29 minute read
Distributed Leadership and Decision-making The benefits in a multicultural context
Support for Effective Decisionmaking
In 2004, the FDA emphasised the importance of using translational science to understand the relationships between pharmacological action and clinical utility, safety and their potential as surrogate endpoints. In a recent analysis of the clinical development success rates from 2006-2015 in over 7000 projects, those that utilised patient selection biomarkers had a 3-fold better likelihood of approval from Phase 1 studies (1). Even in these cases, the overall success from phase 1 is still significantly less than evens. The sobering conclusion is that within the 9 years of focus on translational approaches, the most likely outcome of a drug discovery project is failure. However, there are areas to consider to help make appropriate decisions.
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Technologies
Artificial intelligence (AI) and advanced machine learning techniques are becoming more popular and a number of companies use these approaches as a core business platform. The scope of activities ranges from de novo design to clinical trials and patient selection (2,3). Significant reductions in cost and cycle time are becoming evident with AI based approaches and it is likely they will become an invaluable resource (3).
The advances made over the last decade have supported decisionmaking in the pharmaceutical industry. However, other system effects have a consequence on the overall success rate of programs.
Collaboration
Developing a novel medicine requires working with a number of interrelated and distinct professional perspectives. Different medicine modalities such as chemical, biological or non-molecular entities have to be researched and evaluated with assessment of the likelihood of them being effective and safe. They need to be manufactured to specific control standards, gain access to appropriate markets and distributed to where they are needed.
It is perhaps not surprising that collaboration between these professional approaches improves success. For example, a study of drug discovery projects between 1991 and 2015 in leading US Academic Institutions demonstrated that collaboration with Industry resulted in higher probability of success, especially at the later stages of development (4). The ability to work effectively within an academic and industrial collaboration requires effort and skill from both partners.
A collaboration framework of 14 key principles has been developed to support an enabling environment to improve collaboration (5).
Collaboration Principles for Academic Institutions (5)
1. Understand different types of relationship to select an appropriate one 2. Identify Stakeholders 3. Understand the “why” and identify motivations 4. Identify and Appoint suitable people and involve leadership 5. Ensure basic partnership characteristics eg legal agreement, framework, roles
and resources 6. Establish Communication 7. Strengthen dissemination strategies 8. Address the IP 9. Adopt Policies to encourage collaboration 10. Adopt strategy to encourage collaboration 11. Focus on social capital resources eg building trust, common understanding and effective knowledge sharing 12. Set up rewards and incentives 13. Active management of the collaboration 14. Utilise alumni associations to develop long-term relationships with former students
Elements of these have applicability for non-academic institutions. Perhaps one area to exemplify further is that of decision-making. Within the bio-pharma industry, multi-stakeholder collaborations often materialise through venture capital backed biotech companies that realise the value of academic innovation.
Biotech companies and related entrepreneur networks provide the vehicle for these collaboration principles. As the companies validate their technology and grow, many potential collaborations are identified, often attracting new partners.
The “what” we need to do and “why” we need to do it are often the focus for collaborative agreements. This outlines motivations and rewards associated with a variety of activities or tasks. With a high level of complexity and uncertainty in the development of new medicines, developing a framework for “how” decisions are made will be beneficial for all parties, especially in a multicultural context. Differences in cultural contexts such as individualism or collectivism can be managed effectively with clarity on “how” decisions will be made.
A Focus on how we make the Decision
Clear roles in decision-making are important in all businesses. Many decision tools are available and a useful model outlined in 2006 in HBR magazine (6) suggests
decisions involve various members of a team that provide input of data and a suggested course of action, agreement on the recommendation with input on various trade-offs before one person decides. The decision maker has several useful attributes including “good business judgement, grasp of relevant trade-offs, bias for action and a keen awareness of the organisation that will execute the decision”. This approach can be used to transform the performance of organisations at the team and/or organisational level.
However, within the complex, multistakeholder environment of a drug discovery programme the holistic and systemic nature of the business activities can be easily lost by breaking down decisions to a single decision maker. We offer an alternative approach, distributed decisionmaking that provides an opportunity to maintain alignment through various collaboration partners.
For the purposes of this article, we define distributed decision-making as a dynamic process that involves the right people at the right level, at the right time with the right authority to lead the decision-making process. Fundamental to its success is the recognition and facilitation of the interdependencies between peers across the network of decision makers.
