Major Big Pharma Moves, Pressures of Capital Markets at Intersection with Autologous Versus Allogeneic

Behind the Headlines Episode 25

Questions about Real-World Evidence and Supply Chain Security

Ask the Expert

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

Drug Digest September 2025

The 100% tariff on imported drugs will pressure pharma companies to build manufacturing sites in the US or face significant costs.

How 100% Pharmaceutical Tariffs Will Impact Domestic Manufacturing and Supply Chains

Responses to the FDA draft guidance "Considerations for Complying with 21 CFR 211.110"

Stakeholders React to FDA's Push for Quality, Integrity, and Uniformity

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

Coronavirus 2019-nCov novel coronavirus concept resposible for asian flu outbreak and coronaviruses influenza as dangerous flu strain cases as a pandemic. The virus is made up of purple pills. | Image Credit: © lunarts_studio - stock.adobe.com

 a South San Francisco, Calif.-based clinical-stage biotechnology company that specializes in the development of oral solid-dose recombinant vaccines, received notification that 

 a nonprofit manager of R&D collaborations, would be placing a stop work order on a Phase IIb trial of Vaxart’s oral pill vaccine candidate against COVID-19 (1–3).

 signed by Vaxart CEO Steven Lo, the company reported the stop work order to the United States Securities and Exchange Commission (SEC), affirming that it had so far enrolled approximately half of the targeted number of 10,000 participants for the comparative study, for which a contract was reached with the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services (HHS) in June 2024 (3).

“[Vaxart] has, to date, not been provided with any further details, including the reason for such stop work order,” the SEC submission said (3). “As of July 14, 2025, the date of its last meeting, the independent Data Safety Monitoring Board for the trial tasked with assessing the safety of the trial had determined that the study could continue to proceed without modification.”

Yet the stop work order was delivered on the same day that 

 it would be winding down its activities related to 

messenger RNA (mRNA)-based vaccine development

 under BARDA, including the canceling or de-scoping of more than 20 projects worth nearly a combined $500 million (4).

Vaxart was not named among the companies with whom HHS is terminating contracts, or rejecting or canceling proposals, but an HHS spokesperson 

 for the reasoning behind the order by sending 

a link to the Aug. 5 press release from HHS

 (4,5). According to the Fierce Biotech article, Vaxart is not developing an mRNA vaccine, though does use one as the control in a Phase IIb trial (5).

While the SEC filing did say that Vaxart was being allowed to “continue efforts associated with the per protocol follow-up” for those in the study who are already dosed, the stop work order is the latest change of direction in what has become a boomerang of a drug candidate for the company. A previous stop work order in February 2025 led Vaxart to lay off 10% of its workforce, only for that order to be lifted in late April (6,7).

Fierce Biotech reported that the total estimated ceiling for the funding from BARDA for the Phase IIb trial was approximately $460.7 million (5).

® Group has reached out to Vaxart for comment on this latest development but did not receive a response at time of publication. This article will be updated with further information pending receipt of a response.

, accessed Aug. 12, 2025.
2. Advanced Technology International. 

, Aug. 5, 2025 (accessed Aug. 12, 2025).
4. HHS. 

HHS Winds Down mRNA Vaccine Development Under BARDA.

 Press Release. Aug. 5, 2025.
5. Taylor, N. P. 

Vaxart Seeks Answers as BARDA Funding for Stop-Start Vaccine Project Dries Up Again.

Vaxart Provides Business Update and Reports Full Year 2024 Financial Results.

, April 24, 2025 (accessed Aug. 12, 2025).

Articles

Vaxart, a biotechnology company, received a stop work order for its Phase IIb trial of an oral COVID-19 vaccine candidate, coinciding with the HHS's decision to wind down mRNA vaccine projects. Despite enrolling half of the targeted 10,000 participants, the reason for the order remains undisclosed. Vaxart was not listed among companies with terminated contracts, and the order allows continued follow-up for already dosed participants. This development follows a previous stop work order in February 2025, which was later lifted, affecting Vaxart's workforce and funding.

The company is not developing an mRNA vaccine, but had been using one as the control in a 10,000-subject Phase IIb trial.

BARDA Pulls Plug on Vaxart Oral COVID Vaccine Trial After mRNA Rollback

Dave Miller, PhD, discusses how tailored solutions, trust, and lifecycle planning are redefining partnerships in bio/pharmaceutical development.

Collaborative Innovation in CDMOs: Dave Miller, PhD, on Early Engagement, IP Strategy, and Advanced Formulation



In part 1 of our 5-part interview series on the current CDMO landscape, Dave Miller, PhD, chief scientific officer at AustinPx, emphasizes that the role of contract development and manufacturing organizations (CDMOs) is evolving beyond traditional, transactional service models toward deeper, collaborative partnerships. Miller describes this shift as “true co-development,” where innovation and scientific engagement form the foundation of client relationships. Central to the company’s approach is the application of novel technologies, such as its KinetiSol platform, to solve complex formulation challenges through tailored, science-driven solutions.

Miller notes that differentiation in today’s CDMO landscape hinges on high-touch, high-science engagement, intellectual property (IP) protection, and regulatory expertise. Drawing from AustinPx’s history as a former sponsor company, the team leverages extensive experience with the FDA and international regulatory bodies to guide clients in both domestic and global markets. IP retention, including overlooked compositional IP for drug products, is a priority.

The company increasingly engages with partners earlier in the molecule’s lifecycle—often shortly after candidate nomination—to ensure formulation strategies align with clinical and regulatory objectives. This early involvement supports smoother transitions from preclinical to clinical phases and fosters product designs with a clear line of sight toward commercialization.

According to Miller, the future of the CDMO sector lies in “collaborative innovation” that spans the entire spectrum of development, from early-stage design to market readiness. By operating as an extension of the sponsor’s own development team, AustinPx aims to provide customized, end-to-end solutions that address both immediate formulation needs and the long-term protection and differentiation of the therapeutic asset.

Be on the lookout for parts 2-5 to drop in the coming days!

