The Rise of Quality Metrics

The theme for DIA Annual 2014 was to celebrate the past and invent the future. And it looks like the future is a more stringent FDA, requiring more data from sponsors and manufacturing organizations.

The FDA recently established the Office of Pharmaceutical Quality (OPQ) that is tasked with enforcing quality standards throughout the lifecycle of a drug. The Center for Drug Evaluation and Research (CDER) has also proposed that all quality-related functions are reorganized into this single office, creating a concerted effort on improving quality. This couldn’t come at a better time given all the recent headlines of banned imports from plants overseas, raising concerns on the quality of pharmaceutical manufacturing in foreign countries.  Janet Woodcock and Russell Wedyk from the FDA gave an update on the progress of the OPQ at DIA Annual 2014 in San Diego.

Not surprisingly, the OPQ is developing a risk-based approach for decision-making and resource management. If you consider the number of manufacturing plants around the world, increasing number of applications, and complexity of how drugs are manufactured today, workload for regulatory agencies has significantly increased over the past few years. However, the number of inspectors has not scaled proportionally with the workload. In order for risk-based strategies to succeed, adequate data must be collected and analyzed to support decision-making. The OPQ also wants to collect data that will help predict issues while maintaining post-market surveillance.

A list of the most common metrics suggested from stakeholders was collected by the OPQ and mapped to the following categories based on objectives:

• Assess product
• Assess site
• Assess systems
• Operationalize
• Adequacy for downgrading

What was interesting at the conclusion of this exercise was that all the metrics fell under one category, “ability to assess product.” If one of the main objectives is to use quality metrics and other risk factors to select sites for reduced inspection frequency, then inspectors need to have data to assess sites in addition to product.  OPQ is continuing to investigate what metrics are needed to meet all the proposed objectives, and based on the presentation, it will be a broad set of metrics.

So what does this mean for sponsors?  Sponsors are ultimately responsible for drug quality. Rising use of contract manufacturers (CMOs) has made it much more difficult to manage the end-to-end development of a drug, ensuring quality.  Inspections are time- and resource-intensive, and deter from the day-to-day operations. However, investing in tools that provide oversight and show compliance can have significant benefits – less frequent inspections, faster inspections, and significant reduction in compliance risks, resulting in warning letters or plant shutdowns. Sponsors and manufacturing sites need to look beyond a one-dimensional view of just product assessment, e.g. batch failures and complaints, to a more comprehensive view of quality.  Many emerging metrics measure a site’s operational performance and are used for trending and site comparisons.

A standardized set of quality metrics also facilitates sharing of information with team members, partners, and regulatory agencies, using a common language. Sponsors and manufacturing companies need to build confidence with the FDA that the site can execute with high quality, and there is no better way to achieve that goal than to use supporting data.

To learn more on emerging metrics, read a recent article featured in Pharmaceutical Technology Magazine, “One Step Back, Two Steps Forward for Improved Quality Processes.“