FDA Site Selection Model Updated to Include Regional Risk Factors
A late-June 2023 update to FDA’s MAPP 5014.1, “Understanding CDER’s Risk-Based Site Selection Model,” adds new factors to how the agency selects which sites to inspect, most importantly, the general compliance history in the country or region where the company under consideration is located.
CDER’s Manual of Policies and Procedures (MAPPs) are federal directives and documentation of internal policies and procedures. They are publicly available and provide insight into FDA policies and guidance given to its staff. MAPP 5014.1 was originally published in 2018 and made effective September 26, 2018.
In the “Policy” section of the MAPP, the subsection on “Risk Factors” originally included six risk factors pertaining to an establishment under consideration for inspection:
- Compliance history
- Recall history
- Inherent risk of the drug or device
- Inspection frequency and history
- Inspection by a foreign agency, and
- “Any other criteria deemed necessary and appropriate by the Secretary for purposes of allocating inspection resources.”
In the newest revision, the following paragraph was added to the list of risk factors:
“The compliance history of establishments in the country or region in which the establishment is located that are subject to regulation under this Act [the FD&C Act], including the history of violations related to products exported from such country or region that are subject to regulation.”
In plain language, a company located in a country that has had a history of compliance issues, which would include inspection violations and warnings, product recalls, and import alerts, would be considered a higher risk in the calculus used by FDA to determine whether to inspect that company and how often.
Another section gives insight into how the risk score for each site is determined. The factors listed reflect the previous list but add the compliance history of the country or region factor and one more consideration not in the previous revision of the MAPP: patient exposure. Specifically, the additional risk factor is stated as follows:
“Patient exposure (using available information such as data submitted pursuant to section 510(j)(3) of the FD&C Act (21 U.S.C. 360(j)(3) as added by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act).”
Quality Culture Also in Focus
The introduction in the “Policy” section of the MAPP explains that FDA will use the Site Selection Model with defined risk factors to generate the Site Surveillance Inspection List – the prioritized list of sites selected for routine surveillance inspections.
The goals of the inspection program as stated in the original version of the MAPP and also contained in the new revision are to determine whether the inspected sites are following Current Good Manufacturing Practices (CGMP), provide input to the inspected sites to aid in improving compliance, and to better understand current practices in the industry to inform the agency’s efforts in updating policy and guidance.
In the 2023 revision, an additional objective was added: to gain insight into a company’s quality system and by extension the company’s quality culture. Specifically, the paragraph added says a new objective of the program is to:
“Gain insight into the effectiveness of a drug manufacturer’s quality system. In addition, it may inform understanding, to the extent possible, of practices at a facility that not only support meeting CGMP compliance requirements to establish and maintain a robust state of control but also promote a quality culture that allows for exceeding this standard.”
The table at the end of the 2023 MAPP listing revisions seemed to indicate only minor revisions to update references, include quality system effectiveness, and “nonsubstantive editorial changes.” However, a comparison with the difficult-to-find original version, deleted from FDA’s website when the new version was added, tells a different story.
It is valuable to know that (1) companies located in countries with a history of compliance issues now have a higher probability of being inspected, and (2) FDA has a focus during inspection on gaining insight into how companies promote quality culture. While “quality culture” has been a buzzword now for many years, this is one formal indication that the agency expects its inspections to help provide insight into that elusive topic.
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