Dr. Miller brings over two decades of pharmaceutical development experience and has spent his career investigating ways to improve the bioavailability of poorly soluble molecules. As CSO of AustinPx, Dr. Miller leads the pharmaceutics and analytical development teams and oversees the application of the KinetiSol Technology. Prior to his current position, Dr. Miller served as Vice President of Research and Development at DisperSol Technologies and Senior Principal Scientist at Hoffmann-La Roche. Dr. Miller specializes in formulation and processing technologies for improving oral bioavailability of insoluble small molecules. He has applied his expertise toward advancing numerous drug candidates through all stages of development from early discovery to line extension. Dr. Miller is a co-inventor of the pharmaceutical applications of the KinetiSol technology and continues to be a key innovative driver for application and expansion of the platform. He has published over 40 research articles in peer-reviewed journals, authored 8 book chapters, and is co-editor of the First, Second, and Third Editions of the textbook, Formulating Poorly Water-Soluble Drugs. He is a co-inventor on numerous granted and pending patents worldwide. Dr. Miller holds a BS in Chemical Engineering and a PhD in Pharmaceutics from the University of Texas at Austin.

I think from our experience and what we are dealing with, it's much more about partnerships these days than sort of transactional services. True co-development. And at the heart of that is sort of the novel platforms. You know, we have our KinetiSol platform that really is a driving force behind, you know, how we're partnering and developing products with our clients, but also high science, high touch.

You know, we're dealing with very complex formulation problems, and we offer novel solutions and novel insights. So I think it really comes down to just offering differentiating technologies, really focusing on partnering at the scientific level as opposed to just providing commodity services aimed at, you know, providing deliverables on time.

Also, with respect to ex-US partnerships, our clients also still value what they consider IP retention and trustworthiness, not just with respect to intellectual property, but also in regulatory settings as well. We have a long history as a company; in our prior incarnation, we were a sponsor company ourselves, developing our own pipeline of products and clinical development. So we have a long history of dealing with the FDA and other regulatory agencies outside of the United States. So that's certainly helpful for sponsors that are considering their options both domestic and abroad, as to who to select.

And going forward, it's all about differentiation and trustworthiness. And I think that's where we're really succeeding and as offering tailored solutions as well. Not just taking a molecule and putting it into some rigid framework, decision tree-type project progression, but rather, treating each molecule and each problem as unique and developing customized solutions.

So I think that's how we're at AustinPx differentiating ourselves from, from partners abroad, as well as domestically. I think we've seen sort of a paradigm shift towards much earlier engagement in the development and path of a molecule, interacting with us on the front end, shortly after even candidate nomination, toxicology studies, designing formulations, not just for clinic, but also to successfully transfer a molecule from preclinical into clinical development. So really early engagement. Establishing a CDMO partner who's going to be there as a co-developer, you know, the whole way through the process. So having capabilities that span the full spectrum of product development has been key for us. Um, 'cause we feel like the future in the CDMO space is collaborative innovation, and starting from the beginning in planning the development with the partner with all phases in mind and with the full lifecycle of the product in mind. So again, thinking about formulation insights, you know, that are tailored towards the exact phase of development that the molecule’s in now, but also with line of sight to the next step, aligning that with clinical strategy and regulatory positioning.

Also, again, talking about IP, I think compositional IP for drug products has been overlooked. I think a lot of companies focus primarily on the IP around the molecule as being what ultimately protects the asset. But we've kind of developed our approach, again, stemming from our own history as a sponsor company where the drug product, the composition of matter around the drug product, that IP is what really was protecting the asset.

So, we build that into our programs as well, where we're designing delivery systems specific for that molecule, solving simultaneous problems by tailoring the composition. And then in doing so, those problems… and providing the most robust, and high-performing dosage form, we sort of naturally generate novel composition matter IP and we're looking at that from day one.

In collaboration partners, even though it's years out, we're thinking about the full lifecycle of the molecule and protection of the asset on commercialization. So, that's where I think CDMOs… again, going back to just not just offering transactional services and checking the basic boxes of providing deliverables on a given timeline. It's more of an extension of the sponsor's development team and true collaborative innovation co-development. I think that's the expectation now. That's what we're doing.

Videos

Feliza Mirasol is the science editor for 

Tokyo-based Nxera Pharma (Nxera) announced on Aug. 6, 2025 the launch of an expanded drug discovery pipeline targeting obesity and related metabolic diseases. The company’s efforts build on independent research in addition to existing collaborations with Pfizer and Eli Lilly and Company, focusing on a range of validated G protein-coupled receptor (GPCR) targets (1–3).

Nxera’s lead asset is a wholly owned oral small molecule glucagon-like peptide-1 (GLP-1) agonist program, which it developed with differentiated chemistry and managed separately from Pfizer’s PF-06954522. Nxera said in a company press release that the separation allows it to maintain full control over development timelines and strategy.

“Nxera scientists were among the pioneers in elucidating the structure of the GLP-1 receptor and other key receptors being targeted, giving us a clear advantage in developing potentially best-in-class next generation drug candidates. For the past 12 months, Nxera scientists have been advancing a broad metabolic disease pipeline to capitalize independently on our differentiated science,” said Chris Cargill, president and CEO, Nxera, in the release (1).

Multiple GPCR-targeted programs in development

In parallel with the GLP-1 program, Nxera is progressing six additional obesity and weight-management drug programs, including:

three small-molecule agonists targeting GIP, apelin, and amylin

one small molecule antagonist targeting GIP

These programs employ Nxera’s NxWave GPCR-focused structure-based design platform with which the company can identify novel lead molecules with distinctive chemistry. The process combines proprietary NxHit small-molecule libraries with NxStaR proteins for DNA-encoded library screening. The company aims to produce candidates that differ from other drugs in global development.

“Today, we reveal the addition of these programs to our discovery portfolio and are confident in achieving significant progress over the mid-term, delivering clear value for shareholders and patients in the rapidly expanding obesity market, projected to exceed US$100 billion annually in global sales [4],” Cargill added in the release.

