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# CMC Comparability Protocol Guidance
- URL: https://www.fdaweb.com/cmc-comparability-protocol-guidance/
- Published: 2022-10-13T12:00:00.000Z
- Updated: 2026-09-14T18:02:59.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5152961

FDA has published a final guidance, *Comparability Protocols for Postapproval Changes to the Chemistry, Manufacturing, and Controls Information in an NDA, ANDA, or BLA*, to assist applicants and holders of approved NDAs, ANDAs, and BLAs with implementing a chemistry, manufacturing, and controls (CMC) postapproval change by using a comparability protocol (CP). The [document](https://downloads.regulations.gov/FDA-2016-D-0973-0027/attachment%5F1.pdf?ref=fdaweb.com) defines a CP as “a comprehensive, prospectively written plan for assessing the effect of a proposed postapproval CMC change(s) on the identity, strength, quality, purity, and potency of a drug product, including a biological product, as these factors may relate to the safety or effectiveness of the product.”

The guidance says that submission of a CP in an original application or a prior approval supplement to an approved application allows the agency to review a description of one or more proposed CMC postapproval changes, any supporting information and analysis, including a risk assessment, a plan to implement the change or changes and, if appropriate, a proposed reduced reporting category for the change(s).

The document is said to recommend a framework to promote innovation and continuous improvement in the manufacturing of quality products by encouraging companies to employ:

- effective use of knowledge and understanding of the product and manufacturing process;
- risk management activities over a product’s lifecycle; and
- an effective pharmaceutical quality system.

The guidance does not apply to blood and blood components; biological products that also meet the definition of a medical device; or human cells, tissues, or cellular or tissue-based products.