of truth. Networked systems that enable the uniform integration of data and insights into study progress in near real-time help study managers to monitor data trends and quickly answer emerging questions.
As clinical trials continue to evolve in complexity and scale, and the use of wearable technology continues to expand, the role of advanced data management tools will only grow in importance. Not only will they ensure clinical research organisations are able to manage this data, but ultimately, it will pave the way for delivering faster, safer and more effective therapies to people worldwide.
REFERENCES
1. Davis J.R., Nolan V.P., Woodcock J., et al., Institute of Medicine (US) Roundtable on Research and Development of Drugs, Biologics, and Medical Devices
2. Gov.UK, Government issues rallying cry to the nation to help fix NHS, 2024
MacDonald, Senior Director Clinical Data Strategy, Veeva Systems, helping to bring innovation to clinical data management at Veeva Systems. His work is focused on SMBs in Europe.
Philip is the Managing Director at palleos healthcare where his role is focused on life sciences, clinical trials and strategy. He has been at the company for close to 14 years.
Paul MacDonald
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Philip Räth
Getting Lab Data Closer to the Decision Point Keeps Product Release on Track
Since 2022, the FDA has issued more than 600 warning letters for violations of GxP requirements. Regardless of the origin – poor documentation, incorrect data collection, or incomplete training – the cost of a warning letter for noncompliance can derail a manufacturing operation.
In the lab, leaders are laser-focused on maintaining compliance. With existing complex system infrastructures and heavy reliance on manual test execution, the manufacturing lab has an opportunity to streamline operations for reduced risk and increased efficiency. Positive change is underway as the industry moves to improve lab processes and enable more connected, seamless, and automated ways of working.
These changes are not just an incremental improvement but a necessary shift in the way labs operate to stay competitive in today's market. The move towards digital transformation in the lab is becoming increasingly vital, and staying ahead of compliance issues is just one part of the equation. Companies that adopt these modern methods will not only avoid costly compliance issues but will also drive overall business agility and innovation.
Three pillars that can increase lab efficiency include bringing test execution and sample management data onto a single digital platform, improving right first time by having procedure documents and execution in the same system, and enabling review by exception. These advancements can drive productivity while making lab data available much faster, improvements that can keep product release on track.
Bringing Together Test Execution and Sample Management is Possible
Using one system to execute tests and manage sample workflows is possible. However, the typical QC lab infrastructure, which is complex and siloed, is a significant barrier to change.
Many are working to shift the data captured during quality control (QC) processes from paper to modern digital tools.
To execute tests digitally, many organisations are turning to electronic lab notebooks (ELN) and adding them to existing laboratory information management systems (LIMS). The approach helps lab staff move from capturing test data manually to an electronic application, but it doesn’t address the problem to the core. Staff will have to work through two separate systems for test execution and sample management, increasing the risk that data is incorrectly entered or lost throughout the process. This approach also requires repetitive work across different tools to review, load, and distribute the latest approved procedures.
When evaluating how to improve QC lab processes, consider the downside of bringing an ELN to your existing infrastructure. ELNs are typically difficult to configure, take a long time to implement, and can require significant resources, especially since many aren’t GMP compliant and require additional validation.
A LIMS can enable lab staff with test execution and sample management in one solution. Analysts can pull up the latest approved processes, capture test data, and complete sample workflows while referencing procedure documents in a single system.
Using one application to manage key processes simplifies the workflow for staff and removes the need to manage multiple tools and logins. Accessing information and executing critical processes within the LIMS can be a game changer for lab productivity and efficiency.
These efforts can deliver significant benefits beyond the lab. Adopting a LIMS with open APIs makes connecting data across the enterprise easier, bringing together quality assurance (QA) and QC data and content with the company’s MES or ERP. The increased transparency can help identify risk areas and allow teams to take proactive action to ensure product release remains on track.
Ensuring Right First Time Takes Science and Execution
If a company can maximise right first time,
it can drive speed, effectiveness, and cost savings. The metric is a leading key performance indicator (KPI), and the industry is evaluating options to improve it while providing a seamless experience for staff.
Right first time focuses on ensuring the lab has the proper, approved, compliant procedure to test a product and capturing the outcomes in an execution system. Because of the increased risk of executing these processes on paper, companies are adding standalone tools that offer a modern guided experience for users. This might simplify the specific process but increases the complexity of the lab, adding yet another system and login that users will need to learn and manage. If lab staff accesses a system and works off the wrong process, it creates another workflow to correct the error that can impact manufacturing and batch release times downstream.
Some might consider an ELN to address this challenge, establishing a plan to copy text from one system into another. By duplicating the document and manually configuring the process into an ELN, companies are increasing the cost of ownership and overall risks. An ELN drives consistency in the instruments used, ensuring consumables aren’t past their effective date, but is the trade-off in cost and compliance worth it?
Even the best-laid plans can lead to expensive, less-than-expected results. Developing and maintaining test methods takes time, and costs add up quickly. Realistically, using an ELN and replicating or developing procedures likely isn’t a viable alternative for most companies who want to improve right first time.
Using a LIMS that unifies QA and QC provides a single system to access a procedure and record results and observations. This allows procedural documents to always be up to date and qualified since the latest document is available for access in the lab as soon as an approval workflow is completed. The approach doesn’t require reproducing test methods, which can lower costs and save time and effort.
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A LIMS with QA and QC data can block unqualified users from conducting a test they aren’t trained to do. This can save the trouble of the completed test being found invalid, requiring a new test to be performed. If the system can also allow for instrument selection and effective date filters, LIMS could deliver a one-stop-shop solution for most critical lab needs.
Enabling Speed and Efficiency with Review by Exception
Lab data review has traditionally been an exhaustive and tedious process. The industry is looking toward technology to complete as much data review as possible without increasing risks. With all the tests conducted, labs have vast amounts of data to sift through and investigate where deviations occurred. The implications for the business are costly, and finding a solution for exception review is an industrywide priority.
Data collection happens daily, but deviations are rare and not always obvious. With the disconnected lab landscape, exception review happens across instrument systems, LIMS, ELNs, MES, and paper documents. Companies can’t ship their product until a qualified person completes the review. Many have audit trail reviews to look for exceptions not reported by the operator, but it isn’t enough to streamline the process.
A LIMS with exception, detection, and identification can help address some of the time required to conduct data reviews. By using a system that can manage end-toend review by exception while automating processes, companies can save significant effort and shift the focus to high-value activities.
Determining the Best Path Forward to Accelerate Product Release
The future of lab operations depends on the adoption of technology that supports both compliance and efficiency. Companies that are able to streamline these processes not only keep up with regulatory requirements but are also better positioned to scale their operations and innovate at speed. In a world where time to market is increasingly important, labs need to be equipped with tools that allow them to adapt swiftly and maintain the highest standards of quality.
An advanced LIMS system can digitise processes, improve right first time, and
speed up exception reviews so that products can be shipped to market faster. Evaluating LIMS thoroughly and carefully for current capabilities and scalability is vital. Keep an open mind during the evaluation phase if a system does not have all these capabilities in one package. This can drive unexpected collaboration with providers to address longstanding industry challenges.
Manufacturing labs have required turnaround times to complete rework from exceptions or failed procedures, and an advanced LIMS can alleviate this pressure while significantly impacting effectiveness and speed. A solution that unifies QA and QC can reduce overall turnaround times and shorten review cycles, getting companies closer to real-time batch release.
If a company has a legacy LIMS, evaluate whether it is worth keeping that system within a fragmented technology landscape. To make meaningful advancements in right first time, review by exception, and batch release, consider moving forward with a solution that can execute these processes in a single system. It could enable end-to-end execution, real-time access to procedures, and easy employee qualification. With a
single system, batch information can be reviewed, analysed, and released faster to get them quickly into the hands of doctors and patients.
