Behind the Headlines Episode 27

Ask the Expert

Small Molecules, APIs, and Excipients—Trends, Challenges, and Opportunities

Drug Digest September 2025

Artificial intelligence, machine learning, and novel instruments are helping drug developers.

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

J.P. Morgan Report Lists Biologics, Obesity, China

Top Trends Reshaping Pharma R&D

Maria DiPietro is senior vice-president, Operational Solutions Architect & Strategy, ICON Strategic Solutions.

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Partnership is an increasingly important criterium for bio/pharmaceutical sponsors as they seek more bespoke solutions and the flexibility of tailored, blended outsourcing models. Sponsors are consolidating their vendors and utilizing fewer contract research organizations (CROs), but with more expansive and aligned partnerships to find solutions to clinical research challenges and improve their R&D return on investment.

The consolidated CRO landscape, wherein the top CROs capture 70% of total clinical outsourcing spend (1), provides sponsors with large CROs offering fuller suites of services and broader geographic footprints, effectively shifting more importance onto their ability to deliver as partners. This move toward more meaningful partnerships has fueled additional evolution in the CRO-sponsor outsourcing landscape, including in the ways progress and success are measured.

Elaborations on outsourcing methodologies

Over the past two decades, the clinical research landscape has witnessed a significant transformation due to rising protocol complexity and the broadening scope of trials. In response to these changes, outsourcing methods have evolved, adapting to meet the demands of modern clinical research. As such, traditional models such as full-service outsourcing (FSO) and functional-service provision (FSP) have been reshaped to better accommodate new methods in addition to the proliferation of models that go beyond this distinction. This proliferation of new models reflects an ongoing trend in partnership development, fostering deeper, more meaningful collaborations. These collaborations, in turn, have given rise to customized, tailored, and hybridized models that can cater to the unique requirements of each study as scientific and regulatory considerations must be balanced with concerns around addressing patient access, diversity, and patient-centricity.

. Recent data from the Tufts Center for the Study of Drug Development (Tufts CSDD) underscores the dominance of the FSP model in current clinical trial outsourcing. In fact, nearly half of the clinical trials analyzed within the Tufts sample—comprising 117 trials across nine sponsor companies—utilized the FSP model. This represents a significant shift, as just a few years ago, FSO was the prevailing model for more than 77% of sponsor companies (2).

The popularity of FSP aligns with the growing importance of strategic partnerships. FSP offers sponsors greater control and ownership of key assets, a critical factor as clinical research becomes increasingly complex and risk-laden, while the cost of conducting trials continues to soar. According to 2023 ISR Reports, the average spend on clinical trials is expected to continue rising across Phases I–III for small, mid-size, and large sponsors (3). The outsourcing spend as a percentage of these costs will go hand in hand with these increases, likely resulting in additional innovation within the methods used.

. Collaboration between CROs and sponsors has transcended the conventional contract-execution models of the past. While the FSP model remains popular (4), especially among mid-size and large pharmaceutical partners, there is a notable trend toward blended models and tailored solutions.

Today, CROs position themselves as true partners, offering flexibility, consultative support and a deeper level of engagement to meet the evolving needs of sponsors in the face of increasingly complex clinical trials. In parallel, sponsors are embracing a more fluid relationship, characterized by shared governance, common objectives, and greater integration.

Biopharmaceutical sponsor companies will employ combinations of outsourcing methods even within single departments. They may leverage different models or levels of partnership complexity with different vendors or even with just one CRO across multiple scopes, strategically blending solutions. These adjustments in outsourcing strategies reflect the industry’s commitment to adapt and innovate in response to the evolving landscape of clinical research.

Merger and acquisition (M&A) activity in the CRO landscape can be understood as a function of the evolution from single-service provision to integrated, end-to-end solutions providers, and strategic partners. CROs must keep expanding capabilities to offer a “full suite” to their sponsors. And—as is common knowledge in the clinical research industry—the quickest means of innovation or portfolio expansion is acquisition.

The CRO landscape saw a significant year for M&A in 2021. According to 2022 Tufts data, the top clinical CRO segment had a record year in terms of the number and size of the recorded M&A activity, with 13 total transactions. As noted, between 15% and 25% of all M&A transactions in the CRO landscape reflect the pursuit of “novel” or less-traditional capabilities (1). In recent years, this has included augmented analytics and artificial intelligence in addition to technologies and solutions to enable decentralized clinical trials.

. CROs are also engaging in M&A as a means for expanding their footprint to better meet sponsor needs. For example, this could facilitate the ability to move strategic roles into regional hubs or offer lower cost settings. CROs are expanding their networks in ways that allow for more strategic control in these key target areas. However, this expansion is a double-edged sword. Tufts research notes that the inclusion of more countries and more investigative sites contributes to overall execution burden by compounding the complexity of the trial (5).

Intentional, strategic geographies are an important consideration for sponsors. Sponsors are evaluating their footprints for further rationalization while simultaneously seeking to expand into new geographies. They rely on their CRO partners to weave in their own footprint to extend the reach of their trial. The outsourcing models employed in this situation will likely leverage blended services where the CRO can fully support the conduct of the trial in those areas.