Figure 1 outlines the complex relationship between partners involved in the development of a new medicine from the perspective of a biopharmaceutical organisations; they may have many collaborations with smaller partners with a range of programs of activity across all stages of the drug discovery cycle.(Figure 1)
Irrespective of the stage of the activity, the overall goals of these organisations need close alignment to ensure delivery against objectives.
The Biotech board will include Executive, Non-Executive members and the primary investors. The overarching purpose and value proposition to satisfy the unmet need of customers and patients will be aligned through the various partners via a vehicle, often termed the joint steering committee (JSC). Typically, this is a decision-making body for all elements of each collaboration. It must align with the objectives of the Pharma Partner and their board. The activities of each Project will depend on a range of contractors, research, manufacturing and clinical partners, internal or external to the large company. As projects advance, there will also be Government and Regulatory considerations to align activities.
Representation on the JSC is for members of the Biotech and Pharma Organisation. Decision-making maybe by consensus or by vote (democratic) with escalation procedures in the case of non-agreement. One approach would be to have a 2-step process, the first step being mutual resolution provided by the appropriate CEO/Head of R&D and where necessary the second step of going to arbitration.
There are a number of enablers and disablers for decision-making • Stimulation and motivation for development of the task and partnership • The ability to gain support across a spectrum of interested parties • Organisational and Individual resources and demands
Good decisions are not vested in any one person. While command and
Figure 2: Perspectives to explore the dimensions of the decision to be made
control may have a place, effective decision-making will be dynamic involving a range of people, each of whom is able to offer a different perspective. This is most apparent when undertaking a major project that involves a range of disciplines, organisations and cultures.
Decision responsibility will be dynamic reflecting the stage and impact of the project.
The Biotech Board and Primary Investors will agree the purpose of the assignment and the involvement of others to secure that outcome.
The Biotech Project Board will have primary responsibility for the integrity of the project and for maintaining the agreed purpose and standards adopted by each subsidiary Steering Committee.
Each subsidiary Steering Committee will have oversight for their contribution and will manage the various decisionmaking groups ensuring that the right bodies and individuals are involved at the right time for the appropriate purpose.
Routine monitoring will be required to ensure that decisions taken by each of the Steering Committees to ensure they are aligned with the agreed remit and outcome.
Regular feedback will identify required modifications to the assignment whilst resisting mission creep.
At each level of decision-making
Ultimate responsibility: Which body or individual role has ultimate responsibility for the decision? It is the role not the current occupant that carries this responsibility.
Crucial commitment: Which bodies or individual roles must be genuinely committed to the decisions reached? Without this commitment they will be able to undermine the decisions taken.
Vital contribution: Which individual roles have a responsibility to contribute essential information so that well informed decisions can be taken? These contributors will be unable to veto the decisions taken but can destabilise the process by withholding or distorting their information.
Decision impact: Which roles will be affected by decisions taken and must be made aware of those decisions.
Those involved in the decisionmaking process will change over time. Clarity around the roles of those involved in the process will avoid confusion and unnecessary competition and conflict.
The differing decision perspectives
Distributed leadership and decision responsibility will change over time and incorporate a range of perspectives. Figure 2 details the spectrum and boundaries reflecting the needs of the decisions required. Each spectrum should be viewed as independent of the others.
Starting with the Response Imperative, a question to consider is “does the response need to be immediate, based on our current experience?” or is it more “remote, based on the application of our knowledge?”
Other perspectives to consider are the focus of the response, the authority
needed for decision-making, consideration of the source of information and how knowledge is applied.
This approach also identifies the urgency and the organisational level of response. The next consideration, is the individuals involved in making the decision.
The impact of the individual
Decisions-makers require the essential technical knowledge and skills. It is no longer appropriate to involve a person because of their status or the fact that they have time on their hands. Those with the necessary knowledge, skills and experience are the people who can make the greatest contribution.
But over and above this is the impact of the individual. Each person has a unique thinking pattern that means they will concentrate on different aspects of the decision-making process. • Some will be focused on gathering information and seeing different ways of approaching an end point. We refer to this as Researching • Some will focus on determining what is to be done, what is important, and will weigh the pros and cons. We refer to this as Intending • Some will focus on implementation, the timing and consequences of action. This we refer to as Committing
If those involved in the decision-making process are focused on different stages, they will be less likely to reach a decision where there is a common understanding and where there is genuine commitment to implementation of the decisions taken.
