Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs): Guidance for FDA Reviewers and Sponsors

Description

This guidance document provides to you, sponsors of a human gene therapy investigational new drug application (IND), recommendations on the chemistry, manufacturing, and control (CMC) information to include in an original IND. This guidance also applies to combination products that contain a human gene therapy biological product in combination with a drug or device as part of the final product. Also, this guidance instructs FDA CMC reviewers about the information to record and assess as part of an IND review, taking into consideration the various manufacturing challenges for these products.

Scope & Applicability

Regulatory Context

• 21CFR312.22§ 312.22 General principles of the IND submission.

  (a) FDA's primary objectives in reviewing an IND are, in all phases of the investigation, to assure the safety and rights of subjects, and, in Phase 2 and 3, to help assure that the quality of the scientific evaluation of drugs is adequate to permit an evaluation of the drug's effectiveness and safeRead 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 →

• 21CFR211.192§ 211.192 Production record review.

  All drug product production and control records, including those for packaging and labeling, shall be reviewed and approved by the quality control unit to determine compliance with all established, approved written procedures before a batch is released or distributed. Any unexplained discrepancy (inRead full regulation →

• 21CFR25.30§ 25.30 General.

  The classes of actions listed in this section and §§ 25.31 through 25.35 are categorically excluded and, therefore, ordinarily do not require the preparation of an EA or an EIS:Read full regulation →

• 21CFR1271.250§ 1271.250 Labeling controls.

  (a) General. You must establish and maintain procedures to control the labeling of HCT/Ps. You must design these procedures to ensure proper HCT/P identification and to prevent mix-ups.Read full regulation →

• 21CFR312.6§ 312.6 Labeling of an investigational new drug.

  (a) The immediate package of an investigational new drug intended for human use shall bear a label with the statement “Caution: New Drug—Limited by Federal (or United States) law to investigational use.”Read full regulation →

• 21CFR1271.290§ 1271.290 Tracking.

  (a) General. If you perform any step in the manufacture of an HCT/P in which you handle the HCT/P, you must track each such HCT/P in accordance with this section, to facilitate the investigation of actual or suspected transmission of communicable disease and take appropriate and timely corrective acRead 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 →

• 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 →

• 21CFR610.13§ 610.13 Purity.

  Products shall be free of extraneous material except that which is unavoidable in the manufacturing process described in the approved biologics license application. In addition, products shall be tested as provided in paragraphs (a) and (b) of this section.Read full regulation →

• 21CFR600.3§ 600.3 Definitions.

  As used in this subchapter:Read full regulation →

• 21CFR610.9§ 610.9 Equivalent methods and processes.

  Modification of any particular test method or manufacturing process or the conditions under which it is conducted as required in this part or in the additional standards for specific biological products in parts 620 through 680 of this chapter shall be permitted only under the following conditions:Read 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 →

• 21CFR211.184§ 211.184 Component, drug product container, closure, and labeling records.

  These records shall include the following:Read full regulation →

• 21CFR589.2000§ 589.2000 Animal proteins prohibited in ruminant feed.

  (a) Definitions —Read full regulation →

• 21CFR10.70§ 10.70 Documentation of significant decisions in administrative file.

  (a) This section applies to every significant FDA decision on any matter under the laws administered by the Commissioner, whether it is raised formally, for example, by a petition or informally, for example, by correspondence.Read full regulation →

• 21CFR1271.90§ 1271.90 Are there other exceptions and what labeling requirements apply?

  (a) Donor-eligibility determination not required. You are not required to make a donor-eligibility determination under § 1271.50 or to perform donor screening or testing under §§ 1271.75 , 1271.80 and 1271.85 for:Read full regulation →

• CGMP/Finished Pharmaceuticals/Adulterated

  SV Labs Corporation

  2025-12-23

• CGMP/Deviations/Biologics License Application (BLA)

  Microvascular Tissue, Inc.

  2025-12-16

• Deviations/CFR/Regulations for Human Cells, Tissues & Cellular Products (HCT/Ps)

  Green Valley Fertility Partners

  2025-12-16

• CGMP/Finished Pharmaceuticals/Adulterated

  Catalent Indiana, LLC

  2025-12-11

• Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)

  BioXtek LLC

  2025-12-09

• Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)

  Celularity, Inc

  2025-12-09

• Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)

  Lux Therapeutics LLC dba Ponya Therapeutics LLC

  2025-12-09

• Compounding Pharmacy/Adulterated Drug Products

  PQ Pharmacy, LLC

  2025-12-02

• Compounding Pharmacy/Adulterated Drug Products

  Turbare Manufacturing

  2025-12-02

• CGMP/Finished Pharmaceuticals/Adulterated

  Rhyz Analytical Labs

  2025-12-02

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