. CROs have broader perspectives and insights by nature of their position working across many therapeutic areas, modalities, geographies, etc. In working with a wide range of sponsor companies, CROs often gain a depth of experience and lessons learned that can positively benefit other programs when translated across outsourcing relationships. Sponsors are increasingly interested in leveraging the strategic value of these partnerships, turning to CROs for an infusion of those proven best practices and strategies and collaborating to create leading edge models to optimize delivery.

. In addition to acting as a library for best practices and lessons learned gained from direct experience with sponsors across the industry, CROs are driving adoption of advancing technologies and innovations.

In the modern research landscape, digital technologies are a crucial part of the ways in which sponsors and CROs are delivering and transforming clinical trials. The latest transformational technologies include quantum computing, blockchain, organ-on-a-chip, advanced statistical modeling, Big Data, and artificial intelligence (AI). To better understand sponsors’ attitudes toward these technologies, a survey was conducted among 350 pharma and biotech professionals. When asked “How much do you anticipate digital technologies improving R&D productivity?” 99% believed that they will see significant improvements (6).

The increasing cost and complexity of running clinical trials underscores this drive to leverage technology for efficiency and optimization, but it also adds challenges. Layering complicated tech onto already complex studies has the potential to become detrimental to overall processes. CROs have developed platforms and interoperable technologies to streamline this complexity and have invested both in tech and their personnel expertise to optimise and simplify these processes. Sponsors rely on this balanced, complex basketweave of processes and technologies to enable their trials.

. Of the transformational technologies, Big Data and AI are gaining the most traction. Big Data, and specifically a CRO’s access to data, offers invaluable opportunities for improving clinical research. Extracting meaningful insights from vast data requires computational capabilities to match, thereby driving progress in AI technologies. AI innovations include machine learning and deep machine learning, robotic process automation, and other expert systems that enable CROs to capture, consume, and interrogate more data with more impactful processes.

When it comes to data, the Tufts study found that FSP is now the most common model for both clinical monitoring and data management. These are highly technical areas that are exceptionally labor-intensive, carrying associated study costs. The FSP model can help to reduce costs and improve efficiencies, so employing this model for clinical monitoring makes sense for most sponsors considering this area alone can represent 35–45% of clinical trial costs (4).

. Another new outsourcing development takes the shape of joint innovation agendas. CROs may offer these models to allow larger pharma sponsors to pilot innovations within the structure of a consultative partnership, minimizing some of sponsors’ inherent risk while allowing them to benefit from their CRO’s experience and expertise. ICON has seen an increased interest in this model among its large pharma partners, and it is expected that this trend will continue.

Although CROs often work toward the same goal—bringing meaningful therapies to patients—no two organizations operate the same. As outlined previously, even the outsourcing methods used within a single partnership can vary. However, the lessons learned from one partnership can inform potential models or solutions for another. In this way, CROs can pilot and refine the methods used within partnerships to achieve harmony.

CROs often assume the role of change managers. Implementing digital solutions and new technologies may require new trainings or optimized organizational workflows to accommodate the new capabilities. Both CROs and sponsors must dedicate time and resources into building strong, trusting partnerships that allow for seamless integration. These relationships must also be backed by deliberate processes, controls, and governance structures to support joint operations and allow for clear measurement against shared goals.

. Tracking the success of a partnership operating within a new outsourcing model may be challenging. A selection of carefully identified partnership metrics representing these key categories can lead to mutual success in strategic partnerships. Four foundational categories for partnership metrics can provide meaningful data to guide decision-making: finance, quality, operations, and relationship health. Based on the specific goals, deliverables and context of each partnership, more granular key performance indicators can be selected for each of these metrics categories to provide the clearest mechanism for evaluating performance.

The bespoke solutions and continued evolution within clinical trial operations and the technologies they utilize will continue to fuel progress among outsourcing models as driven by CROs. While there are some overarching trends, CROs are tailoring their solutions and models to meet each organization’s unique business needs and they are leading partnership alignment to ensure predictable delivery with the highest quality standards. Looking forward, the author expects increased adoption of blended solutions and deeper and more meaningful strategic partnerships among industry players. In addition, there will be further development around benchmarking and standardization of models and terminology to allow for robust business cases informed by custom metrics.

Tufts. Impact Report: Analysis & Insight into Critical Drug Development Issues. 

 CSDD. Volume 24, Number 6–November/December 2022

Getz, K. Insights into Outsourcing Practices and Oversight Effectiveness. 

2023 CRO Market Size & Growth Projections. Industry Standard Research, 2023.

Lamberti, M.J.; Smith, Z.; DiPietro, M.; Barry, J.; Getz, K. Outsourcing Model Usage and Its Relationship to Clinical Trial Performance. 

 CSDD. Volume 25, Number 3–May/June 2023.

ICON Digital Disruption Survey. Digital Disruption in Biopharma How Digital Transformation Can Reverse Declining ROI in R&D.

When referring to this article, please cite it as DiPietro, M. Elaboration, Expansion, and Evolution in Outsourcing of Clinical Research. 

Articles

The rising complexity of clinical research protocols has necessarily expanded the CRO landscape. 

Elaboration, Expansion, and Evolution in Outsourcing of Clinical Research

Kate Coleman is Principal Quality and Compliance Consultant with Arriello Ireland.

