Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Chris Spivey

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While his focus was on balancing personal freedom versus state power, 18th century political theorist John Locke’s following thought could arguably be applied to current pharmaceutical regulators’ attitudes when he famously declared, “the end of law is not to abolish or restrain, but to preserve and enlarge freedom” (1). While those currently reading sundry observations listed on an FDA Form 483 will feel significantly “retrained”, the intent of regulations is to allow a fair and equal access to a playing field that encourages participation by as many novel and creative solutions, as applied to disease states, as humanly possible.

Regulating Innovation, Quality, and Risk eBook January 2024

Anshul Mangal, president and general counsel of Project Farma, stated, “The FDA aims to streamline the approval process for platform technologies, leveraging the Omnibus Appropriations Act of 2023 to facilitate referencing prior manufacturing data during the review process. Encouraging more gene therapies to seek accelerated approval and improving harmonization with global regulators, especially for rare diseases will be of critical importance. Additionally, the FDA is launching the START pilot to support small companies developing gene therapies for rare pediatric diseases, drawing lessons from the COVID-era Project Warp Speed. If the pilot is successful, it could become a permanent program dedicated to supporting the mission. The agency’s continued support will be paramount in propelling the therapeutic pipeline forward and teeing up the sector for another year of groundbreaking achievements” (2).

As innovation accelerates, pharmaceutical regulators continue their path of maintaining proportion, balance, and restraint. Please enjoy the following articles which, in many ways, fully embody that ethos.

Locke, J. Second Treatise of Civil Government 1690.

Mangal, A. JP Morgan Healthcare Conference Summary. LinkedIn (accessed Jan. 18, 2023).

Pharmaceutical Technology/Pharmaceutical Technology Europe

Regulating Innovation, Quality, and Risk 

When referring to this article, please cite it as Spivey, C. Moderating Innovation to Equipoise Risk. 

, Regulating Innovation, Quality, and Risk eBook January 2024.

Articles

As innovation accelerates, pharmaceutical regulators continue their path of maintaining proportion, balance, and restraint. 

Moderating Innovation to Equipoise Risk

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - © Artur - stock.adobe.com

The Alliance for mRNA Medicines (AMM) will convene a meeting of global regulatory leaders in Washington, D.C from April 4–5, 2024. The core topic will be to assess the merits of a potential single shared regulatory streamlined platform pathway through FDA, the National Medical Products Administration (NMPA), the Ministry of Health, Labor, and Welfare

MHLW), the European Medicines Agency (EMA), the Pharmaceuticals and Medical Devices Agency (PMDA), the International Council for Harmonization (ICH), stakeholders, and others. Each jurisdiction will likely diverge—ultimately, but hopefully after having initially worked through a common “shared tree trunk” schematic for messenger RNA (mRNA) current good manufacturing practice (CGMP) compliance.

The meeting is intended to discuss what that tree trunk might look like and what it might further grow into. Realistically, a single tree trunk isn’t a good metaphor, and instead we should perhaps be thinking in terms of multiple trunks—as in a copse, thicket, spinney, or grove. Functionally, there isn’t just one type of structural modality. So be it self-amplifying RNA (saRNA) or circular RNA (circRNA), handling and manufacturing aspects vary significantly. As they also do in terms of quantities, potency profiles, or absorption, distribution, metabolism, and excretion (ADME) considerations, or when discussing a generalized vaccine versus personalized oncology vaccines, gene editing, chimeric antigen receptors (CAR-T), antibodies, or protein replacement therapies.

Still, Peter Marks, director of the Center for Biologics Evaluation and Research at FDA, has long been supportive of the concept of a shared regulatory mRNA platform pathway, telling 

, “With over a billion doses administered, the COVID-19 mRNA vaccines have demonstrated the value proposition of this safe and effective platform in viral respiratory diseases. We anticipate that additional studies may expand the reach of mRNA vaccine technology.”

Meanwhile, activities such as mRNA vaccine production currently fall into catch-all categories like “genetic immunogens, derived from principles defined for plasmid DNA vaccines and gene therapy vectors. For vaccine development, the World Health Organization’s (WHO) guidelines around the quality, safety, and efficacy of plasmid DNA vaccines [are] regarded as a basic overarching guideline applicable for the development of RNA-based vaccines” (1). The coming meeting is timely. EMA has called for input into an mRNA regulations guideline for influenza vaccines and beyond (2).

