Use of a comparability protocol will aid post-approval CMC changes, US FDA

The pre-release document entitled ‘Comparability Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and Controls [CMC] Information’ was published in the Federal Register today as a revised version of a similarly named draft guidance published in February 2003​ and withdrawn last May.

The draft provides recommendations to drug manufacturers on implementing CMC post-approval changes through the use of a comparability protocol (CP) which the US Food and Drug Administration (FDA) says will “provide more flexibility”​ when filing procedures for a notification of change in a condition established in an approved application.

According to the FDA, a CP is a well-defined, detailed, written plan for assessing the effect of specific CMC changes in the identity, strength, quality, purity, and potency of a specific drug product as these factors relate to the safety and effectiveness of the product.

The changes covered under the protocol and the specific tests and studies that will be performed are used to demonstrate that specified CMC changes do not adversely affect the product

While the submission of a CP is optional, using an approved CP will be a benefit for drugmakers, the Agency says in the new guidelines. “Manufacturers whom fall within the scope of this guidance will not have to submit commercial scale CMC information on postchange products to FDA before making the proposed changes.”​

The FDA adds the guidance will establish a framework to promote manufacturing of quality drug products by employing the following:

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

-          A robust control strategy

-          Risk management activities over a product’s life cycle

-          An effective pharmaceutical quality system

The draft guidance is open for comment for the next 60 days.