EPM Sep/Oct 24 by EPM Magazine

THE LATEST INSIGHTS FROM ASTRAZENECA

EMBRACING INNOVATION TO MEET FUTURE PACKAGING NEEDS MAMMALIAN BIOPROCESS INTENSIFICATION

Sep/Oct 2024

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Sep/Oct 2024 | Volume 24 Issue 4

REGULARS

5. EDITOR’S DESK

Meet our sales team at CPHI Milan.

6. A SMALL DOSE

Covering the latest developments in pharma.

14. COVER STORY

SHL Medical shares how to revolutionise drug-device development.

FEATURES

8. COATINGS & CAPSULES

Systech discuss the counterfeit epidemic in the industry.

10. PACKAGING

Tjoapack examine the increasing need for innovative solutions in pharmaceutical packaging.

13. FORMULATION

Colorcon explores drug delivery innovation for the future.

19. REGULATION

Broughton outline the key elements of stability testing for drug delivery devices.

20. DRUG DELIVERY & DEVICES

Owen Mumford Pharmaceutical Services highlights the advantages of switching from 3-step to 2-step auto-injectors.

22. DRUG DELIVERY & DEVICES

Terumo Medical Care Solutions, Pharmaceutical Solutions Division shares an MDR framework for the future.

25. DIGITAL HEALTH

AI experts at ArisGlobal discuss how large language model-enabled AI will sharpen drug safety.

28. DIGITAL HEALTH

M3 explores the advantages of market research for digital marketing campaigns.

30. EXHIBITOR PREVIEW

An exhibitor’s preview for the upcoming CPHI show in Milan.

33. BIOFERMENTATION

Suanfarma, shares how to enhance innovation by integrating biofermentation.

34. CONTRACT MANUFACTURING

Almac Pharma Services highlight the advantages of outsourcing to CMOs and CDMO.

25 20 14 22

33 13 28 30 19

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PRODUCTION

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ROB'S GOT THE REINS

You might see “Editor’s Desk” in big type on this page, but in fact, this letter is coming not from the editor but from me, Rob Anderton, Head of Portfolio Sales – Pharma. Having been part of this magazine for well over a decade, and as we transition to a new editor, I thought it was an opportune moment to take the reins and share some thoughts directly with you, our valued readers.

I’m particularly excited to announce that I will be attending CPHI in Milan this October. Despite my long tenure with the magazine, this will be my ﬁrst opportunity to experience the Milan edition of this pivotal event. The last time CPHI was held in Milan, COVID-19 restrictions were still very much in place, hindering travel and faceto-face interactions. The absence of such restrictions now feels like a signiﬁcant milestone, one that

underscores the resilience and innovation within our industry.

Reﬂecting on the journey we’ve all been through, it’s clear that everyone featured in this edition has, in some way, contributed to overcoming the challenges posed by the pandemic. Their relentless pursuit of excellence and commitment to advancing pharmaceutical science have played a part in ensuring that COVID-19 restrictions are thankfully a thing of the past.

platforms are revolutionising patient engagement and clinical trials. On the topic of contract manufacturing, Almac shares their expertise on navigating the complexities of global supply chains in a post-pandemic world.

We also have compelling discussions on coatings and capsules with insights from Systech, and explore advancements in formulation with an article from Colorcon. For those interested in the latest in packaging, Tjoapack o ers a fascinating look into sustainable and secure packaging solutions.

Address changes should be emailed to subscriptions@rapidnews.com

European Pharmaceutical Manufacturer is published by Rapid Life Sciences Ltd. European Pharmaceutical Manufacturer is distributed in electronic and print formats to a combined readership of 14,000 pharmaceutical manufacturing professionals.

Volume 24 Issue 2 Mar/Apr 2024

While every attempt has been made to ensure that the information contained within European Pharmaceutical Manufacturer is accurate, the publisher accepts no liability for information published in error, or for views expressed. All rights for European Pharmaceutical Manufacturer are reserved and reproduction in part or whole without written permission is strictly prohibited.

In this issue, we’re proud to showcase a diverse range of articles and features that highlight the cutting-edge developments shaping our industry. We delve into the latest in drug delivery and devices with insightful pieces from Owen Mumford and Terumo, exploring how innovative technologies are enhancing patient outcomes. Our cover story focuses on SHL Medical, shedding light

EDITOR’S DESK

As we gear up for CPHI, don’t miss our Exhibitor Proﬁles, providing a sneak peek into the companies that will be making waves at the event. And for those with a keen interest in biofermentation, SuanFarma presents an in-depth analysis of current trends and future prospects.

robert.anderton@rapidnews.com

on their groundbreaking work in advancing selfinjection solutions.

The realm of digital health is ever-expanding, and contributions from Aris Global and M3 provide a deep dive into how digital

I wholeheartedly encourage you to reach out and connect with me during the event. It’s an excellent opportunity to discuss how our magazine can support your goals and amplify your achievements within the industry. If you’re reading this after CPHI, please don’t hesitate to contact me via email. I’m always eager to explore how we can collaborate and continue driving our industry forward.

Thank you for your continued support and engagement with our publication. Together, we can foster a community that not only shares knowledge but also inspires innovation across the pharmaceutical supply chain.

A small dose

Big pharma behemoths

Johnson & Johnson have agreed to a payment of $700 million to settle allegations that the Company mislead its customers about the safety of its talc-based products.

This follows an investigation by no less than 42 U.S. States and Washington DC, although Johnson & Johnson did not admit wrongdoing, despite withdrawing the product from the North American market back in 2020.

Johnson & Johnson announced a settlement in principle in January after having to face thousands of lawsuits over talcum powder containing traces of asbestos blamed

Johnson & Johnson Reaches $700 Million Talc Case Settlement

Following the 2020 North American withdrawal, the Company stopped selling talcbased baby products globally.

for causing ovarian cancer, many of these are still ongoing.

Following the 2020 North American withdrawal, the Company stopped selling talc-based baby products globally as of last year, switching instead to corn starch as the main ingredient.

“No amount of money can undo the pain caused by Johnson & Johnson’s talc-laced products, but today families can rest assured that the company is being held accountable for the harm it caused,” New York Attorney General Letitia James explained in a statement.

As reported by Reuters, Johnson & Johnson twice tried to resolve the litigation by placing into bankruptcy a subsidiary it created to contain its talc liabilities, but courts rebu ed both attempts.

In a statement to AFP, Johnson & Johnson Worldwide Vice President of Litigation Erik Haas said the company “continues to pursue several paths to achieve a comprehensive and ﬁnal resolution of the talc litigation. We will continue to address the claims of those who do not want to participate in our contemplated consensual bankruptcy resolution through litigation or settlement.”

ASTRAZENECA’S BREAST CANCER DRUG COMBINATION

TRUQAP

FAILS IN LATE-STAGE TRIAL

The CAPItello-290

Phase III trial for Truqap (capivasertib) in combination with paclitaxel in patients with locally advanced (inoperable) or metastatic triple-negative breast cancer (TNBC) did not meet the dual primary endpoints of improvement in overall survival (OS) versus paclitaxel in combination with placebo in either the overall trial population or in a subgroup of patients with tumours harbouring speciﬁc biomarker alterations (PIK3CA, AKT1 or PTEN).

Breast cancer is the second most common cancer and one of the

leading causes of cancer-related deaths worldwide. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC is deﬁned as negative for all three. In the 1st-line setting, approximately 59,000 patients with TNBC are treated with medicine. Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN a ect approximately 35% of patients with TNBC.

Peter Schmid, MD, Barts Cancer Institute, London, and principal investigator for the trial said: “Despite modest advances, triple-negative breast cancer remains one of the most challenging forms of disease to treat due to the lack of known actionable

biomarker targets, and chemotherapy-based regimens continue to be the mainstay of treatment. While the CAPItello-290 trial results have not shown what we hoped, they provide important information to further understand this aggressive form of breast cancer where patients are in urgent need of new treatments.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, added: “We are committed to advancing science for patients in some of the most challenging cancers, including this heterogeneous subtype of breast cancer. While we are disappointed in the CAPItello-290 outcome, these results will further our understanding of the role of the PI3K/AKT pathway in breast cancer as we continue our clinical research across the Truqap clinical development programme and across our pipeline.”

The safety profile of Truqap in combination with paclitaxel in CAPItello-290 was broadly consistent with the known safety profile of each medicine with no new safety concerns identified. Data will be shared in due course.

Truqap is currently being evaluated in Phase III trials for the treatment of breast cancer (CAPItello-292) and prostate cancer (CAPItello-280 and CAPItello-281) in combination with established treatments.