There is now a strong trend toward taking what has worked so well in infectious disease treatment—there is a wealth of data generated during the COVID-19 pandemic response, to refer to Marks’ comment—and marrying this in a hybrid, or often combination therapy, approaches. “Having agreed upon templates to work from as a new basic starting point,” says the AMM executive director, Clay Alspach, “will serve to accelerate exciting and potentially game changing treatments.”

Alspach also noted the recent approval of ARCT-154 (from Arcturus and CSL), a sa-mRNA COVID-19 vaccine for initial vaccination and booster for adults 18 years and older, through Japan's MHLW. Alspach states, “second generation approaches, such as self-amplifying and various novel emerging methods, need to be better coordinated and their manufacturing processes optimized. Regulatory compliance is a huge part of that picture.”

Andy Geall, inaugural AMM board chair and CEO of Replicate Biosciences (working on self-replicating RNA) calls for more frequent international dialogue on both the science and also the regulations involved, due to the extreme speed with which technologies were advancing and converging. He emphasized, “there needs to be a coordinated effort to educate the public about what’s coming, because this is arriving at a speed that no one is used to. This isn’t traditional pharmaceutical development. This is coming at light speed, and with such an array of different approaches and technologies. We need to get out in front in terms of education for the public, our governments, the regulators to help de-mystify all of this for them.” Over and above combating vaccine disinformation, Geall returned to the scope and scale of impending innovation, saying, “We have people working in rare diseases. We’ve got gene editing happening,gene therapy, not forgetting vaccines in infectious diseases, oncology, and even early work in neurology. It’s not scary; it’s just an unknown to the nonscientists.And we need to communicate clearly why all of this is so positive and positively transformative” (3).

The Regulatory Environment for the Development of mRNA Vaccines during COVID-19

EMA. Concept Paper on the Revision of the Non-clinical and Clinical Module of the Influenza Vaccines Guideline. 

Geall, A.; Alspach, C.; Kuhn A. Introduction to the Alliance of mRNA Medicine, 11th International mRNA Health Conference, Berlin, Nov. 1, 2023.

Regulators from around the world will gather to help shape the mRNA and RNA therapeutics landscape at an exceptional April 2024 Washington, D.C. convocation.

A Platform for mRNA Platforms

Education bridge, acquiring academic knowledge | Image credit: © Pixelbliss - stock.adobe.com

Close to a Giffen good, depending on the therapeutic area, pharmaceutical products defy fundamental economic laws. Bad years are not so bad as they still exhibit an upward-sloping demand curve, while good years can be a bonanza. An overlooked obvious truth about the pharmaceutical industry is that it is a chimera of strong competing opposites—a 1980’s Kombi van powered by jet engine thrusters, piloted by overly exuberant alternating with pessimistic MBA graduates. Through this lens, the stop/start progress and the multitudinous lurches toward both extreme success and extreme failure can be more clearly comprehended. On a deeper level still, pharmaceuticals are also a lifesaving endeavor inextricable to civilization’s forward march on one hand, while helping to extend and enrich each individual’s personal life on the other. In its inherently selfish human nature, the sector is thus well insulated from those deepest of natural financial troughs.

With this in mind, in gathering perspective on 2024’s industry performance, 

® asked industry workers for comments on challenges and opportunities. Responses were cross referenced with those from 

’s annual employment survey (1) as a validation and quality control check.

The time and expense required to train and retain operators—and then to re-train them again when increasing molecular diversity for a new therapeutic requires the process to begin anew—is a commonly heard challenge. Christa Myers, senior fellow, Aseptic & Sterile Products, CRB, related that, “there is a lot to learn and be able to speak to within this highly technical side of the industry. Character and personality matter. An operator needs to be able to follow protocols for manufacturing of a quality product. Each also needs to be able to think in a quality improvement mindset in order to plan for corrective actions and preventative actions (CAPAs). Your operators are your most valuable asset and should be trained and treated as such” (2).

