Regulatory resources
An annotated index of the FDA CBER guidance, ICH guidelines, and regulations that govern cell and gene therapy development, organized by the stage at which each becomes decisive. Every link points to the Agency's or ICH's own page. Entries were verified in November 2026; guidance status changes, so confirm the current version at the source.
How to find guidance
Three sources cover nearly everything a CGT program needs.
- CBER's Cellular & Gene Therapy Guidances page (fda.gov) lists every CGT-specific guidance, final and draft, newest first. It is the authoritative index; the selections below are drawn from it. Draft guidances state the Agency's current thinking and are routinely applied in review even before finalization.
- FDA's guidance search (fda.gov → Regulatory Information → Search for FDA Guidance Documents) covers cross-cutting topics the CGT page does not: formal meetings, expedited programs, eCTD, GCP, and the ICH guidelines FDA has adopted. Filter by "Biologics" and by "Draft" or "Final."
- ICH (ich.org) publishes harmonized guidelines in four series: Quality (Q), Safety (S), Efficacy (E), and Multidisciplinary (M). FDA issues each adopted ICH guideline as its own guidance, so the same document is reachable from either site; the FDA copy is the one to cite in a U.S. submission.
Two habits make the difference between consulting guidance and applying it. First, read the Federal Register notice and the docket for a draft guidance; the comments and the Agency's responses at finalization often answer the question the guidance text leaves open. Second, keep the guidance's date against the program's timeline: a program that reaches IND two years after a draft was issued should expect the final version, and should ask at INTERACT or Pre-IND how the Agency intends to apply it.
Guidance by stage
Selected for relevance to T cell, TIL, and nonviral genome-editing programs. Not exhaustive.
Engaging the Agency
Meeting types, timing, and what each forum is for.
- Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Final, August 2026
Defines the six formal meeting types (Type A, B, B-EOP, C, D, INTERACT), their timelines, and package expectations. The reference for choosing which meeting to request. - OTP INTERACT Meetings CBER program page
Eligibility, how to request, and where to send an INTERACT meeting request for products regulated by the Office of Therapeutic Products. - Interactions with the Office of Therapeutic Products CBER program page
Overview of informal and formal interaction opportunities across development. - Frequently Asked Questions: Developing Potential Cellular and Gene Therapy Products Final, August 2026
The Agency's own answers to the questions it receives most often across CMC, nonclinical, clinical, and meeting practice. Read this before any first meeting request.
Nonclinical and proof of concept
Study design, model selection, biodistribution, and editing-specific safety.
- Preclinical Assessment of Investigational Cellular and Gene Therapy Products Final, November 2013
The foundational nonclinical guidance for CGT products: species and model selection, pharmacology, toxicology, and biodistribution expectations. - ICH S12: Nonclinical Biodistribution Considerations for Gene Therapy Products ICH guideline adopted by FDA, May 2023
Harmonized recommendations for the design of nonclinical biodistribution assessments of gene therapy products. - Safety Assessment of Genome Editing in Human Gene Therapy Products Using Next-Generation Sequencing Draft, April 2026
Expectations for off-target, on-target structural, and genomic-integrity assessment of editing products. - Human Gene Therapy Products Incorporating Human Genome Editing Final, January 2024
Product design, manufacturing, nonclinical, and clinical considerations specific to genome-editing products. - Considerations for the Use of the Plausible Mechanism Framework to Develop Individualized Therapies Draft, February 2026
A framework for individualized therapies targeting genetic conditions with known biological cause; relevant where conventional evidence generation is infeasible. - Leveraging Prior Knowledge in the Development of Human Gene Therapy Products Incorporating Genome Editing Draft, June 2026
When and how data from a platform or a prior product version may support a new editing product.
Chemistry, manufacturing, and controls
Control strategy, potency, comparability, starting materials, and the path to BLA.
