Description
This guidance is intended to provide industry with answers to frequently asked questions (FAQs) and commonly faced issues that arise during the development of cellular and gene therapy (CGT) products and is intended to help facilitate the development of safe, effective, and high-quality CGT products. The FAQs represent common questions directed to the Agency and span multiple disciplines, including regulatory review, chemistry, manufacturing, and controls (CMC), pharmacology/toxicology (PT), clinical, and clinical pharmacology.
Scope & Applicability
Product Classes
10Guidance focuses on innovative designs for clinical trials of these products.; Innovative designs for clinical trials of CGT products.
Human cells, tissues, or cellular or tissue-based products defined in 21 CFR Part 1271
Specific category for CMC guidance
Specific category for CMC guidance
Tumorgenicity studies are usually necessary for pluripotent stem cell-derived products
Includes allogeneic and autologous cell therapies
A type of ATMP involving recombinant nucleic acids or viral vectors.
Cells or tissues from a donor for use in another individual.
Cells and tissues used in the manufacture of products for the same individual.
Sponsors should consider follow-up using RWD from the index date of CGT use.
Stakeholders
5responsible for justifying omission of studies
Individuals preparing and submitting IND applications
Institutional Review Board providing study approvals
The submitter will be contacted by the RPM who will provide a BQ number; Regulatory Project Manager provided as a contact.
FDA staff member involved in informal interactions
Regulatory Context
Attributes
2Physical, chemical, biological, or microbiological properties
study duration should be informed by the biodistribution profile
Identified Hazards
Hazards
2Adventitious agent requiring testing on cell culture harvest.
Risk associated with gene therapy products integrated into the genome
Related CFR Sections (12)
- 21CFR312.56§ 312.56 Review of ongoing investigations.
(a) The sponsor shall monitor the progress of all clinical investigations being conducted under its IND.Read full regulation →
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 21CFR50.52§ 50.52 Clinical investigations involving greater than minimal risk but presenting the prospect of direct benefit to individual subjects.
Any clinical investigation within the scope described in §§ 50.1 and 56.101 of this chapter in which more than minimal risk to children is presented by an intervention or procedure that holds out the prospect of direct benefit for the individual subject, or by a monitoring procedure that is likely tRead full regulation →
- 21CFR211.166§ 211.166 Stability testing.
(a) There shall be a written testing program designed to assess the stability characteristics of drug products. The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include:Read full regulation →
- 21CFR1271.80§ 1271.80 What are the general requirements for donor testing?
(a) Testing for relevant communicable diseases is required. To adequately and appropriately reduce the risk of transmission of relevant communicable diseases, and except as provided under § 1271.90 , if you are the establishment that performs donor testing, you must test a donor specimen for evidencRead full regulation →
- 21CFR1271.75§ 1271.75 How do I screen a donor?
(a) All donors. Except as provided under § 1271.90 , if you are the establishment that performs donor screening, you must screen a donor of cells or tissue by reviewing the donor's relevant medical records for:Read full regulation →
- 21CFR1271.50§ 1271.50 How do I determine whether a donor is eligible?
(a) Determination based on screening and testing. If you are the establishment responsible for making the donor-eligibility determination, you must determine whether a donor is eligible based upon the results of donor screening in accordance with § 1271.75 and donor testing in accordance with §§ 127Read full regulation →
- 21CFR312.30§ 312.30 Protocol amendments.
Once an IND is in effect, a sponsor shall amend it as needed to ensure that the clinical investigations are conducted according to protocols included in the application. This section sets forth the provisions under which new protocols may be submitted and changes in previously submitted protocols maRead full regulation →
- 21CFR312.31§ 312.31 Information amendments.
(a) Requirement for information amendment. A sponsor shall report in an information amendment essential information on the IND that is not within the scope of a protocol amendment, IND safety reports, or annual report. Examples of information requiring an information amendment include:Read full regulation →
- 21CFR312.47§ 312.47 Meetings.
(a) General. Meetings between a sponsor and the agency are frequently useful in resolving questions and issues raised during the course of a clinical investigation. FDA encourages such meetings to the extent that they aid in the evaluation of the drug and in the solution of scientific problems conceRead full regulation →
Related Warning Letters (10)
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
- 2025-12-11
CGMP/Finished Pharmaceuticals/Adulterated
Catalent Indiana, LLC
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
DeVere Manufacturing Inc.
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
CDL Services, Inc. DBA Technichem
- 2025-12-09
CGMP/Finished Pharmaceuticals/Adulterated
Seaway Pharma Inc.
- 2025-12-02
Compounding Pharmacy/Adulterated Drug Products
PQ Pharmacy, LLC
See Also (8)
- Establishment and Operation of Clinical Trial Data Monitoring Committees: Guidance for Clinical Trial Sponsors (Status: Final)
- Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs): Guidance for Industry (Status: Final)
- Sponsor Responsibilities - Safety Reporting Requirements and Safety Assessment for IND and Bioavailability/Bioequivalence Studies: Draft Guidance for Industry (Status: Draft)
- Use of Data Monitoring Committees in Clinical Trials (Status: Draft)
- Conducting Clinical Trials With Decentralized Elements (Status: Final)
- Neglected Tropical Diseases of the Developing World: Developing Drugs for Treatment or Prevention (Status: Final)
- Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics: Guidance for Industry (Status: Final)
- Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products: Draft Guidance for Industry (Status: Draft)