A further complication is the fact that each person will have their own interaction needs at each of these three stages. • Some will think by talking so will embrace any opportunity to share their thinking. They may be sharing broad ideas or issuing an instruction; it is not always easy to tell • Some will think privately and will only contribute when they feel there is something worth contributing. As a consequence, they may deprive the decision-making group of an important contribution.
Neither is right or wrong; both have their strengths and weaknesses. The important thing is to recognise these patterns and to accommodate them in a way that makes decision-making as comprehensive and effective as possible.
Senior Leaders may also consider the development of the enablers of decisionmaking skills as an important part of the learning and development of both the individual and the organisation.
Benefits of a distributed approach
Shared responsibility for decisions increases ownership and is better able to maintain the focus on the overall purpose of the assignment.
No one person has the knowledge, skills, experience and ability to fully understand the trade-offs to be made; a decision that builds on the strengths of all those involved will be a more rounded and sustainable decision.
Identifying the roles and relationships will prevent decisions being taken on autopilot; assumptions will be challenged and a common platform agreed.
Thinking in terms of roles and responsibilities rather than named individuals will encourage objective and no-judgemental decisions and avoid the blame game.
Working in this way allows for greater agility and an ability to respond deliver under pressure without feeling under personal attack.
Conclusion
We have defined distributed decisionmaking as a dynamic process that involves the right people at the right level, at the right time with the right authority to lead the decision-making process. Fundamental to its success is the recognition and facilitation of the interdependencies between peers across the network of decision makers.
Maintaining alignment of purpose, process and people across a major multicultural project is complex and difficult.
The risks associated with such assignments can be reduced by introducing the monitoring and feedback routines to maintain an unerring focus on purpose and outcome that is robust and involves all players.
Risk is also reduced by understanding the dynamic nature of key decisionmakers and the contributions essential to secure success.
The overarching Steering Committee does not know all the answers, but has a responsibility to facilitate a decisionmaking process that secures ownership and genuine commitment to implementation of the decisions taken.
References are available at www.pharmafocusasia.com
AUTHOR BIO
Sherril Kennedy PhD is a reputed organisation development consultant, specialising in the characterisation and analysis of human decision-making. She works with Boards and senior Executives to highlight, define and eliminate dysfunctional decision-group behaviours, embedding sustainable, scalable processes to ensure the success of an organisation or business into the future.
Andrew A Parsons CWP is an experienced leader in the life science industry with a track record of innovation in medicines and business processes. He was the head of migraine and stroke research and VP Preclinical Drug Discovery (CEEDD) in GSK, working multiculturally with a range of partner organisations.
Accelerating Next Generation Vaccine and Therapy Research and Unlocking Deeper Analytical Insights
To empower scientists, researchers and laboratory professionals in Asia’s pharmaceutical industry on their journeys to deliver next generation vaccine and therapy, Thermo Fisher Scientific has announced new instruments, workflows, software, and industry collaborations.
KAPIL KHULLAR, Senior Director, Growth Strategies and Application Excellence for Chromatography and Mass Spectrometry solutions, Asia Pacific and Japan, Thermo Fisher Scientific
As the biopharmaceutical industry continues to push the boundaries of science, Thermo Fisher Scientific is continuing to advocate for the use of new technologies, workflows, and stronger industry collaborations.
Among the newest innovations are those focused on improving each of the critical steps in an end-to-end mass spectrometry workflow. These innovations include new analytical instruments, consumables, workflows, and software solutions that enable leading-edge biological research that spans the molecular spectrum—from targeted and small molecule quantitation and advancements in high-throughput quantitative proteomics and bio-molecular characterisation to a revolution in intuitive, AI-driven software.
All of these are aimed at empowering scientists, researchers, and laboratory professionals to generate new analytical insights and accelerate next-generation vaccine and therapy development.
Enabling Next Generation Therapies
Professionals in proteomics and biopharmaceutical laboratories who are working in drug discovery and R&D applications need to unlock the ability to clearly decipher complex mixtures of large molecules with simultaneous charge detection for analysis of previously unmeasurable analytes.
As such, Thermo Fisher has added a new Thermo Scientific Direct Mass Technology mode for its Thermo Scientific Q Exactive UHMR Hybrid QuadrupoleOrbitrap mass spectrometers that lets manufacturers analyse the characteristics of biotherapeutics in greater detail throughout development. This development will enable laboratory professionals to improve material quantitation and accelerate biopharma development.
