FDA Releases Long-Awaited Quality Metrics Guidance


For the past few years, FDA has been considering measures to improve drug quality.  The Agency’s efforts were reinforced in 2012 with the passage of the Food and Drug Administration Safety and Innovation Act, which allowed the agency to use performance measures, or quality metrics, “to assess a facility’s quality system to assure product quality.”  In January 2015, after much anticipation, FDA launched the Office of Pharmaceutical Quality (OPQ) with the goal of “creating a drug quality program as robust as the programs the agency already has in place for drug safety and efficacy.”

Part of the goal of creating the new FDA Office is to oversee drug quality throughout a product’s lifecycle, rather than focusing on pre- and post-market review. Through its surveillance, FDA says OPQ will be able to help the Office of Regulatory Affairs (ORA) “prioritize inspections … to try to mitigate quality problems before they lead to a recall or the need for an enforcement action.”  This, the Agency says, could prevent future problems, since “the majority of drug shortages stem from quality concerns.”

Quality Metrics

Originally, FDA had planned to release its guidance on quality metrics by the end of 2014, but delays eventually pushed back its release.  Since its launch, OPQ has been tasked with reviewing all new drug applications—for new and generic products—for manufacturing quality, in parallel with FDA’s other review bodies.  With the release of its new draft guidance, entitled “Request for Quality Metrics”, FDA is giving more details to industry on its approach to quality metrics, as well as asking industry for its input in specific areas that are still being considered.

At its basis, FDA plans to use its authority to collect records “in advance of or in lieu of” an inspection, under section 704(a)(4)(A) of the FD&C Act to gather various quality metrics data records.  The Agency says it will use these records to “further develop [its] risk-based inspection scheduling.”  For companies with robust quality metrics data, this information could be used to “reduce the inspection frequency at an establishment.” I n cases where the data raises issues, FDA says having the quality metrics data will allow it to “improve the efficiency and effectiveness” of the inspections.  For now, the agency foresees its use of quality metrics to be used primarily for reducing inspection frequencies.

FDA says it will request the following 10 baseline quality metrics from companies as part of its analysis:

·       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 out-of-specification (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 annual product reviews (APRs) or product quality reviews (PQRs) were completed within 30 days of annual due date for the product.

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

The Agency is also asking for input on five “additional, optional metrics as evidence of manufacturing robustness and a commitment to quality.”

·       Senior Management Engagement—Was each APR or PQR reviewed and approved by the following: (1) The head of the quality unit, (2) the head of the operations unit, (3) both, or (4) neither?

·       Corrective Action and Preventive Action (CAPA) Effectiveness—What percentage of your corrective actions involved re-training of personnel (i.e., a root cause of the deviation is lack of adequate training)?

·       Process Capability/Performance—A “yes” or “no” value of whether the establishment’s management calculated a process capability or performance index for each critical quality attribute as part of that product’s APR or PQR.

·       Process Capability/Performance—A “yes” or “no” value of whether the establishment’s management has a policy of requiring a CAPA at some lower process capability or performance index.

·       Process Capability/Performance—If “yes” to the previous question—What is the process capability or performance index that triggers a CAPA? If “no” to the previous question—please do not respond.

FDA was asking the public for comment on the draft guidance by 28 September 2015, and planned to hold a public meeting on the Guidance on 24 August 2015.

REFERENCE:  RAPS; 28 JUL 2015; Michael Mezher

Leave a Comment