FDA's Global Gene Therapy Pilot Program: Will 2024 mark the maturation of gene therapy approvals?

The FDA's recent announcement of the Collaboration on Gene Therapies Global Pilot program marks a significant step in the agency's efforts to streamline international regulations for gene therapies in a new and exciting way-- a way that could be transformative for gene therapy developers and investors in this space.

In his recent talk, Peter Marks, M.D., Ph.D, director of the FDA’s Center for Biologics Evaluation and Research said that the idea of an international gene therapy collaboration “finally has some traction,” which he said was “probably helped by the pandemic.” The Collaboration on Gene Therapies Global Pilot (CoGenT) will include initially include regulatory members of the International Council for Harmonisation (ICH), including the EU, the US, Japan, Canada, and Switzerland. According to Regulatory Focus, an FDA spokesperson told Focus the pilot is “still in the early stages of development” and Endpoints News has reported on Marks recent comments, calling out that "FDA is setting out to streamline international regulations of gene therapies."

international gene therapy collaboration “finally has some traction” - Peter Marks, M.D., Ph.D, director of the FDA’s Center for Biologics Evaluation and Research

Key Elements of the Collaboration on Gene Therapies Global Pilot program

1. International Collaboration: The FDA is actively engaging with international partners, global regulators, and the World Health Organization (WHO) to explore the possibility of a "concurrent collaborative" review process for gene therapy applications. This collaborative approach underscores the agency's commitment to establishing uniform global standards for evaluating and regulating cell and gene therapy products.

2. Efficiencies in Clinical Development: The lack of uniform global standards for gene therapy clinical trials, post-market following and other clinical development regulatory milestones poses a challenge for biologic drug developers in this space. The FDA's emphasis on harmonization efforts in this area is expected to facilitate more efficient clinical development, offering developers a clearer regulatory pathway for their gene therapy products-- a good sign for biotechs in this space that can help derisk investment.

3. Impact on Rare Diseases: The FDA's intensified focus on gene therapies and rare diseases is evident through the launch of the FDA 'Operation Warp Speed'-like pilot program for rare diseases in September 2023 aimed at accelerating the approval process for rare disease products. This strategic focus reflects the agency's commitment to expediting the development and approval of innovative therapies for patients with rare and life-threatening conditions.

Why should biologics product developers and investors keep an eye on this program?

For biologic drug developers, the FDA's Collaboration on Gene Therapies Global Pilot program carries immense significance. The program offers the potential to simplify the regulatory landscape, reduce barriers to global market access, and create a more predictable pathway for the development and approval of gene therapy products. By aligning international regulations and standardizing evaluation processes, this initiative is poised to promote innovation, drive investment, and ultimately improve patient access to life-changing gene therapies.

FDA's proactive approach to global regulatory harmonization of gene therapies through the Collaboration on Gene Therapies Global Pilot program signifies a pivotal moment for biologic drug developers-- and investors in this space, which has assumed relatively high risk (and arguable setbacks in the investment landscape for gene and cell therapies in late 2023). This new FDA program sets the stage for greater collaboration, efficiency, and clarity in the development and regulation of gene therapies, paving the way for transformative advancements in biologic drug development and rare disease treatment.

What set the stage in recent international collaboration on Drug Approvals?

Not only was Operation Warp Speed a domestic and international success in accelerating Covid vaccines and fostering a cross-Agency conversation on accelerating the regulatory process, the FDA Oncology Center of Excellence (OCE) initiated Project Orbis launches in May 2019 setup a pilot framework for concurrent international approvals of oncology drugs-- which has allowed dramatically faster international approvals for 13 new drugs in oncology to date.

International collaboration on approvals not only reduces time and administrative burden, but has a public health impact allowing patients to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, regardless of whether the product has received FDA approval. Pivotal clinical trials in oncology are commonly conducted internationally and these global trials are increasingly important for investigating the safety and effectiveness of cancer drugs for approval in the United States. Future drug development may benefit by establishing a greater uniformity of new global standards of treatment, leading to the optimal design of these important trials.

Marks said one of the lessons learned from the pandemic is that “global regulators realize that what we do is more common than divergent. What we do at FDA has a lot in common with the European Medicines Agency.” He added that “there are some subtle differences, we do some things that they don’t do and vice versa, but if we can harmonize our requirements and pull forces to review these products, we can make it much more attractive for people to go into this rare disease area.”

"global regulators realize that what we do is more common than divergent. What we do at FDA has a lot in common with the European Medicines Agency.” - Peter Marks, M.D., Ph.D, director of the FDA’s Center for Biologics Evaluation and Research

Can the Gene Therapies Global Pilot program Speed up gene therapy drug development and Approvals?

The sort answer is a resounding yes. The new Gene Therapies Global Pilot program has the potential to speed up the approval process for gene therapies. By facilitating collaborative review of gene therapy applications alongside global regulatory partners, the program aims to streamline international regulations, harmonize evaluation processes, and promote greater efficiency in clinical development. This collaborative approach and emphasis on global regulatory harmonization are designed to create a more predictable pathway for the development and approval of gene therapy products, ultimately expediting the approval process for these transformative therapies.

