FDA Announces a “Flexible Approach” on Chemistry, Manufacturing and Control for Cell and Gene Therapies

On January 11, 2026, FDA posted an announcement about its “flexible approach” to overseeing chemistry, manufacturing, and control (CMC) requirements for cell and gene therapies (CGTs), specifically, flexibilities in clinical development, commercial specifications, and process validation.

While the announcement largely reflects existing policy and practice, it may clarify ambiguities in certain cases. FDA believes the announcement of its flexible approach will help expedite product development and guide FDA’s evaluation of the development strategies for biological products.

Background on CMC Requirements for Cell and Gene Therapies

The statutory and regulatory requirements for CMCs are generally the same for all biological products. Thus, the legal standard is often the same for simple biologics such as small proteins as for the most complex CGTs. In practice, however, CGTs, which are regulated by FDA’s Center for Biologics Evaluation and Research (CBER), present unique CMC challenges, as the products are inherently complex and often manufactured in small batches. Some are even individualized for each patient, starting with the patient’s own cells or tailored to the patient’s genes or specific mutations, necessitating sophisticated manufacturing processes under significant time constraints.

Recognizing that CGTs present unique considerations that may not be present for other biological products, CBER has issued several key guidance documents expanding on the Agency’s thinking regarding CMC for CGTs, including:

• In January 2020, FDA released its final guidance on CMC Information for Human Gene Therapy Investigational New Drug Applications (INDs), which provided recommendations to sponsors on how to provide sufficient CMC information in an IND to assure the safety, identity, quality, purity, and strength of their product.
• In July 2023, FDA released a draft guidance on Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products, which described FDA’s current thinking on the management and reporting of manufacturing changes for CGT products based on a lifecycle approach and necessary comparability studies to assess the effect of manufacturing changes on product quality.
• In November 2024, FDA released a draft guidance with Frequently Asked Questions on Developing Potential Cellular and Gene Therapy Products, which addressed a variety of questions related to product development, including critical quality attributes, process characterization or validation, and manufacturing changes.

These guidance documents outline FDA’s historically flexible approach with respect to CMC for CGTs, but questions remained about FDA’s expectations on CMC for CGTs.

FDA Policy Priorities for Cell and Gene Therapies

Expediting CGT product development has been one of FDA’s key policy priorities in the Trump Administration. FDA has announced several initiatives with respect to CGTs, including:

• In June 2025, FDA held a Roundtable on CGTs, and Dr. Martin Makary, the Commissioner of Food and Drugs at FDA, committed to “continue the successes of the FDA in facilitating the regulatory process for these conditions and these products. We are also going to try and improve by creating more efficiencies.” During the Roundtable, several speakers remarked on the need for regulatory flexibilities that better reflect the realities of developing CGTs for ultra-rare diseases. In response, Dr. Vinay Prasad, Director of CBER, stated FDA is fully committed to providing flexibilities for therapies targeting rare conditions.
• In November 2025, Director Prasad and Commissioner Makary introduced the “New Plausible Mechanism Pathway” in the New England Journal of Medicine as part of FDA’s efforts to expedite the development of CGTs. The pathway is intended to support market entry for personalized therapies where a randomized trial is not feasible, such as cell and gene therapies for ultra-rare conditions with a clearly defined molecular or cellular abnormality as the causal defect.

FDA’s announcement on CMC for CGTs is the latest effort by FDA to streamline and accelerate CGT development.

FDA’s Proposed Flexibilities to CMC Requirements

On January 11, FDA published a new webpage describing its flexible approach for CGTs. These flexibilities largely align with FDA’s past guidance related to CMC for CGTs, though FDA’s announcement clarifies FDA’s expectations with respect to certain aspects of CMCs for CGTs. Specifically:

• Clinical Development Flexibilities: If a manufacturing change is minor, CBER will not require overly stringent or onerous comparability data demonstrating the comparability of the pre-change and post-change product. This is aligned with the Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products and CMC Information for Human Gene Therapy Investigational New Drug Applications (INDs) guidance.
• Commercial Specification Flexibilities: As appropriate and when justified, CBER will consider flexibility on product release specifications for CGT Biological License Applications (BLAs). Upon demonstration of consistent product quality, CBER will also consider requests to revise release specifications based on post-approval manufacturing experience. This is aligned with the Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products and Frequently Asked Questions on Developing Potential Cellular and Gene Therapy Products guidance.
• Process Validation Flexibilities: CBER reminds sponsors that there is no requirement to manufacture three PPQ lots as part of process validation and that its review will consider whether the PPQ protocols justify the proposed number of lots. This is aligned with the Frequently Asked Questions on Developing Potential Cellular and Gene Therapy Products guidance.

FDA also encouraged CGT sponsors to consult with review divisions throughout the product development process.

Takeaways from FDA’s Announcement on CMCs for CGTs

Sponsors of CGTs should keep the following in mind as they develop their CMC strategy in light of FDA’s new announcement:

1. All CGTs must comply with the applicable CMC requirements in the Federal Food, Drug, Cosmetic Act (FDCA), the Public Health Service Act (PHSA), and FDA’s regulations. FDA’s announcement did not change the legal requirements with respect to CMCs for CGTs nor did it announce any new enforcement discretion policy. FDA’s announcement provides additional clarity on how sponsors can meet CMC statutory and regulatory requirements, but the underlying legal requirements have not changed.
2. Given the alignment between FDA’s past guidance on CGTs and the announced CMC flexibilities, in practice, sponsors may not see a significant change in how FDA reviews and assesses CMCs for CGTs. Sponsors should continue to work closely with FDA and seek advice early and throughout product development on their CMC strategy.
3. While the announcement discusses flexibilities on CMC, especially at early stages of development, sponsors should closely monitor and address CMC challenges as they arise to avoid larger CMC issues later in product development, potentially delaying product approval.

If you have any questions concerning the material discussed in this client alert, please contact the following members of our Food, Drugs, and Devices practice.