European Commission Get CSL Seqirus to Produce Bird Flu Vaccines

The European Commission’s Health Emergency Preparedness and Response Authority (HERA) as part of its mandate on preparedness, has signed on behalf of participating Member States, a joint procurement framework contract for the supply of up to 665,000 pre-pandemic vaccine doses of the up-to-date Zoonotic Inﬂuenza Vaccine Seqirus, as well as an option for a further 40 million doses over the duration of the contract. Thanks to this contract the participating Member States will have access to medical countermeasures to prevent avian ﬂu.

The vaccine is intended for those most exposed to potential transfers of avian influenza from birds or animals, such as poultry farm workers and veterinarians. It aims to prevent the spread or potential outbreaks of avian influenza in Europe, protecting citizens and livelihoods. The vaccine is the only preventive zoonotic avian influenza vaccine currently authorised in the EU.

Fifteen EU and EEA Member States are participating in this voluntary procurement with the company Seqirus UK Ltd. The contract allows each participating country to consider their public health context and order vaccines depending on national need. The contract will run for a maximum of four years. Shipments are currently being prepared to Finland for immediate vaccinations of the workers at risk of exposure, at the Member State’s request. Shipments to other participating countries will follow.

Seqirus UK Ltd has an EU wide modified marketing authorisation for this vaccine for use in adults, which protects against flu caused by H5 strains of the influenza A virus.

The EU’s mechanism of joint procurement is laid down in the EU’s Joint Procurement Agreement for Medical Countermeasures, which is signed by 36 countries, including all EU and EEA Member States. The mechanism allows the participating countries to jointly procure medical countermeasures on a voluntary and ﬂexible basis. These countermeasures include vaccines, therapeutics, medical devices, and these can be used as an alternative or to complement to procurement at national level.

The Agreement secures a more equitable access to speciﬁc medical countermeasures and improves the security of supply, together with more balanced prices for the participating countries. The Agreement also contributes to the EU-level preparedness for public health crises or pandemics.

MAPPING THE COUNTERFEIT AND DIVERSION EPIDEMIC IN THE PHARMACEUTICAL INDUSTRY

Stephan Von Schilcher, Global Strategic Account Manager at Systech

Counterfeiting and diversion plague every industry, and no brand is immune to the health and livelihood risks posed. The international trade in counterfeit and pirated goods made up roughly 2.5% of world trade in 2019, while fake goods accounted for up to 5.8% of all imports into the European Union. These ﬁgures will undoubtedly increase in the coming years. This persistent threat a ects manufacturers, retailers, and consumers across global markets.

Meanwhile, product diversion – the unauthorised distribution of products to unintended markets or unauthorised retailers – poses an equally widespread challenge across industries.

SURGE IN COUNTERFEIT AND DIVERTED PHARMACEUTICALS

Counterfeit pharmaceutical products can lead to severe injuries, disabilities and, in some extreme cases, death. These fakes not only endanger health but also erode brand integrity and customer trust, diverting sales and causing revenue loss.

According to the World Health Organization, the drug diversion and counterfeiting industry generates €400 billion annually. This presents a signiﬁcant risk to patient safety, as individuals fail to receive the e ective, lifesaving medicines required. The repercussions include quality control issues, brand dilution and a decline in consumer loyalty.

According to the World Health Organization, the drug diversion and counterfeiting industry generates €400 billion annually.

This rise in counterfeit and diverted pharmaceuticals has been driven by the exponential growth in consumer willingness to buy products online, caused by an uptick in e-commerce and COVIDdriven demand. With this extended appetite to purchase goods online, many are willing to take greater risks to secure a good deal.

This market trend has led to an increase in the number of fraudulent online pharmacies, meaning they are not selling products that move through a legitimate supply chain. For example, a customer in the United Kingdom purchasing products online from a German pharmacy is likely connecting somewhere in Thailand or the Middle East, receiving goods that were not what they originally purchased – whether it be counterfeit, expired, or mislabelled by bad actors to increase their proﬁts in the e-commerce market.

We also see this issue with giant e-commerce platforms. For instance, while Amazon has its transparency programme – which is

supposed to protect products – there are vast numbers of suppliers within Amazon selling counterfeit products. Despite selling the products, Amazon has no control over this, which opens channels for counterfeit and diverted products to enter the supply chain.

Moreover, the growth in counterfeit and diverted pharmaceuticals has been driven by low supply but high demand for various products.

For instance, counterfeit versions of Ozempic are being produced at an alarming rate. The prescription drug’s popularity has surged in recent months due to its promotion as a means for quick weight loss for patients. This popularity has resulted in shortages, creating an opportunity for counterfeiters to introduce fake Ozempic into the market.

Not only do counterfeit and diverted drugs pose serious health risks to patients, but they also cause ﬁnancial losses for manufacturers and damage brand credibility. However, by implementing a proactive approach, pharmaceutical companies can collectively address the extensive counterfeit and diversion issue to identify, trace and authenticate the right goods.

COMBATTING THE PROBLEM

To overcome the counterfeit and diversion issues currently plaguing the pharmaceutical industry, it is imperative for organisations to implement a multi-solution proﬁle as opposed to a one-size-ﬁts-all solution. This strategy necessitates applying di erent tools in

response to the problem. For instance, each product ought to be serialised in order to track it through the supply chain, ensuring it remains within legitimate channels. Serialisation enables brands to allocate unique identiﬁers to each item, allowing for real-time tracking and monitoring of products, making it di cult for diverted products to go unspotted.

Using tracking and tracing technology ensures pharmaceutical ﬁrms can follow a product journey throughout the supply chain. Manufacturers can monitor the movement of their goods, hyperaccelerating the identiﬁcation process and empowering them to address and combat counterfeit products.

Pharmaceutical organisations should also consider utilising next-generation solutions powered by artiﬁcial intelligence (AI) and machine learning (ML) to tackle drug diversion and counterfeits. Through ML, companies can upload a high-resolution model of the brand’s artwork to a system trained by AI to look for defects, di erences, and anomalies. Once the entire model is trained, a consumer can take a picture of the product they are viewing and upload it to the system to compare that image against the approved, trained model so that any discrepancies are highlighted.

Nevertheless, the most important steps the pharmaceutical industry can take to tackle counterfeiting and diversion revolve around education and raising awareness. The onus is on brands and healthcare professionals to educate patients. This education can

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include teaching patients the di erences between genuine and counterfeit drugs, reminding them to buy medications from trusted sources only and advising them to be cautious when browsing online pharmacies. This education will further empower patients to recognise signs of counterfeits and encourage them to verify products before use.

To e ectively combat counterfeiting, a programmatic approach is required, rather than just technology deployment. Combining people, processes, technology, and time is critical to ensure consumer safety and loyalty and protect brands and revenues. Importantly, companies must collaborate to accurately identify, trace, and authenticate the right products.

Packaging Innovation: A New Era of Biopharmaceutical Packaging Solutions

Packaging is crucial in pharmaceuticals, protecting the integrity, safety, and e cacy of treatments throughout the supply chain and enabling product traceability. The pharmaceutical packaging market is projected to grow from $110.55 billion in 2024 to $176.94 billion by 2032, at a CAGR of 6.06%.

As the biopharmaceutical industry evolves with innovative products and changing regulations, packaging innovators must adapt to maintain compliance, meet product demands, and cater to patient needs.

DRIVING THE DEMAND FOR PACKAGING INNOVATION

Several trends drive the demand for innovation in drug packaging manufacturing, processes, and products:

Increasing Prevalence of Biologic Drug Products

Biologics are becoming more prevalent to address unmet medical needs, including chronic and rare diseases. In 2023, biologics accounted for 31% of the 55 new molecular entities approved by the FDA’s Center for Drug Evaluation and Research.

Unlike traditional smallmolecule drugs, biologics are highly sensitive, requiring strict and controlled environments throughout development, manufacturing, and supply. They depend on parenteral administration and must be manufactured in sterile conditions. Deviations from required conditions can shorten

James Bury, Director Technology at Tjoapack examines the increasing need for innovative solutions in pharmaceutical packaging, emphasising cutting-edge approaches and emerging technologies that address changing packaging requirements.

shelf life. Therefore, appropriate packaging solutions, e ective monitoring, and cold-chain logistics are essential to ensure drug viability upon receipt by healthcare professionals or patients.

Safeguarding Drug Products

Throughout Supply

Biopharmaceutical supply chains face risks like drug counterfeiting and tampering.

Drug Counterfeiting: In 2023, the U.S. Drug Enforcement Administration conﬁscated 80 million counterfeit pills laced

with fentanyl, signiﬁcantly higher than in previous years. Counterfeit drugs pose severe threats to patient safety and compromise global supply chain integrity. Biopharmaceutical companies must implement robust solutions to combat counterfeit drugs.