REFERENCES
1. FDA, Warning Letters (from 2022-2024), 2024
Ashley McMillan, senior director, Veeva Vault LIMS strategy is responsible for goto market strategy, customer engagement, and business development for the Vault LIMS application. During her time at Veeva she has led growth strategy for the Quality space across several different products and markets, including supporting the launch of Vault QMS and Veeva's pursuit in the Contract Services and Generics markets. Ashley received her Bachelor of Science degree in biology and music from Boston College and a Master's degree in biotechnology from Columbia University.
Ashley McMillan
Harnessing AI in Pharmaceutical Supply Chains: A Strategic Imperative
The pharmaceutical industry is at a pivotal moment in its evolution, as artificial intelligence (AI) and machine learning (ML) technologies reshape supply chain dynamics to better meet modern demands. Historically, pharmaceutical supply chains have faced numerous challenges, from managing fluctuating demand to safeguarding product integrity, particularly for temperaturesensitive goods like biologics and vaccines.
As the world becomes more interconnected and the demand for pharmaceutical products rises, stakeholders must balance operational efficiency with reliability, regulatory compliance, and cost control. AI and ML are emerging as vital tools to address these complexities, driving innovation in how companies approach inventory management, logistics, and planning.
The 2024 LogiPharma AI report, which surveyed 100 European life sciences supply chain leaders, provides valuable insights into AI’s transformative impact across the sector. This report reveals that AI is no longer a luxury or a “nice-to-have” in pharmaceutical logistics – it is becoming a strategic imperative. As the industry witnesses a shift toward a data-driven, interconnected ecosystem, AI is poised to be the foundation on which resilient, transparent, and responsive pharmaceutical supply chains are built. This article explores the key areas where AI is making a difference, the current challenges of widespread adoption, and the strategic potential AI holds for the future.
AI's Role in Optimising Inventory Management
The application of AI in inventory management is becoming a priority for many pharmaceutical companies, with 40% of survey respondents indicating a strong focus on using AI and ML technologies to optimise inventory. In the pharmaceutical industry, managing stock levels and anticipating changes in demand are critical to maintaining both product availability and cost-efficiency. AI’s predictive capabilities
allow pharmaceutical companies to accurately forecast demand based on historical data, current market trends, and predictive analytics.
This level of accuracy is particularly valuable in situations where there are sudden and unexpected surges in demand, such as during the COVID-19 pandemic, which can place enormous pressure on supply chains. Through demand forecasting, AI helps pharmaceutical companies prepare for these scenarios, making it possible to prevent stockouts or shortages and ultimately ensuring that patients have access to the medications they need.
AI’s role in inventory management also extends to reducing holding costs. By identifying optimal stock levels, AI-driven models minimise warehousing expenses by determining how much inventory should be held to meet forecasted demand without overproduction. This balance is crucial in the pharmaceutical industry, where regulatory constraints, expiration dates, and the need for cold storage further complicate logistics.
When applied effectively, AI helps manage warehousing in a way that both reduces costs and minimises the risk of stock depletion. In this way, companies can avoid the costly and wasteful consequences of expired products, particularly relevant for perishable and temperature-sensitive items. By optimising inventory levels and
reducing waste, AI-driven supply chains can also enhance their sustainable practices by minimising the environmental impact of overproduction and disposal.
Building Confidence with Rapid ROI Expectations
AI’s growing role in the pharmaceutical supply chain is also reflected in the rapid return on investment (ROI) that companies expect from these initiatives. The report reveals that 51% of respondents anticipate seeing ROI from AI and ML investments within two to three years. This indicates a strong confidence in AI’s ability to deliver tangible business benefits in the near term. As pharmaceutical companies continue to integrate AI into inventory forecasting and logistics systems, they see improvements in decision-making processes and operational efficiency. The swift ROI timelines make it easier for businesses to justify AI investments and allocate resources towards expanding their digital capabilities.
For many companies, the initial results of adopting AI-based tools are promising, with improvements seen in reduced stockouts and better visibility into supply chain inefficiencies. Thanks to AI-powered tools, supply chain managers gain real-time insights into the health of their inventory, tracking shipments, identifying potential delays, and proactively managing disruptions. This enhanced visibility allows companies to take pre-emptive action, reducing waste and costs
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associated with delays or lost shipments and increasing overall operational efficiency.
Strengthening Collaboration with AIDriven Supply Chains
A key element of AI’s adoption in the pharmaceutical sector is the growing emphasis on collaboration among trading partners, including suppliers, manufacturers, and logistics providers. However, the report also highlights a significant gap in this area, as only 11–25% of supply chain trading partners are currently engaged in AI-driven processes. This indicates that, while the benefits of an interconnected, AI-enabled ecosystem are clear, widespread adoption among all trading partners is still limited. For AI-driven collaboration to be fully effective, pharmaceutical companies need to extend
these technologies across their entire network of partners. The creation of shared data platforms and predictive insights facilitated by AI allows supply chain partners to operate in a more transparent, cohesive manner, which is particularly valuable for tracking and quality control for sensitive products like vaccines and biologics.
AI-Powered Digital Transformation in Planning
The report also underscores the importance of digital transformation in supply chain planning, especially in processes such as Sales and Operations Planning (S&OP). According to our survey, 44% of respondents prioritise digitalisation strategies focused on planning processes, recognising that AI-enabled planning can improve agility
and responsiveness to market shifts. By integrating various data sources – such as sales forecasts, market trends, and production schedules – AI enhances companies' planning capabilities, allowing them to dynamically adjust to demand fluctuations.
This agility is especially valuable in an industry where regulatory shifts, supply chain disruptions, and global healthcare demands can quickly impact production and distribution timelines. Enhanced planning capabilities ultimately help pharmaceutical companies reduce bottlenecks, align production with demand, and respond more effectively to changes, supporting better overall supply chain efficiency.
Enhancing Cold Chain Integrity Through AI
In addition to optimising planning processes, AI is proving particularly valuable in managing cold chain logistics, which are essential for transporting temperature-sensitive pharmaceuticals. The report highlights that 69% of pharmaceutical companies have implemented automated alerts for temperature excursions or delays in their cold chain logistics. These alerts allow for continuous real-time monitoring of environmental conditions and ensure that any deviations in temperature are promptly addressed. AI’s ability to support cold chain integrity is essential in maintaining the efficacy of products such as vaccines, biologics, and other temperature-sensitive treatments. By receiving instant alerts when temperature or humidity thresholds are breached, logistics teams can act immediately, thereby reducing the risk of spoilage and ensuring patients receive safe, effective treatments.
The integration of AI into cold chain logistics also reduces the financial and reputational risks associated with damaged or ineffective products. Some companies are even exploring advanced AI implementations, such as the use of drones or autonomous vehicles equipped with AI sensors, to improve cold chain monitoring during transport. These technologies further enhance the industry’s capability to safeguard temperature-sensitive products, supporting both product quality and patient safety.
Transforming Quality Control and Compliance with AI and Machine Learning
In an industry bound by strict regulations, AI’s role in monitoring production parameters and identifying deviations in real-time is invaluable. By streamlining documentation, data collection, and reporting, AI-based systems facilitate regulatory compliance
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and help maintain product quality. Machine learning algorithms used in quality control can detect anomalies – such as contamination risks or quality inconsistencies – that might not be apparent through traditional methods. As a result, AI not only supports compliance with stringent industry standards but also contributes to cost-efficiency by reducing the chances of costly recalls or production shutdowns.
The Expanding Future of AI in Pharma Supply Chains
The role of artificial intelligence in pharmaceutical supply chains is set to expand significantly as the technology matures, bringing profound advancements to how the industry forecasts demand, enhances security, and manages orders. As highlighted in the 2024 LogiPharma AI report, as applications are becoming more sophisticated, the sector is likely to witness wider adoption of predictive analytics for forecasting new drug demands, AI-driven security systems to prevent counterfeit drugs, and fully automated order mana-gement. These capabilities position this technology as an essential component of the pharmaceutical supply chain, enabling improved accuracy, agility, and reliability.
