5/6 October 2023
The US Food and Drug Administration has initiated a comprehensive new organisation of its inspection activities. One of the key elements of this initiative is the Quality Metrics Program. This program will throw a complete new light on the compliance status of each manufacturing site. So far there were only two categories: GMP compliance or non-compliance. There was no benefit for industry to improve the overall quality as long as the manufacturing site was rated to be in GMP compliance.
The chances have been good that a non-compliance situation would not be discovered by FDA inspectors. The frequency of inspections - especially those in foreign countries - was not meeting internal FDA standards. Instead of inspections at least every two years, some facilities have not been inspected for a long period of time and thus have developed a "culture of non-compliance". When they finally were inspected, some major GMP deviations were discovered and caused comprehensive compliance actions such as FDA Warning Letters and Import Alerts. This has resulted in some serious drug shortages because medicinal products were only manufactured at very few manufacturing sites.
The FDA Quality Metrics initiative aims at asking each production site (APIs, medicinal products, Biotech, OTC etc) to provide data about the "quality level" in the manufacturing site. By this, FDA will be able to see from the data how well the quality system is maintained and how successful the quality system will affect the quality of the medicinal products.
At the 17th APIC Conference on APIs FDAs Russel Wesdyk presented details on how FDA will collect data from the companies. The Food and Drug Administration Safety and Innovation Act (FDASIA) Title VII, section 706 gives US FDA the authority to collect Quality Metrics. Over the last year a number of meetings have been organised in order to discuss potential Quality Metrics with stakeholders. As an outcome of these meetings the following Quality Metrics are of high interest for FDA:
Lot Acceptance Rate = the number of lots rejected by the establishment in a year divided by the number of lots attempted by the same establishment in the same year.
Right First Time Rate = the number of lots with at least one deviation by the establishment in a year divided by the number of lots attempted by the same establishment in the same year.
Product Quality Complaint Rate – the number of complaints received by the manufacturer of the product concerning any actual or potential failure of a unit of drug product to meet any of its specifications, divided by the total number of lots released by the manufacturer of the product in the same year.
Invalidated Out-of-Specification (OOS) Rate – the number of OOS test results invalidated by the establishment, or contracted establishment in a year divided by the total number of tests performed by the establishment in the same year.
Annual Product Review (APR) on Time Rate – the number of APRS generated within 30 days of annual due date at the establishment divided by the number of products produced at the establishment
Management Engagement – the most senior manager that signed each annual product review, reported as one of the following: (1) none specified, (2) line quality manager, (3) site operations manager, or (4) corporate executive manager.
- Performance Question 1 – A “yes” or “no” value of whether the establishment calculated a process capability or performance index for each critical quality attribute as part of that product’s APR.
- Performance Question 2 - A “yes” or “no” value of whether the establishment has policy requiring a CAPA at some lower process capability or performance index.
- Performance Question 3 – If “yes” to question 2 – what is the process capability or performance index that triggers a CAPA. If “no” to question 2 – please do not respond.
Corrective and Preventative Action (CAPA) Rate – the number of corrective or preventative actions that were initiated due to an APR, divided by the total number of APRs generated.
The FDA will use the Quality Metrics in a learning period of approx. one year. After that learning period serious compliance actions will be the consequence for not reporting to FDA. The next steps will happen very soon. The FDA is planning to publish the Draft Guide on Quality Metrics in the next months to come.