- CMC Information for Human Gene Therapy Investigational New Drug Applications Final, January 2020
What Module 3 must contain for a gene therapy IND, section by section. - Content and Review of CMC Information for Human Somatic Cell Therapy INDs Final, April 2008
The cell therapy counterpart: Module 3 expectations for cellular products. - Potency Assurance for Cellular and Gene Therapy Products Final, November 2026
Supersedes the 2011 potency-tests guidance; frames potency as a strategy spanning process design, in-process controls, characterization, and release. - Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products Draft, July 2023
How to assess and report manufacturing changes during development and after licensure. - CMC Flexibilities for Developing Human Cellular and Gene Therapy Products for a Biologics License Application Final, May 2026
The flexibilities CBER applies to CGT products heading to BLA, including process performance qualification and analytical validation with limited lots. - Considerations for the Use of Human- and Animal-Derived Materials in the Manufacture of CGT and Tissue-Engineered Products Draft, April 2024
Qualification and testing of raw and ancillary materials of biological origin. - Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products Draft, April 2024
Testing expectations for expanded allogeneic cell populations. - Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus Final, January 2020
RCR testing during manufacture and patient follow-up for retroviral and lentiviral products.
Product-class and clinical guidance
CAR-T, retinal, rare disease, early-phase design, and long-term follow-up.
- Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products Final, January 2024
CMC, nonclinical, and clinical considerations specific to CAR-T products, including vector, cell-source, and multiplexed-product issues. - Human Gene Therapy for Retinal Disorders Final, January 2020
Product, nonclinical, and clinical considerations for gene therapies administered to the eye. - Human Gene Therapy for Rare Diseases Final, January 2020
Development considerations where the population is small, including natural-history data and trial design. - Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products Final, June 2015
Dose selection, staggering, safety monitoring, and population choice for first-in-human CGT trials. - Studying Multiple Versions of a Cellular or Gene Therapy Product in an Early-Phase Clinical Trial Final, November 2022
Umbrella-style evaluation of product variants under one clinical program. - Innovative Designs for Clinical Trials of Cellular and Gene Therapy Products in Small Populations Draft, September 2025
External controls, Bayesian and adaptive designs, and natural-history comparators for rare-disease CGT trials. - Long Term Follow-up After Administration of Human Gene Therapy Products Final, January 2020
Risk assessment and long-term follow-up design, including for integrating and genome-editing products. - Expedited Programs for Regenerative Medicine Therapies for Serious Conditions Final, February 2019; draft revision September 2025
RMAT designation and the other expedited programs available to regenerative medicine products.
ICH guidelines
Harmonized quality, safety, efficacy, and multidisciplinary guidelines; FDA issues adopted ICH guidelines as guidance.
- ICH Quality guidelines (Q series) ICH index
Of most use to CGT programs: Q5A(R2) viral safety, Q5D cell substrates, Q5E comparability after manufacturing changes, Q6B specifications for biological products, Q2(R2) and Q14 analytical validation and development, Q8(R2), Q9(R1), and Q10 pharmaceutical development, risk management, and quality system, Q11 drug-substance development. - ICH Safety guidelines (S series) ICH index
S6(R1) preclinical safety evaluation of biotechnology-derived products, S9 nonclinical evaluation for anticancer pharmaceuticals, S12 nonclinical biodistribution for gene therapy products. - ICH Efficacy guidelines (E series) ICH index
E6(R3) Good Clinical Practice, E8(R1) general considerations for clinical studies, E9 statistical principles, E2A clinical safety data management. - ICH Multidisciplinary guidelines (M series) ICH index
M3(R2) nonclinical safety studies to support clinical trials, M4 Common Technical Document (the Module 3, 4, 5 structure an IND and BLA follow).
Regulations
The binding requirements behind the guidances.
- 21 CFR Part 312: Investigational New Drug Application eCFR
IND content, sponsor and investigator obligations, safety reporting, and clinical holds. - 21 CFR Part 601: Licensing eCFR
Biologics license applications and, in 601.12, changes to an approved application. - 21 CFR Part 1271: Human Cells, Tissues, and Cellular and Tissue-Based Products eCFR
Donor eligibility, current good tissue practice, and the 361 HCT/P criteria. - 21 CFR Parts 210 and 211: Current Good Manufacturing Practice eCFR
CGMP for finished pharmaceuticals, applied in a phase-appropriate manner to investigational products.
Begin with a program, a question, or a portfolio.
Most engagements begin with a short call to establish where the program stands and which decision comes next, whether it concerns regulatory strategy, manufacturing, nonclinical development, clinical readiness, intellectual property, or the disposition of a portfolio.