Quality Metrics, Inspection Protocols are Priorities for CDER Quality Office
Developing a quality metrics program and its new inspection protocol project are two ongoing top priorities for CDER’s Office of Product Quality, according to Office director Michael Kopcha. Speaking at the Drug Information Association’s annual meeting in Philadelphia 6/30, Kopcha said quality metrics will help the agency “better monitor the current status of products and facilities across the inventory of FDA-regulated sites, and assist with risk-based surveillance inspection planning.”
Last year, FDA released a draft guidance on “Request for Quality Metrics” that outlined the data FDA plans to request from pharmaceutical and biologic manufacturers as part of the risk-based inspection program. FDA expects that quality metrics calculated from data that it collects will provide objective measures that, when used with additional internal data, will provide the agency with indicators of the effectiveness of pharmaceutical manufacturing quality systems,” the guide says.CDER has said that quality metrics will be input into its compliance database to inform “our understanding of the overall quality across the industry, and identify the outliers to set our inspection priorities. We've had a risk model that we have used for many years and we want to get up several levels in sophistication on that model and have real-time data feeding into that to assess the highest risk facilities.”
“While FDA recognizes the value of quality metrics, we also recognize that individual data points and metrics are not solely indicative of the state of quality of the establishment or products,” the guidance said. “Rather, FDA intends to use quality metrics data in context with other sources of quality data... FDA expects that the initial use of the metrics will be to consider a decreased surveillance inspection frequency for certain establishments. For example, establishments that have highly controlled manufacturing processes have the potential to be inspected less often (as a lower priority for inspection) than similar establishments that demonstrate uncontrolled processes (as a higher priority for inspection). In addition, FDA intends to consider whether these metrics may provide a basis for FDA to use improved risk-based principles to determine the appropriate reporting category for post-approval manufacturing changes.”
The office’s new inspection protocol project (NIPP) is intended to provide a better approach to monitor quality, Kopcha told attendees. The quality-focused, semi-quantitative approach will use streamlined and structured inspection reports. “So when inspectors go out to a site, it will be more standardized in terms of their inspection so companies know what that inspection will look like,” he explained. “So there should be a clearer understanding of what we will be looking for when we come in to do an inspection.”
OPQ has previously said that NIPP protocols will utilize expert investigator questions and assessment approaches. NIPP is expected to increase the quality focus of investigator assessments, so that facilities and behaviors found to exceed basic compliance can be recognized as such. Following successful piloting, NIPP-developed protocols will be incorporated into new mobile technology to capture investigator findings and assessments and better support investigators while traveling and during facility inspections.
An additional priority is to continue to perfect OPQ’s team-based integrated quality assessment (IQA) of ANDAs, NDAs, and BLAs, according to Kopcha. Under this approach, which has been applied to all original submissions for over a year, a team of subject-matter experts perform a quality assessment of an application based on risk and knowledge management. “Close collaboration and communication among disciplines in a team environment yields better decision making,” he said, adding that it assures the application is measured by uniform quality standards and promotes consistent regulatory practices for both brand and generic drug products.
Kopcha’s presentation also outlined OPQ’s Desired Future State – a unified risk evaluation for brand and generic products that integrates the structured risk assessment with the existing drug product knowledge base. The evaluation should provide a risk profile and ranking of a drug product’s critical quality attributes during the pre-marketing phase, and may also include information on the manufacturing site and quality system. It will also be used in the post-marketing phase to assess proposed changes and the associated risks to product quality. Ideally, it will provide a comprehensive summary of the current state of quality for all approved NDAs/ANDAs of a particular drug product, “potentially allowing for individualized regulatory oversight of post-approval changes,” he said.