This is because the Direct Mass Technology mode augments the UHMR Hybrid QuadrupoleOrbitrap mass spectrometers with charge detection
The Thermo Scientific™ AccelerOme™ automated sample preparation platform with the Thermo Scientific™ AccelerOme™ sample preparation kit
capabilities, allowing direct mass determination of hundreds to thousands of individual ions in a single spectrum. As a result, laboratories can measure mass for complex heterogeneous mixtures of multiple charged components, unlocking new and rich insights into proteoforms, biotherapeutics and next-generation drug modalities.
For proteomics researchers, the Thermo Scientific AccelerOme Automated Sample Preparation Platform improves reproducibility in sample prep, a longstanding bottleneck preventing wider use in biomarker discovery for disease detection and research into new therapies.
Very simply put, the AccelerOme Automated Sample Preparation Platform eliminates the need for labour-intensive, manual sample preparation for LC-MS analysis, including the associated method development and reagent sourcing. Automated sample preparation also overcomes the challenge of maintaining reproducibility with manual methodologies, and the new platform’s pre-built validated methods and kit format reagents further reduce any risk of user error.
A new Thermo Scientific µPAC Neo HPLC Column improves column-to-column reproducibility within proteomics and biopharmaceutical research applications as part of an end-to-end liquid chromatography-mass spectrometry (LC-MS) workflow. This further simplifies complex bottom-up proteomics analyses, enabling wider use in the discovery and detection of cancer and other disease biomarkers, and the development of new therapies and vaccines ranging from COVID to cancer and rare diseases.
Essentially, the µPAC Neo HPLC column provides proteomics and biopharmaceutical research laboratories with a new micro-pillar array column as part of an end-to-end LC-MS workflow that will simplify complex bottom-up proteomics analyses, complete with a detailed startup protocol. This helps
users accelerate their experimental setup with the reassurance of high-level performance across every component of the workflow.
Unlocking Deeper Analytical Insights
Scientists in biopharmaceutical, proteomics, and small molecule settings can enable more comprehensive analysis of their data with the latest software updates. New features enable researchers to extract more information from their new and existing data, streamline data interpretation, and standardise reporting with increased ease of use.
The new cloud-based Thermo Scientific Ardia platform integrates data across multiple chromatography and mass spectrometry instruments, letting biopharmaceutical and proteomics scientists share previously siloed data, simplifying analyses and unlocking deeper insights into new diagnostics and therapies that could reach the point of care sooner.
New Thermo Scientific BioPharma Finder 5.1 software uses advanced algorithms to improve biotherapeutic characterisation, an increasing priority as industry and regulators build stricter quality controls into the production of complex new biotherapies and vaccines.
For proteomic scientists, Thermo Scientific Proteome Discoverer 3.0 software interprets data from Thermo Scientific Orbitrap mass spectrometers and applies artificial intelligence (AI), giving researchers a faster method to identify and analyse billions of possible protein interactions in humans, insights that accelerate discovery and development of next-generation drugs and vaccines.
Lastly, for forensic toxicologists, clinical research toxicologists, employee drug testing facilities and wellness organisations, expanding the Thermo Scientific Tox Explorer Collection onto the Thermo Scientific Orbitrap Exploris Mass Spectrometer platform, provides an all-in-one LC-MS toxicology solution to solve complex analytical challenges and increase laboratory productivity.
Cross Industry Collaboration
Thermo Fisher has entered a relationship with TransMIT GmbH Center for Mass Spectrometric Developments to promote a mass spectrometry imaging (MSI) platform for spatial multi-omics applications in pharmaceutical and clinical laboratories.
TransMIT will combine its proprietary scanning microprobe matrix-assisted laser desorption/ ionisation (SMALDI) MSI and 3D-surface MSI technology with the exceptional high resolution accurate mass (HRAM) power of Thermo Scientific Orbitrap MS instrumentation.
TransMIT’s AP-SMALDI5 AF ion source coupled with Orbitrap MS technology enables spatial distribution mapping of a variety of molecules such as biomarkers, metabolites, peptides or enzymatically digested proteins by their molecular masses. This approach can be applied to omics applications such as metabolomics, lipidomics, proteomics, glycomics and to pharmaco-kinetic studies in a variety of tissues.
AUTHOR BIO
Kapil Khullar is Senior Director, Growth Strategies and Application Excellence, Chromatography and Mass Spectrometry in Asia Pacific and Japan, Thermo Fisher Scientific. A veteran of 25 years in the analytical science industry, Dr. Khullar attained his PhD in analytical chemistry from the Indian Institute of Technology Delhi.