Tampering: The World Health Organization estimates that around 10.5% of medicines worldwide are substandard or falsiﬁed. These can include repackaged products with inferior ingredients or altered labels to disguise their true origin. Patients consuming

counterfeit therapies may not receive necessary treatment or could be exposed to harmful products, leading to serious health consequences. Pharmaceutical companies’ reputations can also su er if associated with ine ective or harmful counterfeit products.

Maintaining Compliance with Regulations

Regulations are continuously revised to ensure the highest safety standards. The Drug Supply Chain Security Act (DSCSA), enacted as Title II of the Drug Quality and Security Act in 2013, outlines steps for developing systems to achieve interoperable, end-to-end electronic traceability of drug products at the package level. Companies must comply with the DSCSA by November 27,

2024. Failure to comply could result in delays, impacting patient access to critical treatments.

Meeting Sustainability Objectives

Governments are implementing measures to address climate change, reduce carbon emissions, and minimise waste. The European Union proposes that all packaging must be recyclable, with plastic components comprising a minimum percentage of recycled material by January 1, 2030.

Introducing recyclable materials into pharmaceutical packaging is challenging due to considerations like drug compatibility, durability, and regulatory approval. Packaging in direct contact with medicinal products is exempt until January 1, 2035. Companies must ﬁnd innovative and sustainable packaging solutions to meet these initiatives.

Enhancing Biologic

Manufacturing and Distribution with Packaging Innovation

Packaging solutions that consider patient and product needs are crucial for product viability and convenience. The industry is moving toward pre-ﬁlled syringes (PFS), which patients can self-administer, increasing usability, adherence, and convenience. With more treatments targeting rare and chronic diseases, there is a growing need for smallervolume drug products. PFS handle smaller volumes and accommodate diverse dosage solutions.

Biologic products are sensitive and prone to aggregation and degradation, impacting safety and e cacy. They require controlled environments and cold chains throughout supply to remain

stable and e cacious upon receipt by the patient.

Secondary packaging protects the primary packaging and drug product during delivery. When transporting temperature-sensitive products, smart packaging can monitor external temperatures throughout transit, reducing temperature excursions and notifying organizations if they occur. This ensures product stability throughout distribution and maximises shelf life.

The introduction of smart labels enables real-time monitoring. These labels contain processors like RFID chips or NFC technology that track and send data to receivers, feeding into a central database. Real-time tracking of temperature and environmental conditions ensures the integrity and safety of pharmaceuticals. Companies can use data from excursions to understand root causes and prevent recurrence.

Safeguarding Drug Products Throughout the Supply Chain

Protecting drug products throughout the supply chain ensures they reach patients in the same condition they were shipped. Incorporating distinct identiﬁers on packaging via serialisation safeguards against counterfeit products. The DSCSA serialisation measures strengthen the FDA’s ability to protect consumers from counterfeit, stolen, or contaminated drugs by enhancing detection and removal from the supply chain. The EU’s Falsiﬁed Medicines Directive serves a similar role.

Smart labels enhance serialised tracking, carrying more data than traditional labels to meet serialisation regulations. Packaging innovators are also applying tamper-evident seals on outer packaging, such as blister packs, perforated caps, or foil stickers. As of February 9, 2019, the EU requires most prescription medicines and certain over-the-counter drugs to include anti-tampering devices on exterior packaging, making tampering evident.

Pioneering Sustainable Packaging in the Biopharmaceutical Industry

Sustainability in packaging is a signiﬁcant concern due to environmental e ects. Strategies to meet sustainability objectives include:

Eco-friendly Materials: Using biodegradable plastics, recycled paper, and compostable materials reduces environmental burden.

Reduced Packaging: Optimising designs minimises unnecessary components and drives cost savings.

Postponement Packaging: Finalising products closer to the point of use reduces waste, inventory costs, and lost products.

Improved Distribution E ciency: Optimising transportation routes and delivery schedules reduces environmental impact and improves delivery times.

By integrating these technologies, industry moves closer to a circular economy and contributes to global sustainability goals.

CONTINUOUS INNOVATION WITH EMERGING TECHNOLOGIES

To meet stringent regulations, sustainability goals, and drug product needs, packaging experts must continuously innovate and integrate advancing technologies to drive e ciency and ensure product safety and viability.

Blockchain-Enhanced Serialisation: Blockchain technologies enhance security by providing tamper-proof digital records of all

transactions. This blockchainguided supply chain enables real-time tracking of drug packs’ temperature and location via wireless sensors and GPS devices, promoting data visibility and ensuring product quality.

Artiﬁcial Intelligence (AI) Drives E ciency: AI can enhance packaging workﬂows. Integrating AI into production lines enables predictive maintenance, minimising risks and delays. Deep-learning AI models provide robust inspection by adapting to changing environmental conditions, enhancing quality control, and optimising manufacturing processes.

Automation Optimises

Packaging Lines: Automated systems optimise supply chain management through enhanced track-and-trace. Monitoring inventory reduces waste, improves e ciency, and prevents counterfeit medicines. Automation minimises manual handling, reducing human error and waste, and helps ensure product sterility.

THE FUTURE OF PACKAGING

Packaging plays a critical role in protecting drug integrity and e cacy from manufacturer to patient. Biopharmaceutical companies must prioritise packaging in supply chains to guarantee safety, compliance, and uninterrupted supply.

Partnering with specialised contract packaging organisations (CPOs) provides support to implement new packaging processes and strategies to meet changing regulatory requirements and evolving product needs while optimising packaging processes. With expertise and infrastructure for packaging innovation, CPOs can help harness emerging technologies to drive productivity and enhance serialisation.

Enhancing Drug Delivery: INNOVATION FOR THE FUTURE

The e ectiveness of drug delivery systems is pivotal in improving patient outcomes, enhancing drug e cacy, and increasing adherence to treatment. The complexity of today’s medications has raised the stakes for pharmaceutical companies, making innovation in drug delivery a key focus. At its core, e ective drug delivery ensures the right amount of active pharmaceutical ingredient (API) is delivered at the right time, to the right location in the body, while minimising side e ects.

Drug delivery encompasses a variety of methods, from the traditional oral tablets to more advanced systems. The challenge lies in optimising these systems to ensure that the API reaches its intended target in a controlled, reliable manner. As such, innovations in controlled release, ﬁlm coatings, functional excipients and desiccant packaging are leading the way in addressing these challenges.

THE POWER OF CONTROLLED RELEASE SYSTEMS

Controlled release technologies have reshaped how medications are delivered. By gradually releasing the API over an extended period, these systems provide a more consistent therapeutic e ect, reducing the frequency of dosing. This not only improves the patient’s experience but also enhances treatment adherence—a critical factor in chronic conditions.

At Colorcon, we have taken a leading role in advancing controlled release systems

Beth Tran, Global Business Manager, CR Excipients, Colorcon

through our Corelease™ product line. Corelease technologies are engineered to simplify drug development and manufacturing processes, o ering precise control over the release proﬁle of APIs. This precision ensures that the drug maintains its e cacy over time while minimising adverse e ects.

With over 60 years of innovation, Colorcon’s dedication to controlled release technology helps pharmaceutical companies accelerate product development and improve the performance

of their products. These systems allow for more e cient manufacturing processes, reducing the complexity and cost of bringing new drugs to market.

THE ROLE OF FILM COATINGS AND EXCIPIENTS

Film coatings play a vital role in pharmaceutical drug delivery. They protect the drug from environmental factors and can be customised to meet regulatory requirements. At Colorcon, we o er a range of ﬁlm coatings that allow companies to design tablets

with unique branding while enhancing their functionality. Our coatings are also formulated to provide a superior patient experience, with improved swallowability and taste masking, when needed.

In addition to coatings, functional excipients are critical to ensuring the drug product is manufacturable and stable. Excipients support the API by improving solubility, enhancing bioavailability, and contributing to the overall e ectiveness of the drug. Our excipients are backed by comprehensive application data, helping pharmaceutical companies streamline development and create robust, high-quality products.

THE FUTURE OF DRUG DELIVERY

As the pharmaceutical landscape evolves, the demand for innovative drug delivery systems will only grow. Pharmaceutical companies must navigate regulatory hurdles, patient preferences, and the need for greater e ciency. At Colorcon, we are committed to helping our partners overcome these challenges by providing reliable, high-performance solutions that transform drug development and delivery.

Pharmaceutical companies must navigate regulatory hurdles, patient preferences, and the need for greater e ciency.

By focusing on cuttingedge controlled release technologies, advanced ﬁlm coatings, functional excipients and desiccant packaging, we empower pharmaceutical companies to optimise their drug delivery strategies, drive manufacturing e ciency, and ultimately improve patient outcomes.