By embedding such innovations into daily operations, pharmaceutical companies are better positioned to meet patient needs, ultimately enhancing the accessibility and affordability of essential medications. The advantages of AI-driven processes create a competitive edge for companies that embrace the technology, delivering benefits in both operational resilience and patient outcomes. For an industry often navigating complex regulatory, logistical, and healthcare challenges, these advancements offer a transformative path forward.
In this rapidly evolving environment, AI has shifted from being a mere efficiency tool to a vital driver of innovation and an essential part of patient-focused supply chains. With AI fuelling digital transformation across the pharmaceutical landscape, companies are empowered to address industry challenges with new levels of precision and speed, ensuring that critical treatments reach patients worldwide. For pharmaceutical companies dedicated to advancing their supply chains, AI presents a clear route to heightened accessibility, cost-efficiency, and excellence in operations,
establishing a new benchmark for reliability in global healthcare logistics.
Will Robinson
With over a decade of industry experience, Will Robinson, Conference Director, LogiPharma, is responsible for the strategic direction, editorial content, and commercial growth of a £7m+ portfolio of events as part of the Worldwide Business Research (WBR). With its flagship event, LogiPharma Europe, having taken place in April 2024, as Conference Director, Will works with various leading pharma companies and supply chain heads to decipher industry trends, devise effective approaches, and curate top-notch content. With an attendance of around 200 speakers and 2000 participants, LogiPharma strives to create a platform that facilitates insightful discussions and fosters industry connections.
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AI in the Pharma Cold Chain
While AI in the pharma cold chain promises exciting possibilities, achieving these benefits won’t be a sprint but a marathon. The journey towards fully integrating AI requires overcoming numerous operational and technological challenges, including data inconsistencies, varying levels of digital maturity among stakeholders, and concerns over data privacy and security. This all begins with a critical first step: data standardisation.
Imagine a world where AI seamlessly optimises the pharma cold chain. Predictive analytics prevent temperature excursions before they occur and real-time adjustments guarantee timely delivery of life-saving medications. Such capabilities would dramatically improve operations and patient care. But these advancements hinge on establishing consistent and reliable data practices as well as a strategic, phased approach to AI implementation.
Currently, the adoption of AI in the pharma cold chain remains more aspirational than operational. Without uniform data practices and gradual development, AI technologies cannot effectively learn from past incidents or accurately predict future challenges.
A Long Road to Digital Transformation
The pharma cold chain, critical to delivering temperature-sensitive medications, has historically faced significant challenges in technology adoption. Early systems relied on manual checks and basic data loggers, which only provided temperature information after shipments arrived – often too late to prevent spoilage. Limited real-time monitoring and the lack of standardisation across logistics providers made it difficult to maintain consistent temperature control, especially in global shipments.
As the industry has evolved, so has the potential for digital solutions. However, AI remains underused across the pharma cold chain because of differences in digital maturity levels, where some companies are equipped with advanced technology, while others face infrastructure gaps.
The Essential Role of AI-ready Data
To turn the promise of AI applications into reality, addressing the data issue must be the top priority. The accuracy and reliability of AI insights depend heavily on data consistency across the industry, as well as the use of explainable AI (XAI) models. Unlike traditional “black-box” AI models that make decisions without revealing their logic, XAI models are designed to show the reasoning behind their predictions, allowing stakeholders to see and understand the factors contributing to each outcome. This transparency is crucial in the pharma cold chain, where understanding why certain routes, maintenance actions, or inventory levels are recommended helps companies make informed, reliable decisions.
But without consistent, high-quality data, even XAI models may struggle to offer meaningful insights, as their explanations will be based on incomplete or flawed inputs. This lack of transparency can lead to confusion or mistrust in AI’s recommendations, ultimately undermining the entire AI integration process and jeopardising patient safety.
For example, imagine a scenario where different pharmaceutical distribution centres record temperature excursions in varying ways. Some centres might log that an excursion occurred without specifying the degree of deviation, while others provide precise temperature details. Additionally, the duration of these excursions might be recorded inconsistently, sometimes in hours, minutes or even through text descriptions.
As a result, the AI system may struggle to accurately assess the risk of product spoilage, potentially leading to inaccurate risk evaluations. When the impact of a temperature deviation on the quality of the medication isn’t clear, products may be discarded unnecessarily, causing avoidable waste and increased cost. The absence of uniform data can also complicate the attempts to identify the root causes of these excursions, making it harder to implement effective preventative measures.
By establishing a standardised framework for data across the industry, these inconsistencies can be eliminated, paving the way for AI systems to function effectively. This
means developing clear guidelines for data terminology, measurement units and data recording practices. Once these standards are in place, AI can begin to analyse and predict with greater accuracy, providing better outcomes for the entire supply chain.
While data sharing is essential to fostering collaboration, it’s equally important to set clear boundaries. Developing secure, standardised frameworks can help protect sensitive, proprietary information while enabling stakeholders to share insights that benefit the industry as a whole.
To maintain the quality and reliability of the data, all stakeholders in the supply chain must rigorously validate their data, maintain transparency in AI decision-making, and conduct regular audits. Trust in AI stems directly from this foundation, making it essential that these steps are seen as nonnegotiable for successful AI adoption and operation.
Adopting AI as a Long-term Strategy
Effective AI adoption will be a gradual process focusing on long-term gains rather than immediate results. The goal is to make sure that each phase of implementation is grounded on a solid foundation of reliable data.
A phased approach is particularly effective in pharma cold chain logistics, starting with foundational steps like data standardisation and pilot projects, and gradually moving to advanced applications like real-time tracking and predictive analytics. Each stage builds on the previous one to maximise stability and accuracy.
For instance, initial phases might focus on collecting and standardising data. Later phases could involve implementing basic AI systems for monitoring, gradually advancing to more sophisticated predictive analytics and real-time adjustments. This continuous improvement requires collaboration among pharmaceutical companies, logistics providers and technology partners to coordinate and effectively integrate all efforts.
Collaboration works best when it respects data ownership and ensures that shared
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insights align with common goals without compromising competitive information. Technologies like federated learning or blockchain can support this process, enabling secure data-sharing without direct exchanges.
The Benefits for all Stakeholders
The advantages of integrating AI into the pharma cold chain are extensive and impact everyone involved. AI-driven insights will optimise routes, reduce waste and lower costs. This means pharmaceutical companies can streamline their logistics, distributors can better achieve timely deliveries and patients receive their medications reliably.
Beyond these basic efficiencies, AI can add considerable value through real-time tracking and predictive capabilities. For instance, AI systems can monitor cargo locations, conditions, and compliance with temperature requirements, providing deeper insights into the entire logistics process. This visibility allows companies to identify patterns and trends that might otherwise go unnoticed. Predictive analytics can also analyse external factors, such as weather patterns or port congestion, to suggest proactive route adjustments and avoid delays.
AI’s contribution to sustainability is another significant benefit. By optimising energy consumption in temperaturecontrolled units, adjusting cooling cycles based on cargo needs and environmental
conditions, and forecasting demand more accurately, AI could reduce the overall carbon footprint of the pharma cold chain. For example, AI can recommend fuelefficient routes, reducing emissions without compromising delivery speed. These adjustments also translate to cost savings, as AI-driven inventory management helps companies avoid overstocking, streamline inventory, and cut holding costs.
Looking ahead, AI holds great promise for streamlining compliance processes, from automating temperature and location data records to easing the burden of regulatory checks and audits. With predictive maintenance, AI could also detect potential issues with equipment early on, preventing unexpected breakdowns and shipment disruptions.
But the future of AI in the pharma cold chain depends heavily on collaboration and partnership. Sharing data and insights among stakeholders can enhance the entire supply chain. For instance, AI can work in tandem with IoT devices for real-time monitoring and with blockchain technology to provide enhanced security and transparency. Logistics partners can share real-time data on transportation conditions, such as temperature and time spent in each location, with pharmaceutical companies, helping them understand and mitigate risks in the supply chain. Pharmaceutical companies can
use AI to analyse this data and make informed decisions about their shipping strategies and packaging choices.