Many agree with training staff as a number one priority, as does Harry Benson, director of Human Performance Services at Commissioning Agents (CAI), who says, “finding, hiring, and retaining the workforce for many operational departments is a significant challenge—possibly the biggest barrier to growth opportunities and closing the drug shortage gaps. For this reason, the industry is giving much more attention to the availability of a skilled or trainable workforce in their site selection and expansion process.”

, this workforce challenge is commonly perceived as the biggest obstacle for industry progress, and is even mentioned, with variations, in the “others” category of 

, with frequent comments such as “ I’d like to add that the onboarding and general information flow is horrible, and newcomers are completely left alone” or, “[there is a] lack of experience in the industry and common sense.”

. Bio/pharmaceutical workplace challenges. | Image credit: © 

Connie Leech, global director of Quality, Compliance, and Regulatory at CAI, puts an apostrophe on this, stating, “the post-pandemic workplace is uncertain, constantly changing, and ideal for workers with a breadth of knowledge and skills who thrive in ambiguity.”

Regulators asked to keep pace with innovation, shortages, and transparency

Ashleigh Dawley, director, Regulatory Affairs & Compliance, Integrated DNA Technologies, points out that, “The recent FDA approval of the first CRISPR [clustered regularly interspaced short palindromic repeats]-based gene therapy—which was just a vision a little over a decade ago—signals continued interest in the power of the CRISPR-Cas9 technology, as reflected in the more than 40 registered clinical trials globally to date. This rapidly evolving technology has the power to unlock innovation and future patient impact that we cannot even imagine today.” She continues, “An ongoing challenge remains in the ability of regulatory agencies to scale and grow with the pace of innovation. Of the current 40 active clinical trials globally, 23 of those are occurring in the [United States]. If successful, [FDA] could face challenges with regards to creating the infrastructure with the needed staffing resources and expertise to support regulatory reviews and approvals and enable the delivery of promising therapies to patients in need.”

Agne Vaitkeviciene, CEO of Memel Biotech and VP at LithuaniaBIO agrees. “As of today, [the] main obstacle in the pathway of new ATMPs [advanced therapy medicinal products] development is regulatory environment. Especially in [the] European Union. Changes in regulations comes slower than expected and leave Europe behind [the] US, Japan, and UK [United Kingdom]. Still, there are hundreds (543) of companies in Europe developing ATMPs and over [a] thousand (1235) in North America for a reason. Reaching patients, who could benefit for cell and gene therapeutics becomes significant, and improvements in regulatory landscape have to adjust faster to allow the access to the therapies. Together with regulatory approaches, reimbursement is one other obstacle that joint community efforts worldwide are trying to solve. Applying optimization in manufacturing processes and [a] fast marketing approval system might contribute to lowering ATMPs costs.”

Communication, a key asset during pandemic vaccine development and deployment, is being called back into question. Thomas Hartman, president & CEO of the International Society for Pharmaceutical Engineering says, “Both the FDA and drug manufacturers will need to focus on earlier communication and collaboration to mitigate shortages and avoid facility shutdowns. This is especially true of generic manufacturers–many of which are either shifting from generic medicines because of a lack of profitability or closing down entirely. Alongside the FDA’s mobile app and web portal dedicated to reporting drug shortages, the introduction of new technologies in digital validation and data management will improve visibility within manufacturing and allow for early communication to the FDA regarding potential disruptions.”

Hanns-Christian Mahler, CEO of ten23 health, says he thinks of this line from Star Trek when approaching a challenge: “things are only impossible until they are not (Cpt Picard, Enterprise).” This certainly was borne out by recent Vertex and CRISPR Therapeutics approvals in the UK and US for Casgevy, alongside bluebird bio’s Lyfgenia, the first approved gene edited therapeutics, and Arcturus’ARCT-154 approval in Japan, the first self-amplifying messenger RNA (sa-mRNA) COVID-19 vaccine.

