North America LRA Watchdog

North America LRA Watchdog—February 2026

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Adam Lee, MS
Thermo Fisher Scientific
United States

J. Wade Atkins, MS, MT (ASCP) SBB, CQA (ASQ)
National Institute of Health
United States

With the new year underway, CBER (Center for Biologics Evaluation and Research) continues to discuss and publish their new approaches to bring cell and gene therapy to market. Recently, an ambitious list of guidance documents was published outlining their plans to update, create, or finalize guidance documents in 2026. So far this year, the FDA appears to be focusing on streamlining the review of cell and gene therapies with specific discussion of more flexible review of the CMC of early phase products and discussion of ways to modernize trial design and analysis. These and other documents further demonstrate the agency’s commitment to a different approach for reviewing the unique challenges of cell-based therapeutic products. A list of activities, guidance documents and opinion pieces released by the FDA includes:

FDA held a roundtable on cell and gene therapies in June of 2025. In it, Commissioner Dr. Martin Makary pledged to continue facilitating regulation and “create more efficiencies.” Speakers emphasized the need for regulatory flexibility, and CBER Director Dr. Vinay Prasad affirmed FDA’s commitment to providing that flexibility for therapies targeting rare conditions.
FDA CBER OTP Public Listening Meeting: Leveraging Knowledge for Facilitating the Development and Review of Cell and Gene Therapies - September 18, 2025. Three different individuals from ISCT Leadership presented at the meeting presenting challenge faced by developers of cell and gene therapy products as well as potential solutions to those challenges.
Conducting Clinical Trials with Decentralized Elements; Guidance for Industry, Investigators, and Other Interested Parties - October 16th, 2025
FDA’s New Plausible Mechanism Pathway – November 2025
Increased flexibility on requirements for cell and gene therapy - January 11th, 2026
Use of Bayesian Methodology in Clinical Trials of Drug and Biological Products; Draft Guidance for Industry — January 12th, 2026.
Guiding Principles of Good AI Practice in Drug Development — January 14th, 2026.

We welcome these additions to the regulatory landscape in the US and look forward to seeing their implementation in product review.

Moving forward, industry now looks to CBER’s publicly shared guidance agenda that is now shared with the public. While it is uncertain if the FDA will update every document on the list, at the very least, the topic’s inclusion signals agency interest but could also foreshadow the dominating policy discussions this upcoming year. It is not unreasonable to expect that some of these documents could influence regulatory submissions and compliance strategies. In short, this list warrants attention from sponsors who rely on these materials as new frameworks can emerge.

Below is a methodical approach to track the current status of topics of interest to the cell and gene therapy community and presented in the guidance agenda from CBER. Please note that some items on CBER’s list such as vaccines and allergy testing were excluded in this article for increased focus on cell and gene therapy related topics. The brief overview is informational and should not be interpreted as predicting or presuming any future changes to the guidance.

Guidance	Current Status	Brief Overview
Recommendations for Testing Blood Donations for Human T- lymphotropic Viruses I and II.	New guidance in development.¹	To be published.
Considerations for the Use of Human- and Animal- Derived Materials and Components in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products.	Draft guidance available.	Outlines how sponsors should assess and control human and animal derived raw materials used in manufacturing of cell, gene, and tissue engineered products to mitigate safety and quality risks. Emphasizes risk management process, adventitious agent risk management, and material characterization to ensure consistent production.
Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products.	Draft guidance available.	Describes recommended safety testing for donor-derived cells that are expanded for use in cell-based medical products, covering identity, sterility, mycoplasma, adventitious viruses, endotoxin, genetic stability, and tumorigenicity. Emphasizes testing for Master and Working Cell Bank as well as primary cell expansion in culture.
Potency Assurance for Cellular and Gene Therapy Products.	Draft guidance available.	Defines how to establish a potency strategy, linking assays to mechanism of action and setting acceptance criteria. Emphasizes the relevant regulatory framework and developing a potency assurance strategy and acceptance criteria.
Potency Assessment of Active Immunotherapy Products.	New guidance in development.²	To be published.
Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products.	Draft guidance available.	Addresses on how to manage and justify manufacturing changes for CGT products. Emphasizes considerations, regulatory reporting, and comparability assessment and report.
Post Approval Methods to Capture Safety and Efficacy Data for Cell and Gene Therapy Products Draft guidance available Focuses on post-approval monitoring for CGT products using pharmacovigilance, registries, real world data, and use of registries to design, collect, and analyze data to maintain regulatory confidence after approval.	Draft guidance available.	Focuses on post-approval monitoring for CGT products using pharmacovigilance, registries, real world data, and use of registries to design, collect, and analyze data to maintain regulatory confidence after approval.
Chimeric Antigen Receptor (CAR) T Cell Products: Development Considerations for Non-Oncology Indications.	New guidance in development.	To be published.
Considerations for Clinical Study of Porcine Derived Solid Organs for Xenotransplantation.	New guidance in development.	To be published.
Considerations for Testing, Sampling, and Archiving of Xenotransplantation Products.	New guidance in development.	To be published.
Expedited Programs for Regenerative Medicine Therapies for Serious Conditions.	Draft guidance available.	Provides pathways to accelerate development and review of regenerative medicine therapies for serious conditions (e.g., RMAT designation), outlining criteria and evidentiary expectations.
Establishing a Plausible Mechanism Supporting Approval of Individualized Therapies to Treat Rare Genetic Disorders.	New guidance in development.³	To be published.
Leveraging Prior Knowledge in the Development of Human Gene Therapy Products Incorporating Genome Editing.	New guidance in development.⁴	To be published.
Recommendations to Reduce the Risk of Transmission of Mycobacterium tuberculosis by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).	Draft guidance available.	Provides screening and donor eligibility recommendations to minimize tuberculosis transmission via HCT/Ps. Emphasizes potential, severity, and appropriate screening measures.
Recommendations to Reduce the Risk of Transmission of Human Immunodeficiency Virus (HIV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).	Draft guidance available.	Provides donor screening, testing, and deferral recommendations to minimize HIV transmission via HCT/Ps. Emphasizes potential, severity, and appropriate screening measures.
Recommendations to Reduce the Risk of Transmission of Hepatitis C Virus (HCV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).	Draft guidance available.	Provides donor screening, testing, and deferral recommendations to minimize HCV transmission via HCT/Ps. Emphasizes potential, severity, and appropriate screening measures.
Recommendations to Reduce the Risk of Transmission of Hepatitis B Virus (HBV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).	Draft guidance available.	Provides donor screening, testing, and deferral recommendations to minimize HBV transmission via HCT/Ps, using validated assays. Also covers handling/labeling practices to ensure product safety.
Recommendations to Reduce the Risk of Transmission of Disease Agents Associated with Sepsis for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).	Draft guidance available.	Provides donor screening, clinical assessment, and testing recommendations to reduce sepsis-related pathogen transmission in HCT/Ps. Emphasizes potential, severity, and appropriate screening measures.
Recommendations for Determining Eligibility of Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).	Draft guidance available.	Defines how to assess donor eligibility for HCT/Ps through medical history, physical exam, risk screening, and required infectious disease testing to ensure product safety. Emphasizes donor eligibility, donor screening, and donor testing.
Recommendations for Validation and Implementation of Alternative Microbial Methods for Testing of Biologics.	New guidance in development.	To be published.