According to Nxera, its pipeline strategy addresses several industry and clinical priorities such as:

long-term weight maintenance through convenient, scalable oral therapies

treatment of obesity-related co-morbidities, including cardiovascular, renal, and liver diseases

reduced side effects and tailored options for populations such as the elderly, post-menopausal women, and patients with sarcopenia.

Beyond obesity and metabolic disorders, Nxera continues research in neurology, gastroenterology, and immunology, applying the same GPCR-targeted discovery methods.

Pfizer program discontinued, future discussions planned

Separately, Pfizer recently ended development of its Phase I small-molecule GLP-1 agonist PF-06954522 in early August 2025 (5), which originated from a collaboration with Nxera. The decision, according to Nxera, was due to portfolio reprioritization rather than safety concerns. Nxera plans to discuss with Pfizer the possibility of advancing GLP-1 molecules identified during their joint research.

Nxera’s announcements underscore a broader trend in obesity drug development: expanding beyond injectables into oral therapies, diversifying receptor targets, and applying high-throughput, structure-based screening to accelerate discovery. With obesity drug sales forecast to surpass $100 billion annually, the field is poised for increasingly intense scientific and commercial activity.

Nxera Launches Broad Proprietary Pipeline Targeting Obesity and Chronic Weight Management

. Press Release. Aug. 6, 2028.
2. Pfizer. 

Sosei Subsidiary Heptares Enters Strategic Drug Discovery Collaboration with Pfizer Inc. Focused on GPCR Targets Across Multiple Therapeutic Areas

. Press Release. Nov. 30, 2015.
3. Nxera Pharma. 

Sosei Heptares and Lilly Enter Multi-target Collaboration and License Agreement in Diabetes and Metabolic Diseases

. Press Release. Dec. 16, 2022.
4. McKinsey & Co. 

GLP-1s Are Changing Obesity Care. What Comes Next

? mckinsey.com, June 1, 2025 (accessed Aug. 11, 2025).
5. Waldron, J. Pfizer's Embattled Obesity Program Loses Another GLP-1 Over Poor Data and Strong Competition. 

, Aug. 5, 2025 (accessed Aug. 11, 2025). 

https://www.fiercebiotech.com/biotech/pfizers-embattled-obesity-program-loses-another-glp-1-drug

Tokyo-based Nxera Pharma has launched an expanded drug discovery pipeline targeting obesity and related metabolic diseases, leveraging collaborations with Pfizer and Eli Lilly. Their lead asset is a proprietary oral GLP-1 agonist program, developed independently from Pfizer's discontinued PF-06954522. Nxera is advancing multiple GPCR-targeted programs, including small-molecule agonists and antagonists, using their NxWave platform. The pipeline aims to address long-term weight maintenance, obesity-related co-morbidities, and reduced side effects. The company continues research in neurology, gastroenterology, and immunology, applying GPCR-targeted methods.

The new targeted pipeline will advance Nxera’s oral GLP-1 agonists, novel GPCR targets, and structure-based drug design to address obesity and related health conditions.

Nxera’s New GLP-1 and GPCR-Targeted Drug Programs Aim to Advance Obesity and Metabolic Disorder Therapies

, PhD, is senior manager, scientific affairs at bioMérieux. Email: 

Stem cells - undifferentiated (immature) cells on the background of a DNA helix, 3d rendering | Image Credit: © ustas - stock.adobe.com

As personalized, life-saving treatments advance with the widespread adoption of cell and gene therapies (CGTs), diagnostic quality control partners face a critical challenge: adapting traditional methods to meet faster production timelines and the limited shelf life of cell therapy products while ensuring accuracy and reliability in results. The urgency of delivering these therapies to patients necessitates a reevaluation of existing quality control frameworks. Traditional methods that may have been sufficient for conventional pharmaceuticals often fall short when applied to the dynamic and sensitive nature of cell and gene therapies. This adaptation requires not only technological innovation but also a shift in mindset toward more agile and responsive quality control processes.

New therapies, new quality control processes

Cell and gene therapy manufacturers face significant quality control testing challenges due to the complex and highly variable nature of these therapies. One of the primary challenges is the need to develop novel testing methods that can accurately assess the unique attributes of these products. Unlike traditional pharmaceuticals, cell and gene therapies are living products, which means their characteristics can change over time and under different conditions. This variability necessitates the development of testing methods that can provide reliable and reproducible results despite these fluctuations.

Additionally, the limited number of viable sampling strategies poses a significant hurdle. Given the precious and often scarce nature of cell and gene therapy products, extensive sampling for quality control purposes is not always feasible. Manufacturers must therefore devise strategies that maximize the information obtained from minimal sample volumes, ensuring that enough product remains available for therapeutic use. Concerns over raw material consistency further complicate the quality control landscape. The biological nature of these therapies means that raw materials can vary significantly from batch to batch, potentially impacting the final product's quality and efficacy. Ensuring consistency in raw materials is crucial for maintaining the integrity of the therapy.

The potential for cross-contamination is another critical concern. The manufacturing processes for cell and gene therapies often involve handling multiple products simultaneously, increasing the risk of cross-contamination. Implementing stringent contamination control measures is essential to prevent this and ensure the safety and purity of the final product. Moreover, the need for rapid results to minimize patient wait times adds another layer of complexity. Patients awaiting cell and gene therapies often have urgent medical needs, making timely delivery of these treatments critical. Quality control processes must therefore be optimized to provide quick and accurate results without compromising on thoroughness.

All these challenges must be addressed while adhering to strict regulatory standards. Regulatory bodies have established rigorous guidelines to ensure the safety, efficacy, and quality of cell and gene therapies. Manufacturers must navigate these regulations carefully, ensuring that their quality control processes meet all necessary requirements.

Minimizing 'over-testing' to maximize product

An emerging consideration unique to cell and gene therapies is the need to develop a testing plan that minimizes over-testing, thereby maximizing the amount of sample, or product, available for patient use. This is particularly important given the often-limited availability of these highly specialized and valuable products. Strategic decisions in testing—such as choosing the right testing partner, streamlining upstream and downstream processes, and ensuring automation and accuracy—can facilitate a faster, more efficient path from lab to patient. By carefully selecting a testing partner with expertise in cell and gene therapies, companies can leverage specialized knowledge and advanced technologies to optimize their testing protocols.

