Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Issued by the FDA

This formal ICH Guidance document (here) describes the entire post-approval lifecycle management of changes that are to be made after initial approval of a regulatory submission.

The document is quite comprehensive but, as always, because of inherent differences in the various regulatory authorities, there are limitations to its universal application.  As the guidance document notes, “Options for possible regulatory convergence regarding the association of a certain type of change with a particular category when reasons for being different from other regulatory authorities are not clearly established.”

The document goes on to discuss these changes in general terms that require prior approval (product established conditions), which pose the highest risk for impacting drug product quality, to changes that may be made by prior agency notification (the typical changes-being-effected supplements) (moderate risks) to those changes that may just need to be documented at the firm (the lowest risk – note there may be annual reporting requirements for some of these low-risk changes).

Q12 describes the Post-Approval Change Management Protocol (PACMP), which most of us have known as a Comparability Protocol and permits a firm to make changes based on a pre-agreed-upon protocol for making a particular type of change.

The requirements for each type of post-approval change for each regulatory authority may have different requirements, including differences in stability testing, but most follow the applicable ICH stability guidance.  There are also two appendices that address established conditions and the principles of change management that provide additional guidance, but, because of the extensive numbers and types of potential changes, these provide general guidance.  If you don’t see your exact situation, you may need to discuss it with the regulators.

Take time to review this important document as it is designed to attempt to standardize the general harmonized guidance on how to deal with changes to your product over its entire lifecycle.