Vijay Kumar is the acting director of the Office of Therapeutic Products (OTP) within the FDA's Center for Biologics Evaluation and Research (CBER), the regulatory super office established in 2023 to oversee the rapidly expanding cell and gene therapy landscape. With a mandate spanning gene therapies, stem cell and cell-derived therapies, therapeutic vaccines, tissue-based products, and xenotransplantation, OTP sits at the frontier of some of the most scientifically complex products moving through the US regulatory system. In this interview, Kumar discusses the evolution of the office's internal structure and scientific capabilities, the rationale behind FDA's recent emphasis on CMC flexibility for cell and gene therapy developers, recent draft guidances, and OTP's priorities in modernizing the development and review process as the field approaches an inflection point of real-world translation.
Can you start by outlining the mandate of the Office of Therapeutic Products within the FDA?
The Office of Therapeutic Products (OTP) sits within the US FDA’s Center for Biologics Evaluation and Research (CBER) and was established in 2023 through the reorganization of the former Office of Tissues and Advanced Therapies. We created the OTP as a dedicated “super office” in response to both the rapid growth and increasing scientific complexity of advanced therapeutic products, particularly across the cell and gene therapy (CGT) space. Within CBER, we operate alongside other major product offices such as the Office of Vaccines Research and Review (OVRR) and the Office of Blood Research and Review (OBRR), with a mandate focused on ensuring the safety, purity, potency, and effectiveness of the biologic products under our mandate.
That mandate spans a broad and increasingly sophisticated range of therapies, including gene therapies, stem cell and stem cell-derived therapies, terminally differentiated cell therapies, therapeutic vaccines, blood- and plasma-derived products, tissue-based products such as vascular, nerve, and cartilage tissues, as well as certain biologic-device combination products. We also oversee highly specialized and emerging areas such as xenotransplantation. More recently, for example, FDA approved a gene therapy-device combination product for an inherited form of hearing loss associated with OTOF gene variants, which reflects the increasingly advanced and technically complex nature of the products now moving through the regulatory system.
To support this expanding field, OTP was structured across six specialized offices covering areas such as gene therapy, cellular therapy, tissue- and plasma-derived products, clinical evaluation, and pharmacology and toxicology. Across those offices, we currently have 14 divisions and 33 branches, reflecting both the scale of the organization and the depth of expertise required to oversee these rapidly evolving therapies. The structure was designed to strengthen specialized scientific capability, improve coordination across disciplines, and support more efficient and consistent regulatory review as advanced therapies continue to move further into the mainstream of modern medicine.
Speaking specifically to CGTs, how is the FDA adapting its scientific and regulatory capabilities to keep pace with the field?
The CGT space is currently going through what I would describe as a hyper-growth phase, driven by advances in technologies such as base editing and increasingly precise methods of delivering therapies into cells. At the same time, growing public awareness of successful patient outcomes has accelerated momentum across the sector, particularly as many of these therapies have demonstrated the potential to significantly alter disease trajectories and, in some cases, offer curative benefit. As the number of approved therapies and incoming submissions continues to rise, we have had to evolve both organizationally and scientifically to remain responsive to the pace and complexity of innovation.
One of our primary priorities has been ensuring that OTP’s internal structure and expertise evolve alongside the science itself. We have focused heavily on building subject matter expertise across disciplines that are becoming increasingly important to advanced therapies, including areas such as bioinformatics and clinical pharmacology. Beyond that, we have expanded engagement with stakeholders across academia, industry, patient communities, and professional organizations through a combination of formal sponsor interactions, workshops, town halls, and broader scientific dialogue.
Manufacturing has also emerged as a central area of focus given the inherent complexity of CGTs, particularly as products move from laboratory development towards commercial scale-up. There are challenges around manufacturing consistency, comparability, dosing, and immunomodulation, all of which require increasingly sophisticated regulatory oversight. In response, FDA has introduced programs such as the Platform Technology Designation Program, which allows sponsors to leverage prior knowledge from established technology platforms, as well as the Advanced Manufacturing Technologies Designation Program, which supports innovative manufacturing approaches including automation and other technologies intended to improve scalability, reliability, and product quality.
