The product lifecycle is a well-known concept in quality circles that is finding increasing use in the pharmaceutical and medical device community.  Key to the understanding of a product are the elements of Chemistry, Manufacturing and Controls (CMC) [description, manufacturing process, facilities and equipment, and associated control strategy] that assure process performance and quality. These elements, when defined in the NDA, ANDA, or BLA, become the products Established Conditions (EC). Once the application is approved, sponsors must evaluate any changes to EC to determine whether and what reporting is required on the change. There is a body of guidance available on which elements are considered EC; however, the agency is concerned that there remains confusion on this topic that could have a negative impact on change management activities and discourage continual improvement.

To address these concerns, the agency issued a draft guidance in 2017 to describe how the concepts in the ICH draft Guideline for Q12 can be applied under the U.S. regulatory framework. The FDA draft guidance mirrors the ICH guideline in clearly describing what parts of the manufacturing process and analytical procedures are considered ECs and how they should be managed in the product lifecycle, including instructions for management and reporting of the change through the sponsor’s Pharmaceutical Quality System.

In mid-February, the FDA announced a pilot program calling for nine applicants to propose ECs in their original NDA, ANDA, or BLA or prior approval supplement to an application. The proposed ECs should be supported by an appropriate justification that takes into consideration the applicant’s development approach and risk to product quality consistent with ICHQ12 and other guidelines. The purpose of this pilot is to give the agency experience in

• assessing proposed ECs (i.e., explicit ECs);
• engaging with applicants during the review cycle to refine proposed ECs;
• ensuring assessment decisions are made without negatively impacting the ability to meet user fee timeframes; and
• identifying agreed-upon ECs at the time of approval

The initial pilot program closes on May 30, 2019. Those interested in participating should submit a written request to the CDER-OPQ-Inquiries@fda.hhs.gov mailbox and include the specific details listed in the pilot program notification.

Text Copyright © 2019 Katrina Rogers