Collaborative efforts can lead to innovative solutions that no single player could achieve alone. By working together, stakeholders can develop reliable and effective AI systems, improve data quality and ultimately ensure the safe and efficient delivery of vital medications.
Building Trust in AI Systems
While AI offers extensive benefits, its integration into the pharma cold chain also raises important ethical and security considerations. AI systems in supply chains handle sensitive business and product information, including proprietary data on shipment conditions, routes, and compliance records, which must be protected.
A breach of this data could compromise not only competitive business information but also impact patients indirectly. For instance, if a breach exposed sensitive shipping routes or cold chain protocols, it could result in delays or even sabotage of critical medication shipments, ultimately affecting patient access to vital drugs.
In the context of AI, these privacy concerns are heightened, as AI models require large datasets for training and decision-making. Unlike traditional systems that process data for isolated tasks, AI systems continuously analyse and aggregate information, making them more susceptible to privacy risks if hacked or misused. Additionally, AI’s ability to draw inferences from data, sometimes beyond the initial scope, means that even seemingly benign data can reveal sensitive insights when combined with other sources.
To address these risks, collaboration must prioritise robust safeguards that protect sensitive data. Secure practices such as encryption, access controls, and transparent data-sharing agreements ensure that progress isn’t made at the expense of privacy or competitiveness. By aligning on these principles, stakeholders can foster trust in AI systems while mitigating potential vulnerabilities.
Another critical concern is the potential for bias within AI algorithms, which could result in unfair or skewed outcomes, even in the context of cold chain shipments. For instance, an AI model trained primarily on data from specific regions or equipment types might prioritise certain routes or
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maintenance schedules over others, not because of efficiency but because of historical data patterns. This could lead to delays or inadequate protection for shipments in lessrepresented areas or climates.
To mitigate these risks, it’s essential for companies to monitor AI systems regularly and feed them with accurate, diverse data. Transparency is also vital, as clear insights into AI’s decision-making processes help prevent unintended biases. Companies also need robust security protocols specific to AI, including data encryption, secure access controls, and regular audits of AI models to prevent unauthorised inference or data manipulation.
Additionally, the automation AI introduces may impact jobs within the logistics sector, presenting an opportunity for companies to reskill employees to work alongside AI. For example, employees might require training in data analysis to interpret AIgenerated insights, familiarity with predictive maintenance systems to respond to alerts, or knowledge of compliance protocols to verify that AI-supported processes meet regulatory standards. As AI becomes more integrated, traditional roles may evolve, requiring a blend of logistics expertise and digital literacy.
This shift could create new roles within the logistics chain, such as “AI Logistics Coordinators” who specialise in managing AI-driven tools for route optimisation or temperature monitoring, or “Predictive Maintenance Specialists” who oversee AI
systems used for equipment maintenance schedules. Rather than AI replacing humans, these roles would enable employees to work in tandem with AI, using technology to enhance decision-making while companies support staff through targeted training programmes.
By addressing these ethical and security considerations, stakeholders in the pharma cold chain can build a responsible framework for AI integration that balances innovation and accountability.
The Future of AI in Pharma Cold Chain
The journey towards fully integrating AI in the pharma cold chain begins with data that is fed to the systems. Without high-quality data that flows as the lifeblood of AI systems, we cannot achieve the accurate and reliable predictions needed to instil trust in the technology.
To achieve the required level of standardisation, pharmaceutical companies, logistics providers, and technology partners must work together to implement rigorous data validation processes, maintain transparency in AI decision-making, and conduct regular audits.
This collaborative environment is necessary to AI’s success in the cold chain. When companies share data securely and effectively, AI becomes a valuable tool for every stakeholder. By focusing on these longterm strategies and fostering a collaborative environment, the industry can achieve
significant advancements in efficiency, reliability and patient care.
As technology continues to evolve, the strategic implementation of AI over time will be crucial in meeting the growing demands of the pharmaceutical industry. Future developments in AI, such as federated learning, could enhance data analysis without compromising privacy, while blockchain integration could improve data security. Predictive capabilities will also advance, allowing AI to offer even more precise insights into supply chain risks. Embracing this marathon with a clear vision and cooperative spirit will lead to a brighter, more efficient future for all involved.
Otto Dyberg is the CIO at Envirotainer. He has extensive experience in the IT field and has worked in several different industries for the past 20 years. Prior to joining Envirotainer, he was the Swedish CIO at one of the world's largest public transport operators – Keolis. He has also worked as a Global IT Manager at worldleading Eye-tracking company Tobii. He had his own consultancy firm and worked several years as CTO and coach in the incubator industry and with start-ups.
Otto Dyberg
Pharmapack Subsection
Bio-based Plastics: A Bridge to Sustainable Devices
There is one material used with ubiquity across the pharmaceutical industry. In one way or another, it enables nearly every drug treatment given today. It has become so fundamental to medicine, that it is treated in a vast number of cases as part of the medicine itself. It is used because of a well-understood and repeated safety record, and because it enables high-volume, reliable, and repeatable manufacture, and is made from a commonly extracted raw material.
It is, of course, the range of synthetic materials called plastics. Yet despite being easy to work with, and to make safe for medical use, it is difficult to manage at the end of its life, doubly so for drugcontaminated medical devices typically made from the higher-performing end of the plastic spectrum.
At end of life, plastic medical waste is either sent to landfill or incinerated. It is vanishingly rare for recycling to be considered.
Combination products, capitalised in the case of the FDA term ‘Combination Product’, consist of a device element and a drug element, which combine to provide the necessary efficacy – the drug formulation is designed to work with the device, and vice versa. Intrinsically, they are proven and regulated in combination.
Ideally, the often-plastic device element would be designed based on circular design principles, to eliminate waste and pollution, circulate products and materials (at their highest value), and regenerate nature, as defined by the Ellen MacArthur Foundation. Circular design in practice is typically achieved by design for device reuse or full recyclability. However, this switch does not come without possible impacts on usability, and therefore efficacy, and is currently not compatible at scale with the end-of-life disposal that is required today.
The environmental impact of plastic is also an important consideration for devices which are on sale today, or are soon to become
marketed products, where expensive and time-consuming development work is already complete. Circular design should be pursued, but it cannot deliver an instant impact.
What we are left to work with then, is the plastic materials themselves. Even better if we can remove the dependence on the extraction of oil and gas for their production.
Vectura’s Open Inhale Close (OIC) device is a good working example of the device element of a combination product. It has been developed with ease-of-use (to help patient compliance), and therefore medical efficacy in the hands of patients, at the core of its design philosophy. The OIC, therefore, makes great use of a small number of robust injection-moulded plastic components, and with conventional end-of-life considerations. The OIC Device has a significantly lower component count than other blister-based open-inhale-close DPI devices, including devices for which it was designed to be a substitutable generic device.
As a simple-to-assemble and lightweight dry powder inhaler, the OIC’s environmental impact is driven predominantly by the volume and processing of the plastics used in its construction.
In using the OIC as a case study, plastic options are presented, explored, and, crucially, implemented into the OIC device with input from stakeholders across Vectura.
More Sustainable Plastics
There are options available when it comes to the origin and processing of the plastics. These are potential options for use in devices:
• Conventionally recycled plastics –products that contain post-industrial or post-consumer waste. These are not suitable for medical applications. Proving the safety of these plastics is close to impossible and the variability in product-quality challenging.
• Closed-loop recycling – returning moulded scrap to be resupplied. This is not suitable for medical applications. Regrind, where scrap moulded material is ground down and remoulded at the
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moulding site, is often forbidden, and this is a less-controlled version of regrind.
• Chemical recycling – products which are of virgin quality but produced with feedstocks derived from chemical recycling. This has the potential to meet the needs of medical device applications, however, it is not industrialised.