For more information, please visit: www.thermofisher.com/accelerome
SGS HEALTH SCIENCE
Integrated solutions for quality and compliance
As a leader in the Testing, Inspection and Certification (TIC) industry, SGS aims to increase cooperation and agility across its global network to leverage competencies. SGS India Managing Director – Shashibhushan Jogani, talks about SGS’s strategic focus on the Health Science industry, how its key investments in India will make the latest new-age technology available to native pharma companies and help to reduce cost for customers and result in faster turn-around time.
Shashibhushan Jogani, Managing Director, SGS India
How does SGS look at India as a potential market for health science services and its capabilities to support the health science industry?
India is a major hub for manufacturing and exports of pharmaceutical products. These extend from APIs, drug intermediates to finished products. The Indian pharmaceutical industry has been consistently delivering a YoY growth over the past decade. The salient factors behind this boom in exports for India are price competitiveness as well as quality. As per the latest industry reports, nearly 60 per cent of the world’s vaccines and 20 per cent of generic medicines are manufactured from India. India also ranks at third position worldwide for Pharma production by volume and 14th by value. (Source: Ministry of Commerce & Industry). This clearly establishes that the Indian pharmaceutical industry is a key contributor which is defining and shaping the global arena.
Our Health Science services can add significant value with specialist services extending from exploratory development, testing, regulatory support, safety studies and clinical research, to commercial QC and post-market testing. Delivered with high accuracy, integrity and scientific rigour, these solutions are supported by state-ofthe-art laboratories, and a rich pool of local as well as global expertise that give us the confidence to meet the vast requirements of this industry. Pharmaceutical products are strictly guided by regulations which are a combination of legal, administrative, and technical measures that governments across the world take to ensure the safety, efficacy, and quality of medicines, as well as the relevance and accuracy of product information. Our regulatory support services offer a huge benefit to clients by helping them to navigate through these complex regulations and to comply with local and international standards and therefore increased market access.
How does SGS stay on top of fast changing pharmaceutical market requirements and the complex regulatory environment?
Our team focuses on increasing the cooperation and agility across our global network. This is helping us to leverage the vast pool of expertise and competence that is available across our entire network and successfully meet the versatile requirements posed by our clients. It also helps us to keep abreast of changing dynamics of the industry as well as the regulatory landscape.
What are the advanced solutions and features that SGS has introduced to emerge as a leader in the TIC industry?
SGS has been consistently leading the TIC industry with integrated solutions to address various customer requirements, help customers to meet stringent standards
SHASHIBHUSHAN JOGANI was appointed as the Managing Director of SGS India including the sub-region of Bangladesh and Sri Lanka in June 2021. Prior to this appointment, Shashi was leading the SGS Indonesia operations as Managing Director. In a career spanning 20 years at SGS Group, he has held various executive roles within the company, including Indonesia Country Business Manager, India Business Director for Systems and Services Certification (now Knowledge) as well as Head of Strategic Transformation for the South-East Asia Pacific region. Shashi joined SGS in 2003 as a Business Controller for SGS India before assuming numerous key leadership roles across the company.
along their supply chain and improve the quality of life in society by assuring the quality, safety, sustainability and security in the health, wellness, and nutrition industries.
Our vision is to become the most digital company in the TIC industry. As part of this process, we have accelerated our Digital & Innovation strategy to create new products and services, improve customer experience and automate our operations. We are leveraging new transformational technologies like artificial intelligence (AI), robotics and applying automations, through several new digital platforms to improve our efficiencies, deliver operational excellence and continuously improve customer experience. Our focus on use of advanced technologies also benefits on various compliance aspects which eventually help our clients in accelerating product development and go-tomarket of new drugs and formulations for patients.
Recently, we have made two significant and strategic investments in India. These are: 1. Advanced Analytics (AA) laboratory within our Navi Mumbai campus. 2. An Advanced Centre of Testing (ACT) within our Chennai laboratory. These two capability enhancements provide us a clear edge over the existing technologies that are available in the market.
The Advanced Analytics laboratory is equipped with new generation infrastructure for performing Extractable & Leachable (E&L) studies, assessment of Nitrosamines, Genotoxic impurities etc. in pharmaceutical materials.