There is so much historical process habit in the bio/pharmaceutical industry that it can often be paralyzing to growth, most especially when confronting new modalities. Renee A. Hart, president and chief business officer, LumaCyte, thoughtfuly observes. “I have used the analogy before that the leaning Tower of Pisa is a great example of where process and technology sits in many verticals. Companies think that layering on new processes, people, and tools into already complex infrastructures will somehow check the box of driving innovation. Those organizations that choose not to invest in change management and continue to stack new processes on top of old will find themselves leaning so far away from growth that in time they will find their organizations are actually moving backwards. Process inefficiencies create unnecessary obstacles and bottlenecks to advancing the development and delivery of lifesaving treatments and cures, we can definitely do better.”

These therapeutics “herald new ways of thinking, new types of testing and validation, and new types of manufacture and end-point monitoring. Following on from the revolutionary COVID-19 vaccines, what comes next is more complicated, more difficult to price for reimbursement, and more effective in terms of cure rates. The toothpaste is out of the tube, and the industry must learn to adapt to take best advantage of what is becoming available, no matter how messy the process” (3). As can be seen in 

, cell and gene therapies are widely considered the biggest opportunity going forward.

. Opportunities in the bio/pharmaceutical industry. | Image credit: © 

When considering the evolving toolkit now available to pharmaceuticals, Michelle Fraser, head of Cell & Gene Therapy, Revvity, says, “notably, there are also technologies poised to edit mRNA rather than the genome, inducing transient changes, and addressing genetic alterations influenced by environmental factors through epigenetic modifications ... The trajectory points towards increased sophistication, efficacy, and safety in these therapeutic interventions … expect to see a surge in the adoption of more intricate gene editing approaches, signaling a year marked by significant advancements in the refinement and application of these transformative technologies.”

Personalization requires yet more systems convergence

While progress on advanced therapeutic medicinal products is now undeniable, a new type of effort begins in earnest. That consists of bringing still more technologies into alignment for these treatments to be deployed and accessed. Casgevy requires access to facilities specializing in bone marrow transplantation, for example, which necessitates knowledge transfer from hospital and medical staff being feedback to pharmaceutical scientists.Thermo Fisher Scientific and the University of California San Francisco (UCSF) established one of the early direct connections to hospital treatment, with a current good manufacturing practice facility adjacent to the UCSF medical center. About this movement toward distributed manufacturing (some term it near patient, or spoke and hub), Michel Lagarde, executive vice president and chief operating officer of Thermo Fisher, observed, “cell therapies represent a rapidly emerging field of biotechnology with tremendous promise for future therapeutic applications … with a record number of cell therapy approvals granted in the last two years, and CAR-T therapies becoming earlier treatment options, we’re in a golden age of biology, where new technologies and partnerships are evolving and transforming clinical care” (4).

This makes turning the page to the year 2024 a metaphorical, as well as literal, leap year. Pharmaceutical manufacturing is now (pun intended) an embedded part of the hospital-patient system.

2023 Pharmaceutical Technology/Pharmaceutical Technology Europe Employment Survey

Spivey, C. Hi-Fidelity Fill/Finish for Biologics. 

Spivey, C, New Medicines, Markets, and Manufacture: CRISPR for Sickle Cell Disease and β-thalassemia, 

Kurtzmen, L. Thermo Fisher Scientific Opens Cell Therapy Facility at UCSF to Accelerate Development of Breakthrough Therapies. UCSF press release,
March 27, 2023.

Chris Spivey is the editorial director of 

When referring to this article, please cite it as Spivey, C. Leap Year. 

Revolutionary therapies restructure pharmaceutical manufacturing.

Leap Year

We have to stick to the facts. a group of scientists working together in a lab.| Image credit: © Courtney H/peopleimages.com - stock.adobe.com

® survey audience members to see what has remained the same and what has shifted, regarding pharmaceutical workforce attitudes toward their jobs, their current employers, and the general direction the industry is heading. The industry’s response to COVID-19 has had the most significant measurable impact on the way both business and manufacturing processes were managed in the past two or three surveys. In 2023, the largest observable shift was brought about by the steady emergence of advanced therapeutic medicinal products (ATMPs). The last half of 2023 was a watershed moment for pharmaceuticals, given the industry saw the first set of approvals for gene edited therapies, as well as for a self-amplifying messenger RNA vaccine. But everyone experienced the year through the lens of the products and activities their own company sells. In this way, one can say of pharmaceutical manufacture, “All happy families are alike; each unhappy family is unhappy in its own way” (1). Let’s examine survey responses to see what these differences might be founded upon (2). There is a gulf between survey responses such as “struggling industry full of scientific brains lacking leadership, mentoring, and training” or “Party’s over–hunker down, folks,” to “Aside from a few ‘deplorables’, the industry is in good condition’’, “volatile, encouraging, innovative, nerve-wracking”, or “Incredible advances and treatment options.”