• Bio-based plastics – products made or derived from naturally occurring materials as a replacement for fossil feedstocks. This is suitable for medical applications and solutions are commercially available.
Bio-based Plastics for Medical Devices
In their manner of production, bio-based plastics for medical applications differ to what might conventionally be referred to as bio-plastics.
By mixing equivalent feedstocks to fossilbased materials with those derived from biobased sources during polymer manufacture, and accounting for this in the output, identical bio-based and fossil-based resins can be produced at the same time. Figure 1 provides an overview of the production process for medical device plastics.
1. Green feedstock derives from biocircular sources, for example, methane from anaerobic digester using only waste products
2. Mass-balanced approach means fossil and green feedstocks are mixed during production but accounted for separately
3. Segregated bookkeeping approach is certified by ISCC+
4. Bio-based resins are identical to conventional resins
This process means that for any given material, there can be a fossil-based version and a bio-based version that are interchangeable with one another, at least from a technical perspective, with the regulatory impacts in need of consideration. As such, biobased resins are available for many commonly used plastics in medical devices.
For Vectura’s portfolio of devices, most of the plastic materials selected have bio-based versions commercially available.
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In the case of Vectura’s OIC device, all injection-moulded plastics have a biobased equivalent that can be used as a drop-in, provided the risk of the change can be adequately resolved, where that risk is primarily regulatory in nature, but may extend to supply chain risks.
Environmental Impact
The benefits of bio-based plastics on sustainability and the environment derive from reducing the need to extract and refine virgin raw materials. Typically, these are fossil in origin, but may extend to other mined substances. The effect is doubled given the bio-based feedstock source is waste, therefore endowing circular design properties into the material.
Using bio-circular (waste) sources reduces the negative externalities associated with other plant-based plastics (bioplastics), where the feedstock is usually a crop. This can compete with food-crop production and creates biodiversity loss as an opportunity cost from land use.
The lifecycle for carbon dioxide emissions from bio-based plastics are substantially reduced when compared with fossil-based equivalents. Figure 2 compares the emissions from device-plastics supply for three of Vectura’s key drug delivery devices, all dry powder inhalers, using data from material suppliers. By considering the carbon footprint of the raw plastic material elements only, the actual carbon emission reduction can be easily derived for a typical annual production of three million devices, though this does not consider the full lifecycle of the device.
Further benefits include the localisation of feedstock production. Typical waste sources, invariably food waste, are universal, meaning the feedstock supply chain does not need to
rely on geopolitics and the associated supply tensions placed by the global distribution of natural resources, as is the case with oil and gas.
Impact to the Medical Device
Of course, this seemingly straightforward switch has to consider the impact on safety and efficacy of the final drug product.
Documentation that defines material properties and accreditations, along with ISCC+ certification from the material suppliers, is reviewed against device material requirements and provides the evidence that the bio-based material is viable.
Whilst the bio-based materials are fundamentally identical to the conventional
materials, and theoretically there should be no change in the risk profile to the device function or patient safety, according to guidance,1 they could still be treated as a material change from a regulator perspective, and therefore the associated regulatory risks and impacts must be considered. Indeed, the risk here is invariably down to needing to satisfactorily evidence the identical properties of bio-based materials to a regulator as proof the change would not impact efficacy or safety, rather than necessarily proving it through experimentation. That being said, without suitable regulator engagement, this remains unproven.
All these risks, however, can be avoided by changing the device design definition to bio-based plastics before device verification and validation (V&V). For the OIC, as with most devices that are part of combination products, V&V includes bio-compatibility testing. with the target drug formulation and dosage, this sets material choices due to the cost and timescale of the tests. The Extractable and Leachable (E&L) of the biobased materials are identical to the fossil materials, though either option would need assessing against any change in drug product, use, or posology. For OIC, this had not been started prior to the selection of bio-based materials. Subsequent proprietary projects using the OIC device platform with bio-based materials would only need to repeat V&V activities associated with a change of target drug.
Figure 1: Medical device plastics production incorporating bio-based feedstocks
Figure 2: Estimated CO2 reduction from using commercially available bio-based version of plastic grades for three bio-based Vectura devices. The LOMI and Gyrohaler® devices are both approved devices as part of combination products.
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Open Inhale Close, or OIC, device is a blister-based DPI designed for multi-dose applications. It has only 3 user steps: Open, Inhale and Close. It makes use of the versatility of injection moulding and Vectura’s proprietary technologies to offer simplicity of design, low component count, intuitive user interface, digital connectivity readiness, generic device substitutability and low cost.
There is, invariably, a cost impact to the approach, and questions of supply chain resilience to consider. However, the cost
impact is approximately one per cent at a product level, which is bearable given the large carbon footprint reduction. Similarly,
supply chain risks are either identical to fossil grades due to co-production or improved by the distribution of feedstock production.
Conclusion
and
Next Steps
Short-term steps to improve the sustainability of medical devices can be taken now.
The implementation of bio-based plastics is best done at the early stages of development, but slot-in solutions, where available, allow bio-based material selection to be utilised at mould tool qualification, just prior to design verification and validation in the development cycle.
In theory, bio-based plastics can be applied to marketed and close-to-market products. The question of applicability to marketed devices is still an open one, and where some guidance in the approach to regulation is required. Understanding among all stakeholders is needed to allow the considerable impact of legacy plastics supply to be reduced using bio-based plastics.
Longer-term, a concerted effort is needed across the industry to drive change to minimise the impact of single-use plastics at end-of-life. This could be achieved by adopting fully circular design principles with better end-of-life management.
REFERENCES
1. FDA Guidance (2017): Guidance for Industry and Food and Drug Administration Staff. Deciding When to Submit a 510(k) for a Change to an Existing Device.
Philip Smith
Philip Smith is a Mechanical Engineer and Principal Engineer at Vectura Limited. Vectura is a leading specialist inhalation CDMO that provides innovative inhaled drug delivery solutions that enable customers to bring their medicines to market. With differentiated proprietary technology and pharmaceutical development expertise, Vectura has the device, formulation, and development capabilities to deliver a broad range of complex inhaled therapies. Vectura has contributed to the success of 13 inhaled medicines launched by our partners and licensees.
The
Stoelzle Glass Group: Advancing Sustainability in Glass Packaging for Pharma and Healthcare
Stoelzle Glass Group stands as a premier manufacturer of high-quality primary packaging glass, catering to a diverse array of sectors including pharmaceuticals, healthcare, spirits, perfumery, cosmetics, and food & beverages.
Glass, made entirely from natural raw materials, is ideal for pharmaceutical and healthcare packaging. Recognising glass as one of the most sustainable packaging materials, Stoelzle's commitment to environmental responsibility is evident in their gold status in the EcoVadis sustainability rating, achieved for the third consecutive year. This prestigious recognition places Stoelzle in the top five percent of evaluated companies, underscoring their dedication to decarbonisation, continuous innovation, and environmental protection, highlighting the significant strides they have made over the past years.
As an energy-intensive industry, Stoelzle has set scientifically based decarbonisation targets validated by the Science Based Targets initiative (SBTi). The company's ambitious goals include a 50% reduction in CO2 emissions (Scope 1 and 2) by 2030, aiming for net zero by 2050. Stoelzle is one of the few European glass manufacturers with climate targets recognised by SBTi.
The company's comprehensive sustainability strategy focuses not only on environmental goals but also includes social aspects and the supply chain. Energy savings, the transition to renewable energy, and decarbonisation are central concerns. Over the past years, the Group has
implemented substantial projects at their Pharma production site in Köflach, Austria, such as a process and energy management system, significantly improving energy efficiency and achieving energy savings. Municipal water consumption was reduced by around 50% through targeted measures during the refurbishment of the furnace. Since 2020, Stoelzle has installed large rooftop photovoltaic systems on warehouses and office buildings, producing approximately 3,610 MWh of green electricity per year. The inclusion of cullet, or recycled glass, helps minimise the use of primary raw materials and reduce the carbon footprint through energy savings.
