FDA Issues Quality Metrics Draft Guidance Document for Comment

FDA released the anticipated draft guidance document for quality metrics on July 28, 2015, detailing the types of data the agency plans to request of drug manufacturers, the uses it plans to make of the data, and the quality metrics it plans to calculate.

The document, Request for Quality Metrics, Guidance for Industry, outlines FDA’s authority to require owners and operators of establishments that manufacture, prepare, propagate, compound, or process human drugs to provide records and information for inspection under section 704 of the Federal Food, Drug, and Cosmetic Act. It also describes the initial set of requests FDA intends to make to certain owners and operators.

As described in the guidance document, FDA intends to apply the quality metrics program for risk-based inspection scheduling, to predict and mitigate drug shortages, improve the inspection process, and improve FDA’s evaluation of drug manufacturing and control operations. Failure to report quality data “may elevate an establishment’s predicted risk in FDA’s prioritization of inspections and many lead to an earlier inspection.” Products associated with an establishment that does not report as required under section 704 (a)(4) (A) may be deemed adulterated and subject to enforcement action.

Planned quality metrics
In the draft guidance document, FDA lists four quality metrics it intends to calculate for each product and establishment, where applicable:

• Lot Acceptance Rate = 1 – x (x = the number of specification-related rejected lots in a timeframe divided by the number of lots attempted by the same establishment in the same timeframe).

• Product Quality Complaint Rate = the number of product quality complaints received for the product divided by the total number of lots of the product released in the same timeframe.

• Invalidated Out-of-Specification (OOS) Rate = the number of OOS test results for the finished product invalidated by the establishment divided by the total number of OOS test results divided by the total number of tests performed by the establishment in the same timeframe.

• Annual Product Review (APR) or Product Quality Review (PQR) on Time Rate = the number of APRs or PQRs completed within 30 days of annual due date at the establishment divided by the number of products produced at the establishment.

FDA also requested comment on three proposed optional metrics assessing the engagement of senior quality and operations personnel in annual product reviews and product quality reviews; reporting the percentage of corrective actions that involve re-training of personnel; and reporting on the establishment’s process capability or performance index.

Specific data to be reported
The draft guidance document lists the following data types to be reported.

• The number of lots attempted of the product

• The number of specification-related rejected lots of the product, rejected during or after manufacturing

• The number of attempted lots pending disposition for more than 30 days

• The number of OOS results for the product, including stability testing

• The number of lot release and stability tests conducted for the product

• The number of OOS results for lot release and stability tests for the product which are invalidated due to lab error

• The number of product quality complaints received for the product

• The number of lots attempted which are released for distribution or for the next stage of manufacturing the product

• If the associated APRs or PQRs were completed within 30 days of annual due date for the product

• The number of APRs or PQRs required for the product.

FDA intends to request that establishments submit quality metrics data reports for a one-year period that begins after the agency issues its requests, as specified in the request. Reports would be due within 60 days of the end of the reporting period. The data would be segregated in in the report on a quarterly basis. Submission would be through the FDA Electronic Submissions Gateway.

The draft guidance document is available for review on FDA’s website. Comments and suggestions can be submitted for 60 days on regulations.gov.

View the Request for Quality Metrics draft guidance document