21 CFR 211.110 - Sampling and Testing of In-Process Materials and Drug Products

Overview:

21 CFR 211.110 establishes requirements for the sampling and testing in-process materials and drug products to ensure batch uniformity and integrity. 

It mandates written procedures for in-process controls, monitoring manufacturing variability, and validating process performance. Key control procedures include weight variation, disintegration and dissolution testing, mixing adequacy, and bioburden testing. 

The regulation requires in-process specifications to align with final product standards and be determined using statistical methods when applicable. Additionally, it enforces identity, strength, quality, and purity testing during production, with rejected materials subject to quarantine to prevent improper use.

(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 established to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. Such control procedures shall include, but are not limited to, the following, where appropriate:

(1) Tablet or capsule weight variation;

(2) Disintegration time;

(3) Adequacy of mixing to assure uniformity and homogeneity;

(4) Dissolution time and rate;

(5) Clarity, completeness, or pH of solutions.

(6) Bioburden testing.

(b) 

Valid in-process specifications for such characteristics shall be consistent with drug product final specifications and shall be derived from previous acceptable process average and process variability estimates where possible and determined by the application of suitable statistical procedures where appropriate. Examination and testing of samples shall assure that the drug product and in-process material conform to specifications.

(c) 

In-process materials shall be tested for identity, strength, quality, and purity as appropriate, and approved or rejected by the quality control unit, during the production process, e.g., at commencement or completion of significant phases or after storage for long periods.

(d) 

Rejected in-process materials shall be identified and controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for which they are unsuitable.