A specification is characterized as a compilation of tests, references to analytical methods, and relevant acceptance criteria, which consist of numerical limits, ranges, or other standards for the tests outlined. It delineates the criteria that a drug substance or drug product must meet to be deemed acceptable for its intended application.
The term “conformance to specifications” indicates that the drug substance and/or drug product, when evaluated according to the specified analytical methods, will satisfy the established acceptance criteria.
Specifications represent essential quality standards that are proposed and substantiated by the manufacturer and sanctioned by regulatory bodies as prerequisites for approval. They form a component of a comprehensive control strategy for the drug substance and drug product, aimed at ensuring product quality and consistency.
Additional elements of this strategy encompass thorough product characterization during development, which serves as the foundation for specifications, as well as compliance with Good Manufacturing Practices; for instance, appropriate facilities, a validated manufacturing process, validated testing procedures, raw material assessments, in-process evaluations, stability assessments, and so forth.
Specifications are selected to verify the quality of the drug substance and drug product rather than to achieve complete characterization and should concentrate on those attributes deemed beneficial in guaranteeing the safety and efficacy of the drug substance and drug product.
Release versus shelf-life acceptance standards
The concept of varying acceptance criteria for release compared to shelf-life specifications is relevant solely to drug products; it involves the implementation of more stringent criteria for the release of a drug product than those applied to its shelf-life.
Instances where this may be relevant include levels of assay and impurities (degradation products). In both Japan and the United States, this notion may only pertain to internal criteria, rather than to the regulatory release criteria.
Consequently, in these regions, the regulatory acceptance criteria remain consistent from release through to shelf-life; however, an applicant may opt to establish stricter internal limits at the time of release to enhance the assurance that the product will stay within the regulatory acceptance criteria throughout its shelf-life. In the European Union, there exists a regulatory obligation for separate specifications for release and shelf-life when they differ.
In-process tests
Tests that may be conducted during the production of either the drug substance or drug product, rather than as part of the formal series of tests performed prior to release.
In-process tests that are solely utilized for the purpose of adjusting process parameters within an operational range, such as the hardness and friability of tablet cores intended for coating and the weights of individual tablets, are excluded from the specification.
Certain tests carried out during the manufacturing process, where the acceptance criteria are either identical to or more stringent than the release requirements (for instance, the pH of a solution), may be adequate to fulfill specification requirements when the test is incorporated into the specification.
Nevertheless, this method should be validated to demonstrate that test results or product performance characteristics remain consistent from the in-process stage to the finished product.