On November 9-10, 2015 Sparta Systems sponsored the 2015 PDA Pharmaceutical Quality Metrics Conference in Bethesda, MD. This event included over 180 attendees from the pharmaceutical industry, FDA, Parental Drug Association (PDA) and media. Participants were eager to hear from FDA about the current direction they are taking regarding which quality metrics will be considered in the new regulations. FDA was not specific on the exact date when the new guidance will be released and mentioned ‘sometime in 2016’.
The regulation expectations, currently under review, will impact the way pharmaceutical companies report to the FDA on specific quality metrics. This is critical because recently patients have been negatively impacted by recalls and drug shortages and this trend is on the rise. The current criteria under consideration as mandatory may include the following:
Lot Acceptance Rates, Product Quality Complaint Rates, Invalidated Out-of-Specification Rates, Annual Product Review (APR) on Time Rates, Product Quality Review (PQR) on Time Rates, Senior Management Engagement, and CAPA Effectiveness.
FDA is requesting quality metrics that are per product and per manufacturing site. The drug manufacturer will begin collecting the quality metrics for one whole year. The raw data elements will need to be provided to the FDA within 60 days after that year of data gathering. The expected raw data elements to be included are the following: Total of Attempted Lots, Total of Rejected Lots, Total of Attempted Lots that were Pending Disposition, Total of out of specification (OOS), Total of Lot Release and Stability Tests Conducted, and the Total of OOS that were Invalidated by Lab Error.
One presenter from a large pharmaceutical company commented that most expectations about the metrics are aligned with their current quality management strategy, but was looking to understand more around what’s the need for annual product reviews (APR). Currently, they maintain their quality records and review annually. That report includes batch data, product recall information, number of complaints and returned items. Good business tools are used to measure overall health of the quality system to understand if they are manufacturing the best products for the patients/consumers. The state of control should include metrics such as batch results (failures) and deviations. Quality shepherds the overall APR process. The speaker commented that complexities in business require flexibility and recommended that FDA’s Quality Metrics program should use a risk-based approach and start on a smaller scale. Furthermore, do not include non-dose limiting products so manufacturers have an opportunity for trial and error. There will also be time required to get the right systems in place to gather and report on the required data requirements.
Some other topics discussed during the conference included Performance Based Regulations which will measure for quality of the drug product, measure the quality of the site and the effectiveness of manufacturing systems. The goals are for Operational Excellence and Quality of Products, not just for signatures and compliance.
The site selection model will help determine where the FDA goes based on product volume information, incident Information and recall information and having the quality metrics feed into the model, will play a large role. They anticipate using site scores based on metrics like product and process, facility factors (type, size, etc.) and last inspection date. The objective is not just about finding risky manufacturers, but estimate the state of quality and finding those sites that exceed expectations to be on the FDA’s “Dean’s List”.
The required metrics will be used with statistical analysis to determine relationships and correlations to quality. There will be a learning period while information is gathered, which will last at least a year.
Many companies use many disparate systems due to mergers and acquisitions. In fact, the speaker asked for a show of hands in the room who has been impacted from M&A and 90% of the room raised their hands. This illustrates the level of data management complexity resulting from mergers and acquisitions. In this environment, there is not one single source of truth but instead data needs to be pulled from several systems in order to gain the full picture of quality metrics. The first step will be harmonization of the data.
Failures are good, as they can lead to improvements. When reporting to leadership on the state of quality management, hiding metrics to make things look “green” is a bad industry trend and does happen often. Some companies will need to change their culture, so that red is important and shouldn’t be hidden but rather addressed and remediated quickly to prevent future product issues, understanding that deviations and OOS’s should exist. This overestimation of quality success or a ‘green scorecard’ is also a regional concern. In certain countries, reporting such deviations is frowned up so for leadership to understand there is an issue with the product, is much harder to address.
Regardless of the final FDA outcome of required quality metrics, key performance indicators for manufactures should be measuring quality results and those results should be used to make the best product for the public.