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FDA’s Pharma Manufacturing Quality Metrics Research
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Quarterly Report on Quality Culture

This article was published in the November/December 2016 edition of Pharmaceutical Engineering® magazine in the Quarterly Report on Quality Culture. In the world of pharmaceutical production, it is universally understood that a robust quality system provides key elements of assurance and oversight for manufacturing processes: It ensures that patients are provided with medications that are safe, effective, and reliably produced at a high level of quality. Despite recent advances in the manufacturing sector, however, quality issues continue to arise that can result in recalls, withdrawals, or harm to patients. Quality issues have also been linked to the rise in critical drug shortages.1 Regulatory agencies currently assess the risk profile of manufacturing sites based primarily on their compliance history, as seen in warning letters and field reports, in conjunction with records on product recalls, and market-based quality problems. These are not necessarily the most informative measures and, by their nature, provide historical or lagging data or signal detection. More relevant data relating to the state of quality, provided in advance, would better inform the risk factors that might predict quality problems and future drug shortages. This could become a valuable source of information for risk-based assessments and inspection scheduling of pharmaceutical manufacturing operations around the world. The US Food and Drug Administration’s (FDA) approach to quality oversight has evolved in recent years.

The new Office of Pharmaceutical Quality (OPQ) has made it a priority to establish a more sound basis for ensuring that pharmaceutical products meet high quality standards throughout their life cycle. The FDA draft guidance proposed a set of standardized manufacturing quality metrics. The establishment and collection of these metrics could provide various stakeholders—from industry to regulators—with greater insight into the state of quality at a given manufacturing facility and allow stakeholders to better anticipate and address quality issues and their associated risks while simultaneously reducing unnecessary regulatory burden. As part of this initiative, the FDA has recently awarded a research grant∗ to Switzerland’s University of St. Gallen to help establish the scientific basis for such metrics and integrate quality in its ongoing operational-excellence (OPEX) efforts.

OPEX Program

The Institute of Technology Management at the University of St. Gallen (ITEM-HSG) is a global academic leader in establishing solid and meaningful OPEX programs. For more than a decade it has worked hand in hand with the pharmaceutical industry to develop widely accepted global programs. These programs have positioned ITEM-HSG at the forefront of promoting, measuring, and monitoring operational excellence in the pharmaceutical industry. St. Gallen has been responsible for the largest independent benchmarking project in the pharmaceutical industry since 2004, with 334 global manufacturing sites contributing key performance indicators (KPIs), in addition to providing rich qualitative data on organizational enablers for excellence. The institute’s experience in metrics tool development and access to this global industry data set, coupled with experienced independent data analysis resources, uniquely position the St. Gallen OPEX project team to contribute significantly to the FDA/OPQ initiative on quality metrics.

Key Objective

In support of the OPQ’s commitment to transform the assessment of drug quality from a qualitative to a quantitative or semi-quantitative expertise-based assessment, the key objective of this project is to evaluate potential quality metrics candidates, including those suggested in the FDA’s June 2015 draft guidance,2 and propose how they may be utilized to monitor the status of product and facility quality across the inventory of FDA-regulated sites. The proposed quality metrics will facilitate the effectiveness of current manufacturing controls, improve delivery of key quality outcomes in manufacturing operations, and seek to establish significant correlations to the underlying quality culture of an organization. More relevant data relating to the state of quality, provided in advance, would better inform the risk factors that might predict quality problems and future drug shortages FDA has recently awarded a research grant to Switzerland’s University of St. Gallen to help establish the scientific basis for such metrics and integrate quality in its ongoing operational-excellence efforts Based on St. Gallen’s extensive global OPEX database and nearly 15 years’ experience in research and collaboration with the pharmaceutical industry, the research team will evaluate and propose meaningful, measurable, and reportable potential quality metrics candidates, including quantitative and quality culture–related indicators.

Research Approach

The St. Gallen OPEX model is a comprehensive excellence model able to map site performance from an overall system perspective. It comprises factors related to quality as well as cost- and time-related KPIs, and evaluates dozens of enablers that affect these KPIs. This well-established pharmaceutical program can show, based on data, that the very foundation of superior overall excellence is quality. The research strategy will be executed in five stages:

Stage 1: The current FDA metrics concepts contained in the "Request for Quality Metrics – Guidance for Industry"2 will be examined in detail, and the underlying research assumptions will inform further work. For the Stage 1 hypothesis evaluation, the research team will rely on existing data from the St. Gallen global OPEX database.

Stage 2: Researchers will develop a set of quality metrics suitable for overall system performance. Quality will be built in at its very foundation. The system will be described from supplier inputs to final delivery and will also comprise maintenance-related data, enablers, cultural indicators, and classical operational performance figures. This stage will be summarized and evaluated using a gap analysis procedure between the proposed St. Gallen metric sets and the FDA guideline metrics. The main objective is to determine if the limited set of KPIs given in the draft guidance can display a comparable base for an overall system-based evaluation, such as the St. Gallen model.

Stage 3: Based on the gap analysis and Stage 1 outcomes, the research team will propose possible modifications of the set of metrics and examine potential implementation challenges.

Stage 4: The team will use its industry access to check the practicability of the proposed metrics. Implementation hurdles and issues will be discussed and documented, based on case study research. Interaction with industry, however, will commence at the beginning of the project and continue throughout.

Stage 5: The team will create an overall research report to document progress and results and conclude findings. Intermediate and final results will be discussed in open public meetings with the FDA and industry in the United States, Europe, and Singapore.

Collaboration

St. Gallen will collaborate on this project in Ireland with Nuala Calnan, PhD, at the Dublin Institute of Technology (DIT), and in the United States with Prabir Basu, PhD, former Executive Director of the National Institute for Pharmaceutical Technology and Education. The key objective of this project is to evaluate potential quality metrics candidates, including those suggested in the FDA’s June 2015 draft guidance By: Thomas Friedli, PhD Prabir Basu, PhD Nuala Calnan, PhD

2017 ISPE Quality Culture and Quality Metrics Conference Take advantage of the early registration deadline expended to 21 March 2017. The 2017 ISPE Conference on Quality Culture and Quality Metrics will provide a collection of practical, powerful tools and a comprehensive behavior-based approach for improving quality culture as a means of delivering enhanced quality outcomes. The conference will also provide the latest data and insights for operationalization of quality metrics across the supply chain.  Learn more about the conference and how to register.  

  • 1International Society for Pharmaceutical Engineering. "Drug Shortages Prevention Plan: A Holistic View from Root Cause to Prevention." October 2014. http://www.ispe.org/drugshortagespreventionplan.pdf
  • 2 a b US Food and Drug Administration. "Request for Quality Metrics – Guidance for Industry." July 2015. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm455957.pdf