Description
We, FDA, are providing you, investigational new drug application (IND) sponsors, with recommendations concerning IND submissions for microbial vectors used for gene therapy (MVGTs) in early-phase clinical trials. MVGTs meet the definition of “biological product” in section 351(i) of the Public Health Service (PHS) Act (42 U.S.C. 262), when such products are applicable to the prevention, treatment, or cure of a disease or condition of human beings. This guidance focuses on the chemistry, manufacturing, and control (CMC) information that you should submit in an IND for MVGTs and provides an overview of preclinical and clinical considerations for these products.
Scope & Applicability
Product Classes
8Subject of the guidance document regarding IND submissions.; Subject of the guidance document recommendations
Microbial Vectors used for Gene Therapy products listed in the testing appendix.
Products that could proliferate in necrotic tissues.
Specific example of an MVGT product entailing risk of sepsis.
Referenced in the context of shedding studies guidance.
A type of ATMP involving recombinant nucleic acids or viral vectors.
Microbial Vectors Used for Gene Therapy products discussed throughout the guidance.
Products reviewed by OVRR, distinct from MVGTs.
Stakeholders
3Target audience for the recommendations in the guidance.
Entity responsible for submitting applications under section 524B
outsourced operation provider
Regulatory Context
Attributes
6Measurement of potency for biological products
Testing required specifically for lyophilized or dried final products.
Measurement of live organisms in the microbial vector product.
The path by which the MVGT is delivered to the body.
freedom from contaminating organisms
Characteristic to be evaluated after multiple passages
Identified Hazards
Hazards
4Safety concern regarding viral contamination
A clinical risk that may serve as a stopping rule.
A potential risk for anaerobic microbial products.
Potential safety concern in parenteral products
Related CFR Sections (7)
- 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 →
- 21CFR25.40§ 25.40 Environmental assessments.
(a) As defined by CEQ in 40 CFR 1508.9 , an EA is a concise public document that serves to provide sufficient evidence and analysis for an agency to determine whether to prepare an EIS or a FONSI. The EA shall include brief discussions of the need for the proposal, of alternatives as required by secRead full regulation →
- 21CFR25.31§ 25.31 Human drugs and biologics.
The classes of actions listed in this section are categorically excluded and, therefore, ordinarily do not require the preparation of an EA or an EIS:Read full regulation →
- 21CFR211.165§ 211.165 Testing and release for distribution.
(a) For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. Where sterility and/or pyrogen testing are conducted on sRead full regulation →
- 21CFR610.12§ 610.12 Sterility.
(a) The test. Except as provided in paragraph (h) of this section, manufacturers of biological products must perform sterility testing of each lot of each biological product's final container material or other material, as appropriate and as approved in the biologics license application or supplemenRead full regulation →
- 21CFR312.33§ 312.33 Annual reports.
A sponsor shall within 60 days of the anniversary date that the IND went into effect, submit a brief report of the progress of the investigation that includes:Read full regulation →
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read 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)
- Guidance for Industry: Providing Regulatory Submissions to CBER in Electronic Format -- Investigational New Drug Applications (INDs) (PDF) (Status: Final)
- Study of Sex Differences in the Clinical Evaluation of Medical Products (Status: Draft)
- Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products: Guidance for Industry (Status: Final)
- Study Data Technical Conformance Guide - Technical Specifications Document (Status: Final)
- Frequently Asked Questions — Developing Potential Cellular and Gene Therapy Products (Status: Draft)
- Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products (Status: Final)
- Rare Diseases: Considerations for the Development of Drugs and Biological Products (Status: Final)
- Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry (Status: Final)