Ask the Expert: Post-Approval Changes

Susan J. Schniepp, distinguished fellow at Nelson Labs, and Siegfried Schmitt, PhD, vice president, Technical at Parexel, provide advice on how to handle post-approval changes in this episode of Ask the Expert. The drug manufacturing process is never static, explains Schmitt, and therefore, companies should anticipate future changes from either production volume, process optimization, or technological innovation. The key question is how much of this can be anticipated and addressed before filing.

Schniepp outlines the regulatory mechanisms available, focusing on the system in the United States. With prior-approval changes, companies wait for the FDA to sign-off before implementing. For changes being effected in 30 days (CBE-30), companies can proceed after a 30-day waiting period absent an objection by the FDA objection. CBE is an even faster pathway rarely used today. She notes companies sometimes register alternative methods (eg, both high-performance liquid chromatography and ultra-high-pressure liquid chromatography) at filing time to build in flexibility. Schniepp recommends comparability protocols as a useful tool for managing scale-up changes.

According to Schmitt, pre-approval submissions typically prioritize speed to market, though companies should also consider requesting pre-approval for anticipated changes to avoid the time and cost burdens of post-approval processes, particularly costly Type II variations in Europe. However, resource constraints often limit how much forward planning occurs before approval, because teams are focused on the approval itself.

Schniepp highlights annual reportable changes (eg, certain equipment upgrades or method changes with demonstrated comparability) as another avenue requiring less regulatory scrutiny, urging companies to carefully study relevant guidance documents.

Schniepp emphasizes that a company’s risk tolerance should drive its change-management strategy; some organizations are highly risk-averse and prefer prior approval, while others are more comfortable leveraging annual reports for faster implementation. Both experts agree there’s no one-size-fits-all approach; each company must develop its own change management strategy based on its specific risk appetite and resources.

Click the video above to watch Sue and Siegfried answer the question: “We are coming to a regulatory filing, and we know there's a possibility of post-approval changes being pre-approved. Do you have any advice?”

About the Speakers

Susan J. Schniepp is distinguished fellow at Nelson Labs and a member of PharmTech's Editorial Advisory Board.

Siegfried Schmitt is vice president, Technical at Parexel and a member of PharmTech's Editorial Advisory Board.