Scott Gottlieb, MD, Commissioner of the US Food and Drug Administration (FDA), outlined the steps that the agency is taking to more fully integrate the agency’s drug-review programs with its facility evaluations and inspections for human drugs. He made his comments on the August 31, 2017 edition of FDA Voice, the blog of the FDA.
In June 2017, the FDA issued a concept of operations (ConOps) white paper to discuss how the Center for Drug Evaluation and Research (CDER) and the Office of Regulatory Affairs (ORA) will work in a vertically integrated, programmatically aligned environment regarding application review and inspections and the compliance activities associated with them. The ConOps applies to pre- and post-approval, surveillance, and for-cause inspections and provides an operating model for facility evaluations and inspections for human drugs. The ConOps is part of an overall restructuring of field activities based to be around the programs the agency regulates rather than around geographic regions.
The new agreement between CDER and ORA is intended to leverages two efforts to ensure alignment between FDA’s field professionals and the agency’s review staff. First is the use of “Integrated Quality Assessment” teams. Gottlieb says that this new, team-based approach aligns field and review staff so the agency can make closer consideration of all elements that create risk, including the drug substance, the drug product, manufacturing processes, and the state of facilities.
He also outlined the previously announced structural realignment of ORA. The FDA moved ORA’s previous geographically organized staff and management into program-aligned commodity areas, more closely mirroring the organizational model of FDA’s centers and the industries the agency regulates. “This step enhanced the Integrated Quality Assessment, and the new concept of operations that operationalizes these approaches, by enabling better alignment between our field professionals and the review staff who evaluate the products that are being manufactured in the facilities that we inspect,” said Gottlieb in his blog post. “The unifying hallmark of the integrated quality assessment team and the concept of operations agreement is the closer integration of the professional staff charged with inspecting facilities and the review staff involved in evaluating applications. Experts in our drug program and our field force,will be aligning their efforts. We believe that this sort of collaboration can better inform the work done across each of these domains. Our inspectional force will benefit from insights that might be offered by the review teams who have carefully evaluated products being manufactured. Meanwhile, our review staff will benefit from the deeper understanding they will glean through more direct and regular contact with the professionals who are inspecting facilities and seeing the kinds of things that can go wrong during the manufacturing process.”
The new framework between CDER and ORA, embodied in the concept of operation, outlines the responsibilities and workflow that CDER and ORA employees will follow. The new model will cover pre- and post-approval Inspections, surveillance Inspections, and for-cause inspections at domestic and international drug manufacturing facilities that FDA oversees.
The changes also are in line with the agency’s goal to improve the generic-drug review process. As part of the commitments made by FDA in the context of the Generic Drug User Fee Amendments II (GDUFA II), the agency agreed to communicate final surveillance inspection classifications to facility owners within 90 days of an inspection. Gottlieb said that the new operating model will be a key element in meeting these obligations. He said that the FDA will begin to operationalize this agreement this fall, with application to all human drugs.
“We hope that by communicating more quickly with product developers when manufacturing problems are identified, this agreement will help make inspectional issues less likely to cause approval delays or prolong the time it takes to get important products to patients who can benefit from them,” said Gottlieb in his blog post. “As we continue to implement this new structure, we may update other related aspects of our inspectional programs, and how we organize our regulatory activities.”