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Operational changes at FDA and CDER aim to improve global market monitoring.
A greatly expanded range of regulated food and drug products, now produced all over the world, has prompted FDA commissioner Margaret Hamburg to seek new ways for FDA to handle its more complex and far-flung regulatory responsibilities. Hamburg formed a high-level agency-wide group in 2013 to assess and make recommendations for improving alignment of FDA centers with its inspection field force. The result is a new Program Alignment Group (PAG) plan to integrate more closely center and field oversight functions through “commodity-based and vertically-integrated regulatory programs.”
At the same time, the Center for Drug Evaluation and Research (CDER) is implementing a major reorganization designed to bolster programs and policies to ensure drug quality. After two years of planning, CDER director Janet Woodcock is establishing a new “super” Office of Pharmaceutical Quality (OPQ), a move that reflects Woodcock’s “one voice for quality” approach that coordinates review, inspection, and research activities related to drug quality.
Field and center integration
FDA’s program alignment process will revise inspection functions carried out by the Office of Regional Affairs (ORA), which manages operations for inspecting and overseeing compliance for all FDA-regulated products and companies in the United States and abroad. For drugs, a main initiative is to form an ORA pharmaceutical inspectorate, a cadre with specialized expertise to inspect and evaluate manufacturing facilities for both human and animal drugs throughout the world. CDER staff may participate in certain inspections and will provide more input into inspection scheduling, operations, and enforcement actions. Field force specialization will involve more training, and ORA laboratories will become more specialized (1).
These operational changes will be spelled out in a five-year Pharmaceuticals Action Plan that will be developed in 2015 by ORA, CDER, and the Center for Veterinary Medicine (CVM). These parties will calculate future resource levels needed to shift from a regional oversight structure to a dedicated drug surveillance program, a process that will involve assessing the number of field investigators, compliance officers, and managers for the new program. The program will develop enforcement standards, policy guides, and guidance and clarify field and center responsibilities for issuing warning letters, enforcement actions, and decisions related to compounding, clinical disqualifications, and recalls.
Key to formulating a multi-year, risk-based process for scheduling plant inspections and monitoring imports for ORA, CDER, and CVM is to overhaul and update manufacturer registration and inventory databases. This involves “harmonizing” center and ORA data systems, using common facility identifiers, product codes, and software platforms that permit all parties to access information on field inventory, applications, facilities, adverse events, and risk information. To this end, FDA issued guidance in October 2014 advising manufacturers to use DUNS numbers (Dun and Bradstreet’s Data Universal Numbering System) for a unique facility identifier (UFI) system (2).
Once the program is established, CDER will supply ORA with an annual surveillance priority list that provides a basis for an ORA work plan for the coming year. A pilot for team-based domestic and foreign drug quality inspections has been launched to ensure that these changes enhance field and center agreement on where regulatory action is required.
FDA’s Center for Biologics Evaluation and Research (CBER) should experience less disruption from this initiative to integrate field and center inspection activities, as an ORA Team Biologics has been in place since 1997 for cellular therapies and blood products, with CBER reviewers regularly participating in field inspections. Still, a Biological Products Action Plan will be developed to improve CBER’s plant registration data system and support a risk-based approach for setting priorities on facility inspections. In 2015, CBER and ORA will update existing Team Biologics procedures and identify gaps in training and policies.
Another important PAG change is to establish a central Bioresearch Specialization Action Plan for agency bioresearch monitoring (BIMO) activities. A dedicated corps of ORA investigators will conduct BIMO inspections for drugs and biologics, as well as other regulated products.
Changes at CDER
Meanwhile, CDER’s reorganization will go live Jan. 5, 2016, shifting to OPQ most functions of its Office of Pharmaceutical Science (OPS). OPQ will evaluate the CMC (chemistry, manufacturing and controls) submissions for drugs, biotech therapies, and generic drugs and conduct research on drug formulation and manufacturing issues (3).
OPQ also will oversee the process for scheduling and conducting preapproval and surveillance inspections now carried out by CDER’s Office of Compliance (OC). OPQ will become responsible for certain functions related to risk analysis and informatics in planning inspections now handled by OC’s Office of Manufacturing and Product Quality, and oversight of bioequivalence testing and non-clinical studies will move from OC to CDER’s Office of Translational Sciences. These changes will enable OC to focus on compliance and enforcement activities, including recalls, supply chain security, and unapproved drugs.
Woodcock will head OPQ on an acting basis, assisted by deputy director Lawrence Yu, who has been serving as acting director of OPS for the past year. Steve Kozlowski will continue as director of OPQ’s Office of Biotechnology Products, and Cindy Buhse remains acting director of the Office of Testing and Research. New offices will process CMC applications for new drugs (acting director Sarah Pope Miksinski) and for lifecycle drug products (acting director Susan Rosencrance), respectively. Other new OPQ operations include an Office of Program and Regulatory Operations, an Office of Policy for Pharmaceutical Quality, and an Office of Process and Facilities. An OPQ Office of Surveillance will develop written standards and inspectional procedures, led on an acting basis by Theresa Mullin, currently director of CDER’s Office of Strategic Programs where she has headed up the development of quality metrics for assessing manufacturing operations and products.
These changes aim to achieve uniform quality oversight for new drugs, generic drugs, and over-the-counter products by providing a single drug quality assessment “that captures the overall OPQ recommendation on approvability,” Woodcock stated. Manufacturers will benefit from feedback on quality deficiencies earlier in the review cycle, and FDA will be able to provide a more uniform quality program across domestic and foreign manufacturing sites, as well as for all drug product areas. The result, Woodcock believes, will be “consistent approaches, a transparent process, and clear standards to which the regulated industry must conform.”
Woodcock has voiced these goals repeatedly in the past two years, emphasizing the need to instill a “culture of quality”, as opposed to compliance, throughout the bio/pharmaceutical industry. She emphasized at the FDA/PQRI conference in September the importance of moving from a “rule-based” to a “risk-based” approach based on common understanding of what constitutes real risk in pharmaceutical products. Field inspections will shift from “writing traffic tickets” to full product assessment--not just negative observations but what the manufacturer is doing well. This intelligence will support a “pharmaceutical platform” with a complete inventory of regulated facilities around the world (e.g., location, ownership, products, surveillance information). CDER has been piloting its team-based review approach this past year, and Woodcock anticipates “rapid evolution” of these initiatives over the next few years.
1. FDA, PAG action plans, www.fda.gov/aboutfda/CentersOffices/ucm392733.htm, accessed Nov. 11, 2014.
2. FDA, Specification of the Unique Facility Identifier System For Drug Establishment Registration, Guidance for Industry (November 2014).
3. CDER, CDER reorganization, www.fda.gov/AboutFDA/CentersOffice/OfficeofMedicalProductsandTobacco/CDER/ucm418347.htm, accessed Nov. 11, 2014.
Article Details Pharmaceutical Technology
Vol. 28, Issue 12
Citation: When referring to this article, please cite it as J. Wechsler, "FDA Realigns Drug Inspection and Manufacturing Oversight," Pharmaceutical Technology 28 (12) 2014.