FDA Describes How it Selects Manufacturing Sites for Inspections
[Thursday, September 6, 2018]

It is no secret that FDA cannot inspect all drug manufacturing sites, so it prioritizes certain kind of sites based on internal selection criteria. But till yesterday, the details of the selection process were not publicly known. Yesterday FDA released its internal policy for selecting and prioritizing drug manufacturing sites for inspections providing a new insight into which sites should expect more audits than others. Over the years, the rules for FDA inspections have evolved from requiring periodic inspection of all drug manufacturing sites producing FDA-regulated products, to risk-based approach whereby only sites with high-risk processes and products are inspected. Each year FDA’s Office of Surveillance, within the Office of Pharmaceutical Quality, creates a Site Surveillance Inspection List (SSIL) based on several risk factors from its Catalog of Manufacturing Sites, and forward the list to the Office of Regulatory Affairs to schedule inspections. These risk factors include type of site and the material manufactured at it, its compliance history, reports of deviations, and reports of violations. The SSIL only applies for routine surveillance inspections and does not include pre-approval inspections, post-approval inspections and for cause inspections. Also excluded from the SSIL are manufacturing sites for excipients, clinical trial material, compounding pharmacies and medical gas sites. The purpose of these inspections is to evaluate the compliance status of a given organization, and if not compliant, give the company a list of findings to be addressed to bring them into compliance. If a site has been inspected by another FDA-recognized competent regulatory agency, FDA will defer its inspection, provided the other agency did not have any major findings. Additionally, the inspections are also used by FDA “to better understand current practices in drug manufacturing for the purpose of updating the CGMP requirements, regulatory policy, and guidance documents.”  FDA conducts about 5000 surveillance inspections each year, about 60% of which are conducted at foreign manufacturing sites. FDA observed that overall the manufacturing sites involved with FDA regulated drugs have a high compliance rates both in and outside the US. This is also reflected in the number of Warning Letters issued by FDA for GMP violations. In the year 2017, FDA conducted 5063 GMP inspections, of which 3025 were foreign-based, and FDA issued about 120 Warning Letters during the same period. FDA believes this to be an indicator that its policies to conduct risk-based and focused inspections by the reorganized and modernized inspection program is working.  Although there are few specifics in the policy that would help an organization predict when they could be inspected by FDA, as a general rule an organization likely has less probability of an FDA inspection if has had a successful PIC/S audit, has had no major compliance issues in the last 4 years, and has not been in negative publicity.