The Advanced Centre of Testing in Chennai takes quality testing to the next level with solutions like Digital Sensory Analysis using the electro sensing devices like the electronicnose(e-nose) and electronic-tongue (e-tongue) which provide unbiased, accurate and repeatable measurements, allowing identification and classification of aroma mixtures and taste. These advanced digital sensory methods help to improve the palatability of oral solutions to make them acceptable to patients. It also reduces the potential safety risk to trained human sensory panels due to exposure to harmful agents and cuts back huge expenses for organisation to recruit, train and maintain taste panelists. Applications of these tools in the pharmaceutical industry plays a key role in measuring and comparing the taste-masking efficiency of formulations produced with different masking techniques, offodour investigations, development of placebos for blinded clinical testing, sensory features ageing overtime, comparing the taste of test medicines or generic products with benchmarked products etc.
What is your outlook for the next 5 years and your plans for future growth and investments in health science?
We are very optimistic and excited about the growth of the health sciences industry in India and plan to accelerate our investments in India within this sector. Our focus is to align our services and scale with that of the industry, especially in the Biologics and Biopharmaceutical arena.
We not only plan to invest in new technologies and equipment, but also to leverage the technologies, platforms and quality systems that are already established at our network labs in US, EU to cater to the needs of our clients and the industry in India as well as the region. The integrated drug development and testing facilities that we plan to set up will drastically reduce the dependency that Indian biopharma companies have at present, on Contract Research Organisations (CRO’s) in US and EU. These new facilities would be capable of meeting our client requirements and facilitate faster product development and go-to-market. Another important area that we are working to expand our footprint is the testing of medical devices.
Our outlook for the next few years is to accelerate our focus and investments into strategic industry segments within health sciences and leverage the competence across our global network to deliver these services and excellence to our clients. Agility within the global network is something we are strongly focusing upon. We are also making significant investment in our employees, new technologies and platforms to improve customer experience and automate our operations. These strategic actions and investments would help us to secure a strong customer base and a healthy, organic top-line growth that reinforces our leadership position in the TIC industry.
Maintaining a Drug’s Bioavailability and Masking Taste with Microencapsulation
Microencapsulation possesses numerous advantages for many pharmaceutical applications: it's an effective means of converting a liquid to a solid, it provides taste masking, and it ensures controlled release capabilities. But partnering with a CDMO that possesses microencapsulation experience and expertise is integral to the product’s ultimate clinical and commercial success.
Nathan Dormer, Director of Drug Product Development, Adare Pharma Solutions
Today’s formulation challenges are as diverse as they are demanding–from increasingly insoluble new chemical entities (NCEs) to highly bitter drugs, to increased regulatory emphasis on patient acceptance–arriving at a final dosage form that has commercial potential is a more complex proposition than ever.
Microencapsulation, the process by which particles are co-formulated with a polymer or other excipients to improve palatability, modify release rate or enhance bioavailability, possesses a number of advantages for many pharmaceutical applications. An effective means of converting a liquid to a solid, taste masking a bitter active pharmaceutical ingredient (API), or ensuring controlled release, microencapsulation offers the encapsulated drug protection from environmental factors, flexibility in dosage form, and an array of other benefits.
There are several technologies available for microencapsulating drugs. Finding a contract development and manufacturing organisation (CDMO) possessing the experience and expertise necessary to optimise a drug’s efficacy and manufacturing during formulation is integral to the product’s ultimate clinical and commercial success. To do so requires companies to understand not only their own molecule, but the distinctions between technologies and among potential manufacturing partners, as well as the financial and therapeutic pitfalls often associated with unoptimised processes.
The Factors that Affect a Drug’s Efficacy
For oral drug formulations, there are three primary characteristics pharmaceutical companies must consider in their development paradigm to optimise a drug’s efficacy: solubility, permeability, and bioavailability. Arguably the single most important measure of a drug’s efficacy is its bioavailability, or the amount of unchanged drug which reaches systemic circulation. There are a number of physicochemical factors which impact bioavailability, including a drug’s solubility, its hydrophobicity, and its pKa. There are also various external factors, including whether a patient has consumed food, the relative health of a patient’s gastrointestinal tract, and whether a formulation has been tampered with prior to administration.
The reasons for poor bioavailability are equally diverse. They can include poor solubility, degradation in the gastrointestinal tract, interactions with food, insufficient time to ensure absorption, drug efflux pumps such as p-glycoprotein, hepatic first-pass
metabolisation, and other factors. Addressing these requires a comprehensive approach to formulation, one that considers physical modifications to the size of the molecule, carriers that optimise dispersion, chemical modifications to the pH or salt content of the drug, and other methodologies.