In April 2023, another milestone was achieved with the installation of batch preheating at the Köflach site. This innovation reduces energy consumption for melting raw materials by more than 8%, allowing for annual energy savings of 4000 MWh. Looking to the future, Stoelzle plans substantial investments to significantly enhance the electrification of their glass production processes and maximise the efficient utilisation of waste heat. As a member of the International Partners in Glass Research (IPGR), the company is working on an energyefficient furnace.
Comprehensive Packaging Solutions
Stoelzle is committed to minimising environmental impact while delivering high-quality packaging solutions through a One-StopShop approach, by supporting every stage of the glass supply chain, from product development and in-house decoration to the supply of compatible closures. Leveraging expertise in caps and closures, the company offers key services such as compatibility assessments for neck finishes, drop tests for insert suitability, and support for customer audits of closure manufacturers. To maintain high standards, the Stoelzle quality team conducts regular audits, ensuring consistency across manufacturing partners. The company is pioneering sustainable caps and closures for various applications, adhering to strict pharmaceutical and food safety standards. The innovative carbon-free closure systems are fully recyclable, helping to reduce waste, CO₂ emissions, and environmental harm. With a keen eye on market trends
and technological advancements, Stoelzle continuously seeks new developments to provide the best solutions for its customers.
A New Range of Well-being Packaging with Increased Recycled Content
Stoelzle's new PharmaCos line is a comprehensive packaging solution for the wellbeing and healthcare industries. This line features an extensive range of glass jars and flat-shoulder bottles. The PharmaCos range is designed with sustainability at its core. The amber glass contains an impressive 73% recycled content, while the flint glass includes 38% recycled material. Combined with the lightweight design of the bottles, this line offers a highly sustainable option for healthcare packaging. All products are manufactured in a pharmaceutical-grade environment, ensuring adherence to the highest standards of quality and safety.
With its unwavering commitment to innovation and sustainability, Stoelzle Glass Group continues to set the standard for environmentally responsible glass packaging solutions across a wide range of industries.
Celebrating 10 Years of VarioSys: An Unforeseeable Success Story
Interview with the Masterminds Behind VarioSys, Dr. Friedrich Haefele and Bernd Wieland
VarioSys entered the market ten years ago and has since revolutionised pharmaceutical production. What was needed was a highly versatile system capable of handling various delivery systems – syringes, cartridges, and vials – while accommodating different filling quantities within a single isolator. This approach contrasted sharply with the traditional method of permanently installing separate filling and closing systems within an isolator for each type of container.
This challenging task was successfully accomplished by the specialised machine manufacturer Bausch+Ströbel in collaboration with isolator manufacturer SKAN, and with the invaluable guidance and support
of Dr. Friedrich Haefele, Vice President Biopharma Fill & Finish Boehringer Ingelheim.
The past ten years have proven that this development was the right choice at the time. Over 100 systems have been sold worldwide to date, and demand remains strong, as noted by Bernd Wieland, Director of Regional Sales & Business Development at Bausch+Ströbel. This is mainly thanks to the system's continuous improvement over time. Like Dr. Friedrich Haefele, Bernd Wieland has been a driving force behind the development from the very start.
As they both remember very well, this success story was not foreseeable at the outset. Dr. Haefele recalls, "It all started for me back in 2009. At that time, I was the department head of the Bio-Pharmaceuticals Division at Boehringer Ingelheim. I had access
to a small filling line for liquid and lyophilised vials, but I saw the need to upgrade our lyophiliser line to comply with current technical standards. We had a state-of-the-art system for filling pre-filled syringes, but it couldn’t be adapted for processing vials. Even then, I was looking to add significantly more flexibility to our production process."
A Company Deeply Committed to Innovation and Receptive to Customers' Ideas and Needs
Haefele promptly brought this idea to Bausch+Ströbel, a company with which he had a long-standing relationship. "I have always seen Bausch+Ströbel as a company deeply committed to innovation and receptive to customers' ideas and needs," Haefele emphasises, "This relationship has been invaluable to us throughout the development and implementation of the
VarioSys concept." The development team was further strengthened by the addition of Skan, an isolator manufacturer.
The First System was Commissioned in California in 2014
It took a few more years before the system was ready for launch. "In 2014, we successfully installed the first VarioSys filling machine at our sister company in Fremont, California," says Haefele. His enthusiasm was so great that he showcased the system in a presentation at the PDA conference in Munich later that year. Additional systems were later commissioned at various Boehringer facilities, including sites in China and Germany.
Dr. Haefele attributes VarioSys' success to its flexibility, and in particular its adaptability to various delivery systems and the reusability of the isolator. "Today, an isolator costs nearly as much as a filling line, this is why it is crucial to utilise these resources efficiently" he explains. For this reason, a range of processing modules were developed to work seamlessly with a specialised isolator as needed.
The Challenge: Fitting a Full Range of Functions into a Very Compact Space
"A major challenge for our engineers was to create fully functional modules within the extremely limited space provided by the VarioSys isolator," recalls Bernd Wieland. The effort was well worth it. "Today, VarioSys is recognised for its compact and spacesaving design" he adds. More importantly, VarioSys signifies a major step forward in pharmaceutical production thanks to its exceptional flexibility. By combining
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diverse applications and interconnecting modules into process lines, a wide variety of pharmaceutical manufacturing configurations can be achieved.
The Key Advantage of VarioSys: Its Ability to Handle Both Ready-to-use Containers and Bulk Components
"The ability to use a rinsing machine and a sterilising tunnel with VarioSys means that it can process both ready-to-use containers and bulk components", says Dr. Friedrich Haefele, highlighting a crucial feature from his point of view. Bernd Wieland adds, "This makes VarioSys suitable not just for low volumes, such as sample production, but also for small production runs". Wieland noted that VarioSys can easily process 4,500 containers per hour and explained, "Our
newly developed SFM 5205 module achieves these high outputs while maintaining 100% in-process control."
With over 100 units sold worldwide and a continued commitment to progress, the team behind VarioSys is dedicated to pushing the boundaries of pharmaceutical production. The continued strong demand for this product confirms that they are on the right track. In a constantly changing environment, VarioSys remains a cornerstone of today's pharmaceutical industry. Its exceptional adaptability to new requirements, coupled with the highest levels of safety and efficiency, makes it an indispensable resource for companies of all sizes, from large pharmaceutical enterprises to cutting-edge start-ups.
No birthday party is complete without a cake.
On board from the start: Bernd Wieland, Director Regional Sales & Business Development at Bausch+Ströbel (left), and Dr. Friedrich Haefele, Vice President Biopharma Fill & Finish Boehringer Ingelheim (right).
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Bag-on-Valve: An Attractive Airless Packaging
Airless packaging of liquid products has become a cornerstone in industries where product integrity, longevity, and precise dispensing are critical. Among these packaging options, Bag-onValve (BoV) technology stands out as an attractive solution, offering some unique advantages.
Bag-on-Valve is designed to keep the product completely isolated from external air. It uses a flexible, multi-layered laminated bag housed within a standard aerosol can. The product is sealed in the bag, while compressed air or nitrogen occupies the space between the bag and the can. When the actuator is pressed, the pressurised gas squeezes the product out through the valve without any air entering the packaging. This makes BoV a true airless system, ensuring that the product remains free from oxygen, contaminants, and microbial exposure, even after repeated use.
What is Bag-on-Valve Technology?
Bag-on-Valve technology is an advanced aerosol system where the product and propellant are separated. The core components of the system include:
1. Flexible Laminated Bag: A multi-layered pouch) that contains the product, protecting it from oxygen and contaminants.
2. Aerosol Can: A standard aluminum houses the bag and provides structural stability.
3. Propellant: Compressed air or nitrogen is used as the propellant, filling the space between the bag and the can.
4. Actuator and Valve: These components control how the product is dispensed.
When the actuator is pressed, the propellant exerts pressure on the bag, dispensing the product through the valve without it ever coming into contact with the propellant. This mechanism ensures the product’s integrity and in some cases sterility, even with repeated use.
