In February 2003, FDA published a draft guidance entitled “Comparability Protocols: Chemistry, Manufacturing, and Controls Information.” Last month, the Agency replaced the 13 year old draft guidance with a revised and updated document. The new draft guidance, entitled “Comparability Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and Controls Information,” will provide more flexibility with regard to the implementation of advanced control approaches and includes recommendations for applicants submitting a comparability protocol (CP) to FDA.
Although the draft guidance touches on a number of different topics, an emphasis is placed on the content recommendations for CP submissions. As such, the draft guidance states that CP submissions should provide FDA with the applicant’s plan for the implementation of proposed changes, and should include the following information:
The summary should provide a brief description of the following:
“The proposed change(s) should be described in sufficient detail to enable the Agency to evaluate the relevancy and adequacy of the CP.”
“Supporting information submitted with the CP should demonstrate your understanding of those aspects of the product, manufacturing process, and control strategy that are relevant to the proposed change(s).”
In addition, FDA also states that “the amount of supporting information that should be provided will depend on, and be commensurate with, the complexity of the product and the planned change. For any information that is already submitted in the same NDA, ANDA, or BLA, simply indicate where this information can be found (e.g., provide the volume and page number).”
“The CP for the proposed change(s) should describe, in sufficient detail for FDA to assess the CP, the specific tests and studies to be performed, including analytical procedures to be used and criteria to be achieved, to demonstrate the lack of adverse effect on the product quality. These tests and studies should be performed at commercial manufacturing scale.”
FDA recommends that the following items be included:
In its draft guidance, FDA states that following:
“We recommend that you propose an appropriate reduced reporting category for implementation of each change (i.e., an annual report, CBE, or CBE-30). FDA will evaluate your proposed reporting category as part of its review of the CP submission and communicate any concerns about your proposal. FDA approval of the submission containing the CP will include your proposed reporting category, if appropriate, for each of the specified CMC changes.”
In addition, FDA notes that in some cases, the appropriate review division may recommend that the changes be submitted in a regular Prior Approval Supplement (PAS) rather than a CP. The division may suggest this if the complexities associated with the change(s) pose an unacceptably high risk to the product’s quality.
The draft guidance also provides the following recommendations concerning the content of a CP submission:
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