Description
This guidance is intended to help manufacturers meet the requirements in the Agency's current good manufacturing practice (CGMP) regulations (2l CFR parts 210 and 211) when manufacturing sterile drug and biological products using aseptic processing. This guidance replaces the 1987 Industry Guideline on Sterile Drug Products Produced by Aseptic Processing (Aseptic Processing Guideline). This revision updates and clarifies the 1987 guidance.
Scope & Applicability
Product Classes
10products 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.
Elements exposed to aseptic conditions making up the sterile finished drug product
sponsors should consult specific guidances for these products
less frequently, injectables
often used for filling and packaging respiratory care products
often used for filling and packaging ophthalmics
Injectable products subject to specific inactive ingredient rules.
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
Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition
Scope of manufacturing considerations
Stakeholders
6personnel who must receive training on Listeria control
Person whose actions may cause a product to be deemed adulterated
The quality control unit responsible for oversight and observation of media fills.
Facilities referenced in 21 CFR 200.10(b)
Personnel responsible for conducting CGMP training
must review and approve manufacturing changes
Regulatory Context
Attributes
10Conditions with personnel present and operations ongoing
A set of conditions encompassing upper and lower processing limits
An airflow moving in a single direction to reproducibly sweep particles away
An airflow moving in a single direction and in parallel layers
The time of exposure at a given temperature that causes a one-log reduction
A microbiological term that describes the formation of a single macroscopic colony
Action Levels for Aflatoxin in Animal Feeds - 683.100
established microbial or airborne particle level giving early warning
A breach of isolator integrity should normally lead to a decontamination cycle
A characteristic of sampling required to ensure statistical confidence.
Identified Hazards
Hazards
6Control of pyrogens in sterile products
A substance that induces a febrile reaction in a patient.
Output attribute considered an EC in minimal approach
steps with the greatest potential for exposure to particle contamination
Risk associated with tattoo inks that can lead to infection.; Risk associated with insanitary conditions in tattoo ink preparation
Potential for contamination of covered produce; Known or reasonably foreseeable hazards in water
Related CFR Sections (20)
- 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 →
- 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 →
- 21CFR211.100§ 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 →
- 21CFR211.188§ 211.188 Batch production and control records.
Batch production and control records shall be prepared for each batch of drug product produced and shall include complete information relating to the production and control of each batch. These records shall include:Read full regulation →
- 21CFR211.186§ 211.186 Master production and control records.
(a) To assure uniformity from batch to batch, master production and control records for each drug product, including each batch size thereof, shall be prepared, dated, and signed (full signature, handwritten) by one person and independently checked, dated, and signed by a second person. The preparatRead full regulation →
- 21CFR211.194§ 211.194 Laboratory records.
(a) Laboratory records shall include complete data derived from all tests necessary to assure compliance with established specifications and standards, including examinations and assays, as follows: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 →
- 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 →
- 21CFR211.110§ 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 →
- 21CFR210.3§ 210.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the act shall be applicable to such terms when used in this part and in parts 211 , 225 , and 226 of this chapter .Read full regulation →
- 21CFR211.113§ 211.113 Control of microbiological contamination.
(a) Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile, shall be established and followed.Read full regulation →
- 21CFR211.42§ 211.42 Design and construction features.
(a) Any building or buildings used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction and location to facilitate cleaning, maintenance, and proper operations.Read 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 →
- 21CFR211.111§ 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 →
- 21CFR211.167§ 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 →
- 21CFR211.94§ 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 →
- 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 →
- 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 →
- 21CFR211.28§ 211.28 Personnel responsibilities.
(a) Personnel engaged in the manufacture, processing, packing, or holding of a drug product shall wear clean clothing appropriate for the duties they perform. Protective apparel, such as head, face, hand, and arm coverings, shall be worn as necessary to protect drug products from contamination.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 →
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)
- Alternative Tools: Assessing Drug Manufacturing Facilities Identified in Pending Applications (Status: Final)
- CPG Sec. 430.200 Repacking of Drug Products - Testing/Examination under CGMPs (Status: Final)
- CPG Sec. 425.300 Computerized Drug Processing; Source Code for Process Control Application Programs (Status: Final)
- CPG Sec. 410.100 *Finished Dosage Form Drug Products in Bulk Containers - Applications of Current Good Manufacturing Practice Regulations* (Status: Final)
- CPG Sec. 400.210, Radiofrequency Identification Feasibility Studies and Pilot Programs for Drugs (Status: Final)
- Reference Guide for the Nonclinical Toxicity Studies of Antivial Drugs Indicated for the Treatment of N/A Non-Life Threatening Disease Evaluation of Drug Toxicity Prior to Phase I Clinical Studies (Status: Final)
- Preparation of Investigational New Drug Products (Human and Animal): Guidance for Industry (Status: Final)
- Review of FDA's Implementation of the Drug Export Amendments of 1986 (Status: Final)