Advantages of Bag-on-Valve
1. Sterility and hygiene
One of the most critical benefits of BoV
is its ability to maintain the product's integrity throughout the product’s shelf life. The laminated bag protects the product from exposure to external contaminants, while sterilisation using gamma irradiation can ensure compliance with sterility standards.
2. Long shelf life
The multi-layered bag acts as a barrier against oxygen, preserving the product's efficacy and reducing the need for preservatives. This feature is particularly important for oxygensensitive formulations.
• Product Dispensing: Achieves up to 99% product evacuation, minimising waste.
• Ease of Use: BoV systems allow dispensing at any angle, making them user-friendly for patients and healthcare providers alike.
• Applications: Supports a wide range of products, from liquids and gels to foams and creams, making it suitable for medical, pharmaceutical, and cosmetic uses.
• Environmental Impact: Uses eco-friendly non-flammable propellants like compressed air or nitrogen and is compatible with recyclable materials such as PCR aluminum cans.
Applications and Market Niches
While both BoV and other airless systems have carved niches in industries like cosmetics and personal care, BoV excels in highly regulated environments such as medical devices. Its ability to maintain sterility makes it ideal for saline sprays, wound care products, and eyewashes.
Nasal sprays are one of the most widespread applications of BoV technology. Products like saline solutions and seawater nasal sprays benefit from BoV’s hygienic delivery and ability to maintain sterility. Simply Saline, Sterimar, and Vicks Sinex are well-known brands in this category.
Leading BOV-manufacturers
Aptar is the global leader in BOV systems, offering customisable BoV components tailored to the pharma and medical device market. A similar offering is available from Coster.
As leading BOV packaging manufacturers like Aptar, Coster and PowerContainer (PCC) continue to innovate, the potential for BoV to shape the future of medical liquid packaging is large. The future of BoV technology is bright, with ongoing innovations aimed at addressing current challenges and expanding its applications.
PowerContainer has introduced the Corsair system, an innovative non-VOC (Non Volatile Organic Compounds) delivery solution that combines a bag-on-valve pouch with a rubber sleeve that replaces the propellant. The Corsair combines low-pressure dispensing with compatibility for standard filling processes, making it an interesting and environmentally friendly option for applications such as saline nasal sprays.
Another interesting development is BOV’s with metered-dose systems: These systems will allow precise dosing for various products, ensuring consistent quality from the first use to the last. BoV systems with separate chambers for two different liquid components are also available opening up possibilities for complex formulations.
There are several contract manufacturers offering production of medical device and pharma bag-on-valve products. Notable examples include the global CMO group Fareva, Formulated Solutions in the US, and Aurena Laboratories based in Sweden.
Conclusion
Bag-on-Valve (BoV) technology is an innovative airless barrier system that ensures product integrity throughout its entire shelf life while enabling nearly 100% product evacuation. The user-friendly spray packaging is highly valued for its convenience and reliability.
Magnus Hedman
Magnus Hedman, Co-founder, Chairman of the Board, Aurena Laboratories AB
Packaging
German Manufacturer Showcases High-performance Lubricants at Pharmapack 2025
For the first time, Chemie-Technik, the German manufacturer behind the globally recognised ELKALUB brand of high-performance lubricants, is participating in Pharmapack 2025. The company will present its specialised lubricants tailored to the stringent demands of the pharmaceutical industry. The production and packaging of pharmaceutical goods require adherence to strict regulatory standards to ensure safety, precision, and efficiency.
ELKALUB meets these requirements with a comprehensive range of NSF H1registered lubricants, including greases, oils and sprays. These products are designed to ensure smooth machine operations while mitigating risks such as contamination and production downtime.
A Customised Approach for Pharmaceutical Manufacturers
Chemie-Technik emphasises customisation, offering bespoke lubricant solutions to address the unique needs of pharmaceutical production lines. Whether simplifying complex lubrication processes or navigating evolving regulatory landscapes, ELKALUB supports its clients every step of the way.
“Changing global regulations, such as the shift toward PFAS-free lubricants, can create challenges,” explains Technical Sales expert Christian Hof of the company’s founding family. “We proactively monitor these changes and recommend compliant, efficient alternatives, ensuring our customers remain ahead of compliance requirements.”
Trusted by Industry Leaders
Leading equipment manufacturers trust ELKALUB products for the initial lubrication of their machines. The company’s research and development team collaborate closely with clients to create tailor-made solutions that enhance machine reliability and efficiency. Backed by a global distribution network, Chemie-Technik guarantees consistent, highquality supplies, regardless of geographical location.
Benefits of ELKALUB Lubricants
Pharmaceutical manufacturers can expect the following benefits when using ELKALUB products:
• Maximum Safety: NSF H1 registration ensures compliance with strict safety standards.
• Integrated Lubrication Concepts: Comprehensive solutions for all production needs.
• Reduced Downtime: Enhanced machine performance and reliability.
• Global Support: A robust sales and service network ensures worldwide availability and local regulatory compliance.
Excellence Rooted in Tradition
Established in 1956, Chemie-Technik remains a family-owned enterprise managed by the second generation of its founding family. With a team of 35 experts based at its headquarters in Vöhringen/Württemberg, the company handles development, production, and in-house sales. A global network of representatives, including independent distributors, provides operational sales and on-site customer support.
The company is dedicated to continuous improvement, maintaining ISO 9001 certification for quality management since 1997, and ISO 14001 certification for environmental performance since 2008. ChemieTechnik supplies its high-performance lubricants to leading companies across
multiple industries, including printing, food, pharmaceuticals, automotive, and tool manufacturing.
A History of Innovation
Chemie-Technik has a long-standing reputation for innovation, introducing the first H1-registered lubricant to the market in 1995. Today, its expertise in the printing, packaging, and food processing industries seamlessly translates to the pharmaceutical sector, making ELKALUB a trusted name for companies operating packaging and filling lines.
Visit Chemie-Technik at Pharmapack 2025
At Pharmapack 2025, Chemie-Technik aims to connect with contract manufacturing organisations (CMOs), original equipment manufacturers (OEMs), automation specialists, and other key players in the pharmaceutical packaging and filling industry.
Explore ELKALUB’s range of highperformance lubricants and discover how they can enhance safety and efficiency in pharmaceutical production. For more information, visit ELKALUB Lubricant’s stand (C23) at Pharmapack 2025 or find their comprehensive product catalogue online.
From Germany to the World—ChemieTechnik: Pioneering Lubricant Excellence Since 1956.
Christian Hof
Christian Hof, Technical Sales expert, member of the company's founding family
Packaging
Driving Sustainability in Pharma: Pharmapack’s Vision for Change
Ahead of Pharmapack Europe 2025, an event that has been integral to driving pharmaceutical sustainability over the last decade, Silvia Forroova, Informa Market’s Director of Partnerships & Sustainability shares her thoughts in what lies ahead.
In an era of increasing environmental awareness, the pharmaceutical industry is facing significant sustainability challenges. From reducing energy consumption through more efficient process chemistries and improving waste management to reshaping how sustainability stories are told, the sector must balance advancing eco-friendly practices and recycling while meeting ever tightening regulatory requirements and drive to improved patient centricity – which has often meant more complex and harder to recycle devices.
My role at Informa spans three key areas: encouraging behavioural change in the pharma industry, improving our own operational practices, and fostering collaboration through the Sustainability Collective. At Pharmapack, an event at the heart of pharma’s drug delivery and devices sector, we have continued to try and harness our ability to bring the industry together – to proffer new learnings, insights and working groups on key themes. One such new initiative is the Sustainability Collective – more on that shortly – and taking lessons from our own research. For example, many of the stakeholders at our events reported to us that they find the story telling aspects of sustainability and employee engagement to be a key challenge.