From a clinical and regulatory perspective, expedited pathways such as Fast Track, Breakthrough Therapy Priority Review, and Accelerated Approval, Regenerative Medicine Advanced Therapy (RMAT) designation, continue to play an important role. Beyond these formal pathways, we have also introduced several pilot programs aimed at supporting rare disease and advanced therapy development, including the CMC Development and Readiness Pilot (CDRP), the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot, the Rare Disease Endpoint Advancement (RDEA) Pilot Program, and the Collaboration on Gene Therapies Global (CoGenT Global) Pilot. These initiatives reflect a broader regulatory evolution within OTP as we continue refining our structure, operations, and review frameworks to keep pace with advances across the cell and gene therapy landscape.
At the beginning of the year, the OTP made an announcement about increased CMC flexibility for CGT products. Can you tell us about these flexibilities and what they might mean for manufactures?
Our recent emphasis on CMC flexibility reflects the experience we have accumulated as the number of approved CGTs has continued to grow. As the field has expanded, so too has the diversity of sponsors entering the space, ranging from large pharmaceutical companies to smaller biotechnology firms and start-ups. Many of the flexibilities highlighted in FDA’s recent communications were already being applied in practice on a case-by-case basis depending on the product, its risks, and the sophistication of the sponsor. What we are trying to do now is create broader awareness and greater regulatory clarity around how those flexibilities can be used appropriately to support development across the sector.
A central part of this approach is the application of a phase-appropriate current Good Manufacturing Practice (cGMP) framework, under which manufacturing expectations evolve according to the stage of product development. Early-stage investigational therapies are not expected to meet the same manufacturing requirements as commercial products, although quality, safety, and process control remain essential throughout development. As products move into later-stage clinical trials and towards commercialization, expectations around process validation, comparability, consistency, and quality systems become progressively more robust. In parallel, we are taking a risk-based approach to comparability assessments while considering where prior knowledge and existing platform experience can be leveraged appropriately to support development and reduce unnecessary duplication.
However, that flexibility does not come at the expense of product quality, potency, safety, or efficacy. We evaluate a wide range of product-specific factors during review, including whether a therapy is gene edited, its persistence in circulation, route of administration, disease indication, and the availability of alternative treatment options. Decisions around which flexibilities can be exercised are made through a deliberate and iterative process involving close interaction between OTP reviewers and sponsors. The broader objective is to facilitate patient access to potentially transformative therapies while maintaining the scientific and regulatory standards expected of advanced therapeutic products.
Most recently, the OTP released a draft guidance regarding the use of next-generation sequencing to evaluate the safety of gene therapies. Why is this an important step within regulatory review?
Next-generation sequencing (NGS) is an important example of how we are evolving alongside advances in science while continuing to strengthen internal expertise in areas such as bioinformatics. In the context of genome-edited therapies, NGS plays a central role in enabling the rapid and detailed analysis of genetic material, particularly in identifying off-target edits and unintended genomic changes that may arise during treatment.
The recently issued draft guidance is intended to provide sponsors with greater clarity around how FDA currently approaches the safety evaluation of these therapies. This is highly important given that genome editing may introduce permanent or long-term changes within treated cells. The guidance focuses on helping developers demonstrate the intended therapeutic benefit of genome-edited products while reducing risks associated with off-target edits, unintended on-target effects, chromosomal rearrangements, and broader loss of genome integrity. To support these assessments, we have invested significantly in scientific capabilities including bioinformatics teams, laboratory infrastructure, high-performance computing, and advanced sequencing technologies.
Long-term follow-up also remains an important and evolving consideration as genome-edited therapies continue to advance. We are very much a learning organization that continuously incorporates new scientific insights and real-world experience from approved therapies into our regulatory thinking while remaining responsive to emerging technologies and safety considerations. As additional long-term data become available, particularly around durability and delayed effects, we will continue refining our approach and adapting our regulatory frameworks accordingly. The broader objective is to ensure that scientific oversight evolves in parallel with the technologies themselves so that innovation can continue advancing alongside a rigorous and continually improving understanding of long-term safety.
