The Food and Drug Administration (FDA) has released an internal policy related to risk-based scheduling and prioritization of surveillance inspections for drug manufacturing facilities. This transparency-related development is one of several steps discussed by FDA Commissioner Scott Gottlieb in a statement summarizing new and ongoing actions the agency is taking to meet the challenges of increasingly globalized drug manufacturing. For example, in addition to conducting risk-based inspections, in recent years FDA has reorganized its inspectorate on a product-centered rather than regional model, and has begun to explore and enter into mutual recognition inspection agreements with other national and international regulators, such as the European Union and the inspectorates of its member states. Each of these efforts offer benefits to regulated industry and other stakeholders, as well as to FDA. We discuss the risk-based inspection policy below.
In addition to the initial approval-related inspection by FDA, drug manufacturing facilities are subject to periodic surveillance inspections, and there are other potential inspections as well (e.g., “for cause” inspections related to specific concerns). FDA’s recent policy sheds some light on the agency’s approach to routine surveillance inspections. In brief, it is a risk-based model in which the agency considers multiple factors, such as the inherent risk of the drug product being manufactured at the facility, the facility’s compliance history, and the time since last inspection.
Risk-Based Surveillance Inspections
The recent FDA policy statement (Manual of Policies & Procedures (MAPP) 5014.1) was issued by the Office of Pharmaceutical Quality (OPQ) in the agency’s Center for Drug Evaluation and Research (CDER). The MAPP formalizes and clarifies FDA’s risk-based approach to the scheduling of routine surveillance inspections, though we note that the agency has been moving in the direction of risk-based inspections for some time. It has not always been easy for regulated industry and other stakeholders to discern which factors are most important in the agency’s scheduling of inspections. While the MAPP is not the equivalent of a crystal ball (e.g., it does not explain how the various factors are weighted or provide an inspection-scheduling algorithm), it does provide some useful insight.
The risk factors are summarized here:
- Facility compliance history;
- Inherent risk of the drug product manufactured or otherwise handled at the facility;
- Inspection frequency and history, including whether there has been an inspection within the last four years;
- Whether the establishment has been inspected by a recognized foreign inspector; and
“[a]ny other criteria deemed necessary and appropriate” for allocating inspection resources.
The risk factors are used to generate a risk score for each site. According to the MAPP, scoring of risk components is based on either empirical evidence collected by the agency, subject matter experts’ judgment, or a combination of both.
Following inspection, FDA evaluates the findings and assigns a classification into one of three categories: (i) no action indicated, which means the agency found no objectionable conditions during the inspection; (ii) voluntary action indicated, which means the FDA found objectionable conditions, but is not recommending immediate regulatory action, and (iii) official action indicated, which means the agency found objectionable conditions and may pursue regulatory action. The findings are likely to be considered relevant in the scheduling and prioritization of future inspections.
FDA also recently updated its inspection classifications database. The database provides information about recent classifications of inspections of manufacturing facilities, and provides transparency to the industry and other stakeholders.
Inspection Program Alignment
In addition to how often inspections occur, an ongoing area of focus, particularly for facilities manufacturing increasingly complex products, has been the training and experience of FDA inspectors and investigators. As part of addressing this, FDA has reorganized its field inspection service around product expertise, rather than the decades-old regional focus. A primary benefit is to allow inspectors to develop additional product-specific expertise. Regarding the program alignment initiative, Dr. Gottlieb noted that, “…we modernized the structure of our field organization, including inspection operations, to direct our focus and organization around the types of programs we regulate. Previously, we had organized our field activities and resources based on geographic regions. The new structure, which focuses resources based on areas of specialization, allows us to better align the expertise of our staff with our commitments.”
- FDA’s recently-released policy provides additional insight for manufacturers and other stakeholders regarding factors considered by FDA in scheduling and prioritizing routine surveillance inspections. Companies should consider how to incorporate this information into their manufacturing policies, as well as their inspection-specific procedures.
- Among other things, firms should review and consider the potential risks related to the type of drug product being manufactured, as well as previous compliance and recall history.
- FDA is taking numerous actions to make inspections more efficient, targeted, and risk-based, and to reduce inefficiencies and challenges posed by multiple regional or national regulators and inspectorates.