CDER recently published a new Manual of Policies and Procedures (MAPP 5014.1) for the site selection model used by CDER staff to prioritize manufacturing sites for routine cGMP inspections. The goal of the changes associated with the MAPP is to promote the effective and efficient use of FDA resources to address the most significant public health risks.
The underpinnings of this MAPP originate in the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), which amended the Federal Food, Drug, and Cosmetic Act (FDCA). Section 507 of FDASIA replaced the fixed minimum inspection interval for domestic establishments (i.e., biennial inspections) with a requirement that FDA inspect domestic and foreign drug establishments “in accordance with a risk-based schedule” that considers the establishments’ “known safety risks” and which are required to be based on the following factors:
- The compliance history of the establishment;
- The record, history, and nature of recalls linked to the establishment;
- The inherent risk of the drug manufactured, prepared, propagated, compounded, or processed at the establishment;
- The inspection frequency and history of the establishment, including whether the establishment has been inspected pursuant to section 704 FDCA within the last 4 years;
- Whether the establishment has been inspected by a foreign government or an agency of a foreign government recognized under section 809 FDCA; and
- Any other criteria deemed necessary and appropriate by the agency for purposes of allocating inspection resources.
This last clause, permitting the use of: “…any other criteria deemed necessary and appropriate” is the basis for the MAPP’s inclusion of the following risk factors for the site selection model, in order to generate a “risk score” for each site:
- Site type (e.g., manufacturer, packager only, control lab only);
- Time since last surveillance inspection (or if the site was never previously inspected);
- FDA compliance history;
- Foreign regulatory authority inspectional history (with an authority deemed capable under section 809 of the FDCA);
- Patient exposure;
- Hazard signals (such as FARs, BPDRs, MedWatch reports, recalls, etc.);
- Inherent product risk, based on:
- Dosage form;
- Route of administration;
- Products intended to be sterile;
- API load (concentration of API in dosage form or unit dose);
- Biologic drug substance or drug product;
- Therapeutic class;
- Narrow Therapeutic Index drugs;
- Emergency use drugs.
The scoring of risk components is based on either empirical evidence collected by FDA, subject matter experts’ judgment, or a combination of both. Official Action Indicated (OAI) sites are removed from routine surveillance inspection planning, meaning that the re-inspection of OAI sites is determined as part of the agency’s enforcement effort. In addition, the following types of sites are excluded from prioritization under this MAPP:
- Human drug compounding outsourcing sites registered under section 503B of the FDCA, (as the inspection schedule for these sites is established by a separate selection process);
- Medical gas sites, (as these are also managed by a separate selection process);
- Excipients (however, these may be inspected when deemed necessary);
- Drugs intended for use only in clinical trials (however, these may be inspected when deemed necessary).
The MAPP goes into effect on September 26th.