By: OM1, November 2025
Cell and gene therapies (CGT) are reshaping medicine, but their potential long-lasting effects demand equally enduring sources of evidence. The FDA’s Center for Biologics Evaluation and Research (CBER) recently released draft guidance, “Post-approval methods to capture safety and efficacy data for cell and gene therapy products”, outlining how sponsors should approach long-term, real-world data (RWD) collection after approval, especially in rare or pediatric populations where premarket evidence is often limited by small sample sizes or length of observation.
Key Takeaways
Long-term follow-up is non‑negotiable
For some CGT products, FDA recommends long-term follow-up (LTFU) observational studies lasting up to 15 years to monitor benefit-risk balance, including through assessment of delayed adverse effects, unknown risks, mortality, and durability of short- and long-term treatment effects. Beyond post-authorization requirements, LTFU for these therapies also serves an important role in supporting patient access, establishing cost-effectiveness, and informing payer decision-making.
Traditional RWD has real limits for CGT
Electronic health records (EHRs), medical claims, and vital statistics can support certain analyses (e.g., utilization, background rates, training AI/NLP). However, they often struggle with rare disease and specialty care variables, may lack sufficient specificity, and can miss data from fragmentation when patients change providers or insurers. When used for LTFU, the methodology must be robust in its ability to apply operational algorithms and computable phenotypes for key outcomes, assess and mitigate the effects of missing data (including the potential for validated extraction of data from clinically rich, unstructured parts of the EHR), and minimize loss to follow-up.
Registries are central
Purpose-built registries, organized systems collecting standardized, curated data are emphasized as the primary evidence tools for CGT. They can capture patient-reported outcomes, disease severity, and specialized data such as genomics and histopathology, enabling robust durability assessments, pediatric growth and development tracking, and malignancy surveillance. A couple of caveats are noted including that representativeness can be a challenge; enrollment and recruitment biases must be managed. Coordinated registry networks may offer high-quality real-world evidence but require fit-for-purpose evaluation before use.
Decentralized methods reduce burden and improve retention
Borrowing from decentralized clinical trials, a virtual/central site model can coordinate remote, electronic, and local clinical interactions for long-term data collection. Patients undergoing these therapies may come from distant locations and may not fall under the care of their CGT provider past the initial assessment phase. Benefits of a virtual/central site-based approach to LTFU include a lower burden to patients, caregivers, and investigators, higher retention, and potentially improved generalizability. As mentioned in the FDA guidance, due to the long duration of follow-up, some studies also include patients that transition from pediatric to adult clinical care during LTFU, which may complicate more traditional models of follow-up. Effective implementations build in flexible protocols, leverage local HCPs and telemedicine, and ensure rigorous tracking of post-approval activities.
Operational and regulatory expectations
Data quality and integrity are paramount. Robust data governance procedures are required to ensure patient privacy is preserved and all data are maintained in a secure environment. Software used to produce and process post-approval data is subject to 21 CFR Part 11 and considerations around IRB approval and informed consent still apply. Sponsors are encouraged to consult CBER early when selecting real-world data sources and designing LTFU strategies.
Why this matters now
CGT pipelines are expanding quickly, while premarket studies remain relatively small. The draft guidance recognizes the practical limits of conventional real‑world data for rare, highly specialized populations and recognizes registries and decentralized approaches as the most pragmatic, scalable path to credible long-term evidence.
Bottom line for Sponsors
The message is clear: design for LTFU from day one.
Invest in fit‑for‑purpose registries, augmented with decentralized collection to minimize patient burden, and build compliant, auditable data systems. This approach makes LTFU feasible, scientifically rigorous, and financially sustainable while delivering the evidence patients, clinicians, and regulators need.
Why OM1 is uniquely positioned for CGT registries
Purpose-built, CFR 21 Part 11 compliant and validated registry platform
OM1 runs validated, audit-tracked registry infrastructure with full 21 CFR Part 11 compliance, enabling post-approval use and seamless traceability from source data to submitted endpoints.
Deep expertise in rare disease phenotyping
Our AI-powered digital phenotyping platform enables precise cohort identification when diagnosis codes are insufficient. This is especially critical for CGT where standard claims and EHR data frequently under-capture disease severity and subtypes.
Experience with validated extractions
Our validated machine learning model estimates outcomes such as disease activity scores using unstructured clinical notes. This fuels the capture of adverse events, key outcomes, and fills gaps in RWD sources making these data more valuable for research and regulatory submission.
Hybrid, decentralized operational model already in market
OM1 registries routinely combine real-world data ingestion, site-less enrollment, PRO capture, and clinical abstraction. This enables long-term follow-up over time without dependency on single-site care continuity.
Enterprise-scale linkage and longitudinal follow-up
Patients are kept in-frame for 5–15 years with links across sites, providers, and insurers, solving the exact data fragmentation problem FDA calls out as an RWD limitation for CGT.