Furthermore, because no two facilities or products are identical in the cell and gene therapy space, diagnostic partners are uniquely positioned to holistically analyze a customer’s development and manufacturing processes. They can provide tailored recommendations to enhance testing efficiency and develop new analytical methods. For instance, next-generation sequencing can be employed to accurately assess critical quality attributes such as cell viability, purity, potency, and genetic integrity. This level of precision is crucial for novel cell and gene therapy products where standard assays may not be suitable. Additionally, diagnostic partners can assist in the validation and implementation of these new methods, ensuring they meet regulatory requirements and industry standards.

Moreover, the dynamic nature of cell and gene therapy development necessitates a flexible and adaptive approach to testing. As new technologies and methodologies emerge, continuous collaboration with diagnostic partners can help companies stay at the forefront of innovation. These types of ongoing partnerships can lead to the discovery of more efficient testing strategies, ultimately reducing time-to-market and improving patient outcomes. By investing in robust testing frameworks and fostering strong relationships with diagnostic partners, companies can navigate the complexities of cell and gene therapy development more effectively.

Recently, bioMérieux has collaborated with various customers to develop customized testing plans that address the unique needs of individual facilities and products across multiple categories in relation to mycoplasma testing. This collaboration has been instrumental in ensuring that the testing protocols are tailored to the specific requirements of each facility, thereby enhancing the accuracy and reliability of the results.

During these conversations, several themes common to a collaborative approach have been regularly mentioned. They are as follows:

 When a sample has a higher cell density, testing an entire batch becomes impractical due to volume and resource constraints. High cell density can lead to challenges in sample handling and processing, making it difficult to obtain representative results from a single batch. The rapid advancement of cell and gene therapy has resulted in limited FDA guidance on the appropriate batch volume to test and whether the focus should be on the cells or the matrix. This lack of clear regulatory direction can create uncertainty for manufacturers, who must balance the need for thorough testing with the practical limitations of their processes. In such scenarios, an experienced partner can provide valuable guidance as new regulations are introduced. By leveraging their expertise and staying abreast of the latest regulatory developments, these partners can help manufacturers navigate the complexities of mycoplasma testing. They can offer insights into the most effective sampling strategies, ensuring that the testing is both comprehensive and efficient.

Selection of relevant species for validation.

 For mycoplasma detection method validation, testing every compendial species is unnecessary. Instead, using a representative selection of common and relevant species encountered in cell culture environments streamlines the process, making it more efficient and cost-effective. This targeted approach ensures that the validation process remains practical while maintaining adequate sensitivity and specificity across potential contaminants. By focusing on the most prevalent and relevant mycoplasma species, laboratories can optimize their resources and reduce the time and cost associated with extensive testing. This approach also allows for a more manageable and focused validation process, ensuring that the methods are robust and reliable for detecting the mycoplasma species most likely to be encountered in the specific cell culture environment.

The validation process should demonstrate sufficient coverage against likely mycoplasma species in the samples. This involves carefully selecting species that are representative of the broader mycoplasma population, ensuring that the detection methods can identify a wide range of potential contaminants. The goal is to achieve a balance between thoroughness and efficiency, providing confidence in the testing results without the need for exhaustive species-by species validation.

With the increasing use of molecular methods like polymerase chain reaction (PCR) for mycoplasma detection, the need to test against every species might be less critical. PCR assays can often detect a broad range of mycoplasma species based on conserved genetic sequences. These sequences are shared among different mycoplasma species, allowing for the detection of multiple species with a single assay. This capability significantly enhances the efficiency of the validation process, as it reduces the need for extensive species-specific testing. Moreover, the use of molecular methods like PCR offers additional advantages, such as increased sensitivity and faster turnaround times compared to traditional culture-based methods. These benefits are particularly important in the context of cell and gene therapies, where timely and accurate detection of contaminants is crucial for ensuring product safety and efficacy.

Analytical testing strategies for upstream and downstream processes. 

Rapid sterility and mycoplasma testing at the upstream stage of cell and gene therapy development significantly reduces the burden on the downstream process by allowing for early detection and mitigation of potential contamination sources. This early intervention is crucial as it helps to identify and address contamination issues before they can affect larger batches of product, thereby reducing product loss and delays. Implementing rapid testing methods upstream ensures that any contamination is detected at the earliest possible stage, allowing for immediate corrective actions. This proactive approach not only prevents the spread of contaminants but also minimizes the risk of compromising the entire production batch. By catching issues early, manufacturers can avoid the costly and time-consuming process of reworking or discarding contaminated products, leading to more efficient use of resources and reduced production costs.

Moreover, this strategy enhances workflow efficiency by streamlining the production process. With early detection and mitigation of contamination, the downstream process can proceed with greater confidence and fewer interruptions. This seamless transition from upstream to downstream stages ensures that the production timeline remains on track, ultimately speeding up time-to-market for cell and gene therapies.

Ensuring product integrity is another critical benefit of rapid upstream testing. By maintaining a contamination-free environment from the outset, manufacturers can uphold the highest standards of product quality and safety. This is particularly important in the field of cell and gene therapy, where the therapeutic products are often highly sensitive and complex. Maintaining their integrity throughout the production process is essential for their efficacy and safety when administered to patients. Rapid sterility and mycoplasma testing contribute to the high safety and quality standards of cell and gene therapy development by providing reliable and timely data on the contamination status of products. These data are essential for making informed decisions about the production process and ensuring that only the highest quality products reach the patients, a proactive approach that ultimately leads to better patient outcomes. By ensuring that cell and gene therapies are free from contamination and produced to the highest standards, manufacturers can deliver safe and effective treatments to patients. This not only improves the health and well-being of patients but also increases their trust in the therapies and the companies that produce them.

The future of cell and gene therapies involves more than just technological advancements; it’s about optimizing every step—from manufacturing to testing—to deliver life-saving treatments more efficiently and with the highest quality assurance. This holistic approach ensures that each phase of the therapy development process is fine-tuned to maximize efficacy, safety, and speed. By focusing on continuous improvement and innovation, the industry can overcome existing challenges and pave the way for groundbreaking treatments that can address previously untreatable conditions.

