Planning of GMP Inspections by FDAs New Quality Metrics Programme

A comprehensive new organization has been initiated by the US Food and Drug Administration(USFDA) for its inspection activities. Quality Metrics Programme is the key element behind this initiative. By means of this programme, the compliance status of each manufacturing site will be assessed. Till date, only two categories exists- GMP compliance or non-compliance and therefore, there is no benefit for any industry to improve its overall quality as long as the manufacturing site was rated to be in GMP compliance.

There were good chances earlier that a non-compliance situation was not discovered by FDA inspectors and also the inspection frequency, in the foreign countries, was not meeting the internal FDA standards. A culture of non-compliance was therefore established as some facilities meant for inspection every two years, were not inspected for a long period of time. Upon the final inspection, thus, it was found existence of some major GMP and comprehensive compliance actions were taken like FDA Warning Letters and Import Letters. This led to a serious shortage of drugs because the manufacturing of medicinal products takes place only at very few manufacturing sites.

By this FDAs Quality Metrics Initiative, each production unit for APIs, medicinal products, Biotech, OTC is asked to provide data about the quality level in the manufacturing site. The FDA hence, keeps a check on the maintenance of the quality system and its successful running for assuring the quality of medicinal products. Details were provided by FDAs Russel Wesdyk at the 17th APIC Conference on APIs about the method of collection of data by the FDA from different companies. The authorization for collecting Quality Metrics is provided to the US FDA by the Food and Drug Administration Safety and Innovation Act (FDASIA), Title VII, section 706. A large number of meetings have taken place last year for discussing the potential Quality Metrics with stakeholders. Based on these meetings, the FDA determined the following Quality Metrics:

  • 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 products 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.

Within the learning period of approximately one year, this Quality Metrics will be used by the FDA. In cases where reports are not provided to the FDA after this learning period, serious compliance actions will be undertaken. The next steps will be followed very soon. This draft guide on Quality Metrics will be published by FDA in the coming months.