FDA continually looks at ways to uphold long-term quality and may one day offer incentives to those who demonstrate Quality Management Maturity (QMM). FDA is currently soliciting feedback on this topic through a survey open until October.
As Dr. Douglas Throckmorton, deputy director for FDA regulatory programs, explained at the virtual 2020 PDA/FDA Joint Regulatory Conference this week, QMM is a collection of business processes needed to consistently implement and maintain quality in the marketplace.
While QMM is built on current Good Manufacturing Practices (cGMP) compliance, it's more than that. “You're building a culture to build in a larger business case for sustained and consistent high quality manufacturing,” said Throckmorton. He added that the focus is on stronger quality management systems that are proactively focused on performance, especially those that reduce adverse events, reduce shortages, and ultimately become more efficient in manufacturing.
(Editor's note: If you're already familiar with QMM, jump to Incentives, below.)
Throckmorton offered a stair-step graphic that encapsulates the pieces. “A critical first step is the cGMPs. Those are standards that we've all applied for decades. We understand them, our inspectorate understands them. They’re the bedrock of what we need to build on,” he said.
The next step is cooperation and consolidation of those recommendations into an international standard, in this case, ICH Q10, which lays out a model for an effective quality management system in manufacturing.
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The third step is QMM. “It’s a culture first and foremost in a particular manufacturing site devoted to quality. It’s about the people, it's about anticipating challenges rather than reacting to them when they occur, it's about putting in place a model that measures quality in a way that allows you to anticipate problems rather than identifying them after the fact and having to respond to them,” said Throckmorton.
Each piece intended to build on the last, and management must set the tone to be successful. The anticipation of challenges should result in better quality, better equipment availability, reduced manufacturing errors, reduced shortages, and greater availability of product for public health. “We believe there’s a case to be made for reduced cost as well. There's less response that has to be made, fewer recalls that have to occur,” he noted. Hopefully these lead to fewer drug shortages.
“Each of those three pieces together, fundamentally, are important to revising and improving the current system. Where we are right now is not low quality—it is a very robust manufacturing sector—this is a way to improve on that robust sector that we think is really important,” he added.
QMM is important to all stakeholders...
- For patients: It's important to have available, reliable and high-quality medicines. Reduced shortages are an essential part of creating the best possible sources for American public health.
- For industry: The key to QMM is informed and intelligent oversight and control over the manufacturing of drugs to assure quality and increased efficiency. Fewer recalls lead to improved corporate reputation. It enables the continued improvement of products through improved understanding.
- For FDA: Throckmorton notes, “It's important to the FDA because we believe that these objective insights into the state of quality allow us to: do our job better, to better target our allocation of surveillance tools, to work with you better, to be more flexible, to create a way that we can all work together to improve the quality of the manufacturing of medicines.” It will also help FDA identify potential vulnerabilities so that they can work with manufacturers to prevent shortages from occurring.
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Data is key
Quality metrics are an important element of understanding QMM and implementing it. These metrics should identify ways to truly assess the quality of a product while it's being manufactured, and look for potential vulnerabilities to manage them, and ideally, forecast and increase the reliability of supply.
FDA will continue to keep an open dialogue with pharmaceutical manufacturers regarding any metrics rollout.
Throckmorton says that CDER has a vision for QMM. “We believe it's important as a system to measure and rate a drug quality manufacturing system. We believe that metrics to identify high-quality systems are an important element to help reward those that deliver high-quality drug products reliably, and without disruption,” he explained.
One goal they have is to provide a way to make high performers known to the marketplace so that those high-quality products can be identified and potentially rewarded. “We're in the process of putting in place a stakeholder input program to understand on a voluntary basis how this system might work and what quality metrics you think would be useful in identifying a high-quality system,” he said of the new benchmarking survey.
An audience question noted that FDA does well at telling industry about sub-standard performance through 483s, warning letters, and so forth, and asked for specifics on how QMM role models might be acknowledged. Other agencies, such as OSHA, recognize high achievers.
They are looking at ways to identify those who manufacture to a high-quality standard. “We want to find a way to reward them in as public away as possible. Exactly what that looks like I can't answer. I hope people participate in that survey,” he said.
Another important premise he noted is that as companies are able to demonstrate understanding and are able to anticipate problems well, the agency may look at changing the way they oversee that facility. “We need to be able to devote resources to the places that need help. We don't need to be devoting resources to a manufacturing site that's already at a high state of readiness and already doing a good job of anticipating manufacturing challenges,” he explained.
Changes in inspectional frequency are one of the concepts Throckmorton has heard people ask about. He hopes people are very granular in their suggestions in the survey.
The survey is open until October, and manufacturers are encouraged to participate here.
Other areas of FDA interest
This effort it is a part of a broader landscape of efforts that the agencies on taking on to support quality manufacturing including the following.
- Advanced manufacturing technologies: “I hope many of you have taken this up on our offer to work with you, to help find ways to improve the efficient manufacturing of complex and challenging molecules.”
- Supply chain, redundancy, resiliency, and information sharing: This is a particular interest of Throckmorton’s. COVID has highlighted the need to improve information sharing to understand the state of quality promptly and efficiently. Under the right circumstances, this will help the industry prevent shortages.
- Global partnerships: “COVID has given us an opportunity to build the global partnerships that we have in place and to make greater use of them. He added that we cannot let this effort slip as COVID potentially improves. Health authorities should be talking, sharing information, and sharing best practices to make certain they are doing the best job to support industry.
- QMM: “I do believe it is a cornerstone of the next step in quality manufacturing. Regulatory convergence is something that I know that is very important to [PDA members]. We've talked a great deal about the importance of regulators finding a way to ask for common sets of requirements wherever possible to aid the efficiency with regards to regulatory activities.”
Throckmorton ended his talk with a unifying message, saying, “Fundamentally, no one is going to be able to do this alone… The last decade has seen a blossoming in terms of the quality, the consistency, the trajectory of positive change in the manufacturing of U.S. pharmaceuticals. I believe we need to continue with that work together. We need to work as an agency to be responsive, science-driven and as flexible as we possibly can to support that work that you all are doing to improve the maturity of the manufacturing of pharmaceuticals. I believe that we can work together to improve the global pharmaceutical quality resulting in improvements in the life of patients, decreased shortages, and increased consistency and quality of products as they're manufactured for those patients to use.”