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The new revision of the International Council for Harmonisation’s (ICH) Q9, Quality Risk Management document utilizes the word ‘effective’ many times throughout, both in the context of quality risk management (QRM) and the pharmaceutical quality system (1). The definition of what ‘effective’ means in this context is different for each company, stakeholder, and facilitator involved in QRM activities, which has facilitated a wide divergence in the application of QRM and risk assessment across the industry. The revised guideline addresses the divergence in stakeholder background and perspective and links this effectively with the bias that has historically been evident in many risk assessments that formed part of existing QRM programs. The new revision accurately states, “subjectivity can directly impact the effectiveness of risk management activities and the decisions made. Therefore, it is important that subjectivity is managed and minimized.” A renewed focus on the basic set-up of the QRM process can significantly aid in meeting this requirement.

This article was peer reviewed by a member of 

The new revision of ICH Q9 was timely, as the pharmaceutical industry had spent many years since the original version was published in 2005 trying to establish the look and feel of effective QRM while also struggling with QRM processes that became increasingly resource hungry and complex. Publication of the new revision in January 2023 heralded a new era in the design and implementation of QRM processes and provided an opportunity for review and re-establishment of the place of QRM throughout the pharmaceutical lifecycle. The new revision offered as its purpose a “systematic approach to quality risk management that leads to better, more informed, and timely decisions” (1).

One of the observations made across the industry since 2005 is the dichotomy of the enthusiasm with which companies have embraced QRM and the struggle they have had with understanding the importance of simplicity, clarity, and pragmatism that should form the basis of any risk management process. The industry is fully bought into the benefits of QRM but, at times, has struggled to fully realize the actual benefit that is possible when this process is implemented effectively. “Commensurate with the level of risk” has become a misnomer, and in some cases, the industry has fallen into a world controlled by failure mode and effects analysis (FMEA) and arduous capturing of information that is never revisited.

Planning of the QRM program and quality risk assessments

The first fundamental that has been often overlooked is the definition and planning of the structure and purpose of the QRM program. Section 4.2 specifically calls out “possible steps used to initiate and plan a quality risk management process,” and these include steps such as definition of the scope, the risk question, the definition of assumptions, and collation of relevant data (1). Often, the practice in reality has commenced with the selection of a tool and immediate commencement of a risk assessment without asking “what do we want to achieve?”. At the simplest level, a QRM program should help to identify quality risks before they occur, safeguarding patients but also reducing the time spent fixing issues that could have been avoided.

Setting boundaries around each risk assessment that is undertaken is a key driver for successful risk assessment. When performing a risk assessment, it is common for a cross functional group of people, who happen to have some availability in their calendar that week, to sit in front of a blank FMEA tool wondering where to begin.

To resolve these situations, every risk assessment should start with a strategy, commencing with setting the scope, and asking questions as follows:

What part of the process are we concerned with?

The scope then leads to the risk question where one formulates the question that will be asked for each process step included in the scope. An example of a risk question would be, “What are the microbial risks that may impact product quality in the filling process from vial depyrogenation to tray-off?”. A well-thought-through risk question or statement performs an important function in making the QRM process efficient and effective. It prevents a risk assessment from taking a wrong turn or going down rabbit holes that cause confusion and derail the whole process.

Section 4.2 of the new revision of the ICH Q9 guideline has provided valuable information relating to this stage of the QRM process and has also encompassed the requirement to include pertinent assumptions in the risk assessment plan. Assumptions also provide additional bricks in the boundary provided by the scope and risk question and assist in the identification of routes to avoid, thus making the process more efficient. A common example is the assumption that personnel will follow procedures—this assumption is hugely valuable as it prevents the time-consuming assessment of the risk of each standard operating procedure (SOP) in the quality system not being followed by personnel, something that is notoriously difficult to mitigate. Assumptions help one to focus on the risk assessment task at hand, which ultimately makes the risk assessment process more efficient.

Once the purpose, boundaries, scope, risk question, and assumptions have been thought through and agreed, a common result is that the correct tool for capturing the risk assessment itself becomes evident. Taking the time to really think about what the risk assessment aims to achieve can really help to ensure it gets off to the right start.

Risk assessment tools are many and varied in the industry, and it is useful to remember that the function of a risk assessment tool is to capture the risk assessment thought process accurately and clearly, ensuring that the information captured therein is logical and available for future readers to understand. A tool may be as simple as a memo to capture a risk decision to something more formal and complex such as the common FMEA tool. Section 5 and Annex 1 of the new revision of ICH Q9 provide comprehensive examples of tools that can be considered and used as building blocks for the ideal tool for the risk assessment
being undertaken.

Once a tool has been selected, the mechanism for scoring the risk levels needs to be considered, and this step in the process is of paramount importance for the prevention of bias and also for ensuring that the risk assessment is meaningful. Many older scoring systems included statistical probabilities for likelihood of occurrence. In today’s advanced pharmaceutical industry, a one in 1000 probability of a contamination event, historically seen as low, is not acceptable. More meaningful barometers of risk must be captured to ensure QRM is effective. For example, when dealing with contamination risk, the number and type of controls in place may be a more meaningful way of establishing likelihood of occurrence.

These scoring systems may need to be altered and adjusted to keep them meaningful, depending on the risk assessment scope. QRM programs where scoring is locked down provides many problems when the risk assessment at hand doesn’t fall neatly into the boundaries mandated by a procedure.

Management and control of subjectivity or bias

The new revision of ICH Q9 states that “subjectivity can be introduced in quality risk management through differences in how risks are assessed and in how hazards, harms, and risks are perceived by different stakeholders” (1). This ‘bias’ that has been common across the application of QRM in the industry has been one of the hurdles to the implementation of truly effective QRM programs.

As mentioned previously, the incorporation of a strong and objective scoring mechanism which is descriptive, clear, and relevant to the risk assessment being conducted can be the biggest control and mitigation against subjectivity and bias in the QRM process. Another area related to risk assessments and often observed during regulatory inspections is the failure to assess all process steps or operations in terms of risk, resulting in relevant risks not being identified, documented, and subjected to the risk question. This is another significant source of bias in the process with process steps that have been historically compliant and trouble free not being considered in the QRM process and then taking companies by surprise when they go wrong. Similarly, steps in the process that have most recently caused issues may be unfairly prioritized in terms of risk due to familiarity, rather than true potential to cause harm.

The definition of a process flow is key to preventing subjectivity and is relatively simple when it is a recognizable process that is undergoing risk assessment. When the subject of the risk assessment does not have an obvious process, it can take effort to establish and document the process flow, but it can be assured that everything done is performed in a step-wise manner and with some patience and cross-functional insight, a process flow can always be determined.

The new revision states, “all participants involved with quality risk management activities should acknowledge, anticipate, and address the potential for subjectivity”, and everyone can comply with this statement by ensuring that each QRM process starts with the establishment of the correct boundaries as defined by the risk question, assumptions, scoring definitions, and process flow description that are included in each of quality risk assessments.

When each of these fundamentals are understood and implemented, the risk assessment process itself becomes relatively straightforward, logical, and efficient. For the overall QRM plan to be effective, the number of risk assessments that form the QRM program should not be allowed to increase exponentially. If this happens, it is certain that preceding risk assessments are not being reviewed and revised, and thus information is lost and the ongoing narrative relating to the process is disrupted. ICH Q9 (R1) describes QRM as “part of building knowledge and understanding risk scenarios, so that appropriate risk control can be decided upon for use during the commercial manufacturing phase” indicating that each time the level of knowledge increases, the knowledge captured in the QRM process should also increase.

QRM is cyclical in nature (i.e., one starts with the initial assessment but as things change, one revisits the previous iteration and ensures that information contained in the QRM plan is constantly updated and revised). The ultimate goal is that the QRM program, and the documents contained within it, can provide a roadmap to any pharmaceutical process or activity, capturing the successes such as innovative design and state-of-the-art controls as well as the risks and potential pitfalls. Ultimately, to be effective, efforts and priorities will be concentrated around these risks, increasing efficiency without compromising patient safety or medicinal product availability.

Deviations are often raised as a result of something going wrong in processes, but interestingly, many companies do not use deviation numbers as an indicator of the maturity of their QRM program. An increasing number of production deviations will often indicate the failure to proactively identify and mitigate risk. This connection between common quality key performance indicators such as deviations, and the QRM program provides an opportunity to continuously assess QRM effectiveness. We should be aiming for a QRM program that will proactively identify risks and failures, giving us the headspace and opportunity to fix issues before they become a time bound problem with potential impact on product quality, patient safety, or drug availability.

®
Vol. 47, No. 12
December 2023
Pages: 28-30

When referring to this article, please cite it as Coleman, K. The ICH Q9 Revision and a Renewed Focus on Quality Risk Management Fundamentals. 

The ICH Q9 revision clarifies QRM implementation for the pharmaceutical industry and expands descriptions of methodology, formality, and risk-based decision making to provide the industry with a solid base from which to build their own QRM programs.

The ICH Q9 Revision and a Renewed Focus on Quality Risk Management Fundamentals 

Felicity Thomas is the former Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

It’s the most wonderful time of the year … unless you are struggling to get a hold of prescription or even some day-to-day medicines as a result of drug shortages! Throughout Europe, there has been a rising shortage of a variety of medicines, including common antibiotics and painkillers, causing, and pardon the pun, headaches to not only patients, but also pharma companies, regulatory bodies, and governments.

From late 2022, numerous countries across Europe started reporting serious issues sourcing important drugs, leading to shortages in supplies. Most notably, supplies of the antibiotic amoxicillin were low along with children’s paracetamol and blood pressure medicine (1).

A survey of 29 European countries, conducted by the Pharmaceutical Group of the European Union (PGEU), revealed that, for most, medicines shortages had been worse in 2022 when compared with the prior year. The three most common causes of shortages were highlighted in the survey as “disruption or suspension of the manufacturing process”; “quota imposed by the manufacturer”; and “unexpected or high increase in demand” (2).

To try and prevent further shortages, the European Commission has adopted a new approach comprising a mechanism to share medicines across the bloc and emergency measures (3). In the United Kingdom, mandatory requirements for companies to monitor and report any potential discontinuations or supply issues with medicines were implemented in 2019 (4).

However, potential supply chain issues can only be mitigated to a certain degree as other, sometimes surprising, global disruptions occur. For example, the COVID-19 pandemic and the war in Ukraine both took supply chains by surprise; however, Brexit has and is continuing to cause difficulties in medicines supply, particularly for the UK.

As shortages of medicines have grown year-on-year since 2000 in Europe (5), it seems as though greater efforts to solve the problem are required.

1. Martuscelli, C. Europe is Running Out of Medicines. 

Medicine Shortages: PGEU Survey 2022 Results

. Survey Report, January 2023.
3. European Commission. 

Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee, and the Committee of the Regions Addressing Medicine Shortage in the EU

. Communication, 24 Oct. 2023.
4. Department of Health and Social Care. 

DHSC Reporting Requirements for Medicines Shortages and Discontinuations

. Guidance Document, 21 April 2021.
5. Louloudi, J.; Morfonios, N.; Zafeiropoulos, K. Why Europe is Chronically Running out of Meds. 

Felicity Thomas is the European/senior editor for Pharmaceutical Technology Group.

When referring to this article, please cite it as Thomas, F. Falling Short. 

Drug shortages across Europe are being exacerbated by increased demand, struggling supply chains, and manufacturer suspensions.

Falling Short

Cheryl Barton is director of PharmaVision, 

The United Kingdom (UK) 2019 Voluntary Scheme for Branded Medicines Pricing and Access (VPAS) will end on 31 Dec. 2023. The UK’s 2019 VPAS succeeded several Pharmaceutical Price Regulation Schemes (PPRS) stemming back to 1957, and negotiations for the new VPAS between the UK government, National Health Service (NHS) England, and the Association of the British Pharmaceutical Industry (ABPI) began in May 2023 (1). The VPAS is one of two schemes, alongside the statutory scheme, that control the prices of branded medicines to the NHS (2).

The new VPAS will take effect from 1 Jan. 2024, and although profit control remains at the centre of the negotiations, the spotlight will be focused on keeping branded drugs affordable. The 2019 VPAs established a rise of 2% per annum from 2018–2023 for branded medicines, but historically, the spending on branded medicine has always exceeded the allowable growth rate (3). The ABPI notes that since 2021, the VPAS rebate resulted in member companies paying around 5% of their revenue back to the NHS and this increased to 15% in 2022 and 26.5% in 2023. It points out that the 2019 VPAS is no longer fit for purpose and needs to be overhauled (4).

On 20 Nov. 2023, a new deal was agreed between the UK government, NHS England, and the pharma industry which should save the NHS £14 billion over five years in medicines costs (5). The 2024 VPAS has reset the annual allowed growth in sales of branded medicines from 2% in 2024, rising to 4% by 2027. All older medicines that have not previously had price reductions will pay a top-up rate of up to 25% plus a base rate of 10% and the top-up will taper down for older medicines that have already been subject to price reductions (5).

Two Big Pharma companies, Eli Lilly and AbbVie, have already pulled out of the current VPAS voluntary pricing scheme (5), and Leslie Galloway, chair of the Ethical Medicines Industry Group (EMIG), warned “a survey showed that 50% of its members were reducing supplies of medicines in 2023 and a further 40% were discussing a reduction” (6). Thus, the 2024 VPAS needed to carefully balance affordability and allowable growth in order for the UK government to meet its goals of promoting better patient outcomes and a healthier population, supporting UK economic growth, and contributing to a financially sustainable NHS (

 UK Government’s and National Health Service England’s goals for 2024 Voluntary Pricing Scheme. 

According to Richard Torbett, chief executive at the ABPI, “This is a tough deal which underlines the essential role innovative medicines and vaccines will play in addressing the health challenges of the future. The industry supports this agreement, despite its restrictions, as it provides important support for patients and the NHS and commits to giving them access to the transformative treatments they need,” (5).

Under the new agreement, the pharmaceutical industry will also invest £400 million over five years through the Life Sciences Investment Programme to drive forward UK innovation, sustainability, and growth. The programme will be ring fenced to support work in:

pioneering clinical trials to bolster the NHS’s capacity to deliver commercial clinical research.

manufacturing helping to position the UK at the forefront of sustainable manufacturing by driving innovative advancements in environmental technologies and cultivating strategic partnerships.

innovative health technology assessments (HTAs) to support access to innovative medicines by developing novel approaches to HTA challenges (5).

The UK Generics and Biosimilar Medicines (BGMA) is concerned that its interests have not been fully considered and wanted more involvement in the VPAS negotiations (7). Disturbingly, some branded generic companies have already withdrawn products from the UK market as the operating environment was unviable (8). A new report shared with 

 indicates that post-Brexit red tape is leading to a significantly higher risk of drug shortages in the UK, in part due to the UK’s ability to acquire and stockpile medicines but also because of non-tariff issues and the difficult economic environment (9).

According to Mark Samuels, chief executive of the BGMA, “we are very disappointed that the price erosion mechanism (PEM) appears to damage competition because of how the reference price is calculated; it will reduce the plurality of medicine suppliers for the NHS, increasing the drug shortage risk … We are also concerned by the scheme using an originator product’s SPC status to confer whether a generic or biosimilar medicine that launches is defined as a new or older product,” (10).

The involvement of NHS England in negotiating medicine pricing and access has increased over recent years particularly, given its role in tendering as the Commercial Medicine Unit was brought in-house and it is the gatekeeper for Patient Access Schemes (PAPs) (11). The new agreement details how NHS England will work with companies to create a new PSP database to encourage local NHS services to partner with manufacturers and encourage the wider use of novel approaches to patient support post treatment (5).

This is one of the biggest economic and political debates that will have a significant impact on NHS patient access to cutting-edge treatments, the financial sustainability of the health service, and the competitiveness of the UK life science sector over the next five years. Although the BGMA is calling for further clarification regarding the reference pricing calculation for generics and biosimilars the new deal appears to be have been well-received by the pharma industry, and the new affordability mechanism for older medicines promises to support lower payment rates for more innovative branded medicines (5). Overall, the 2024 VPAS should allow the life science sector to grow faster than under the previous schemes and strengthen the UK’s global competitiveness.

Negotiations Begin for a New Medicine Pricing Scheme

Consultation Outcome Proposed Update to the 2023 Statutory Scheme to Control the Costs of Branded Health Service Medicines

, Consultation Outcome, Updated 2 March 2023.
3. ABPI. Voluntary Scheme on Branded Medicines. 

 (accessed Nov. 2023).
4. ABPI. At the Crossroads: How a New UK Medicines Deal can Deliver for Patients, the NHS, and the Economy. 

, Proposal Paper, March 2023.
5. ABPI. Landmark Medicines Deal to Boost Nation’s Health, Save NHS £14 Billion, and Support Research Investment. 

, New Release, 20 Nov. 2023.
6. Gershlick, P. Two Big Pharma Companies Leave NHS Pricing Scheme over Punitive VPAS Rebates. 

, Pharma Blog, 17 Jan. 2023.
7. Gershlick, P. 90% of Branded Pharma Could Reduce UK Medicines Supply in 2023. 

, Pharma Blog, 6 Dec. 2023.
8. Gershlick, P. BGMA Seeks Judicial Review to be Involved in New VPAS Negotiations Alongside ABPI. 

, Pharma Blog, 4 May 2023.
9. Gershlick, P. Crippling VPAS Rebate Scheme Killing Availability of Cheaper Generic Medicines. 

, Pharma Blog, 31 Oct. 2023.
10. BGMA. VPAG Heads of Agreement Reaction. 

, News Release, 21 Nov. 2023.
11. Forrest, A.; Thomas, R. NHS Patients Hit by ‘Severe Drug Shortages’ due to Brexit Red Tape. 

Cheryl Barton is director at PharmaVision, Pharmavision.co.uk.


Vol. 35, No. 12
December 2023
Pages: 7–8

When referring to this article, please cite it as Barton, C. Renewing the UK Voluntary Pricing Scheme. 

Renewing the UK Voluntary Pricing Scheme 

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

US Capital Building. | Image Credit: © W.Scott McGill - © W.Scott McGill - stock.adobe.com

In the 30 years that I have been writing about FDA policy and biopharmaceutical research and drug manufacturing, I have not encountered a time as troubling or uncertain as the present. The political battles over medications for abortion, vaccine safety, and shortages in vital medicines undermine long-held confidence and support for the nation’s regulatory system for food, drugs, and medical products. Add to that Congressional delays in reauthorizing national initiatives to prepare for future pandemics, incentives to develop much needed anti-infective medicines, and funding for the highly acclaimed PEPFAR (the US President’s Emergency Plan for AIDS Relief) program, which provides antiviral medicines to combat AIDS around the world.

 Washington reporter, Jill Wechsler, is ending her tenure as a contributing editor to the publication. In January of 1990, Jill’s column, titled “New Era for the Pharmaceutical Industry”, highlighted attacks on the US drug regulatory process that called for stricter regulations. Ironically, if you read Jill’s final column in this issue of PharmTech, it seems that as much as the industry has changed and evolved, some things remain the same.

Jill’s reporting on decades of regulatory and government topics has given her a unique perspective on the pharmaceutical industry that cannot be reproduced, and we here at PharmTech will greatly miss her. We thank Jill for her journalistic integrity, hours of coverage at conferences, countless blog posts, and numerous articles.

We wish her all the best for her future endeavors!

To read Jill’s extensive coverage of FDA and other regulatory news, Jill’s Regulatory Watch column can be accessed on our website at 

Jill covered a variety of topics in her PharmTech Talk blog posts over the years. To read past PharmTech Talk posts, visit 

Jill may be contacted at jillwechsler7@gmail.com. 

Congressional infighting over federal spending furthermore threatens to limit funding and support for FDA as well as the National Institutes of Health (NIH) and vital national health programs. Such developments undermine the nation’s leadership in biomedical research and discovery of cutting-edge medical treatments. The situation could get worse, moreover, if the Supreme Court permits states to limit access to medical products approved as safe and effective by FDA, but with medical uses opposed by certain interest groups.

These and other contentious issues seem to ignore the remarkable success over the past three years of the public-private partnership that linked government funding to industry research to produce treatments able to arrest the spread of COVID-19. And even though FDA policies have long provided the “gold standard” around the world for conducting clinical research to assess the safety and efficacy of untried
therapies, the political attacks on the United States regulatory process are exhausting its leaders and undermining agency morale.

As Washington correspondent for Pharmaceutical Technology®, I have commented extensively on these and a wide range of political, legal, and regulatory developments that have shaped medical product R&D and production in the US and abroad. I became familiar with drug regulation soon after Congress enacted legislation creating the modern generic drug industry and as FDA revised clinical research and regulatory policies in response to the AIDS epidemic. And while it was clear in 2004 that a Medicare drug benefit would greatly expand access to medicines for elderly Americans, it also set the stage for increased government scrutiny of prescription drug prices, as demonstrated by recent events.

Similarly, the biotechnology revolution has opened the door to major advances in treatment of critical medical conditions, laying the groundwork for a whole new industry in the US and abroad. But the growing realization that many Americans struggle to afford those costly new medicines, as compared to citizens in other wealthy countries, has eroded public confidence in pharma and supported calls for patent and pricing reform. Manufacturers now are accepting Medicare price negotiations to avoid being shut out of program coverage, but participation may erode if such policies dry up private investment in the discovery of vital new therapies for patients, as industry predicts.

Although drug shortages will continue to draw more fire on the political front due to antiquated and often unreliable production processes, a main problem is that many of the products now in limited supply are low-cost generic drugs made by companies with limited resources to fund modern manufacturing operations. Innovation in this area may finally gain ground, though, as a way to expand availability of new gene and biotech therapies that are costly to produce and distribute.

The COVID-19 national emergency exposed the fragility of our public health system and public confusion about programs and policies needed for a thriving biomedical research enterprise equipped to further tackle cancer, dementia, and a host of debilitating conditions. I can only hope that policy makers will look for ways to encourage, and not derail, such efforts, and that the nation will support policies and programs that improve the health and well-being of society—and avoids imposing personal beliefs on others that can limit access to life-saving and life-enhancing treatments.

Jill Wechsler is Washington reporter for 

When referring to this article, please cite it as Wechsler, J. Signing Off from Washington. 

FDA and industry face unprecedented political and policy challenges.

Signing Off from Washington 

Mike Hennessy Jr. is the Chairman and CEO of 

High Angle Shot of a Working Desk of an Successful Person in Office with Cityscape Window View. | Image credit: © Gorodenkoff - stock.adobe.com

Pharmaceuticals are entering a transition into a far more complex era of patient therapies, and patient segmentation. It will not be an easy process. It’s an evolution long in the making and welcomed for not only improved treatment outcomes, but also for increasingly realistic “cures”. In such a tightly regulated space, where large financial investments are also required, many unwilling stakeholders will be swept along with this rising tide of new medicines. Who would have seriously considered larger-scale three-dimensional printing of medicines five years ago, or marrying messenger RNA delivery methods with chimeric antigen receptor therapies for reconfigurable patient specific antigen profiles, within the same patient, over the span of a month?

To keep this surging tide heading into workable spaces without swamping all systems, international bodies, such as the International Council for Harmonisation and the World Health Organization, are going to have to be relied on to perform much of the heavy lifting. New financial cooperation models, some of which were trial ran during the COVID-19 pandemic, must also be implemented for consolidated gains to remain real.

With these advances rolling in at a more rapid pace than ever before, our coverage of the pharmaceutical space must also evolve. This year, we have increased our coverage of the daily news, to provide insight at a greater pace. The brand has also rededicated to video coverage, to provide insight from the experts on the frontlines of these advances. Along with these changes, we have amped up our conference coverage, to provide key advances and learnings from major meetings throughout the year, like our coverage from the 11th International mRNA Health Conference and CPHI Barcelona. All these latest insights can be read at 

As we eye up trends and opportunities for 2024, we are truly excited for the fruits of the future. There is so much awaiting us, and we can be guaranteed that the new medicines about to be manufactured, stored, delivered, and received will be more efficacious than ever and worth the efforts. And that is something worth holding on to, something to be proud of.

Mike Hennessy Jr. is the President and CEO of 

When referring to this article, please cite it as Hennessy, M. The Dislocation of Progress. 

Pharmaceuticals are entering a transition into a far more complex era of patient therapies, and patient segmentation.

The Dislocation of Progress

Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.

Q: My company is a contract manufacturer. Our final product inspection process consistently delays timely release of the manufactured products to our clients. Is there a best process/practice for performing final
product inspection?

A: This is not a new problem for the industry. To me, some of the issue is the fact that we call the specific activity of the overall physical product evaluation the “final product inspection.” In my opinion, the physical product evaluation should start at the beginning: the receipt of the individual components (stoppers, vials, labels, etc.) that are used in manufacturing. Each component should pass an incoming quality inspection with defined acceptable quality limits (AQL) and clear directions for rejection of the component should it exceed the AQL. The specific elements to be looked at on incoming inspection will vary depending on the component.

Let’s assume your company manufactures sterile injectable products and the major component you will use in manufacturing is a glass vial. The first step in the process is to perform an incoming inspection of the glass vials. The number of vials to inspect from the shipment will depend on the number of vials contained in the shipment. The sample size to be inspected should be recorded in the appropriate standard operating procedure (SOP). The specific defects to be inspected should also be included in the SOP. When evaluating these defects, most companies employ definitions of critical, major, and minor to the reject/accept criteria. In the case of vials, critical might be defined as likely to cause harm to the patient; major might be defined as leads to impairment to the patient; and minor would be defined as cosmetic defect causing no threat to the patient. Defining the acceptance criteria upfront may save you a lot of time at the end of the process.

Once the vial is accepted, it will be used in the manufacturing process. Defects that exist in the vial after initial acceptance may be detected during this step of the process. Many manufacturing lines have automatic sensors that detect vial imperfections and eliminate the vial from the batch before it is sent for labeling. It is important for the line operators to be trained to recognize when there is an increase in rejected vials because this could mean that the incoming inspection did not pick up the vial defect. Again, if the defect can be detected and categorized at this process stage, it will save time at the product release stage.

The last stage for potential vial inspection before labeling would be visual inspection of the stoppered vial. Some companies perform this step manually with trained visual inspectors while others utilize visual inspection equipment to perform the final inspection of the vial before labeling. Companies using vial inspectors typically focus those inspectors on looking for particulates in the vial, but they should also be trained to recognize vial defects. Regardless of which inspection format is used, there should be SOPs and AQLs governing the inspection process.

Final product inspection results should be included as part of your batch release documentation, so it is important to have repeatable, defined process/processes in place at all stages of the manufacturing process that is/are suitable for the product being inspected. The more time you spend upfront in the component inspection process, the more efficient your final inspection and batch release process will be to ensure timely product release to your clients.

Susan J. Schniepp is distinguished fellow at Nelson Laboratories, LLC.

When referring to this article, please cite it as Schniepp, S. Final Product Inspection: Making the Most of Your Processes. 

Final product inspection results should be included as part of the batch release documentation, says Susan J. Schniepp, distinguished fellow at Nelson Laboratories, LLC.

Final Product Inspection: Making the Most of Your Processes

Charles Ross & Son Company's 42N-18SS Ribbon Blender

ROSS’ Ribbon Blenders are designed to handle a wide range of dry materials, from seasonings and beverage mixes to pharmaceuticals, chemicals, plastics, and agricultural powders or granules. These blenders also incorporate minor liquid components to effectively coat individual solid particles. They are manufactured with long-term performance and quality in mind.

The pictured ROSS Model 42N-18SS is crafted from type 316 stainless steel with interior surfaces polished to a 150-grit finish. With a maximum working capacity of 18 ft³, the blender is direct-driven by a 10-horsepower gearmotor for processing materials with a bulk density of up to 60 lbs/ft³.

The agitator is a solid double ribbon design, designed for center discharge, with internal flanges welded to shaft stub ends and a heavy-duty anti-friction bearing on the non-driven end. The blender includes a two-piece safety grating with half-inch diameter perforations for safe operation while the split folding covers are open. A spray bar with fan-type spray nozzles is installed on the trough via sanitary tri-clamp connections for liquid additions. The blender is operated from a four-inch color touchscreen that includes a cycle timer, start/stop, forward/reverse, and speed controls. The finished product is discharged through a pneumatically operated four-inch dust-tight knife gate valve.

ROSS’ Ribbon Blenders are designed to handle a wide range of dry materials and effectively coat individual solid particles, keeping long-term performance and quality in mind.

Ribbon Blenders

Suncombe’s IsolatorCIP Automatic Cleaning System

Suncombe’s IsolatorCIP automatic cleaning systems provide aqueous, detergent, and/or solvent cleaning of glovebox isolators. IsolatorCIP uses a clean-in-place (CIP) system to reduce the possibility of cross-contamination after each use and remove any product or debris. This design allows for repeatable cleaning of isolators and gloveboxes without a breach of the isolator in the process. The cleaning sequence can be configured to include different water qualities, chemicals, detergents, and sterile hot, cold, and dry air streams. These can be provided at accurately controlled temperatures, flowrates, and pressures.

Using variable recipe-derived configurations, the IsolatorCIP can also be used to clean additional processing equipment enclosed inside the isolator or be fitted onto the in-feed or discharge sides. Incorporating replaceable modules, the base unit is a fully hygienic version, with optional modules for sterile use, including sanitizing and sterilizing configurations.

Suncombe’s IsolatorCIP systems can be integrated with isolators of any manufacturer. With pre-configured mechanical and control interfaces, they minimize the potential for cross contamination and downtime while also ensuring the protection of personnel. The machines are manufactured from type 316 certified stainless steel, and use an easily configured recipe structure, providing confirmation at the successful completion of cycle. Remote control facilities can be incorporated for interfacing with the isolator’s control systems.

Suncombe’s IsolatorCIP automatic cleaning systems provide aqueous, detergent, and/or solvent cleaning of glovebox isolators. 

Automatic Cleaning System

Feliza Mirasol is the science editor for 

Novo Nordisk announced on Nov. 23, 2023 that it will invest more than DKK 16 billion (US$2.3 billion), starting in 2023, to expand its existing production site in Chartres, France. The company plans to significantly increase the capacity of the manufacturing site by adding aseptic production and finished production processes, as well as an extension of the site’s current laboratory for quality control.

With the expanded facilities, the site’s footprint will be more than doubled. The investment includes capacity for glucagon-like peptide-1 products, according to a company press release. Construction projects for the expansion have been initiated and will gradually be finalized between 2026 and 2028. More than 500 new jobs are expected to be created, and production activities are expected to run 24/7 upon completion of construction.

“This significant investment announced today confirms the importance of our French manufacturing site, one of our strategic production sites, as a cornerstone of the growth we are experiencing as a company. By maximizing the skills and infrastructure we already have on the site, we are expanding our capacity in an efficient way,” said Lone Charlotte Larsen, corporate vice-president of Novo Nordisk Production Chartres, in the press release.

“Our continued investments in our manufacturing sites across the globe demonstrate the belief we have in our current and future product portfolio and its relevance for people living with serious chronic diseases,” said Henrik Wulff, executive vice-president, Product Supply, Quality & IT, Novo Nordisk, in the release.

Novo Nordisk will invest more than DKK 16 billion (US$2.3 billion) to expand its production facilities in Chartres, France.

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