In a continuing effort to improve the quality system effectiveness of human drug manufacturing sites, FDA revised MAPP 5014.1, Understanding CDER’s Risk-Based Site Selection Model (Site Selection MAPP or the Policy).

Site Selection MAPP

The Center for Drug Evaluation and Research’s (CDER’s) Manual of Policies and Procedures (MAPPs) are federal directives and documentation of internal policies and procedures. MAPPs are required by law and made available to the public to make CDER a more transparent organization.

The Site Selection MAPP outlines the risk-based approach the Office of Pharmaceutical Quality (OPQ) and Office of Quality Surveillance (OQS), a subpart of OPQ, employ to manage the Site Selection Model (SSM) they use to prioritize manufacturing sites for routine quality-related, i.e., current good manufacturing practice (cGMP), surveillance inspections. Manufacturing sites are assigned a risk score and priority based on a variety of risk factors set forth in the Policy.

An overarching policy goal of the amended Site Selection MAPP is to determine the effectiveness of a drug manufacturer’s quality system. FDA noted in the amended Policy that during inspections it will be looking to determine if a quality system results in a robust state of control and promotes a quality culture that allows for exceeding the cGMP standard. cGMP compliance is the floor and FDA is looking for companies to exceed those standards.

Risk Factors

To bolster quality system effectiveness, FDA added a new risk factor for CDER staff to use in their site selection. The new risk factor relates to the compliance history of establishments in the country or region in which the establishment is located that are subject to FDA regulation for exported products.

Additionally, FDA clarified risk factors associated with patient exposure and inherent product risk. Specifically, the amended Site Selection MAPP instructs OQS to evaluate patient exposure by using available information, such as data submitted pursuant to Section 510(j)(3) of the Federal Food, Drug, and Cosmetic Act, as amended by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act). As amended, Section 510(j)(3) requires registrants of drug establishments to submit to FDA reports on the amount of each listed drug manufactured, prepared, propagated, compounded, or processed for commercial distribution.

With regard to inherent product risk, the Site Selection MAPP lists factors to consider, such as dosage form and route of administration. The Policy does not specify what dosage forms or routes of administration the Agency considers higher risk—it merely lists the risk factors OQS should consider. On its face, the Policy suggests that FDA give equal deference to each risk factor.

That said, the Policy states that risk factors are based on either empirical evidence collected by FDA, subject matter experts’ judgment, or a combination of both. In other words, the weight of a particular risk factor could depend on the subject matter expert evaluating it. Additionally, while manufacturers should already have updated their procedures to comport with the CARES Act, manufacturers should double-check that their procedures include reporting the amount of the drug manufactured.

Moreover, the overall tone of the amended Policy indicates that the Agency is preparing to further enhance its inspection program. As such, manufacturers should confirm ongoing readiness for routine inspections and assess the risk profile of each facility using FDA’s factors to determine if their facility will be a high-priority target.