As evidence of its interest in quality metrics, the FDA published an initial draft guidance in July of 2015 encouraging firms foster a culture of quality and continuous improvement, and signaling its intent to establish a quality metrics reporting program requiring the submission of quality metrics data. A year and a half later (November 2016), responding to comments and some pushback by industry stakeholders, the FDA released a revised draft guidance entitled “Submission of Quality Metrics Data: Guidance for Industry.”

In this latest revised draft guidance, the FDA initiates a voluntary reporting phase of the FDA quality metrics reporting program as a prelude to the eventual mandatory requirement for the submission of quality metrics data. Effectively, this revised draft guidance is a gift from the FDA that establishes a “practice” period for companies to get their quality management program and metrics in alignment with what will eventually become FDA rules on quality metric submission. As the FDA states in the revised guidance, “FDA does not intend to take enforcement action based on errors in a quality metrics data submission made as a part of this voluntary phase of the reporting program, provided the submission is made in good faith.”

While the voluntary program is focused on finished drug products and API manufacturing, all manufacturers may report quality metrics data (e.g., atypical active ingredients, excipient manufacturers). The FDA also notes that participation in the voluntary reporting program outlined in the draft guidance provides an opportunity to demonstrate a commitment to transparency and a willingness to proactively engage with the agency. In other words, participation in this “voluntary” program is a good way to create good relations with the FDA.

Pharmaceutical and biologics manufacturers would be well-advised to become familiar with the program outlined in the FDA’s revised draft guidance on quality metrics, so that they can begin to develop and implement appropriate standard operating procedures (SOPs) and quality management system (QMS) solutions. There are a number of important takeaways in the FDA’s revised draft guidance on quality metrics. In this blog, we’ll detail some of the more noteworthy aspects of the guidance that companies and labs should be paying attention to.

Overview of The FDA Quality Metrics Guidance

Some of the key details contained in the FDA revised guidance on quality metrics include:

The FDA’s objectives for the quality metrics program. As stated in the guidance document, the FDA’s goals behind the publication of this revised draft guidance are to:

• Establish a signal detection program as one factor in identifying establishments and products that may pose significant risk to consumers
• Identify situations in which there may be a risk for drug supply disruptions and engage proactively with manufacturers to mitigate the likelihood of their occurrence
• Improve the FDA’s evaluation of drug manufacturing and control operations
• Help prepare for, direct and improve the effectiveness of establishment inspections
• Use the calculated metrics as an element of the post-approval manufacturing change reporting program with an emphasis on encouraging lifecycle manufacturing improvement

Dates for Voluntary Quality Metrics Reporting. As described in the Notice of Availability (NOA) for the revised draft guidance, the FDA intends to open an electronic portal in January 2018 to begin receiving voluntary submissions of quality metrics data that was generated in 2017.

Metrics to be Reported for Voluntary Program. The quality metrics data described in this draft guidance is produced in the course of manufacturing drugs in compliance with cGMP. The metrics that the FDA is asking establishments to report in this voluntary program are:

• Lot acceptance rate (LAR) as an indicator of manufacturing process performance. LAR is the number of accepted lots in a timeframe divided by the number of lots started by the same establishment in the current reporting timeline.
• Product Quality Complaint Rate as an indicator of patient or customer feedback. PQCR is defined as the number of product quality complaints received for the product divided by the total number of dosage units distributed in the current reporting timeframe.
• Invalidated Out-of-Specification (OOS) Rate (IOOSR) as an indicator of laboratory operation and performance. IOOSR is defined as the number of OOS test results for lot release and long-term stability testing invalidated by the reporting establishment due to an aberration of the measurement process divided by the total number of lot release and long-term stability OOS test results in the current reporting timeframe.

Appendix B of the Guidance helps to define these metrics with clarifying examples which will help companies with their internal definitions. Any questions that an establishment may have about their specific situation when gathering this data can be emailed to: OPQ-OS-QualityMetrics@fda.hhs.gov.

Additional Quality Metrics Recommended. The quality metrics requested for the voluntary program are not intended to be all-inclusive. Manufacturers are encouraged to utilize additional quality metrics in their day-to-day QC operations that are deemed necessary to evaluate a product’s or manufacturer’s quality. Additional metrics may be added to the FDA’s future mandatory quality metrics reporting program. Also, additional metrics, or lack thereof, may be evaluated in an FDA inspection of manufacturing facilities.

