T-40: Comprehensive QOS and Established Conditions: Creating a Path for Flexible Regulatory Approaches to Post Approval CMC Changes

Poster Presenter

Connie Langer

Senior Director
Pfizer Inc
United States

Objectives

This poster discusses a case study of Pfizer’s first comprehensive Quality Overall Summary (cQOS) and proposed Established Conditions (ECs), both of which are integral to the goal to implement post-approval CMC changes with a knowledge- and risk-based level of regulatory oversight.

Method

The cQOS and established conditions were included in a recent New Drug Application for an important oncology product. Following the approval of the product, a post action meeting was held to discuss the challenges and opportunities presented when using these tools.

Results

The cQOS is a synopsis of Module 3 that effectively conveys how enhanced process understanding, product knowledge, and risk assessments are linked to a product control strategy. The narrative provides an integrated summary that shows how and why important aspects of the control strategy that make up the established conditions (ECs) were selected. According to the Step 2 draft ICH Q12 guideline, “the concept of ECs provides a clear understanding between the Market Authorization Holder (MAH) and regulatory authorities regarding the necessary elements to assure product quality and identify the elements that require a regulatory submission, if changed.” The succinct cQOS provided an overall picture of the product and was beneficial, especially for cross-disciplinary reviewers, to quickly discern broader context around specific topics. ECs were included as part of the cQOS, and the framework was further developed to include regulatory reporting categories in alignment with Annex III of the Step 2 draft ICH Q12 guideline. The ECs for the product are the subject of a forthcoming prior approval supplement, which in many instances includes lower regulatory reporting categories, and in some cases management of the changes in the Pharmaceutical Quality System.

Conclusion

These tools have the potential to enable a more efficient regulatory review process, enhance regulatory flexibility, and thereby facilitate continuous improvement in the commercial space. The vision following the implementation of ICH Q12 is to use established conditions to attain a harmonized set of regulatory commitments that are accepted by global regulatory authorities.