Partnering with an experienced testing partner in the cell and gene therapy space is crucial for navigating the complexities of quality control. These partners bring a wealth of knowledge and expertise, helping manufacturers implement robust testing protocols that are both relevant and efficient. They play a vital role in ensuring that tests are not only scientifically sound but also compliant with evolving regulatory requirements. This compliance is essential for gaining regulatory approval and ensuring that therapies meet the highest standards of safety and efficacy.

With scientifically grounded and best practice testing strategies, the industry is poised to scale rapidly. These strategies involve leveraging the latest advancements in testing technologies, such as high-throughput screening and advanced molecular diagnostics, to enhance the accuracy and speed of quality control processes. Moreover, the collaboration between manufacturers and testing partners enables the development of customized testing solutions that are tailored to the specific needs of each therapy and production facility. By addressing the unique challenges of cell and gene therapy production, these solutions ensure that quality control processes are both effective and efficient.

As the industry continues to evolve, the ability to bring more cell and gene therapies to market will have a transformative impact on patient care. These therapies have the potential to provide long-lasting and even curative treatments for a wide range of diseases, from genetic disorders to cancer. By optimizing every step of the development process and ensuring the highest standards of quality control, the industry can deliver these life-saving treatments to patients more quickly and reliably.

Ambili Menon, PhD, is senior manager, scientific affairs at bioMérieux.

®
Vol. 49, No. 7
September 2025
Pages: 26–29

When referring to this article, please cite it as Menon, A. Optimizing Testing in Cell and Gene Therapy. 

The advancement of cell and gene therapies (CGTs) necessitates a reevaluation of traditional quality control methods to accommodate faster production timelines and the unique characteristics of these therapies. Manufacturers face challenges such as developing novel testing methods, managing limited sampling strategies, ensuring raw material consistency, and preventing cross-contamination. Collaborations with diagnostic partners are crucial for optimizing testing protocols, leveraging advanced technologies, and ensuring regulatory compliance. By focusing on efficient quality control processes, the industry can enhance the speed and reliability of delivering life-saving CGTs to patients.

The scaled adoption of cell and gene therapies demands a new era of agile, precise, and efficient quality control methods. Manufacturers and diagnostic partners must collaborate to create innovative, compliant testing strategies that preserve product integrity, meet tight timelines, and deliver life-saving treatments faster.

Optimizing Testing in Cell and Gene Therapy: A Key Driver for Industry Growth and Adoption

Pendulum used for readings and hypnotism swinging with motion blur | Image Credit: © fergregory - stock.adobe.com

Vinay Prasad is resuming his position as head of FDA’s Center for Biologics Evaluation and Research (CBER) just over a week after stepping down (1). “At the FDA's request, Dr. Vinay Prasad is resuming leadership of the Center for Biologics Evaluation and Research,” US Health and Human Services spokesperson Andrew Nixon confirmed in a statement to Reuters (2). Less than 2 weeks earlier, Nixon told Biopharma Dive that “Dr. Prasad did not want to be a distraction to the great work of the FDA in the Trump administration and has decided to return to California to be with his family” (3).

Prasad, an oncologist with prior roles at the University of California San Francisco, the National Cancer Institute, and the National Institutes of Health, was appointed to lead CBER in May by FDA Commissioner Marty Makary (3). His return comes after a short 

departure that began as abruptly on July 30

Gene Therapy Safety and Regulatory Pressures

Prasad’s tenure has unfolded against the backdrop of heightened scrutiny over FDA’s regulation of advanced therapies, particularly gene therapies (3). Criticism intensified following the agency’s handling of Sarepta Therapeutics’ gene therapy for Duchenne muscular dystrophy (DMD). The therapy was linked to the deaths of two teens with advanced DMD. After a third death in a separate experimental therapy from the same company, FDA on July 18 halted shipments of the approved product due to safety concerns (3).

Ten days later, on July 28, the FDA revised its stance, allowing shipments to resume for the primary patient population (3). For pharmaceutical technology professionals, the rapid policy shifts underscore the challenges regulators face in balancing innovation with patient safety, especially for high-risk biologics and gene therapies.

Prasad’s leadership has drawn attention both inside and outside the agency. On July 20, activist Laura Loomer criticized him publicly, calling him a “progressive leftist saboteur” in a blog post (2). His return also takes place amid broader leadership transitions across the FDA and other US health agencies under Health Secretary Robert F. Kennedy Jr (4-6).

For those in drug development and manufacturing, the reinstatement signals continuity at a time when the biologics sector is under intense scientific, regulatory, and political pressure. The events surrounding Sarepta’s therapy highlight FDA’s role in managing cutting-edge treatments that promise significant benefits but also carry serious risks, decisions that can directly influence development timelines, manufacturing scale-up, and market access strategies.


Prasad Returns to FDA, Resuming Head of CBER Role

Vinay Prasad Returns to Role as Top Vaccine Regulator at FDA Days After Leaving US Agency

FDA Shake-Up: Vinay Prasad Exits Amid Tumult in Biologics Oversight

Implications of RFK Jr.’s CDC Vaccine Committee Overhaul for the Pharmaceutical Industry

RFK Jr.'s Removal of Thimerosal from Flu Vaccines Spurs Opposing Reactions

Reaction and Fallout as HHS ‘Winds Down’ mRNA Vaccine Development, Canceling $500 Million in Projects

Vinay Prasad has resumed his role as head of the FDA's Center for Biologics Evaluation and Research (CBER) shortly after stepping down. His leadership tenure has been marked by increased scrutiny over the FDA's regulation of advanced therapies, particularly gene therapies, following safety concerns with Sarepta Therapeutics' gene therapy for Duchenne muscular dystrophy. Prasad's return occurs amid broader leadership changes within the FDA and other health agencies. This reinstatement signals continuity in the biologics sector, which faces significant scientific, regulatory, and political pressures.

FDA reinstates Vinay Prasad to lead CBER as gene therapy safety concerns spotlight regulatory challenges in biotech manufacturing.

