Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products

Description

The management of manufacturing changes presents many challenges for human cellular therapy  or gene therapy  (CGT) products due to the complexity of these products.  We, FDA, are providing you, sponsors of Investigational New Drug Applications (INDs) and applicants of Biologics License Applications (BLAs) for CGT products, with recommendations regarding product comparability and the management of manufacturing changes for investigational and licensed CGT products.   The purpose of this guidance is to provide FDA’s current thinking on 1) management and reporting of manufacturing changes for CGT products based on a lifecycle approach, and 2) comparability studies to assess the effect of manufacturing changes on product quality.

Scope & Applicability

Regulatory Context

• 21CFR601.12§ 601.12 Changes to an approved application.

  (a) General.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 →

• 21CFR312.42§ 312.42 Clinical holds and requests for modification.

  (a) General. A clinical hold is an order issued by FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation. The clinical hold order may apply to one or more of the investigations covered by an IND. When a proposed study is placed on clinical hold, subjectRead full regulation →

• 21CFR211.22§ 211.22 Responsibilities of quality control unit.

  (a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no eRead full regulation →

• 21CFR211.100§ 211.100 Written procedures; deviations.

  (a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. Such procedures shall include all requirements in this subpart. These written procedures, inRead full regulation →

• 21CFR211.110§ 211.110 Sampling and testing of in-process materials and drug products.

  (a) To assure batch uniformity and integrity of drug products, written procedures shall be established and followed that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch. Such control procedures shall be establiRead 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 →

• 21CFR210.2§ 210.2 Applicability of current good manufacturing practice regulations.

  (a) The regulations in this part and in parts 211 , 213 , 225 , and 226 of this chapter as they may pertain to a drug; in parts 600 through 680 of this chapter as they may pertain to a biological product for human use; and in part 1271 of this chapter as they are applicable to a human cell, tissue, Read full regulation →

• 21CFR211.180§ 211.180 General requirements.

  (a) Any production, control, or distribution record that is required to be maintained in compliance with this part and is specifically associated with a batch of a drug product shall be retained for at least 1 year after the expiration date of the batch or, in the case of certain OTC drug products lRead full regulation →

• 21CFR601.2§ 601.2 Applications for biologics licenses; procedures for filing.

  (a) General. To obtain a biologics license under section 351 of the Public Health Service Act for any biological product, the manufacturer shall submit an application to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing aRead 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 →

• 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 →

• 21CFR312.20§ 312.20 Requirement for an IND.

  (a) A sponsor shall submit an IND to FDA if the sponsor intends to conduct a clinical investigation with an investigational new drug that is subject to § 312.2(a) .Read full regulation →

• CGMP/Finished Pharmaceuticals/Adulterated

  SV Labs Corporation

  2025-12-23

• 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

  Owen Biosciences, Inc.

  2025-11-25

• CGMP/Finished Pharmaceuticals/Adulterated

  BRS Analytical Services, LLC

  2025-10-21

• CGMP/Finished Pharmaceuticals/Adulterated

  Dixon Investments Inc. dba ARI

  2025-10-07

• Clinical Investigator (Sponsor)

  Pamela K. Den Besten, DDS, MS

  2025-09-30

• CGMP/Finished Pharmaceuticals/Adulterated

  Janssen Vaccines Corp., A Johnson & Johnson Company

  2025-09-23

• CGMP/Finished Pharmaceuticals/Adulterated

  Wisconsin Pharmacal Company, LLC

  2025-09-02

• Unapproved New Animal Drug Products

  Synergy Animal Products, Inc.

  2025-09-02

• Pre-Storage Leukocyte Reduction of Whole Blood and Blood Components Intended for Transfusion: Final Guidance for Industry (Status: Final)
• Changes to an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture: Final Guidance (Status: Final)
• Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Guidance for Industry: Guidance for Industry (Status: Final)
• Manufacture of Blood Components Using a Pathogen Reduction Device in Blood Establishments: Questions and Answers: Guidance for Industry (Status: Final)
• Comparability Protocols for Postapproval Changes to the Chemistry, Manufacturing, and Controls Information in an NDA, ANDA, or BLA (Status: Final)
• Assessing Donor Suitability and Blood and Blood Product Safety in Cases of Known or Suspected West Nile Virus Infection: Guidance for Industry (Status: Final)
• 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)
• INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information: Guidance for Industry (Status: Final)