There are several technologies that have been employed to enhance the solubility, dissolution, and bioavailability of drugs, as well as to improve their taste and overall palatability. These technologies include those which reduce the size of particles, an important first step in improving the control, stability, appearance, efficacy, and manufacturing of a drug. The most commonly-utilised technique to reduce particle size, micronisation, which can reduce API to a micrometer or, in some cases, nanometer size. This improves the solubility of poorly soluble APIs by increasing the particle surface area-to-volume ratio, accelerating the rate of dissolution. Considering the complexity of bioavailability, however, micronisation and other solubility-enhancing techniques can have a limited impact if the final dosage forms do not also exhibit uniform disintegration and performance. Simply stated, all facets of the product must be designed for consistent disintegration and dissolution.
The Solutions that Ensure a Drug’s Efficacy
Adare, a global technology-driven specialty CDMO providing product development through commercial manufacturing expertise, focuses on oral dosage forms for the pharmaceutical, animal health, and OTC markets, and utilises propriety technology platforms for taste masking and customised drug release. Adare’s Optim m® technology is a melt-spray-congeal process that offers a wide range of modified release options in a powder format, allowing the such powder to mirror an extended-release tablet’s performance. Optim m-produced powder is compatible with many other dosage forms, including liquid suspensions, dispersible tablets, chewable tablets, and granular multi-dose devices.
The primary advantage Optim m offers when compared to other similar technologies is in the uniformity of the particles it produces. Adare’s Precision Particle Fabrication® technology enables particle uniformity with precision engineering, allowing for tighter control of release kinetics, and is the under-pinning technology for Optim m and Strat mTM (a long-acting injectable application).
While there are a handful of melt-spray technologies on the market for microencapsulation, many of them are incapable of producing particles uniformly in size; even small variations in particle size can have implications for the final dosage form’s release rate and potency.
Inconsistency in particle size can lead to content uniformity issues, which sometimes necessitates manufacturing modifications. For instance, during a coating process, if substrate particles are not uniform, a specific coating duration will result in different levels of coating for particles of varying sizes, with differing release rates or taste-masking, which can affect homogeneity of performance within a dose or from dose-to-dose. To address this problem, many manufacturers need to sieve their intermediate particles to create a more consistent particle size. This comes at a literal cost: as much as 30 per cent of what has been produced is subsequently discarded.
Adare’s Microcaps® technology is another example of a microencapsulation technology that can customise a drug’s release profile, provide taste masking, or combine otherwise incompatible APIs. With Microcaps technology, the raw API is directly coated with a thin layer of polymer. This does create a wider size distribution than that achievable with Optim m technology but enables a much higher drug loading on a weight basis. Moreover, Microcaps is an ideal choice for tastemasking high-dose applications, whereas Optimum has more flexibility in taste-masking and extendedrelease for moderate-to-low dose therapeutics. Like Optimum, drugs formulated using the Microcaps technology can be compounded into an array of dosage forms, including powders, dry syrups, orally disintegrating tablets, and Adare’s Parvulet dosage form, which mimics the texture of soft foods such as yogurt to increase swallowability for certain patient populations.
Microcaps and Optim m represent just two of Adare’s solutions for improving a drug’s efficacy and palatability. With a range of barriers and coatings, taste modifiers and suppressants, and API and API solubility modifiers, Adare’s portfolio of dosage form technologies is one of the most comprehensive in the world. These technologies, coupled with a long-standing focus on patient compliance, have positioned Adare as a leader in formulation for specific populations. Adare’s expertise also extends to pediatric formulations, which is a critical consideration for virtually all therapeutics.
By partnering with a CDMO like Adare, companies can identify a format that is the best fit for their drug and target patient population, thereby meeting increasingly stringent regulatory standards and, ultimately, improving patient outcomes through better patient adherence. If microencapsulation is the best choice for your drug, Adare has a portfolio of manufacturing approaches to get the job done.
AUTHOR BIO
Nathan Dormer is the Director of Drug Product Development at Adare Pharma Solutions in Lenexa, KS. Dr. Dormer is a pharmaceutical scientist and bioengineer with over a decade of experience developing microsphere- based solid oral and parenteral/ implantable dosage forms, with an emphasis on controlled release and other innovative formulation concepts.