Prasad Returns to Head FDA’s CBER

Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.

Pink-white and blue-white capsule pills with concept of precision medicine with nanotechnology, proteomics, and advanced artificial intelligence to enhance diagnostics and patient-specific solutions. | Image Credit: ©Artinun - stock.adobe.com

Patient adherence to medication is a challenge. Patients prefer the use of oral medicines over injectable ones for obvious reasons. Therefore, there is an ongoing need to develop personalized and patient-centric delivery solutions, including devices, for the administration of oral medicines that fit patient lifestyles and optimize the safe and effective use of oral medicines. Key attributes include improved taste and ease of swallowing, patient-friendly administration, flexible dosing, and reduced dosing frequencies.

More sophisticated and tailored solutions are emerging, including modified-, sustained-, extended, and controlled-release formulations; smart pills incorporating digital technologies for sensing and reporting; transdermal patches; and subcutaneous implants. New manufacturing methods are also being explored to enable more personalized and patient-centric dosage forms, such as 3D printing of oral solid dosage (OSD) drugs.

Personalized OSD forms aim to improve outcomes and adherence by tailoring medicines to each patient’s needs. “Standard tablets are easy to mass-produce but do not account for differences in age, weight, genetics, or disease progression,” says Bing Xun Tan, pharmaceutical application laboratory manager, Roquette Health & Pharma Solutions. “Customizing dose strength or form maximizes therapeutic efficacy while minimizing side effects, which is crucial for pediatric and geriatric patients,” he notes.

Personalized formulations support drug titration—such as loading and maintenance dosing—as well as body surface area- or weight-based adjustments, which are particularly important in oncology and pediatric care, according to Thierry Jomini, CEO and founder of AbbatiaLabs. In addition, he observes that personalized dosing facilitates safe medication tapering, giving patients a better chance to discontinue treatment optimally, and helps combat issues like antibiotic resistance and drug habituation. Finally, comments Jomini, solid oral forms offer superior stability compared to liquids, enabling global accessibility even in regions without refrigeration, thus ensuring reliable treatment delivery across diverse environments.

Advances like 3D printing, multiparticulate systems, and improved excipients such as pregelatinized starch or mannitol now enable bespoke formulations, according to Tan. Regulators, he adds, are also starting to play a role. FDA’s pediatric exclusivity provision (1), for instance, provides a financial incentive for pharmaceutical manufacturers to conduct and submit pediatric studies supporting the development of age-appropriate dosage forms that could also allow for dose titration. Similarly, in Europe, the Pediatric Use Marketing Authorization (PUMA) (2) incentivizes medicines developed exclusively for use in the pediatric population with data and market protection for product authorization.

“These drivers support the shift from ‘one-size-fits-all’ medicines towards precision approaches that make drug therapy safer, more effective, and better adapted to the patient,” Tan concludes.

Enhancing treatment efficacy through better adherence

The drivers for patient-centric formulation development are similar to those for personalized OSD drugs because both approaches focus on enhancing treatment efficacy and patient adherence by emphasizing individual preferences and needs, says Lydia Marinou, technical sales manager with Adragos Pharma.

As examples, Marinou points out that flexible dosing schedules and dosage forms that align with patients' lifestyles can significantly improve adherence rates, and the use of mobile health applications that gather patient feedback further supports this trajectory. “Successful case studies, such as patient-centric inhalers collecting real-time data, illustrate how understanding patient profiles and medication adherence can lead to more effective and satisfactory treatment outcomes,” she adds.

John van den Anker, chief scientific officer of AbbatiaLabs, agrees that the primary motivation for both personalized and patient-centric products is improved adherence to therapy. “Medications that are easier to administer—whether by patients themselves or by caregivers—significantly increase the likelihood of consistent treatment,” he notes. “Moreover,” he continues, “patient-centric products help reduce dosing errors, which are a leading cause of medication-related issues, particularly in settings requiring precise, bodyweight-based dosing such as pediatric care.”

Patient-centric design, according to Tan, focuses on making medicines easier to use—like easier-to-swallow tablets or chewables, taste-masked forms for children or older adults, or fast-melt options including orally disintegrating tablets (ODTs) for those with dysphagia. “By reducing behavioral and sensory barriers, these designs encourage correct use. Commercially, they appeal to patients, caregivers, and providers seeking better compliance,” he says.

In addition, Tan comments that as lifestyle medicines (like those for weight loss) grow in popularity, there is also a market-driven demand for more lifestyle-friendly, personalized formats. This trend, he observes, mirrors similar trends in nutraceuticals and cosmetics, where personalization is already a significant consumer demand.

Significant overlap between personalized and patient-centric OSD drugs

Consequently, there is a clear overlap between personalized and patient-centric oral solid dosage drugs, as both concepts prioritize ease of use and accuracy in drug administration, according to Jomini.

Tan, meanwhile, views personalized OSD drugs with doses and/or drug combinations customized for individuals as, effectively, a subset of the broader patient-centric approach. “While personalization focuses on pharmacological customization (right drug, right dose), patient-centric design ensures that the dosage form itself is acceptable, convenient, and adapted to the patient’s needs and preferences,” he explains. In practice, Tan notes that advances like 3D printing enable both at once: for example, a chewable, flavored tablet designed for a child that also delivers a precise weight-based dose.

Van den Anker contends that flexible dosing devices—such as POWDOSE from AbbatiaLabs—exemplify this convergence by enabling patients or caregivers to easily and reliably select the precise dose needed, typically in just a couple of simple steps. “These innovations support both individualized treatment regimens and user-friendly administration, making them essential tools for delivering truly tailored and accessible therapies,” van den Anker believes.

Overall, concludes Tan, “patient-centric design provides the usability framework, while personalization ensures pharmacological precision. Together, they represent a shift from viewing the patient as a passive recipient of standardized treatment to an active participant whose unique needs and circumstances shape the final product.”

