FDA Announces New Concept of Operations for CDER and ORA

This week, FDA commissioner Scott Gottlieb, MD, announced that the agency’s Center for Drug Evaluation and Research (CDER) and the Office of Regulatory Affairs (ORA) are implementing a new agreement to integrate drug review programs with facility evaluations and inspections. The new strategy is intended to make better use of expertise and resources within the agency.

The FDA’s concept of operations for the agreement between the CDER and ORA aims to help the agency better handle the growing complexity of the pharmaceutical landscape by ensuring consistency, efficiency, and transparency in its facility evaluations and decision-making. It seeks to define clear roles for staff, improve operational capacity, enhance access to facility and regulatory decision information, and meet user fee commitments.

A key feature of the concept of operations is the establishment of Integrated Quality Assessment (IQA) teams. These teams are led by an application technical lead and managed by a regulatory business project manager. The leaders will oversee a drug substance reviewer, a drug product reviewer, a process/facility assessor, and ORA representatives (for preapproval inspections). Additional roles may be added if necessary. These teams are intended to align field and review staff in order to better share information and to make closer considerations of all elements of risk.

The concept of operations addresses the following types of evaluations and inspections:

• Preapproval facility evaluations and inspections. Preapproval facility evaluations will be led by CDER with the participation of the ORA. The evaluation will determine whether a pre-approval inspection (which would be led by ORA with CDER participation) will be required for regulatory decision-making. CDER’s Office of Surveillance will provide site dossiers, and the IQA team may recommend an inspection. CDER and ORA will collaborate on the decision of whether to make an on-site inspection. The ORA investigator will lead an inspection based on the areas of concern identified by the IQA team.
• Postapproval facility inspections. This inspection type will focus on the process validation lifecycle and manufacturing changes, and will be led by ORA with participation from CDER. The IQA team will identify cases that require these inspections, which may expand to surveillance inspections based on a drug manufacturing inspections compliance program when necessary.
• Surveillance facility inspections. These inspections focus on facilities that manufacture drug products or substances used in drug products. These system-based inspections will identify quality problems or adverse trends in facilities so that mitigation strategies can be implemented. ORA will lead surveillance facility inspections with CDER’s participation at ORA’s request.
• For-cause inspections. These inspections are initiated in response to information or events that call a facility’s compliance into question, and may be used to investigate compliance with sponsor obligations or to follow up on corrective actions. ORA will lead these inspections with appropriate CDER participation.

The new concept of operations follows the FDA’s May announcement of its structural realignment of the ORA. The program alignment created a new organizational model in which the entire reporting chain for the organization’s inspection and compliance staff specialize in a particular commodity. Previously, the ORA had a geographic-based model in which employees conducted work in a variety of program areas, regardless of their specialties.

In announcing the new concept of operations, Gottlieb said, “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.” Gottlieb also suggested that other operations in the FDA could be restructured as well, saying “we’ll continue to build on the opportunities enabled by closer coordination across our functions. We’ll leverage the new efficiency that it offers.”