We are in an era of remarkable innovation in drug development, and the treatment possibilities have never been more exciting. But there’s a catch.

The tools we rely on to deliver these therapies are struggling to keep pace. For emerging medications requiring larger volumes, higher viscosities, or novel formulations, this mismatch can lead to costly delays and complex challenges during the preclinical and clinical trial phases, ultimately a ecting pharmaceutical companies and patients alike.

Rather than solely focusing on expediting individual phases of development for drug-device combination products, SHL Medical has adopted a more holistic approach. Its new reusable electromechanical autoinjector, Elexy, changes how new drugs are trialled and commercialised, shortening these processes.

HOW IT WORKS

Elexy comprises a reusable power unit and a disposable drug cassette that can accommodate both preﬁlled syringes and cartridges, as well as various viscosities and volumes (up to 5 mL).

A patient simply loads a cassette, removes the cap, and presses the device against the injection site.

Beyond its reusability and patient convenience beneﬁts, Elexy’s true impact lies in its advantages for pharmaceutical companies, particularly its ability to speed up time to market.

STREAMLINING PRECLINICAL TRIALS

Mechanical autoinjectors come with limitations when supporting emerging drug

WITH SHL MEDICAL’S ELEXY REVOLUTIONISING DRUG-DEVICE DEVELOPMENT

therapies. Adjusting parameters like injection rate and volume during a preclinical trial is often impractical, given the lack of a preconﬁgured and electromechanical power unit. Preclinical studies using a mechanical device would require multiple autoinjectors to test di erent injection proﬁles, leading to huge time and cost pressures.

Elexy, however, easily accommodates these variations. Its reusable power unit allows researchers to adjust

injection parameters by simply loading a new drug cassette. This adaptability supports in vivo studies, evaluating the performance and tolerability of large-volume injections.

Furthermore, as a hand-held device, the data collected during testing with Elexy reﬂects real-world use more accurately compared to other preclinical delivery options, such as needle sets ﬁxed on the skin with adhesive.

A SIMPLIFIED CLINICAL PHASE

The conventional approach to developing combination products prioritises drug development, leaving the delivery mechanism as a later concern. This brings signiﬁcant risks, uncertainties, and potential delays into the clinical and commercial phases, often requiring costly and timeconsuming bridging studies.

An ideal strategy would involve using an autoinjector during clinical trials to evaluate the entire combination product, bypassing device-related bridging studies. However, this is impractical with singleuse mechanical autoinjectors, since varying doses require signiﬁcant component changes and lengthy timelines to develop new autoinjectors for each test condition. As with preclinical research, Elexy alleviates this burden. By supporting various dose volumes, primary containers, and delivery rates, it makes dose-ranging studies as simple as loading di erent drug cassettes.

Additionally, using an autoinjector to generate clinical data – especially one with a preconﬁgured injection rate – produces datasets that are much more representative of commercial applications.

As Elexy uses a standard primary container, the storage conditions and ﬂuid path also align with the commercial application, leading to shorter bridges and faster time to clinic.

Elexy also avoids another problem: designing singleuse mechanical autoinjectors requires speciﬁc details about the drug and injection, such as volume, rate, depth, and viscosity. This process involves extensive testing and validation, often causing delays or resulting in rushed, suboptimal parameters, or the drug launching in a form other than an autoinjector.

By using Elexy during clinical trials, delivery parameters can be optimised concurrently with drug development, paving the way for an immediate, low-risk transition into a mechanical autoinjector.

DYNAMIC APPLICATIONS

Elexy’s advantages extend into commercial use, particularly for therapies involving multiple doses or chronic conditions. It is particularly e ective for handling ﬂuids that pose challenges for traditional mechanical systems, such as highly viscous liquids or injections requiring precise delivery rates.

The integration of SHL’s Needle Isolation Technology for

cartridge-based delivery further enhances Elexy’s control over factors like cannula gauge and injection depth, ensuring precise and reliable administration, regardless of the primary container used.

For commercial applications involving multiple-dose regimens, Elexy o ers a seamless transition. For example, a starter kit could include the power unit and larger-volume drug cassettes. Once the initial treatment is complete, the patient would then receive maintenance kits with smaller cassettes, all using the same power unit and loading and injection methods.

More generally, the device’s reusability minimises waste, reduces component manufacturing and shipping demands, and lowers overall packaging, storage, and shipping costs.

In the ever-changing landscape of parenteral drug delivery, new self-injection systems are required to address unmet needs—both for patients and in product delivery. Elexy is redeﬁning possibilities in parenteral drug delivery. Its ﬂexibility and e ciency make it easier to evaluate new therapies, accelerate time to market, and provide an enhanced experience for both drug manufacturers and patients.

Elexy’s true impact lies in its ability to accelerate drug development while reducing risks, streamlining the journey om preclinical trials to commercial use.

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A SHORT GUIDE TO STABILITY STUDIES

Stability testing is a vital element of ensuring a drug product is compliant with regulatory requirements, irrespective of whether you are submitting to the Food and Drug Administration (FDA), European Medicines Agency (EMA) or elsewhere. Stability studies ensure drug products remain stable during transportation, distribution, and storage, to maintain e cacy and safety throughout the lifetime of the product. Here Paul Barr, Principal Scientist at scientiﬁc consulting and testing specialist Broughton, outlines the key elements of stability testing for drug delivery devices.

Stability studies provide evidence on how the drug product’s quality varies with time under various environmental factors and is a fundamental test as part of the submission framework for ensuring patient safety. Products that exhibit poor stability are one of the factors that mean that they are unlikely to be approved, and if problems arise later, can be recalled. An example of this occurred in 2018 when Hospira voluntarily removed 24,000 syringes of the injectable “Amidate” from the market, when stability testing confirmed out of specification results. Conducting stability studies can help ensure product safety, e cacy, and compliance, and the resulting data will become crucial to the manufacturer’s regulatory dossier. Due to the various intended outputs from stability studies, they are designed on a caseby-case basis specifically for the drug product and device being tested, considering the desired objective of the study. The studies are carried out under strictly controlled environmental conditions in line with guidance from the International Council for Harmonisation of

Paul Barr, Principal Scientist at scientiﬁc consulting and testing specialist Broughton, outlines the key elements of stability testing for drug delivery devices.

Technical Requirements for Pharmaceuticals for Human Use (ICH) and the World Health Organization (WHO). Manufacturers can create e ective stability programmes by staying on top of ICH guidance changes and paying careful attention to study design.

ICH GUIDANCE

From the outset, the ICH guidance states that the design of the stability study for any drug product should be based on knowledge of the behaviour and properties of the drug substance, as well as experience gained from clinical formulation studies. The ICH o ers guidance on

the proposed length of the study, storage conditions, and sampling frequency based on the product and its intended shelf life. Depending on the product’s intended markets, the ICH guidance suggests corresponding test conditions for the ﬁve climactic zones of the world.

Stability studies involve placing samples into environmentally controlled chambers to determine how the product or substance will change over time when subjected to speciﬁc environmental conditions. Scientists can assess samples periodically for changes in physical, chemical or biological

Stability studies provide evidence on how the drug product’s quality varies with time under various environmental factors and is a ndamental test as part of the submission amework for ensuring patient safety.

makeup, according to the study protocol.

For inhaled medicine drug delivery devices, for example, such as nebulisers, pressurised metred-dose inhalers (pMDIs), and dry power inhalers (DPIs), designing a stability study can be complex as several device-speciﬁc factors need to be controlled. This includes ensuring the particle size remains consistent — this can directly impact the rate of dissolution and bioavailability in the lungs, which can a ect the product e cacy.

Storage and packaging are also key factors to consider. In the case of pMDIs, storage orientation may impact the device’s performance, while DPI products may need to include supplemental studies with the secondary packaging removed (in-use stability) to measure the impact on shelf life, quality, and e cacy against the drug product speciﬁcations.

IN HOUSE VS OUTSOURCE

Designing and implementing stability studies can be challenging, especially for manufacturers that lack stability storage capabilities, testing resources, or specialised analytical chemists. Working with a trusted partner can help manufacturers save time, money, and space when conducting stability storage and testing.

Broughton has been o ering stability study services since 2006 and has the experience of working with in-house scientists to create forwardlooking testing strategies, which are essential in ensuring product safety, e cacy, and compliance. Its experience includes Delivered Dose Uniformity (DDU), extractables and leachables and other areas.

