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USFDA Guidance: Comparability Protocols for Postapproval Changes to CMC in an NDA, ANDA, or BLA

This guidance was finalized and released by the Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) on 143-October-2022.

In this final guidance, original applicants and holders of approved new drug applications abbreviated new drug applications, and biologics license applications (BLAs) will understand how to implement a postapproval change to chemistry, manufacturing, and controls (CMC) through the use of a comparability protocol (CP).

A Comparability Protocol is a comprehensive, prospectively written plan for assessing the effectiveness of a proposed postapproval CMC change(s) on the identity, strength, quality, purity, and potency of a drug product, including a biological product (i.e., product), as these factors may relate to the safety or effectiveness of the product (i.e., product quality).

This guidance recommends a framework to promote innovation and continuous improvement in the manufacturing of quality products by encouraging you to employ:

  • Effective use of knowledge and understanding of the product and manufacturing process

  • Risk management activities over the life cycle of a product

  • An effective pharmaceutical quality system

This guidance applies to CPs submitted in NDAs, ANDAs, BLAs, and supplements to these applications regulated by the CDER and CBER.

Click this LINK to know more about the content & recommendations and important topics including the questions and answers about the comparability protocols.


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