Recent technology advances of note for van den Anker include flexible and user-friendly dosing solutions that allow precise, individualized dosing. He also highlights 3D printing as an emerging and powerful tool for creating customized drug formulations tailored to each patient’s needs; long-acting formulations, which contribute by reducing dosing frequency and improving adherence; and easy-to-swallow formats—such as multiparticulates and dissolvable tablets—that enhance patient comfort and usability, particularly for children and the elderly. “Together, these innovations are transforming the landscape of oral drug delivery toward more tailored and accessible care,” he states.

Manufacturing, scalability, and regulatory complexity challenges

Developing patient-centric and personalized OSD drugs is not a simple endeavor, however. There are several challenges along the way. The biggest hurdles, according to Tan, lie in manufacturing, scalability, and regulatory complexity.

One major barrier highlighted by Jomini is the need for the pharmaceutical industry to invest in new infrastructure, such as equipment for 3D printing individualized doses or systems for filling flexible dosing devices, which also require compatible multiparticulate formulations.

Technologies like 3D printing, adds Tan, are well suited to one-off or small-batch production, but because each tablet is printed layer-by-layer, this method is too slow and costly for large-scale deployment. In addition, he notes that supply chains must also adapt, particularly for excipients. “The sourcing of ready-to-use blends and functional excipients that streamline small-batch production has never been more important,” Tan states.

Furthermore, Tan emphasizes that highly individualized production demands new distribution models, specialized training, and flexible quality systems capable of ensuring consistency and safety for varied products. Regulations need updating as well. “Regulatory frameworks, while evolving, still generally assume mass production of standardized forms. Clear guidance on quality controls, validation, and data protection (especially when handling patient-specific data) is still developing,” Tan says.

Another challenge for van den Anker is the need for development of robust clinical evidence clearly demonstrating that precise dosing leads to better health outcomes. In addition, he observes that for many personalized and patient-centric OSD drugs, “payers must be willing to support potentially higher costs for these advanced therapies in recognition of their benefits in adherence and therapeutic effectiveness.”

Overall, according to Tan, “the crux is how to scale up personalization without compromising cost-effectiveness, safety, or regulatory compliance—challenges that will require not only technological solutions but also reimagined business and regulatory models.”

Regulatory considerations significantly impact the development of personalized and patient-centric OSD drugs, and agencies are adapting their frameworks to better accommodate innovations, Marinou says. She points to incorporation of quality-by-design principles to ensure safety and efficacy as an example.

Regulatory frameworks must continue to evolve, however, to address novel challenges while maintaining safety and quality, according to Tan. “New production methods require robust validation (especially for on-demand and small-scale manufacturing environments), as well as solid quality controls and assured compliance with good manufacturing practices. Handling patient-specific data also demands stringent privacy protections,” he explains.

The approval of patient-customized 3D-printed medicines and devices exemplifies the evolving landscape for Marinou (3–5). She emphasizes, though, that addressing compliance complexities and establishing robust pharmacovigilance systems remain critical for companies aiming to introduce personalized treatments that align with regulatory standards. “Navigating the complexities of compliance is essential,” she says, “particularly as the inclusion of real-world evidence, which allows companies to leverage patient data for adaptive regulatory pathways, becomes increasingly important.”

If delivery is achieved using specialized devices, there are additional regulatory considerations. Products that include a device component—such as a flexible dosing system—may be classified as combination products, which can introduce added regulatory complexity, especially for developers more accustomed to small-molecule drugs, says Jomini. “While this pathway is more common in biologics and injectables, it poses a challenge in the OSD space. Moreover, any medical claims, such as improved outcomes, must be substantiated by robust clinical evidence,” he observes. Despite these hurdles, Jomini does note that specialized regulatory expertise is available to support developers through this process.

Also on the positive side, Tan notes that many pharmaceutical regulatory agencies are already encouraging patient-focused approaches. In addition to the aforementioned pediatric development incentives, he highlights FDA’s Patient-Focused Drug Development initiative (6), which emphasizes incorporating patient perspectives and needs. “Together, these regulatory drivers support safer, more tailored therapies that meet the multifaceted needs of a diverse, global patient body,” Tan says.

Despite the many challenges, developers of OSD drugs are pursuing innovative solutions that support the creation of personalized and patient-centric products designed to increase medication adherence and provide better outcomes.

Tan notes that the ability of 3D printing to enable on-demand, patient-specific tablets with tailored doses and flavors has been demonstrated for pediatric use in hospital trials (7). “Hospital pharmacies are beginning to adopt 3D printers and precise dosing devices to create tailored oral forms at the point of care—such as child-friendly, flavored tablets with exact doses,” he notes.

Fast-melt tablets and dissolvable oral films improve administration for those with swallowing difficulties, while multiparticulate systems, such as pellets and minitablets, enable flexible drug-dose combinations that can reduce pill burden, according to Tan. He points to the OraFID (Sensidose, part of Navamedic ASA) prefilled dose dispenser as simplifying minitablet administration by allowing patients and caregivers to accurately dispense the required dose. “Minitablets and multiparticulates promise superior accuracy and dosing flexibility, allowing complex regimens to be delivered in single capsules or even sprinkles with specific release profiles,” he says.

Other advances highlighted by Tan include improvements to excipient offerings such as plant-based mannitol and other starch derivatives, which ultimately support better taste-masking, compressibility, and customized release profiles. “The industry’s growing understanding of the importance of these factors is driving the development of excipients designed specifically for patient-centric forms and advanced manufacturing, laying the groundwork for truly personalized, user-friendly oral medicines,” he says.

Innovative drug delivery systems, meanwhile, are transforming personalized medicine, according to Marinou. “Nanoscale carriers, such as dendrimers and liposomes, enhance drug solubility and targeting, allowing for treatments such as personalized cancer therapies that deliver chemotherapeutics directly to tumor cells. Layered tablets provide controlled release of multiple drugs, which is particularly useful for the management of chronic conditions, as seen in combination therapies for diabetes. Additionally, smart delivery systems, such as implantable devices that can adjust dosages based on real-time physiological data, represent the future of medication adherence and effectiveness, allowing for tailored treatments that adapt to individual patient dynamics,” she comments.