Switching from 3-step to 2-step auto-injector: VIABILITY AND IMPACT ON PATIENTS

Alex Fong, Head of Insight, Owen Mumford Pharmaceutical Services

The injectable drug delivery market is increasingly ﬁlled with biosimilars, a positive development for patients and healthcare systems, with the NHS estimating savings of around £300 million each year as biosimilar options become more readily available. With numerous drugs able to perform the same function, the choice of drug delivery device presents

one way that pharma companies can distinguish themselves from the competition.

However, with devices that are unfamiliar or more di cult to use, there is a higher likelihood of missed treatments or non-adherence, particularly for chronic conditions where patients may be selfadministering outside a healthcare setting, without support from a healthcare professional. Therefore – as with a switch to a biosimilar from the originator drug – a change of delivery device must ensure continued safety and e ectiveness of treatments for patients.

FORMULATING AN INTERCHANGEABILITY STUDY

A compelling way to demonstrate the viability of alternative drug delivery devices is through an interchangeability study –demonstrating the ease of switching from one product to another.

Yet currently there is a shortage of such studies. To help ﬁll this gap, Owen Mumford Pharmaceutical Services (OMPS) commissioned an independent study evaluating the ability of patients to switch from a familiar three-step auto-injector to a new two-step auto-injector.

The study design followed the recommendations of the FDA guidance document, ‘Considerations in demonstrating interchangeability with a reference product’. Patients familiar with SHL Medical’s three-step DAI device – one of the ﬁrst auto-injectors to be used for home injection – were presented with the twostep spring-powered Aidaptus device from OMPS. The principal di erence between the two devices is that with Aidaptus, patients simply use pressure on the injection site to activate the injection procedure, rather than

pushing a button, removing a step from the process.

Fifty-two participants were involved in the study, with an equal split between participants from the UK and US. Each participant had at least three months’ previous experience using the DAI auto-injector. With patients already familiar with one device, the goal was not to compare the two products but to see how successfully patients could adapt to using the new Aidaptus product for the ﬁrst time.

To truly understand any issues participants might experience, they were given minimal guidance on using Aidaptus, with no training, demonstration or coaching provided. The devices were provided in their unopened original boxes with just the device and instructions for use (IFUs) included. Participants were then asked to administer a total of four injections into an injection pad on the table, alternating between the DAI auto-injector and Aidaptus.

MEASURING SUCCESS

The principal measure of the study was injection success. If a participant was able to administer the injection into the pad – using the device as described in the IFU and only removing once the full dose had been delivered – it was deemed successful.

A secondary measure recorded was injection time, calculated from when a participant placed the autoinjector on the injection pad and

started the injection process through to when the device was removed from the pad.

Researchers also noted if participants examined the device and for how long, whether they read the IFU, and their conﬁdence in performing injections. Demographic factors including participant age, gender, left or right handedness and geographical location, as well as any e ect these factors have on injection success and speed were also recorded. Secondary factors were measured through video analysis of participants.

UNDERSTANDING RESULTS

As mentioned above, the goal of the study was to understand the ease with which patients were able to switch from the familiar three-step device to a new two-step auto-injector. The results revealed that all participants were able to do this

Without access to critical usability data, pharma companies cannot be sure about the viability of placing their drug in a new device alien to patients.

successfully, with no impact on injection success when changing to Aidaptus.

Participants took longer to initially familiarise themselves with Aidaptus – understandable given it was their ﬁrst time using the product. However, the mean injection time fell for the second injection time with each device, indicating the participants felt more comfortable. The mean injection time for the ﬁrst round of injections was 12.6 seconds for DAI and 11.4 seconds for Aidaptus, falling to 8.8 seconds for DAI and 7.9 seconds for

Aidaptus during the third and fourth injections of the experiment.

Though there was a di erence in injection time among some demographic groups – for instance, older users (over 40) tended to take a little longer to complete injections with both devices –this did not inﬂuence injection success.

All participants were able to complete their ﬁrst Aidaptus injection correctly, regardless of whether they had consulted the IFU. Just 23% of participants were categorised as ‘cautious’ meaning they examined the device or IFU before each injection. Most participants needed to look at the IFU only once and then were able to competently switch between the two-step and three step autoinjectors without issue.

THE VIABILITY OF SWITCHING With biosimilars o ering healthcare services a wider variety of clinically identical drugs to choose from, drug delivery devices can be a crucial di erentiator. Yet, without access to critical usability data, pharma companies cannot be sure about the viability of placing their drug in a new device alien to patients.

Any new device should o er the same – or ideally an enhanced – user experience over competitor devices so that patients are not adversely a ected by the change. This study commissioned by OMPS provides a useful demonstration of whether patients can feasibly switch from a three-step autoinjector to a two-step device, without the need for external intervention. This is extremely valuable in de-risking a potential device change, facilitating the decision-making process for pharma companies.

Figure 1: Study design: alternating auto-injection devices

Figure 2: The mean time taken for each injection with DAI® and Aidaptus® (n=52)

MDR Regulation: A Framework for the Future

by Terumo Medical Care Solutions, Pharmaceutical Solutions Division

The European Union’s Medical Device Regulation (MDR) entered into application on May 21, 2021, replacing a regulatory framework for devices dating back to the 1990’s and consolidating three directives into two new regulations. The MDR introduces new or revised responsibilities for manufacturers, distributors, and regulatory a airs and quality management professionals involved with bringing medical devices to market in the European Union, including the establishment of requirements related to unique device identiﬁcation.

Medical devices play a fundamental role in improving health and saving lives. The European Commission estimates there are over 500,000 types of medical devices and in vitro diagnostic medical devices (IVDs) on the EU market.[1] These range from sticking plasters and contact lenses to x-ray machines, pacemakers, hip replacements and even software applications. The medical device regulation, (EU) 2017/745 (MDR), brings EU legislation in line with technical advances, changes in medical science and progress in law-making made since the old directives came into force, and, the commission says, creates a robust, transparent, and sustainable regulatory framework, recognised internationally, for improving clinical safety and creating fair market access for manufacturers and healthcare professionals. Reﬂecting technological

innovation for example, the revised MDR recognises that devices are increasingly combined with pharmaceuticals, biopharmaceuticals and other substances to assist with the diagnosis, prediction, prevention, monitoring, prognosis, treatment or alleviation of disease.

IMPLEMENTATION OF A UNIQUE IDENTIFICATION SYSTEM

The EU database system for medical devices (EUDAMED), has necessitated the inclusion of a unique device identiﬁcation (UDI) system, which is intended to facilitate easier traceability of medical devices, enhance the e ectiveness of post-market safety-related activities, and facilitate monitoring by competent authorities.

Brieﬂy, the UDI system requires that the manufacturer, importer or distributor:

• Creates a UDI incorporating a UDI device identiﬁer (UDI-DI) and UDI production identiﬁer (UDI-PI) that together identify themanufacturer, device, unit of device production and associated packaging

• Places of the UDI carrier on the label of the device, on its packaging or, in case of reusable devices, through direct marking on the device itself

• The UDI speciﬁes storage throughout the supply chain and by healthcare institutions is in accordance with conditions speciﬁed

for the device (e.g., humidity, sterility, shelf-life)

• Maintains an electronic database for UDI’s (the ‘UDI database’), which is part of the EUDAMED database

Use of the UDI system should also improve purchasing, stock management, and waste disposal procedures through the supply chain and in health institutions, but perhaps its most important goals are to reduce medical errors and inhibit the proliferation of counterfeit or unapproved devices.

MOVING FORWARD TOGETHER

In contrast to the European Commission’s Directives, its Regulations do not need to be transposed into national law, so

the MDR reduces the risks of discrepancies in interpretation across the EU market. Transitional periods have been planned to smooth the application of the new regulations, with the provisions related to the designation of Notiﬁed Bodies and the ability of manufacturers to apply for new certiﬁcates under the MDR. The European Parliament later adopted an extension of the transition period for the EU MDR [2]. The key changes include:

• Extension of the transitionalperiod for higherrisk devices (class III and certain class IIb implantable devices) such as pacemakers to comply with EU MDR requirements until December 31, 2027

• Extension of the transitional period for medium and lower-risk devices (other class IIb devices, class IIa, class Im, Is and Ir devices) such as needles and syringes to comply with EU MDR requirements until December 31, 2028

• These extensions are subject to certain conditions, including requirements for market surveillance, quality management systems, and engagement with notiﬁed bodies [2]

Throughout the transition period, several publications have been made available to support MDR implementation. These include guidance on exemptions from the requirements to perform clinical investigations, updates on questions and answers regarding clinical investigations, and updates on importers and distributors. [3]

MDR IIMPLEMENTATION AT TERUMO EUROPE

Terumo Europe received its ﬁrst certiﬁcate under EU-MDR on

May 29, 2020, ahead of other manufactures. This covered four product categories including Nanopass, a pen needle for the subcutaneous injection of insulin.

