Description
The Food and Drug Administration (FDA or the Agency) is announcing the availability of a revised draft guidance entitled “Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act.” This revised draft guidance describes FDA's policies regarding compounders registered under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as outsourcing facilities and the current good manufacturing practice (CGMP) requirements in FDA regulations. Based on feedback from stakeholders and comments received on the initial draft guidance, the guidance is being revised, in part, to reflect further consideration of how CGMP requirements should be applied in light of the size and scope of an outsourcing facility's operations.
Scope & Applicability
Product Classes
8Drugs subject to section 503B
products with default BUD based on water activity
Category of products with specific enforcement policies for release testing.
products requiring aseptic processing and environmental monitoring; General production and process controls for drugs intended to be sterile; Category of products requiring sterility testing before release.
Regulated by CDER and CBER
Subject to 21 CFR part 212
Products requiring sterility assurance and ISO 5 environments; Products requiring sterility testing and specific environmental controls.; products requiring sterility and BUD labeling; products requiring sterility and stability testing; Products requiring sterility or container-closure integrity tests
Compounded products requiring microbiological quality
Stakeholders
4Facilities registered under section 503B; Entities reporting adverse events under Section 503B.
Person whose actions may cause a product to be deemed adulterated
Entities operating under section 503B of the FD&C Act; entity responsible for compounding under Section 503B; Entities compounding drug products under section 503B; Entity responsible for compounding drug products under section 503B.; entity responsible for compounding and labeling; Entity subject to release testing requirements under Section 503B.; entities compounding drugs under Section 503B
Responsible for ensuring the overall quality of the final drug product.
Regulatory Context
Attributes
10Assigned as an expiration date for compounded products; The date after which a compounded preparation shall not be used.; date/time after which the product is to be discarded; BUD used as the expiration date
Microbiological tests required if value is greater than 0.6
Beyond-use date restricted to the last time point at which data remained within specifications
Property of a device that may be changed via established protocols
Time period during which a product may be used after first opening or manipulation.; Maximum time allowed between penetration of container-closure and administration.
Airflow requirement for ISO 5 areas to maintain sterility; Airflow moving in a single direction to sweep particles away.
Quality parameter that must remain unchanged for the policy
quantity that would be produced in the absence of any loss or error
Quality attribute for sterile drug product components
specifications for single-use disposable equipment
Identified Hazards
Hazards
6Environmental factors affecting biological products
A particle that consists of or supports live microorganisms.
A substance that induces a febrile reaction in a patient.
Output attribute considered an EC in minimal approach
Risk associated with tattoo inks that can lead to infection.; Risk associated with insanitary conditions in tattoo ink preparation
managed through procedures and physical segregation
Related CFR Sections (20)
- 21CFR211.46§ 211.46 Ventilation, air filtration, air heating and cooling.
(a) Adequate ventilation shall be provided.Read full regulation →
- 21CFR211.137§ 211.137 Expiration dating.
(a) To assure that a drug product meets applicable standards of identity, strength, quality, and purity at the time of use, it shall bear an expiration date determined by appropriate stability testing described in § 211.166 .Read full regulation →
- 21CFR211.167§ 211.167 Special testing requirements.
(a) For each batch of drug product purporting to be sterile and/or pyrogen-free, there shall be appropriate laboratory testing to determine conformance to such requirements. The test procedures shall be in writing and shall be followed.Read full regulation →
- 21CFR211.198§ 211.198 Complaint files.
(a) Written procedures describing the handling of all written and oral complaints regarding a drug product shall be established and followed. Such procedures shall include provisions for review by the quality control unit, of any complaint involving the possible failure of a drug product to meet anyRead full regulation →
- 21CFR211.170§ 211.170 Reserve samples.
(a) An appropriately identified reserve sample that is representative of each lot in each shipment of each active ingredient shall be retained. The reserve sample consists of at least twice the quantity necessary for all tests required to determine whether the active ingredient meets its establishedRead full regulation →
- 21CFR211.134§ 211.134 Drug product inspection.
(a) Packaged and labeled products shall be examined during finishing operations to provide assurance that containers and packages in the lot have the correct label.Read full regulation →
- 21CFR211.130§ 211.130 Packaging and labeling operations.
There shall be written procedures designed to assure that correct labels, labeling, and packaging materials are used for drug products; such written procedures shall be followed. These procedures shall incorporate the following features:Read full regulation →
- 21CFR211.125§ 211.125 Labeling issuance.
(a) Strict control shall be exercised over labeling issued for use in drug product labeling operations.Read full regulation →
- 21CFR211.122§ 211.122 Materials examination and usage criteria.
(a) There shall be written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, examination, and/or testing of labeling and packaging materials; such written procedures shall be followed. Labeling and packaging materials shall be representatively samplRead 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 →
- 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 →
- 21CFR211.72§ 211.72 Filters.
Filters for liquid filtration used in the manufacture, processing, or packing of injectable drug products intended for human use shall not release fibers into such products. Fiber-releasing filters may be used when it is not possible to manufacture such products without the use of these filters. If Read full regulation →
- 21CFR211.25§ 211.25 Personnel qualifications.
(a) Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. Training shall be in the particular operations that the employee performsRead full regulation →
- 21CFR211.111§ 211.111 Time limitations on production.
When appropriate, time limits for the completion of each phase of production shall be established to assure the quality of the drug product. Deviation from established time limits may be acceptable if such deviation does not compromise the quality of the drug product. Such deviation shall be justifiRead full regulation →
- 21CFR211.160§ 211.160 General requirements.
(a) The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted Read full regulation →
- 21CFR211.87§ 211.87 Retesting of approved components, drug product containers, and closures.
Components, drug product containers, and closures shall be retested or reexamined, as appropriate, for identity, strength, quality, and purity and approved or rejected by the quality control unit in accordance with § 211.84 as necessary, e.g., after storage for long periods or after exposure to air,Read full regulation →
- 21CFR211.84§ 211.84 Testing and approval or rejection of components, drug product containers, and closures.
(a) Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.Read full regulation →
- 21CFR211.82§ 211.82 Receipt and storage of untested components, drug product containers, and closures.
(a) Upon receipt and before acceptance, each container or grouping of containers of components, drug product containers, and closures shall be examined visually for appropriate labeling as to contents, container damage or broken seals, and contamination.Read full regulation →
- 21CFR211.80§ 211.80 General requirements.
(a) There shall be written procedures describing in sufficient detail the receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures; such written procedures shall be followed.Read full regulation →
- 21CFR211.94§ 211.94 Drug product containers and closures.
(a) Drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug beyond the official or established requirements.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/Positron Emission Tomography (PET) Drugs/Adulterated
3D Imaging Drug Design and Development LLC
- 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.
See Also (8)
- CPG Sec. 480.100 Requirements for Expiration Dating and Stability Testing (Status: Final)
- CPG Sec. 480.300 Lack of Expiration Date of Stability Data (Status: Final)
- Expiration Dating and Stability Testing of Solid Oral Dosage Form Drugs Containing Iron: Guidance for Industry (Status: Final)
- CVM GFI #73 (VICH GL3(R)) Stability Testing of New Veterinary Drug Substances and Medicinal Products (Status: Final)
- CVM GFI #5 Drug Stability Guidelines (Status: Final)
- BLA for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System: Guidance for Industry (Status: Final)
- Current Good Manufacturing Practice Requirements for Combination Products: Guidance for Industry and FDA Staff (Status: Final)
- Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products: Guidance for Industry (Status: Final)