With the emergence of next-generation technologies like point-of-care manufacturing and in vivo CAR-T, how is OTP preparing to keep pace with a continually evolving CGT field?
CAR-T therapies represent one of the most scientifically and operationally complex areas within advanced therapeutics because many of those products combine both gene editing and cell therapy technologies alongside highly sophisticated manufacturing processes. As newer approaches such as in vivo CAR-T and point-of-care manufacturing continue to emerge, our focus has centered on several interconnected areas, including product safety, batch-to-batch consistency, durability of response, and advances in manufacturing that may eventually reduce the time and complexity associated with current production models. We are carefully evaluating how different approaches, whether autologous, allogeneic, or in vivo therapies, may alter safety profiles and clinical behavior, particularly when factors such as conditioning regimens, cytokine release syndrome, and other treatment-related toxicities are taken into account. At the same time, dosing remains a major consideration given the difficulty in predicting how long engineered cells may persist in the body, how extensively they may expand, and how those variables ultimately influence both efficacy and safety over time.
Many of these next-generation approaches also introduce broader questions around off-target effects, lipid nanoparticle delivery systems, and other potential long-term risks that still require deeper scientific understanding as the field continues to evolve. As a result, we remain closely engaged through scientific meetings, workshops, internal discussions, and broader collaboration across the sector to ensure that regulatory thinking evolves alongside the technologies themselves. The broader objective is to preserve the transformative potential of these therapies while continuing to identify, evaluate, and mitigate risks in a deliberate and scientifically grounded manner as manufacturing and delivery models become increasingly sophisticated.
Looking forward, what are the key strategic priorities on the table for the OTP?
Our priorities remain focused on ensuring that regulatory science keeps pace with the accelerating complexity of the CGT landscape. A broad range of advances is already reshaping the field, including in vivo CAR-T therapies, NGS, base editing, personalized cancer vaccines, digital health technologies, artificial intelligence, machine learning, and the expanding use of electronic medical records and real-world data. The challenge is not simply adapting to each individual innovation, but understanding how scientific progress, technological capability, and regulatory evolution can collectively accelerate product development and improve patient access to transformative therapies.
As FDA accumulates more experience across approved products and development programs, we continue refining our regulatory approach based on real-world evidence and evolving scientific understanding. One recent example was the removal of Risk Evaluation and Mitigation Strategies (REMS) requirements for approved BCMA- and CD19-directed autologous CAR-T cell immunotherapies following accumulated safety experience with these products. We are also exploring newer regulatory frameworks intended to modernize development and review, including the use of robust pivotal studies supported by confirmatory evidence, Bayesian methodologies in clinical trials, approaches aimed at reducing reliance on animal testing, and broader use of prior knowledge where scientifically appropriate. Ultimately, our focus is on applying these advances in ways that can meaningfully shorten development timelines while preserving the scientific standards expected of advanced therapeutics.
As a final thought, what will be most important in maintaining the FDA’s global leadership in regulation as the CGT field continues to mature and rise in the number of submissions?
Maintaining FDA’s position as a global benchmark in regulation begins with preserving the scientific rigor behind every approval decision. An FDA approval continues to carry significant weight internationally because products undergo an extensive scientific review process focused on demonstrating safety and substantial evidence of effectiveness, and we are not going to lower those standards simply to accelerate market access. Leadership in a rapidly evolving field such as CGT also depends on remaining closely connected to emerging science through continued engagement with academia, laboratories, developers, and the broader research community.
More broadly, there is a significant modernization effort underway across FDA aimed at examining every stage of the product development lifecycle to identify opportunities for improvement, whether through more real-time regulatory interactions, new approaches to balancing pre-market and post-approval evidence generation, or the growing use of artificial intelligence, data analytics, and real-world evidence. CGTs represent the pinnacle of scientific progress in personalized and precision medicine, and the field has now reached an important inflection point. As an organization, we remain committed to evolving our internal structures, review frameworks, and collaborative approach while staying grounded in what I describe as the two strands of OTP’s DNA: gold standard science and common-sense regulation.