The company accelerated its e orts to acquire further certifications and to strengthen its operation to deliver safe medical devices worldwide, and the following products are now also certified: K-Pack II, Neolus, Surflo Winged Infusion Sets, Syringes with fixed needles

Terumo Europe has completed the following actions:

• Technical documentation and quality management system in line with MDR requirements

• Certiﬁcation has been obtained after a successful audit by the notiﬁed body

• MDR implementation in production was done gradually in the course of 2023.

We are ready to support our customers with MDR implementation.

A WORD ON BREXIT…

The United Kingdom withdrew from the European Union in February 2020, and the UK government has since announced it intends to introduce new regulations for medical devices. A transition period has been agreed that will extend the acceptance of CE marked medical devices on the Great Britain market until June 30, 2030. The UK government expects to put in place priority measures to enhance postmarket surveillance, in 2024, with core elements of the new UK framework expected to be in place in 2025 [4].

A SAFER, EFFICIENT, AND UNIFIED SOLUTION

As a core player in the EMEA healthcare market that

Contributing to Society Through Healthcare

Since its inception as Japan’s ﬁrst domestic hypodermic needle manufacturer more than a century ago, Terumo has placed patient safety at the very core of its work.

Terumo Europe shares in the company’s mission to contribute to society by providing valued products and services in the healthcare market, and by responding to the needs of patients and healthcare professionals.

Contact Terumo Pharmaceutical Solutions Division info@terumo-ps.com www.terumopharmaceuticalsolutions.com

manufactures within and imports devices into the EU, Terumo Europe has taken steps to proactively comply with the new regulations, including by implementing a UDI carrier on the primary packaging of its entire product portfolio, including the examples shown earlier. Terumo Europe had previously implemented a UDI carrier on primary packaging for products sold under US FDA regulation. In accordance with the MDR, quality system procedures had to be updated and audited by a Notiﬁed Body for compliance with the regulation.

The new medical device regulation has required manufacturers, importers, and distributors to consider carefully how to implement important and far-reaching new features such as the UDI system, but their ongoing commitment as technology solutions partners has helped Terumo Europe ensure full compliance of its product portfolio to the latest regulations.

The MDR has brought valuable reform that better reflects decades of innovation since the EU’s last directive, and particularly reflects the diversity of medical devices available on the market today. Through the use of a common reference in the UDI that also sets out storage conditions, the MDR provides the opportunity for manufacturers, the distribution network, and healthcare institutions to better control stockholding and reduce waste. Most importantly, by helping to ensure that medical devices are fit for purpose and by limiting proliferation of non-compliant and counterfeit devices, the MDR, and its companion regulation for in vitro diagnostic medical devices, provides a strong framework for protecting patients for many years to come.

REFERENCES

[1] European Commission’s Overview of the medical devices sector, health.ec.europa.eu, accessed February 2024

[2] European Commission Factsheet for Manufacturers of Medical Devices, health.ec.europa.eu, accessed February 2024

[3] eumdr.com, accessed February 2024

[4] Medicines and Healthcare products Regulatory Agency (MHRA)’s Implementation of the Future Regulations, updated January 9, 2024 (gov.uk)

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HOW LARGE LANGUAGE MODEL-ENABLED AI

Will Sharpen Drug Safety & Regulatory Practice

Up to now, the sheer amount of work required in bringing intelligent automation systems up to speed and validating them for life sciences R&D purposes, e.g., to transform adverse event case intake, has threatened to undermine the business case. But now the large language models (LLMs) used to power Generative AI are bringing down those barriers and bolstering compliance. The opportunity surrounds on-the-ﬂy data discovery, ‘in context’ learning, and narrative extrapolation

– in a way that is ‘explainable’ to regulators. Ramesh Ramani and RaviKanth Valigari, AI experts at ArisGlobal, explore what is possible.

Where high volumes of information exist across di erent formats and originate via di erent channels (as in the case of safety monitoring, for instance) - there is a significant administrative overhead involved in distilling any significant findings and making them useable. And it is here that the latest advances in artificial intelligence (AI) and machine learning (ML) o er substantial process transformation potential. Not only in relation to e ciency, but also significantly improved accuracy - once the software knows what it is looking for.

Generative AI (GenAI) technology, using large language models (LLMs), is lighting the way here, quickly understanding what to look out for and ably summarising key ﬁndings for the user – and,

crucially, without the need for painstaking ‘training’ by overstretched teams, or validation of each conﬁguration.

BUILDING TRUST

In a drug development context, Safety and Regulatory requirements present an enormous data burden which consumes vast resources and usually carries a time-based penalty (e.g., linked to prompt adverse event notiﬁcation/ safety reporting or a ecting speed to market). While process automation solutions have

Ramesh Ramani and RaviKanth Valigari, AI experts at ArisGlobal

existed for some time to lighten the manual load and enhance e ciency, there have been two main sticking points up to now: how to swiftly train modern AI algorithms so that they notice only what is signiﬁcant; and how to satisfy the authorities’ need for accuracy and transparency.

LLMs (the vast data banks referred to by GenAI tools), and advanced natural language processing (NLP) techniques like retrieval-augmented generation (RAG), are now being applied to fill these gaps and make advanced automation a safe and reliable reality in key life sciences R&D processes, and crucially without the need for continuous, painstaking oversight. (In simple terms, RAG simplifies the process of finetuning AI models by allowing LLMs to integrate proprietary data with publicly-available information, giving them a bigger pool of knowledge - and context - to draw from.)

CONTEXT MATTERS: APPLYING GENAI-TYPE TECHNIQUES TO NEW DATA

The biggest breakthrough with all of this is that specialised applications can now be developed that can apply GenAI-type techniques, contextually, to data they have not seen before – learning from and processing the contents on the ﬂy.

For drug developers, this has the potential to transform numerous labour-intensive processes, ranging from dynamic data extraction associated with adverse event (AE) intake; to safety case narrative generation; to narrative theme analysis in safety signal detection; to the drafting of safety reports. And solutions for these use cases

are coming down the line. Importantly, carefully combined LLM (Large Language Models) and RAG capabilities are su ciently transparent and explainable to regulators for the technology to be acceptable as safe and reliable. Responsible AI and AI compliance are particularly critical in life sciences use cases, so it is essential that companies deploy solutions that are proven and transparent. The LLM/RAG approach addresses potential concerns about data security and privacy, too, as it does not require the use of potentially sensitive patient data for algorithm training/machine learning. It also stands up to validation, by way of periodic sampling by human team members; sampling which can be calibrated as conﬁdence grows in the technology’s performance - ensuring that e orts to monitor its integrity do not undermine the signiﬁcant e ciency gains that are possible.

CIRCUMVENTING THE ENDLESS VALIDATION CYCLE

The trouble with ML solutions up to now has been the training burden. For instance, in the case of adverse event recording, systems would need to be shown what to look for in the information provided via a range of di erent channels and formats, before extracting and processing it. For each di erent source type, a new conﬁguration of the software would be needed too, pushing up the training overhead, and overall expense including the maintenance burden each time the technology was updated.

LLMs make it possible to bypass the need to train AI models or algorithms on what to look out for and/or what

something means, so that a single technology solution can handle all variations of incoming data. RAG patterns can play a signiﬁcant role here, in explaining a standard operation procedure to an LLM using natural language, so that the system knows what to do with each of many thousands of forms – without the need for special conﬁguration for each relative format.

The potential impact is impressive. Application of LLM-RAG technology to transform AE case intake has been shown to deliver upwards of 65% e ciency gains, with 90%+ data extraction accuracy and quality in early pilots. In the case of safety case narrative generation, the same technology is already demonstrating 80-85% consistency in the summaries it creates. And that is from a standing start, without prior exposure.

RETRIEVING KEY DATA IN CONTEXT = UNPRECEDENTED PROCESS STREAMLINING

The ability to retrieve data in context, rather than via a ‘Control F’ (ﬁnd all) command (e.g. everything among a content set that mentions headaches), could transform a

range of processes linked to safety/adverse event discovery and reporting.

Certainly, it lays the foundation for drug developers to substantially streamline some of their most demanding data-based processes. In due course, these will also include the drafting of hefty regulatory safety reports, with advanced automation generating the preliminary narrative; and narrative theme analysis in safety signal detection. Here, there is vast scope for the technology to help in distilling trends that have not been captured in the structured data. These could include a history of drug abuse, or of people living with obesity, across 500 patient narratives that are potentially of interest. The potential is extremely exciting.

It is this kind of development that is now being avidly discussed at meetings of the industry’s new global GenAI Council. Any hesitation about adopting smarter automation out of reliability or compliance fears has now been superseded by a hunger to embrace new iterations of the technology which directly address those concerns and o er tangible step changes in productivity and e ciency.

