Leap Year

Spivey,Chris;

Leap Year

January 1, 2024

By Chris Spivey

Publication

Article

BioPharm InternationalBioPharm International, January 2024

Volume 37

Issue 1

Pages: 7-10

Revolutionary therapies restructure pharmaceutical manufacturing.

Image Credit: Maria Xelo/MJH Life Sciences using AI

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 1980s 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, BioPharm International® asked industry workers for comments on challenges and opportunities. Responses were cross referenced with those from Pharmaceutical Technology®’s annual employment survey (1) as a validation and quality control check.

Insufficiently trained staff an obstacle

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.”

As seen in Figure 1, this workforce challenge is commonly perceived as the biggest obstacle for industry progress, and is even mentioned, with variations, in the “others” category of Figure 1, 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.”

Figure 1. Bio/pharmaceutical workplace challenges. | Image credit: © BioPharm International

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.”

Investing in change management

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 Figure 2, cell and gene therapies are widely considered the biggest opportunity going forward.

Figure 2. Opportunities in the bio/pharmaceutical industry. | Image credit: © Pharmaceutical Technology

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.

References

Pharmaceutical Technology. 2023 Pharmaceutical Technology/Pharmaceutical Technology Europe Employment Survey. 2023.
Spivey, C. Hi-Fidelity Fill/Finish for Biologics. BioPharm Intern. 2023 36 (10).
Spivey, C, New Medicines, Markets, and Manufacture: CRISPR for Sickle Cell Disease and β-thalassemia, BioPharmInternational.com. Nov. 30, 2023.
Kurtzmen, L. Thermo Fisher Scientific Opens Cell Therapy Facility at UCSF to Accelerate Development of Breakthrough Therapies. UCSF press release, March 27, 2023.