This guidance document is being distributed for comment purposes only. Comments andsuggestions regarding this draft document should be submitted within 60 days ofpublication in the Federal Register of the notice announcing theavailability of the draft guidance. Submit electronic comments to https://www.regulations.gov.

Introduction:

Quality metrics are used throughout the pharmaceuticalindustry to monitor quality control systems and processes and drive continuousimprovement efforts in drug manufacturing. These metrics can also be used byFDA: to help develop compliance and inspection policies and practices, such asrisk-based inspection scheduling of drug manufacturers; to improve the Agency'sability to predict, and therefore, possibly mitigate, future drug shortages;and to encourage the pharmaceutical industry to implement state-of-the-art,innovative quality management systems for pharmaceutical manufacturing. Thisguidance includes an explanation of how the Center for Drug Evaluation andResearch (CDER) and the Center for Biologics Evaluation and Research (CBER)intend to collect data and use quality metrics to help ensure that theirpolicies and practices continue to support continuous improvement andinnovation in the pharmaceutical manufacturing industry.

This guidance outlines FDA's authority to requireowners and operators of such establishments to provide upon request records andinformation that FDA may inspect under section 704 of the 32 Federal Food,Drug, and Cosmetic Act (FD&C Act, or the Act), and describes an initial setof requests the Agency intends to make to certain owners and operators. FDAintends to make its requests at the time this guidance is finalized, and toprovide notice in the Federal Register. In order to receive publiccomment on these requests, this draft guidance describes the data that theAgency plans to request, the uses FDA intends to make of the requested data,and the quality metrics that FDA intends to calculate.

BACKGROUND:

FDA'sapproach to quality oversight has evolved in recent years. CDER and CBER are committedto supporting the modernization of pharmaceutical manufacturing as part of theAgency's mission to protect and promote public health. These efforts also maybe one long-term strategy to mitigate drug shortages by addressing underlyingcauses of shortages, as noted in FDA's Strategic Plan for Preventing andMitigating Drug Shortages. In2002, FDA launched an initiative entitled "Pharmaceutical cGMPs for the 21st Century: A Risk-BasedApproach," to encourage the implementation of a modern, risk-based pharmaceuticalquality assessment system.Theinitiative was published with several goals, including ensuring that regulatoryreview, compliance, and inspection policies continue to support continuousimprovement and innovation in the pharmaceutical manufacturing industry. Sincepublication of the Pharmaceutical cGMPs for the 21st Century, CDER haspromoted a vision of "a maximally efficient, agile, flexible manufacturing sec

FDAused the following criteria to select the quality metrics that it intends to calculateusing requested data when this guidance is final: metrics should be (1)objective, (2) subject to inspection under section 704 of the FD&C Act, and(3) valuable in assessing the overall state of quality of the product andprocess, commitment to quality by the manufacturer, and the health (i.e.,effective functioning) of the associated PQS, while (4) avoiding any unduereporting burden. These metrics are not intended to be an all-inclusive set ofthe quality metrics that FDA could consider useful to assess a product andmanufacturer's state of quality. Also, while FDA has not selected metrics basedon data or information that are readily accessible to the Agency, such asnumber of recalls, these data and information should also be part ofmanufacturers' product- and establishment-specific evaluations. FDA encouragesmanufacturers to routinely use additional quality metrics beyond the metricsdescribed in this guidance in performing these evaluations.

Thequality metrics program is expected to play an important role in addressing risk-basedinspection scheduling and in the prediction, and potential mitigation, of drugshortages. Section 124 510(h)(3) of the FD&C Act was amended by section 705of FDASIA to require that FDA inspect establishments that are required toregister with FDA "that are engaged in the manufacture, preparation,propagation, compounding, or processing of a drug or drugs in accordance with arisk-based schedule established by" FDA. The provision replaced the requirementthat FDA conduct inspections of certain domestic drug establishments at leastonce every two years. Risk-based scheduling helps FDA focus resources onfacilities that present the greatest risk to consumers.

Section510(h)(3) of the FD&C Act provides for a risk-based schedule of inspectionsfor drugs be established according to the known safety risks posed byestablishments that are required to register. These risks are based on certainfactors as outlined in section 510(h)(4)(A-F): (1) the compliance history ofthe establishment; (2) the record, history, and nature of recalls linked to theestablishment; (3) the inherent risk of the drug manufactured, prepared,propagated, compounded, or processed at the establishment; (4) the inspectionfrequency and history of the establishment, including whether the establishmenthas been inspected pursuant to section 704 within the last 4 years; (5) whetherthe establishment has been inspected by a foreign government or agency of aforeign government recognized under section 809 of the FD&C Act; and, (6)any other criteria that FDA deems necessary and appropriate for purposes ofallocating inspection resources. FDA intends to use quality metrics to supportits understanding of the inherent risk of manufacturing establishments andproducts and as the basis for criteria it deems necessary and appropriate forpurposes of allocating inspection resources.

LEGALAUTHORITY:

Discussedabout

·        RecordsAssociated with the Process Validation Lifecycle and PQS Assessment

·        Authorityto Inspect Records and Request Records in Advance of or In Lieu of anInspection

THEUSE OF QUALITY METRICS AND EFFECTS OF NON-REPORTING:

Discussedabout

·        
How FDA Intends to Use Quality Metrics

·        Effects of Non-Reporting (The failure to reportrequested quality data may elevate an establishment's predicted risk in FDA's prioritizationof inspections and may lead to an earlier inspection. In addition, productsassociated with an establishment that does not report as required under section704(a)(4)(A) may be deemed adulterated under section 501 and subject toenforcement action)

REPORTINGOF QUALITY DATA AND CALCULATION OF QUALITY METRICS:

Discussedthe set of requests for quality metrics data that FDA intends to make and givenotice of in the Federal Register at the time the guidance is finalized

·        Who Reports and Who May Contribute to the Report

·        Quality Metrics that FDA Intends to Calculate

FDA intends to calculate the followingquality metrics for each product and establishment, where applicable:

o  LotAcceptance Rate

o  ProductQuality Complaint Rate

o  InvalidatedOut-of-Specification (OOS) Rate

o  AnnualProduct Review (APR) or Product Quality Review (PQR) on Time Rate

·        Optional Metrics Related to Quality Culture and Process Capability/Performance

o  QualityCulture

o  CAPAEffectiveness

o  ProcessCapability/Performance

·        How to Report Quality Data to FDA

APPENDIXA: INSTRUCTIONS FOR QUALITY METRIC DATA SUBMISSIONS

Discussedabout

·        Worksheet for Data Tables

·        Product Specific Information

·        Mandatory Data

·        OptionalMetrics

Draft Guidance: Request for Quality Metrics Guidance for Industry (PDF -250KB)