LLMs make it possible to bypass the need to train AI models or algorithms on what to look out for and/or what something means, so that a single technology solution can handle all variations of incoming data.

HOW PHARMA COMPANIES CAN UTILISE PRIMARY MARKET RESEARCH FOR ROBUST DIGITAL MARKETING CAMPAIGNS

The need for robust research is becoming more urgent as companies face increasing performance pressures, while continuing to scrutinise research budgets.

Pharmaceutical products play in a highly competitive ﬁeld. Understanding the HCP target audience through market research is vital to ensure pharma companies are marketing their products e ectively.

When pharmaceutical marketing teams design their digital marketing approaches, it can be all too tempting to jump straight into the planning stage and start putting tactics to paper. However, creating an approach without audience insight carries with it a risk of working in an echo chamber, where only internal company beliefs and narratives inform the plan, rather than relying on a more robust mix of internal hypotheses and external veriﬁcation. An echo chamber may lead to suboptimal business decisions and costly ine ciencies.

In the dynamic world of pharmaceutical marketing, understanding the target audience is essential for developing e ective approaches that deliver results. Knowing your audience better will always be more advantageous, and lead to a greater proportion of more e ective decisions over time than knowing them less well.

THE IMPORTANCE OF LEVERAGING PRIMARY DATA TO SUPPORT DECISIONS

The healthcare sector is an increasingly data-rich environment. Pharmaceutical companies can leverage data sets on service usage, insurance claims, prescribing, and even relatively newer kinds of data from such sources as HealthTech wearables and genomics.

However, when it comes to informing marketing approaches, data sources are often more limited. For instance, CRM systems tend to capture data on only a small proportion of the relevant HCP universe and tend to be able to analyse only what happened in response to a marketing tactic, not why it happened (or, indeed, what may have worked better).

By contrast, primary market research involves talking directly to the target audience, allowing pharmaceutical marketers to access ﬁrst-hand accounts and experiences from their core demographic. The nature of primary market research means marketers can ask whatever questions they need to ask, including ones about hypothetical or future situations.

Dr Maxim Polyakov is Senior Vice President, Business Intelligence and Research at M3

This becomes particularly valuable, for instance, in a pre-launch environment, when there is no secondary data available as the product is not yet on the market.

Of course, primary market research has its own limitations. For instance, the subjective nature of personal experience means people might not be willing, or able, to tell you exactly what they think in the moment: it would take a research team with a speciﬁc skillset and experience to be able to navigate this successfully. That said, primary market research should be a critical component of every pharmaceutical marketer’s “armoury.”

HOW TO ENSURE YOUR PRIMARY MARKET RESEARCH IS EFFECTIVE

When undertaking primary market research to inform digital marketing (or any other topic), there are several important considerations.

The first step is defining what you want to find out from the research. Do not rely on a vague set of question topics to cover, instead nail down a clear hypothesis (or a set of hypotheses) to test. Do not be afraid to limit the scope of a research project, too, as one project cannot address everything. A better approach might be to run multiple phases of research, with each subsequent phase building on what you have learned in the previous one. You should also consider at this stage whether you feel you can do this research in-house, or if you would benefit from a research partner (e.g., a market research agency).

Secondly, work out how you are going to test your hypotheses. This involves determining the best methodology or combination of methodologies to use, deciding how you are going to deﬁne and screen your target respondents, and creating the research materials to support the process (e.g., a questionnaire or an interview guide). This stage is also where you will need to make sure your research is compliant, and that the materials have appropriate medical and legal approvals in place.

Once all of that is done, the decisive step is to go into the ﬁeld with your research to collect the data and analyse it to draw out the insights and recommendations. If your research was tightly focused on a set of clear hypotheses, this

can be a more straightforward process – you should know what you are looking to prove or disprove. (During ﬁeldwork, you will also need to remember to monitor for any mention of potential adverse events or other safety reporting situations.)

A FEW “WATCH-OUTS”

There are several challenges that pharmaceutical marketers looking to undertake primary market research typically face. For example:

1. Regulation and compliance:

The pharmaceutical industry is heavily regulated, and this extends to primary market research. From navigating data privacy legislation, to avoiding disguised promotion or oversampling, to setting appropriate incentives that are aligned to reasonable value – the list of compliance considerations is long and becomes even more complex if you need to do research across multiple jurisdictions.

2. Finding the right respondents:

Pharmaceutical primary market research also often involves specific audiences, and finding the right respondents, and enough of them, can be di cult. Companies can ensure they maximise their chances through using robust, verified, and profiled panels, as well as ensuring that rigorous screening is in place.

3. Designing and executing research e ectively:

Particular attention should be paid to how research is designed and executed: from picking the right methodology (or a mix of methodologies), to phrasing questions e ectively (they should be impartial, and be able to cut through subjective bias, if required), to running robust analytics and showing the data in an impactful way at the end. The last point here is worth a quick pause: if primary market research is there to enable better decisions, its outputs need to be actionable and clear on the “so what.” Otherwise, there is a risk that all the magniﬁcent work and thinking that went into the research will trip at the ﬁnal hurdle.

The good news, however, is that pharmaceutical marketers do not need to handle this alone. They can typically rely on internal and external expertise: in-house business intelligence teams, and external market research agencies.

CONCLUSION

Not carrying out market research to inform digital strategy leaves marketers open to a whole host of risks. Some of these risks are ﬁnancial. Forging ahead with a strategy (or a campaign) without a good mix of data to back it could lead to costly ine ciencies. And of course, not getting the marketing approach right could have implications beyond ﬁnances, if it also means that a product that can help patients does not gain as wide an adoption as it should.

The pharmaceutical industry is a complicated and competitive space, and developing a stronger understanding of customers can only ever add value.

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An established provider of both drug substance (advanced intermediates and API – small molecules and peptides) and drug product development services, our clients are assured of scientiﬁc continuity from a dedicated project team, resulting in signiﬁcant time and cost savings.

We support drug substance and product analytics across all phases, from early preclinical/clinical development to commercial release, o ering full lifecycle solutions for your unique drug format. Employing over 700 highly skilled analysts across ﬁve locations working in regulatory-approved GMP/ GLP environments, our expert teams have developed 1,000+ analytical methods and validate 250+ methods annually.

Through our continued investment in the expansion of our state-of-the-art services, Almac is your trusted CDMO to provide support across the product development lifecycle.

TERUMO

HALL 20 STAND B45

OUR QUALITY, YOUR SUCCESS

Helping to sustain therapeutic success with every patient, as Part of Terumo Medical Care Solutions, the Pharmaceutical Solutions Division focuses on safely delivering today’s parenteral formulations with ease and comfort in mind. Globally trusted for quality and precision, we o er pharmaceutical and medical device manufacturers around the world comprehensive product design and development services as well as a portfolio of injection, infusion, and primary packaging solutions including CDMO services.

Ready to help develop your best parenteral delivery solutions Our service specialists can help you leverage the tools you need to

COLORCON

HALL 6 STAND D58

overcome ambitious product design, development, regulatory and supply challenges:

• Design and product engineering support

• Materials and compatibility analysis

• Downstream manufacturing optimisation and support

• Global regulatory data and ﬁling guidance

• Kitting and component assembly

Every Terumo customer’s drug delivery challenge is unique and so is our customised approach.

Our experience and insights help us to ﬁnd the best solution for you faster and prepare your products for market more e ciently.

Meet us and discover more at the CPHI Milano 2024.

Colorcon is thrilled to announce that we will be exhibiting at CPHI Worldwide in Milan at Stand #6D58, located in the Excipients zone. As a global leader in ﬁlm coating systems, modiﬁed release technologies, specialty excipients, and functional packaging for the healthcare industry, Colorcon o ers comprehensive solutions that support all stages of solid dosage form design, development, and manufacturing.

This year, we are excited to introduce our groundbreaking Corelease™ Controlled Release Technologies. These innovative excipients simplify the development and manufacturing of controlled-release drug formulations. In addition to Corelease™, we will be showcasing our proven range of excipients designed to streamline formulations, high-e ciency ﬁlm coatings, and extensive variety of functional packaging options to maintain exceptional product quality.

Colorcon is your go-to partner for all solid oral dosage form needs. We o er unparalleled technical, regulatory, and quality support to help optimise costs and provide an outstanding customer experience. Join us at CPHI Worldwide to discover how we can support your pharmaceutical projects.

