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FDA/Quality Metrics Management of FDA-Guidelines: How to implement Quality Metrics?

Author / Editor: Hasse Herlevsen, Gert Moelgaard* / Anke Geipel-Kern

Quality Metrics — Regulatory requirement or business opportunity? — Inspections yes, but only as many as necessary. The FDA has been acting on this principle for many years. With the recent FDA Quality Metrics Initiative, the agency is pushing ahead with this project and is trying to bring greater responsibility to the pharmaceutical industry.

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For more than ten years FDA’s approach to the pharmaceutical industry has been driven by a vision stated as “a maximally efficient, agile, flexible manufacturing sector that reliably produces high-quality drug products without extensive regulatory oversight. The vision was originally stated in FDA’s final report on pharmaceutical quality for the twenty-first century as a vision to modernize the regulation of pharmaceutical manufacturing and enhance product quality.

From Vision to Reality

It takes a long time to turn a vision into reality but there has been significant progress in many areas. One of the most recent FDA initiatives is the regulation for Quality Metrics. As part of the original vision, the term “without extensive regulatory oversight” has been seen with reluctance across the industry, but it may become a reality. Not in the sense that FDA and other regulatory agencies does not care about the regulatory oversight of pharmaceutical manufacturing, but in the sense that they will use other measures than the traditional inspections of pharmaceutical facilities to supplement the toolbox for regulatory oversight.

The risk-based approach to inspections is one of them, the sharing of inspection observations between agencies and even mutual recognitions of inspection findings is another and now the tool of Quality Metrics is added to the toolbox as well. The recent Mutual Recognition Agreement between FDA and EMA is an important step in this direction and there are other important trends to watch.

2018: A new Starting Point for Quality Measurement

The FDA guidance for Quality Metrics has been through several iterations in close cooperation with pharmaceutical companies and industry organizations. It has turned out to be one of the most complicated to implement and the final version of the guidance will become valid as of 2018 or possibly later, but in a very scaled-down version.

Under the revised draft, FDA states that the program will begin with a voluntary phase that will run into 2018, after which the intent was to make it mandatory, although it may be postponed. The starting point is announced as be metrics for:

  • Lot acceptance rate (LAR),
  • Product quality complaint rate (PQCR),
  • Invalidated out-of-specification Rate (IOOSR).

From a regulatory perspective, the increasing complexity of drug product and manufacturing processes makes it difficult to ensure that standards are consistently applied through the product lifecycle and between different drug products and product categories. International differences and technological challenges are part of the complexity of implementing the quality metrics regulation, but in fact is has come a long way towards increased efficiency and effectiveness of quality assessments, mainly focusing on the specific risks to the consumer and individual products.

Quality Metrics Are Not New

FDA states that “Facility managers use a wide variety of control metrics to manage quality of manufacturing processes and products within drug facilities. These product quality control metrics are crucial for effective quality management at manufacturing facilities as well as for quality oversight. As part of a more rigorous and comprehensive approach to drug quality surveillance, FDA is developing plans to collect a subset of such metrics to better monitor the current status of product and facility quality across the inventory of FDA-regulated sites and inform FDA risk-based surveillance inspection planning.

It is also expected that this additional emphasis on quality measurement will provide greater market awareness of drug quality and give manufacturers further incentive to invest in quality manufacturing, reducing the risk of critical drug shortages.” (ref: FDA Office of Pharmaceutical Quality: FDA Pharmaceutical Quality Oversight, 2016).

FDA and EMA - Where are we Headed for?

What will happen on the regulatory requirements is still unclear, especially after the Mutual Recognition Agreement (MRA) between EMA and FDA was signed in 2017. Instead we will focus on another perspective on the new regulations, which has very little to do with the new requirements namely the business opportunities in getting a Quality Metrics Mindset — and not only Quality Metrics Reporting — set up in a pharmaceutical operation.