As the sugar rush of COVID-19 response funding wore off, so too did the number of hours workers put in on average. Hours worked returned to pre-pandemic levels, based on earlier survey results (see 

). This finding was somewhat surprising given conversations held during conferences, but there was perhaps some confirmation bias during conferences, versus survey results. It’s easier in a survey to say ‘I’m not working as hard’ compared with a network contact you are used to doing business with. The final question of the survey asks, “If you could describe the 2023 bio/pharma industry in five words or fewer, what would you say?” And this is where the quote from Tolstoy can most readily be explored.

Figure 1: COVID-19 measures. | Image credit: © 

Figure 2: Are working hours rising or falling? | Image credit: © 

Opinions about the post-pandemic industry were largely positively oriented, from “post-COVID readjustment” and “the 2023 bio/pharma industry has benefitted greatly from covid restrictions.” Responses ranged from “consolidation after covid pandemic rush” to “Great come back after covid.” But some were bleak in their appraisal, with “Pandemic stress, Supply chain collapse” and “Post-pandemic blues” being somewhat frequent responses.

Naturally, one can suppose the technologies and services most involved in the pandemic response, such as vaccine manufacture and distribution, were/are the respondents going through the deepest readjustment phase. One of the features of the pandemic was that it forced everyone to communicate more quickly, clearly, and completely. This seems to have remained.

Karolina Makovskyte, head of Business Development at Caszyme, said, “One positive aspect of CRISPR-Cas technology is the emergence of a more active dialogue about gene editing regulations, particularly in Europe. It is also somewhat linked to another positive aspect, which is increased exploration of the technology by new industries, seeking ways to integrate CRISPR-Cas into their activities.”

Satisfaction with pay in 2023 didn’t move to any great degree versus historical years (see 

). Perhaps the timing of the survey influenced a type of survival-driven satisfaction, as the last half of the year saw several companies markedly reduce workforce numbers as part of restructuring efforts. Pfizer axed approximately 900 staff, as their Covid vaccine reported $1.31 billion in sales, a 70% decline from the year before. “Wall Street had expected $1.53 in revenue. Paxlovid suffered an even sharper drop, with revenue of just $202 million—97% down from last year” (3). Not a big reduction but still significant for a company that sold $100 Billion in product for the first time in 2022. Grifols, a Spanish company specializing in blood plasma therapies, trimmed its operations in the United States by cutting approximately 2300 positions (which amounts to approximately 8.5% of its global workforce). Takeda braced for competitive threats with cuts of nearly 1400 staff, to prepare for generic competition to its diabetes drug Actos. Thermo Fisher Scientific adjusted to changing demands through a series of workforce cuts totally nearly 1300 staff, mainly due to decreased demand for COVID-19 testing products and “evolving economic conditions.” Genentech, Biogen, Catalent, and Amgen also witnessed significant workforce diminutions, while Novavax, Emergent BioSolutions, and Bristol Myers Squibb, round out the list (4).

Figure 3: Salary satisfaction. | Image credit: © 

, job security hit its highest levels during the height of the COVID-19 pandemic. While the survey questions don’t allow enough depth to explored in detail, going back to the Tolstoy metaphor, the workers feeling most secure are likely the staff working on the most promising new advanced therapeutic medicinal products (ATMPs), as this is clearly where the excitement and major new investments are being ploughed into. For example, RoslinCT will manufacture Vertex Pharmaceuticals’ CRISPR-based gene therapy, Casgevy, recently approved for treating sickle cell disease and β thalassemia (5). Novo Nordisk is also planning a US$2.3 billion investment in new French facilities, partly to facilitate extra capacity for glucagon-like peptide-1 products (6). One of the survey respondents summed up the entire industry with the words “Sustained growth with new therapies” while another simply stated “Vaccines, proteins, blood, tissues.”