ENHANCING PHARMACEUTICAL INNOVATION BY INTEGRATING BIOFERMENTATION, CHEMICAL SYNTHESIS, AND TECHNOLOGY TRANSFER

David Blanco, Industrial BD & CDMO Director, Suanfarma

Nature is a vital source of bioactive compounds for drug development, but sourcing these directly can be costly and di cult. To overcome this, the pharmaceutical industry increasingly relies on combining biofermentation with chemical synthesis. Biofermentation sustainably produces complex molecules, while chemical synthesis reﬁnes them into therapeutically viable products. Though challenging, integrating these technologies o ers signiﬁcant advantages, transforming pharmaceutical manufacturing by ensuring a steady supply of new therapeutic agents.

The combination of biofermentation and chemical synthesis merges two traditionally separate fields, o ering significant benefits for producing complex small molecules. Biofermentation, driven by advancements in microbiology and biotechnology, enables the creation of complex molecules that traditional methods cannot easily synthesise. This process uses microorganisms’ genetic code and cellular machinery to produce target molecules, which are then refined through chemical synthesis.

Chemical synthesis allows for precise modiﬁcation and assembly of these complex organic molecules, including those from biofermentation. This approach not only replicates natural molecules but also creates novel compounds with

new properties, crucial for developing therapeutic agents, particularly in cancer treatment.

Combining biofermentation and chemical synthesis o ers numerous technical and economic benefits. Technically, it provides access to a wider array of chemical molecules, enabling the development of therapeutic agents that would otherwise be inaccessible. The ability to synthesise target molecules more e ciently through biofermentation, coupled with the precise modifications a orded by chemical synthesis, results in simplified production processes. This not only reduces costs but also minimises waste, aligning with the pharmaceutical industry’s push toward greener manufacturing practices.

Integrating biofermentation and chemical synthesis can signiﬁcantly reduce production costs by eliminating unnecessary steps in the synthesis process and optimising raw material use. Conducting both processes within the same facility streamlines the supply chain, reduces logistical challenges, and minimises delays, which in turn lowers the risks associated with supply chain ine ciencies. This leads to improved product quality and more reliable manufacturing timelines.

For pharmaceutical companies, combining these technologies under one roof o ers a substantial competitive

advantage. It provides greater ﬂexibility in meeting customer needs, whether for internal projects or external transfers, and allows companies to o er comprehensive solutions across the entire value chain, from development to commercial manufacturing. Suanfarma CDMO exempliﬁes this approach, leveraging its expertise to deliver high-value pharmaceutical products e ciently and sustainably.

THE ROLE OF TECHNOLOGY TRANSFER IN BOOSTING SUCCESS

Successfully integrating biofermentation and chemical synthesis requires a wellexecuted technology transfer process, crucial for transitioning products from development to commercialisation. Platforms like Suanfarma CDMO’s TT&GO are designed to

streamline this process by minimising risks, maximising success, and ensuring e cient industrialisation.

TT&GO adheres to strict GMP standards, systematically identiﬁes potential risks, and accelerates project timelines without compromising quality. Its adaptability allows it to meet the speciﬁc needs of each project, whether for internal or external transfers.

Technology transfer also plays a key role in promoting environmentally sustainable manufacturing practices. By incorporating advanced production methods and energy-e cient technologies, companies can reduce waste, lower costs, and enhance regulatory compliance. This not only fulﬁlls environmental responsibilities but also improves market competitiveness.

In summary, the combination of biofermentation and chemical synthesis, supported by platforms like TT&GO, marks a signiﬁcant advancement in pharmaceutical manufacturing. It enhances the production of complex therapeutic agents while aligning with the industry’s commitment to sustainability and innovation, ultimately improving patient care and contributing to a more sustainable global future. TT&GO demonstrates how structured processes can ensure success in navigating the complexities of modern manufacturing.

UNLOCKING BIO/PHARMA POTENTIAL: THE STRATEGIC ADVANTAGES OF OUTSOURCING TO CMOS AND CDMO

How contract organisations provide ﬂexibility, expertise, and cost savings, and what sponsor companies need to consider for successful partnerships—highlighting Almac’s CDMO services.

Contract organisations, notably Contract Manufacturing Organisations (CMOs) and Contract Development and Manufacturing Organisations (CDMOs), have become integral to the pharmaceutical and biotech sectors. They o er sponsor companies ﬂexibility by providing additional capacity, specialised expertise, and potential cost savings. This is particularly beneﬁcial for smaller bio/pharma companies that may lack extensive in-house resources.

KEY CONSIDERATIONS FOR OUTSOURCING

1. Cost-E ectiveness: A fundamental consideration is whether outsourcing to a CMO or CDMO is more economical than conducting activities internally. This involves assessing access to specialised equipment and personnel, maintaining control over quality standards, and addressing scale-up requirements. The cost of establishing and validating in-house processes can be prohibitive, making outsourcing an attractive alternative.

2. Focus on Core Competencies: Outsourcing allows companies to concentrate on their primary strengths, such as product innovation and strategic development. By

Trevor Clarke, VP Analytical Operations, Almac Pharma Services

delegating manufacturing and development tasks, sponsors can allocate more resources to research and market expansion.

3. Technical Transfer: E ective technical transfer is critical when partnering with a CDMO. Ine cient transfers can lead to delays and increased costs. It’s essential for sponsor companies to have well-deﬁned processes before initiating a transfer. Clear communication and mutual understanding of responsibilities between both parties from the outset are crucial to avoid potential complications.

4. Regulatory Compliance: Adherence to regulatory requirements is nonnegotiable in the pharmaceutical industry. Noncompliance can lead to severe setbacks, including failed pre-approval inspections after signiﬁcant investment in tech transfer and scale-up phases. Thorough vetting of a partner’s facilities and personnel readiness for regulatory inspections is imperative to ensure smooth progression through approval stages.

OUTSOURCING PRODUCT TESTING

Beyond manufacturing, outsourcing extends to analytical testing. CDMOs often possess extensive knowledge from working with diverse product types, including small molecules, peptides, biologics, conjugates, highly potent compounds, and controlled substances. For companies lacking advanced analytical infrastructure, outsourcing testing services can save time and reduce costs.

BENEFITS OF OUTSOURCING TESTING

• Unbiased Results: External testing facilities can provide impartial results, enhancing the credibility of the data.

• Quality Assurance: Reputable contractors adhere to stringent quality standards, ensuring reliable and accurate data essential for regulatory submissions.

• Timely Turnaround: The contractor’s infrastructure and e cient communication channels contribute to faster results, which is vital in accelerating development timelines.

• Access to Complex Testing Services: Outsourcing allows companies to utilise sophisticated testing methods that may not be feasible in-house due to technological or expertise constraints.

• Resource Optimisation: Delegating routine testing frees up internal resources, enabling sta to focus on other critical areas of development and innovation.

COLLABORATIVE SUCCESS THROUGH STRATEGIC PARTNERSHIPS

Successful outsourcing hinges on selecting the right partner. Factors such as technical capabilities, compliance history, quality systems, and cultural alignment should inﬂuence the decision-making process. A well-chosen CDMO can become an extension of the sponsor company, contributing signiﬁcantly to the project’s success.

INDUSTRY EXPERTISE IN ACTION

For example, organisations like Almac o er comprehensive services across the pharmaceutical development spectrum. With state-of-theart facilities and specialised teams, they support projects from initial development through to commercial manufacturing and packaging. Their commitment to quality and regulatory compliance exempliﬁes how partnering with an experienced CDMO can enhance e ciency and reduce risks associated with drug development.

CONCLUSION

Outsourcing to contract organisations presents substantial advantages, including cost savings, access to specialised expertise, and the ability to focus on core business areas. However, it requires meticulous planning and consideration of factors such as technical transfer e cacy, regulatory compliance, and the quality of outsourced services. By fostering strong partnerships with reliable CMOs or CDMOs, pharmaceutical companies can navigate the complexities of drug development more e ectively, ultimately bringing products to market more swiftly and e ciently.

Enabling a Healthier World

De-Risk Your Early Stage Drug Development With Lonza Small Molecules

Our team of experts have a wide range of skills to support you with your early-phase challenges.

AI-Enabled Route Scouting Services

Our experts use a range of retrosynthetic technologies, powered by in-house AI expertise, real-world chemical and commercial data, to help you implement shorter, more efficient synthetic routes for making your NMEs.

Solid Form Screening Services

We will help you determine the most suitable chemical and physical form for your API. Our SFS services are built on a foundation of API characterization, materials science, and problem statement analyses.

Physiologically Based Pharmacokinetic Modeling Services

Using established ADMET Predictor® and GastroPlus® modeling software, linked with an expansive set of in vitro tests, we can identify absorption risks, and select technologies that will enable bioperformance targets to be met.

Scan the QR code or visit us at booth 6A2 at CPHI Milan 2024 to learn more: