By David R. Somers, Senior Industry Analyst, Axendia
Manufacturers and FDA to Measure Product Quality
Summary
The continuing efforts by biologic and pharmaceutical manufacturers to join the FDA to improve product quality, reduce inspection costs, increase the effective monitoring of products and streamline reporting requirements have crossed the Rubicon of mere theorizing, discussion and contemplation into firm and pro-active steps. Those efforts have been aimed at the establishment of acceptable and realistic standards of measurement for product development, testing, implementation, distribution and monitoring. The direction is toward the establishment of acceptable and realistic standards of measurement for product development, testing, implementation, distribution and monitoring. These activities are in concert with the broader effort by FDA to promote innovation, increase stakeholder involvement in quality and enhance the safety of the supply chain.
To support this effort, the International Society for Pharmaceutical Engineering (ISPE) created a cohesive, comprehensive series of criteria for the measurement of critical parameters needed to define and control quality in biologic
and pharmaceutical manufacturing. Subsequently, using many of the metrics developed by the ISPE, the FDA submitted a Request for Quality Metrics Guidance for industry.
HISTORICAL CONTEXT
Starting in 2002, the publication of “Pharmaceutical cGMPs for the 21st Century” initiated a paradigm shift, from “rule-based” to “risk-based” conduct, for all aspects of FDA inspection and evaluations criteria for development, manufacturing and distribution. Given budgetary constraints and the need to place more emphasis on quality, it became the most reasonable course of action to take.
Then in 2012, the passage of FDASIA (See Axendia’s article: FDA to Grade Industry on a Curve – Are You Ready?) created the mandate and statutory authority for the establishment of standards associated with the ‘quality through innovation’ concept. These standards, coupled with measureable and quantifiable metrics, were to be used to gauge control over processes, products and systems that govern regulated activity. In order to reduce the costs and broaden the coverage of monitoring industrial activities associated production, the reporting methodology and fee arrangements for inspections and qualifications were changed to aid FDA in maintaining the highest quality standards.
ISPE QUALITY METRICS PROGRAM
The ISPE effort provided the “nuts and bolts,” needed to implement these changes. Those changes include enhancing FDA’s ability to collect and analyze information to evaluate the degree to which a manufacturer is able to substantiate tangible evidence of control of processes and products during their lifecycles –from design to delivery. 
The standards, having been developed by an international organization, are in step with other international standards and evaluative agencies throughout the world, in keeping with global harmonization efforts.
The ISPE Quality Metrics Pilot Program has issued all of the quantitative metrics identified by FDA as studied and featured in the ISPE Quality Metrics Initiative: Wave 1 Report. In addition, the report included questions on process capability, as well as the concept of quality culture and the effects on quality performance.
The second effort (Wave 2) of the pilot has been undertaken, for purposes of further developing the knowledge of those relationships found in Wave 1, to provide experience in future logistics and activities associated with product-based data and fulfillment of the FDA proposed metrics set.
The two main factors precipitating these changes are (1) costs borne by regulating agencies, and (2) advances in digital data collection and information technology. The latter factor enables FDA to gather and analyze more information in a more timely fashion, but should not lead them to reach hasty conclusions based upon initial observations. “FDA recognizes that any individual data point or quality metric is not solely indicative of the state of quality of the establishment or products; rather FDA intends to use this information in context.”1
METHODOLOGY
The requirement for the previously mentioned evidence of control is manifested through ongoing programs maintaining and evaluating data that relate to product quality. For example, the process analytical technology (PAT) techniques are one of many active engagements which monitor “live” production of product during the course of manufacturing. Periodic and specific reviews of records illustrating representative batches and associated records of complaints and recalls serve as another reflection of the degree to which a regulated entity can verify the safe and effective manufacturing of product. All these benchmarks, once held by those entities and made available when FDA initiated an inspection, will now be submitted digitally at periodic intervals (such as an APR) as part of the risk-based criteria for determining the need for and scheduling of a physical inspection, compliance and quality maintenance.
IMPLEMENTATION
As proposed in the guidance, several criteria for measurements and assessments include rates for Lot Acceptance. Complaints, OOS, APR or PQR, CAPA effectiveness, level of Senior Management involvement, Process Capabilities and Performance. The submissions of data are governed by Appendix A – Instructions for Quality Metric Data Submissions (See Axendia’s article FDA Rolling Out e-Inspections.)
TIME FRAME
Since 2012, there has been steady progress in the development and implementation of the program; of late, the issuance of the calls for comment on the guidance for metrics falls in line with that progress. As Stephen M. Ostroff, acting Commissioner of FDA states, “All told, we have completed more than 70% of the law’s deliverables and we continue to maintain our commitment to a transparent and accessible implementation plan…” (See http://blogs.fda.gov/fdavoice/index.php/tag/fdasia/).
CONCLUSION
As stated in the beginning of this article, efforts like those undertaken by ISPE continue to work in concert with the broader effort by FDA to promote innovation, increase stakeholder involvement in quality and enhance the safety of the supply chain. Unlike previous initiatives that were started and subsequently foundered from uncertainty and repeated reviews, this mandate has had, and continues to maintain, a forward momentum that can only be beneficial for manufacturers, the FDA and, oh yes… the patients.
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1 Request for Quality Metrics Guidance for Industy (Draft), July 29, 2015, pg.2, line 70.
The opinions and analysis expressed in this research reflect the judgment of Axendia at the time of publication and are subject to change without notice. Information contained in this document is current as of publication date. Information cited is not warranted by Axendia but has been obtained through a valid research methodology. This document is not intended to endorse any company or product and should not be attributed as such.