Figure 4: How secure do you feel in your job? | Image credit: © 

Similarly, optimism about future performance was also peaked during the pandemic.Somewhat alluding to the Tolstoy metaphor and also the COVID-19 sugar rush, Barbara Ryan, founder, Barbara Ryan Advisors commented, “It is interesting, however, because the market remains highly bifurcated—companies with good data are able to finance, and often the aftermarket performance is quite positive, as the deals are viewed as a clearing-event lifting the financing overhang. As of press time, there had only been 11 biotech IPOs this year, in contrast to more than 100 each in 2020 and 2021. Sadly, however, too many companies went public in 2020 and 2021 that were at a far-too-early stage in their development (i.e., preclinical, Phase I trials) to be public companies; they were not sufficiently funded to proof-of-concept data. This is where the real pain is” (7). Ryan went on to round out her assessment of the industry, ending on a highly positive note. “The innovation renaissance is alive and well, with record numbers of FDA new drug approvals in each of the past several years. M&A continues to be another bright spot. Beginning in 2025, large pharma will be losing exclusivity for products currently representing over $350 billion in revenue, leaving a huge growth gap that needs to be filled through M&As, licensing, and partnering. Dealmaking has always been a key pillar of the industry’s growth strategies. More good news: according to EY’s Annual Fire Power Report, large pharma has a record $1.4 trillion to fund deals. There have been a total of 30 public biotech acquisitions this year, and 15 of these were above $1 billion each, which surpasses the number in any year for the past 10. As we wind down 2023, the hope will be for rate relief in the year ahead—and substantially improved biotech performance.”And as if on que, the Federal Reserve just suggested three cuts to interest rates in 2024, sending the DOW into record territory by rising 1.4%, to close at 37,090.24 (8).

Pharmaceutical Technology/Pharmaceutical Technology Europe Employment Survey

Q.ai Contributor Group, Pfizer Layoffs Confirmed as Vaccine Manufacturer Drives For Cost Savings. 

Buntz, B. 10 Major Pharma and Biotech Companies that Downsized in 2023. 

Mirasol, F. RoslinCT to Manufacture CRISPR-Based Gene Therapy Casgevy, 

Mirasol, F, Novo Nordisk to Make Multi-Billion Dollar Investment in Expansion of Production Facilities in France, 

Ryan, B. Will Calendar Change Bring an End to Run of Volatility in Biotech? 

Mena, B.; Wallace, A. Buchwald, E. Dow Surges to New Record as Fed Signals Three Rate Cuts in 2024. 

When referring to this article, please cite it as Spivey, C. New Therapies Cry Out for New Skills. 

There are positive indications for future growth.

New Therapies Cry Out for New Skills

The COVID-19 pandemic exposed vulnerabilities in the healthcare system’s ability to provide sustained services, medicines, and assorted basic supplies, such as personal protective equipment. It also exacerbated elements in the system already undergoing decline, like the

academic health centers (AHCs) central mission to connect and integrate patient care, research, education, alongside overall public health. A 

 article published in 2021 points a finger toward the accelerated siloed activities of most specialties and draws attention to micro economics conditions embedded within hospital systems (1), and jibes with a more recent paper from 

 (2), which echoes the precept that even education and training exigencies are exaggerating this siloed skills predicament.

 article outlines that because of COVID-19 there was a “massive reduction in elective medical care [which] reduced patient volumes and consequently revenue to the AHC. At no other point in modern medical history has there been such a synchronous, worldwide disruption of elective medical care. In AHCs, especially in the United States, the transfer of funds to research, education, and community health generally emanate from revenue from positive margins associated with income generated from patient care” (1). Without the dollars necessary to execute new types of investigations, new insights into basic medical science necessarily declines, and a large element of the open end of the funnel for pharmaceutical research becomes increasingly constricted, or in the language of a physician-clinician, think of an occluded artery, and what kind of silent damage that does.