In the near future, van den Anker believes the development of oral formulations for traditionally injectable therapies, such as oral insulins and GLP-1 drugs for obesity and type 2 diabetes, will have significant potential to advance personalized and patient-centric OSD drugs. “These innovations could greatly improve patient comfort and adherence,” he states.

Longer-term, Tan believes artificial intelligence (AI)-driven formulation design and fully decentralized manufacturing will revolutionize production of personalized and patient-centric OSD drugs. “AI models can help predict optimal doses and formulations based on individual patient data, while advanced manufacturing units in pharmacies or clinics produce these custom forms on demand,” he observes. Tan also expects smart ingestible devices and biosensors will eventually provide the added benefit of real-time monitoring and responsive drug release, enabling dynamic personalization (8). “Once the lingering technological and regulatory barriers have been addressed, these developments could create an interconnected, on-demand systems delivering personalized oral therapies at scale within the next decade.”

FDA. The Pediatric Exclusivity Provision: Status Report to Congress, January 2001. 

EMA. Paediatric-use Marketing Authorisations. Ema.europa.eu. Updated July 31, 2025. 

https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/paediatric-medicines-marketing-authorisation/paediatric-use-marketing-authorisations

Alqahtani; et al. 3D Printed Pharmaceutical Systems for Personalized Treatment in Metabolic Syndrome. 

Aprecia. FDA Approves the First 3D Printed Product. Press Release. Aug. 3, 2015, 

https://aprecia.com/resources/press/fda-approves-the-first-3d-printed-drug-product/

Triastek. Triastek's 3D-Printed Gastric Retention Product T20G Receives FDA IND Clearance. Press Release. March 17, 2025. 

FDA. CDER Patient-Focused Drug Development. 

https://www.fda.gov/drugs/development-approval-process-drugs/cder-patient-focused-drug-development

Stoops; et al., Clinical Implementation of a Paediatric 3D-printed Combination of Sulfamethoxazole and Trimethoprim. 

Chai; et al., Utilizing an Ingestible Biosensor to Assess Real-Time Medication Adherence. 

 Dec;11(4):439-44. DOI: 10.1007/s13181-015-0494-8

Cynthia A. Challener, PhD is a contributing editor to

The development of personalized and patient-centric oral solid dosage (OSD) drugs aims to improve medication adherence and therapeutic outcomes by tailoring treatments to individual patient needs. Innovations such as 3D printing, smart pills, and flexible dosing devices are transforming drug delivery, making it more precise and user-friendly. However, challenges in manufacturing, scalability, and regulatory compliance persist. Regulatory frameworks are evolving to accommodate these innovations, emphasizing patient-focused approaches. Future advancements may include AI-driven formulation design and real-time monitoring systems, further enhancing personalized medicine.

New manufacturing methods are being explored, but challenges are still present in personalized medicine development.

Personalized and Patient-Centric Administration of Oral Medicines

Florian Schindler is head of Business Development, ACTEGA GmbH.

Needle of a syringe protrudes through the rubber cap of a vaccine vial with red cap. Focus on the rubber stopper, shallow depth of field |Image Credit: © Henk Vrieselaar – stock.adobe.com

Pharmaceutical packaging, and primary packaging in particular, which is in direct contact with the dosage form (or could potentially come into contact with it), is often much more than mere repositories. It can have an influence on the quality, effectiveness, and safety, as well as applicability, of pharmaceuticals, which cannot be underestimated. Typical examples include injection bottles with sealing plugs used as both repositories and for applying medication. Butyl rubber (e.g., bromobutyl and chlorobutyl, the standard material for manufacturing stoppers) is increasingly viewed with skepticism due to its energy-intensive production, its non-recyclable nature and halogen-containing composition. Therefore, a look at alternative materials, such as thermoplastic elastomers (TPE), is worthwhile, especially with regard to the current per- and polyfluoroalkyl substances (PFAS) debate.

Pharmaceutical stoppers are rather small and inconspicuous, but carry enormous responsibility.Primarily used as closures for injection and drug vials, they are subject to complex and highly regulatory requirements.Stoppers used for parenteral applications (i.e., for injectable and infusion-ready drugs) are in direct contact with the product.Therefore, they must adapt perfectly to the product to ensure its integrity at all times.Annex 9 of the World Health Organization (WHO) 

Guidelines for the Packaging of Medical Products 

(1) stipulates, “The kind of packaging and the materials used must be chosen in such a way that the packaging itself does not have an adverse effect on the product (e.g., through chemical reactions, leaching of packaging materials or absorption), the product does not have an adverse effect on the packaging, changing its properties or affecting its protective function.”

In addition, good container closure integrity (CCI) is essential (i.e., to prevent the leakage of liquids and to maintain the sterility of the vial contents).Furthermore, pharmaceutical closures must meet the relevant requirements of the market in which they are to be offered.The most important chemical requirements can be found in Section 3.2.9 of the 

) (2–4). To meet the criteria of protection, safety, compatibility, and function, a variety of physical and mechanical material properties, as well as processability and sterilizability, must be ensured.Physical-chemical and functional tests are used to check for modifications, penetrability, fragmentation, and self-sealing.

Pharmaceutical packaging, particularly primary packaging, plays a crucial role in maintaining the quality, effectiveness, and safety of pharmaceuticals. Traditional materials like butyl rubber are under scrutiny due to environmental concerns, prompting a shift towards sustainable alternatives such as thermoplastic elastomers (TPEs). TPEs offer advantages like recyclability, energy-efficient production, and compliance with medical standards. The ongoing debate over per- and polyfluoroalkyl substances (PFAS) highlights the need for PFAS-free materials in pharmaceutical applications. TPEs, free from PFAS, are emerging as a promising alternative for pharmaceutical closures.

Thermoplastic elastomers (TPE) offer a PFAS-free solution for stoppers in parenteral packaging, ensuring a safer and more sustainable product.

Featured Content

Behind the Headlines Episode 25

Ask the Expert

Drug Digest September 2025

How 100% Pharmaceutical Tariffs Will Impact Domestic Manufacturing and Supply Chains

Stakeholders React to FDA's Push for Quality, Integrity, and Uniformity