How to Submit Quality Metrics for the Voluntary Reporting Program. Reporting establishments should submit quality metrics reports where the data is segmented on a quarterly basis throughout a single calendar year. Appendix A of the draft guidance contains a description of the quality metrics data elements that are relevant for different business segments/types. Additionally, a revised version of the Quality Metrics Technical Conformance Guide that describes additional technical details will be released soon. Finally, the FDA expects to publish a Federal Register notice providing further instructions on the submission of voluntary reports no fewer than 30 days before the electronic portal is opened.

Both Product and Site Quality Metric Reports Will be Accepted. The FDA will permit establishments to submit data in this voluntary quality metrics reporting program in two formats – by site segmented by product, or by product segmented by site. This allows companies to submit the data in the way that works best for them. That said, the Agency does prefer data segmented by product, because it demonstrates effective control over the manufacturing process for drugs over the entire the supply chain.

Special Considerations for Products Imported/Manufactured Outside the United States. The FDA recognizes that it may be extremely difficult to identify started lots, rejected lots, and OOS results that are manufactured by CMOs that are not in the United States. The FDA therefore allows voluntary reports to contain data from lots not imported with the data from lots that are imported, provided that the manufacturing process for both uses the same process and controls data. Product quality complaint rate (PQCR) data, however, should be collected only for drugs that are imported, intended for import or manufactured in the United States.

Optional Comment Field Within Quality Metrics Report.  Reporting establishments can submit a comment of up to 300 words with their quality metrics report in order to explain anomalous data or report any plans for quality improvement. As the guidance explains, comments “may describe special situations, such as natural disasters, the use of emerging technology, or describe the manufacturing supply chain or a plan for improvement.” The FDA “may refer to the comments if unusual data trends are identified, or in preparation for an on-site inspection.”

Mandatory Quality Metrics Reporting Will Eventually be Implemented. After data collection in 2018, the portal accepting voluntary submissions of quality metrics data will be closed and the FDA will begin data analysis. Once this analysis is complete, the FDA will share on its website what it has learned from the voluntary phase of the reporting program, and also initiate notice and comment rulemaking to develop it’s mandatory reporting program.

Quality Metrics Reporters List Will be Published. Upon completing analysis of the data from the voluntary quality metrics reporting program, the FDA will publish a list of the companies that participated in this voluntary reporting phase on its website. The reporting establishments in this list will be broken down into product and site report categories, and then tiered based on how much quality metric data was reported. The FDA feels this list may be useful for:

• Establishments within the pharmaceutical manufacturing industry as one element of a robust outsourcer or supplier selection process.
• Healthcare purchasing organizations, healthcare providers, patients, and consumers in sourcing drugs.

Key Quality Management System Takeaways for Manufacturers

In order to submit data that is in alignment with this new revised quality metrics draft guidance, product owners will need to choose between submitting data organized by product or site. While the FDA prefers data organized by product, gathering the metrics by product across the entire supply chain will be more involved than by site. Manufacturers will likely need to redesign their quality metrics dashboards and management review process to be able to facilitate consistency in quality practices across the enterprise and partners. The following recommendations may be helpful in adjusting quality management systems to meet the new guidelines:

• Appropriate dashboard KPIs need to be determined and defined prior to implementing system that aggregates data for the dashboard.
• The quality system should contain policies and procedures that validate that information is funneling to the dashboard as intended and assure the appropriate level of data visibility by management provided by the dashboard.
• KPIs in the dashboard should align with requirements outlined in the FDA revised draft guidance, and include clear definitions that include data standards.
• Individuals manually entering source data should receive proper training on proper policies and procedures.
• Review of KPI targets should occur on a regular basis. Assessments should be regularly conducted to identify poor performance in order to drive corrective action plans.

Conclusion

With the release of this revised guidance document of the submission of quality metrics data, the FDA continues to encourage pharmaceutical manufacturers to implement a modern, risk-based quality management system as part of its mission to protect public health. The FDA’s grand vision is for the pharmaceutical industry to shift from a culture of compliance and rules to a culture of quality, where quality protocols are built into every process. While this revised guidance outlines a voluntary program for submission of quality metric data, a mandatory program is coming. Manufacturers would therefore be wise to utilize this voluntary phase to take a hard look at their quality systems maturity and begin to focus on how quality metrics are defined, collected, organized, verified and reported. Manufacturers will need to review their quality metrics management and reporting systems, identify any gaps in data collection, and take steps to bring systems into alignment with the metrics program guidelines. Manufacturers who take these steps now will avoid the hassle of being forced to make these changes under accelerated timelines later, and will reap the financial and customer loyalty benefits that come with producing quality products

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