In fact, some pharmaceutical companies struggle to effectively communicate their sustainability efforts sufficiently to drive the behavioural change across their workforce. Whether its pitching new initiatives to investors or engaging employees in daily eco-friendly actions like proper recycling, companies need to prioritise clarity and inclusivity in their messaging. Once engaged, employees will bring new ideas forward. In our own offices we recently conducted training sessions on using the recycling
bins – when we asked, we found that most employees did not use them just because they were unsure of how to. This simple step significantly improved waste management, demonstrating how small behavioural changes can lead to substantial results.
On a bigger scale, Pharmapack is now powered by renewable energy. Tulipe are our sustainability partners for 2024 – they undertake tremendous work in distributing pharmaceutical donations to humanitarian organisations. At the upcoming event we will display our largest ever sustainability platform with a record number of sessions, working groups and showcases such as the Sustainability Centre and a dedicated Partners Village, all of which are done to underscore a collaborative approach.
A cornerstone of Pharmapack’s sustainability initiatives is the Sustainability Collective, a dynamic group of industry leaders launched earlier this year. The Collective aims to drive change through shared expertise, grassroots movements, and actionable solutions tailored to companies of all sizes. Smaller firms often seek guidance on starting their sustainability journeys, such as tools for calculating carbon footprints, while medium-sized companies need support in communicating their sustainability efforts. Larger corporations focus on crafting compelling narratives to attract investors. Through initiatives like pre-event webinars and networking breakfasts, the Sustainability Collective fosters dialogue and empowers organisations to integrate sustainability into their operations. Polymeris, which is helping advance innovation in sustainable plastic polymers through collaborations, will run an innovation tour focused exclusively on plastic polymers. Adelph, another key event partner, contributes to shaping Pharmapack’s content and engaging expert speakers.
Pharmapack has reimagined its content offerings to reflect a deeper emphasis on sustainability. Traditional topics such as innovations in blister packs and glass packaging remain integral, but the event now delves into broader sustainability challenges and solutions. Programmes like the Polymeris innovation tour, which focuses exclusively on sustainable plastic polymers,
Silvia Forroova
Silvia Forroova, Director of Partnerships & Sustainability, Informa Market
highlight advancements in material science and showcases how collective innovation can address the environmental impact of the pharmaceutical industry.
Recognising the importance of engaging the next generation of leaders as a broader CSR activity, Pharmapack has also launched initiatives like the Rising Stars programme. This platform provides young talent with opportunities to learn, network, and contribute to the industry’s sustainability efforts. Mentorship programmes have evolved to include peer-based learning, where professionals at similar stages in their careers share strategies for advancement. This approach complements traditional mentoring relationships, fostering a more inclusive and empowered workforce within the pharmaceutical sector.
Sustainability trends across the pharmaceutical industry are gaining momentum, driven by innovations in eco-friendly packaging, efforts to reduce carbon footprints, and the push for transparent, sustainable supply chains. Many organisations are investing in renewable energy and energy-efficient manufacturing processes to minimise environmental impact. Events like Pharmapack are instrumental in accelerating these trends, offering a platform for stakeholders to share knowledge, forge partnerships, and showcase groundbreaking solutions.
Pharmapack’s commitment to sustainability extends beyond hosting an event; it is about building an ecosystem where meaningful and lasting change can thrive. By uniting leaders through the Sustainability Collective, Pharmapack is helping companies take action toward a greener future. Whether assisting a start-up in identifying tools to measure its carbon footprint or supporting larger firms in refining their sustainability narratives, the event is proving that collective action is the key to driving systemic change. As the pharmaceutical industry continues to innovate and adapt, the lessons learned, and connections forged at Pharmapack will play a pivotal role in shaping a more sustainable future.
Pharmapack 2025: Europe’s Leading Packaging and Drug Delivery Event
As we enter 2025, the pharmaceutical industry is thriving, driven by postCOVID growth, revolution in drug delivery, and market optimism bolstered by increased investment and private equity support. All eyes turn to Pharmapack Europe 2025, taking place on the 22nd-23rd of January in Paris. Building on the success of CPHI Milan, the event promises a premier platform for networking, strategic partnerships, and insights into drug packaging and delivery technologies shaping the future of healthcare.
This year's event will host 364 exhibitors and 5,700 executives from 70+ countries, making it the largest in Pharmapack's history. It will feature 70+ sessions across sustainability, contract packaging, device development and large-volume drug delivery.
A highlight of Pharmapack is its focus on sustainability, with Sustainability Learning Labs offering solutions for greener pharma packaging.
“As we look into the year ahead, the pharmaceutical sector is accelerating toward a future where sustainability, innovation, and collaboration take centre stage. This year, we’re not only fostering a thriving community for R&D and start-ups but also driving meaningful conversations on sustainable packaging and circular economy principles. Pharmapack 2025 is about bringing the industry together to bridge scientific breakthroughs with practical, scalable solutions that make an impact—ultimately advancing patient care and global health. It’s a space where transformative ideas meet the real-world needs of tomorrow.” added Sherma Ellis-Daal, Brand Manager at Pharmapack.
The agenda offers an exploration of advancements in pharmaceutical packaging and delivery. Highlights include breakthroughs in ophthalmic drug delivery, emergency packaging, and reusable autoinjectors. It addresses challenges in highviscosity and large-volume drug delivery, focusing on patient-centric, self-administered
products while balancing personalisation with standardisation. A dedicated sustainability track will showcase eco-friendly initiatives, covering sustainable blister packaging, nextgeneration glass vials, and responsible plastic use in devices. The programme concludes with a panel on supply chain collaboration for sustainability, positioning Pharmapack 2025 as a key event for pharmaceutical packaging and drug delivery.
Detailed Event Overview
Step into Pharmapack Europe 2025 to uncover the newest trends and visionary strategies within the industry. This year’s event will convene an impressive roster of industry pioneers including BD, Schott, Aptar, West Pharmaceuticals, Terumo, Berry, PCI services, and NIPRO pharma packaging.
Pharmapack 2025 brings a lineup of new initiatives and event highlights. The Sustainability Theatre offers a two-day programme, reflecting Informa’s and the industry’s commitment to environmental responsibility. Kicking off with a unique Walking Tour on Day 0, visitors and exhibitors are invited to explore the destination, culminating in a networking drinks session to foster connections.
Day 2 starts with a morning charity run, where participants “run for a cause” and contribute to impactful donations. The Diversity Breakfast Session will explore inclusive packaging design approaches, particularly addressing the needs of people with disabilities and restrictions. Pharmapack 2025 also features interactive and sustainability workshops, along with a “Meet the Speaker” networking lunch for the Device & Packaging Innovation track.
The Pharmapack Awards are undergoing an exciting transformation. We’re thrilled to introduce a refreshed approach that celebrates both commercialised products and pioneering breakthroughs in pharma packaging and drug delivery. The Awards are more inclusive than ever and open to all industry participants, free of charge. The Awards Ceremony is taking place on the first evening of Pharmapack. Recognising the market’s desire for a metamorphis, we’re providing nominees with exposure.
Shortlisted entries will be featured in the Product Gallery, giving attendees the opportunity to engage with the products and meet the innovators behind them.
The Pharmapack Awards 2025 has introduced three new categories designed to spotlight leadership, innovation, and excellence.
• Patient-Centricity Award: Recognises packaging or drug delivery designed to improve patient adherence and health outcomes.
• Eco-Design Award: Commends sustainable innovations focused on recyclability, carbon footprint reduction and environmental impact.
• Primary Packaging Innovation: Recognises standout achievements in packaging development.
• Drug Delivery & Device Innovation: Focuses on advancements in drug delivery systems.
The production and packaging of pharmaceutical products are subject to strict regulations. We offer a comprehensive lubricant concept with NSF H1 registered specialty products designed precisely for these conditions. With ELKALUB lubricating greases, oils, and sprays, your machines will not only run smoothly but also avoid possible downtime. Additionally, our products protect you from potential product recalls due to contamination. You can count on us.