The impact of the Gene Therapies Global Pilot program on the timeline for gene therapy approvals is expected to be significant. By streamlining international regulations, enhancing collaborative review processes, and promoting global regulatory harmonization, the program is poised to accelerate the timeline for gene therapy approvals. The harmonization of evaluation processes and the creation of a more predictable regulatory pathway are likely to reduce barriers and inefficiencies, ultimately leading to shorter approval timelines for gene therapy products. Furthermore, the program's focus on rare diseases and its commitment to expediting the approval process for these products indicate a strategic effort to improve patient access to innovative gene therapies within an expedited timeframe. Overall, the program is anticipated to positively impact the timeline for gene therapy approvals, fostering a more efficient and predictable regulatory environment for these transformative therapies.

What could the program mean for CMC development and the often-complex gene therapy manufacturing considerations?

Chemistry, Manufacturing, and Controls (CMC) regulations for gene and cell therapy products encompass a range of specific requirements tailored to the unique characteristics of these innovative therapies. These regulations address aspects such as the manufacturing process, quality control, product characterization, and stability testing, reflecting the complex nature of gene and cell therapies. While there is a concerted effort to standardize CMC regulations globally, differences in regional requirements and guidelines still exist.

The FDA's Gene Therapies Global Pilot program is poised to have a notable impact on Chemistry, Manufacturing, and Controls (CMC) regulatory professionals involved in the development and approval of gene therapies-- reducing much of the uncertainty that goes into Module 3 dossier prep at both early stage and approval stages for gene therapies.

Here are a few key impacts:

1. Simplifies Global Regulatory Documentation & Reduces both Risk, Rework, and Country-specific CMC Complexities: CMC regulatory professionals will benefit from the program's efforts to streamline international regulations for gene therapies. This harmonization of regulatory requirements across global markets will reduce the complexity and ambiguity of compliance efforts, facilitating a more consistent and predictable regulatory landscape for CMC professionals.
2. Enhanced Collaboration and Communication: The program's emphasis on collaborative review processes with global regulatory partners will require CMC professionals to strengthen their communication and collaboration skills. The need to align with international regulatory standards and engage in concurrent collaborative reviews will necessitate effective coordination and communication among CMC teams, regulatory agencies, and partners worldwide.
3. Streamlined Evolution of Industry Standards: The program's focus on establishing uniform global standards for evaluating and regulating gene therapy products will contribute to the evolution of industry standards for CMC professionals. As regulatory requirements become more harmonized, CMC professionals will need to stay updated on international best practices and adapt their strategies to align with evolving global standards.
4. Improved Efficiency in Product Development: CMC regulatory professionals will experience improved efficiency in the development and approval of gene therapy products due to the program's intent to create a more predictable pathway for regulatory approval. This streamlined process could lead to faster development timelines and reduced barriers to global market access, allowing CMC professionals to navigate a more efficient regulatory pathway.

Here's an overview of CMC regulations for gene and cell therapy products and their relationship to global standardization, including the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

In which areas do we most need international harmonization for gene therapy?

Despite efforts for global harmonization, variations in regional requirements persist. Regulatory agencies such as the U.S. FDA, the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan have specific guidelines for gene and cell therapies. While these guidelines share commonalities, differences in terminology, specific requirements, and documentation expectations exist.

Additional harmonization is needed for specific CMC Requirements gene therapies. Gene therapy products often utilize viral vectors for gene delivery. CMC regulations for gene therapies encompass guidelines for the manufacturing, testing, and characterization of viral vectors, taking into account safety, purity, and potency considerations. Similarly, cell therapy products involve the manipulation of cells for therapeutic purposes. CMC regulations for cell therapies address the sourcing, manufacturing, expansion, and storage of cells, as well as the processes for maintaining cell identity and purity.

The International Council for Harmonisation (ICH) brings together regulatory authorities and pharmaceutical industry experts to develop harmonized guidelines for drug development and registration. While ICH guidelines cover a broad range of topics, efforts to harmonize CMC regulations for gene and cell therapies are ongoing within the framework of the ICH's Quality, Safety, and Efficacy guidelines. These efforts aim to align CMC requirements across regions to facilitate global development and registration of gene and cell therapy products, but have not received full adoption to date. This renewed FDA push for international collaboration in gene therapies may signal a positive change in the near future for international standards in this area.

Summary and Key Takeaways

In summary, CMC regulations for gene therapy products are specific to the unique attributes of these innovative therapies, encompassing manufacturing, quality control, and product characterization requirements. While global harmonization efforts, including those within the ICH framework, seek to standardize CMC regulations for gene and cell therapies, regional differences continue to influence specific requirements. Ongoing initiatives and collaborative programs (ie Project Orbis, Operation Warp Speed, etc.) aim to bridge these gaps and establish a more harmonized regulatory landscape for gene and cell therapy products.

Overall, the Gene Therapies Global Pilot program holds the potential to positively impact CMC regulatory professionals by fostering a more harmonized, collaborative, and efficient regulatory environment for gene therapies, thereby shaping the way for advancements in CMC regulatory practices.

We will continue to follow the early experiences with this program-- what are your thoughts?

Angela Johnson, PhD, RAC is the head of global regulatory compliance for Cytiva and lecturer on regulatory strategy at Northeastern University. She has led two venture-backed biotech regulatory teams to IPO and held leadership roles at IQVIA, GE Healthcare, and APAC consulting firms in drug development, and is an active member of the Regulatory Affairs Professionals Society (RAPS) and regulatory board member of the American Society of Cell & Gene Therapy (ASGCT), with more than 30 publications on regulatory and drug development.