Stephen O’Rahilly, from the Institute of Metabolic Science, University of Cambridge, makes clear that this is not new news. “Concerns about the future of the clinician–scientist have been expressed for many decades. In 1984, Gordon Gill wrote of ‘the end of the physician scientist’ as he observed academically oriented US doctors move into basic science labs to learn the new techniques of molecular biology. In the following decades, fewer medical doctors remained active in biomedical science. In the 1980s, physicians represented 4.5% of the US biomedical research workforce: that has dropped to 1.5% today”(2).

As a counterbalance, the conditions for federally funded physician-scientists at national institute of health (NIH) programs have rode this wave out in considerably better shape. While “several international and national biomedical funding agencies such as Horizon 2020 (EU), Wellcome (UK), Cancer Research UK, Australian Research Council, German Research Foundation (DFG), and others have offered costed extensions, no-cost extensions, scope changes, paperwork reductions, and other flexibilities to their grantees that may enable continued research funding during the height of the pandemic” (1). However, that trend is not sufficient nor something to be leaned on, as “already, the transition to independence, and maintenance of an independent research program, are major leak points in the career pipeline of physician-scientists during which many leave academic medicine, and the pandemic may further hobble promising careers. Broad hiring freezes have swept across universities and AHCs throughout the world, further decreasing potential opportunities and resources to bring the next generation of physician-scientists into the field” (1).

The reason to ring the alarms bells more vigorously now is that physician-scientists “account for nearly ∼40% of winners of Nobel Prizes in Physiology or Medicine and some 70% of chief scientific officers of major pharmaceutical companies and NIH institute leadership, their retreat from research is expected to have a profound impact on medical sciences” (1). For the overall health of the medical and pharmaceutical innovation pipeline, the time to look the other way has long since passed.

Rao, R.; Dlouhy, B.; Capell, B.; Akeju, O. The Endangered Physician-Scientist and COVID-19. 

O’Rahilly, S. Academic Clinician–Scientists Risk Becoming an Endangered Species. 

Clinician-Scientists are vital innovation spark plugs, accounting for 40% of Nobel awards in Physiology or Medicine, and two thirds of Big Pharma CSOs.  

The Decline and Fall of the Clinician–Scientist

There has been speculation around what manufacturing platforms, if any, can consolidate sufficient market share to dominate either specific operations (e.g., fill/finish) or more broadly, a full spectrum production suite of integrated operations. For the foreseeable future at least, it will likely be a mosaic of product solutions, but some manufacturers are clear in their own goals and strategies. In December 2023, it was announced that “The international technology group Körber signed an agreement on a close partnership and the acquisition of a minority share of the Franz Ziel GmbH” (1). The partnership requires regulatory oversight approval to be finalized.

The Körber team has been providing some thought leadership on the topic of how best to position itself within the broader market, for some time. Their website has a central message stating “at a time when new technologies and business models are rapidly entering the market, complexity increases. Interconnected solutions will allow us to realize our full potential in creating customer value. By supplementing our portfolio through strategic partnerships, we become more adaptable to customer needs. This is why, at Köerber, we invest in ecosystems” Their chief of sales Officer, Rami Jokela, more specifically calls out that,

the more diverse the challenge, the greater the value of the ecosystem. That is when a multi-company approach is the most beneficial” (2).

Olaf Ziel, CEO and owner of Franz Ziel, clearly share the overarching strategy perspective, as their company earlier this year also partnered with

Watson-Marlow to launch a new integrated solution to fast-track cell, gene, and biological therapies

Of the agreement with Körber, Ziel stated in a press release (1), “The joint further development to a turnkey provider, access to the global sales and service network, the potential in the areas of digitization, Pharma 4.0, software and AI solutions, and last but not least, access to expanded production capacities were convincing arguments for entering into this partnership.”

At the moment in Germany at least, biopharmaceutical manufacturing is trending toward greater partnering and ecosystem interoperability.

Franz Ziel. Körber Strengthens Partnership With Franz Ziel Gmbh and Acquires Minority Share. Press Release https://www.ziel-gmbh.com/en/home/ (accessed Dec. 22, 2023).

Körber. Koerber.com. (accessed Dec. 22, 2023).

Is increasing molecular diversity pushing manufacturing ecosystem consolidation toward turnkey solutions?