FDA draft guidance details real-world data expectations for postapproval monitoring of cell and gene therapies 

The US Food and Drug Administration (FDA) has issued a September 2025 draft guidance titled “Postapproval Methods to Capture Safety and Efficacy Data for Cell and Gene Therapy Products” that explains how sponsors should generate postapproval evidence using real-world data (RWD), registries, and decentralized or remote data collection approaches outside of traditional clinical sites. The guidance was released alongside two companion drafts under the Prescription Drug User Fee Act (PDUFA VII), which is the seventh authorization for fiscal years 2023 to 2027. 

When finalized, “this draft guidance… will represent the current thinking of the Food and Drug Administration,” but “is not binding on FDA or the public.” Its purpose is to outline methods and approaches for capturing postapproval safety and efficacy data for cell and gene therapies (CGTs). The guidance adopts a lifecycle evidence approach. The draft notes that as, “during premarketing clinical development, the number of patients receiving CGT products is typically limited, further postapproval data can strengthen understanding of long-term safety and effectiveness and guide clinical use and regulatory decisions." 

RWD and real-world evidence (RWE) sit at the center of the approach. Sponsors are encouraged to engage early with the Center for Biologics Evaluation and Research (CBER) on data-source selection, including through the Advancing Real-World Evidence Program. Strong governance is expected, with auditable processes, privacy safeguards, and documented data-quality controls. The guidance also states that “software programs used to produce and process postapproval data are subject to 21 CFR part 11,” and notes that digital health technologies may support remote capture. 

On fitness for use, the agency is direct about the limitations of routine data: 

“Administrative medical claims, vital statistics, and electronic health records (EHRs) are not typically designed to collect data for evaluation of safety or effectiveness of medical products.”  

To address this, sponsors should run feasibility assessments to confirm representativeness, pre-specify computable phenotypes and algorithms in protocols, plan uninterrupted longitudinal follow-up from the index CGT exposure, monitor shifts in clinical practice over time and set transparent methods for missing or fragmented data, including linkage or validated proxies where justified. Appropriate applications include utilization profiling, estimation of outcome rates, and establishing background rates for outcomes such as malignancy or cardiovascular events. The draft also notes that RWD may be used for “training of Artificial Intelligence (AI) and Natural Language Processing (NLP) machine-learning models to develop computable phenotypes” for safety or effectiveness outcomes. 

Registries feature prominently as structured, longitudinal resources that can address limitations in routine data. The guidance defines a registry as “an organized system that collects clinical and other data in a standardized format for a population defined by a particular disease, condition, or drug exposure.” It highlights uses such as durability assessment, malignancy surveillance, growth and developmental tracking in pediatric recipients, and monitoring pregnancy and fertility outcomes after conditioning regimens. Sponsors are urged to plan for representativeness and retention so that registry cohorts reflect treated populations over time. 

To reduce burden and improve retention across long follow-up periods, the draft endorses decentralized data collection using local healthcare professionals, telemedicine, and in-home assessments. It notes that this model: 

“Can play a critical role in capturing and assessing postapproval efficacy and safety data for CGT products, because it provides a new paradigm of data collection that is more accessible and less burdensome.”  

Protocols should specify which data elements are captured remotely, how effectiveness and adverse events are assessed locally, and where participants receive routine and urgent care. Institutional review board oversight and informed consent remain applicable in the postapproval setting. Pediatric programs may require long observation and careful transition of care into adulthood. 

Two companion drafts were issued at the same time. “Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations” provides nonbinding FDA recommendations for planning, design, conduct, analysis, and endpoint selection in rare or small populations, detailing requirements, and innovative designs to support licensure and effectiveness assessment. “Expedited Programs for Regenerative Medicine Therapies for Serious Conditions” explains regenerative medicine advanced therapy designation and the use of fast track, breakthrough, accelerated approval, and priority review, describes routes to engage CBER, and applies to regenerative medicine therapies regulated as biologics under section 351 of the Public Health Service Act. 

Comments are requested by November 24, 2025 for the small-population trial-design draft and December 24, 2025 for the postapproval methods draft. Overall, the postapproval guidance sets clear expectations for RWD-enabled, long-term evidence generation that balances small premarket datasets with robust postmarket monitoring of CGTs.