At the cGMP conference sponsored by pharmaconference.com earlier this month, FDA’s compliance wing encouraged pharmaceutical companies to ensure that they demonstrate “quality maturity,” and offered specifics about what FDA wants to see. Like my grandmother used to say this time of year about the best corn to make corn pudding, there is a difference between “old” and “mature.” You don’t have to be old, to be mature. The quality organization recipe FDA is promoting applies equally to startups and to established manufacturers and sponsors of medical products. FDA’s advice on mature quality systems also applies equally to medical device companies and to pharmaceutical companies.
Preliminarily (a word I doubt my grandmother used very often), we should note that FDA’s advice on these points is not incorporated in binding statute or regulations, or even in published guidance documents. Nonetheless, by following the advice offered by FDA on these issues, regulated industry can more likely avoid adverse findings during regulatory inspections, and find pathways to remediation that FDA will more likely accept, after adverse inspections.
Several FDA speakers at the conference (agenda here) discussed the importance of having mature quality systems, but the most specific advice was offered in a PowerPoint delivered by Theresa Mullin, FDA’s Associate Director for Strategic Initiatives for the Center for Drug Evaluation and Research and entitled “Update from FDA CDER.”
Summarizing the Quality Metrics Research Final Report by the University of St. Gallen in Switzerland, Morrison described the appropriate steps to ensure “quality maturity” as follows (emphasis is added):
- Optimized set-up and cleaning procedures are documented as best practice process and rolled out throughout the whole plant.
- A large percentage of equipment on the shop floor is currently under statistical process control.
- For root cause analysis, the firm has standardized tools to get a deeper understanding of the influencing factors for problems.
- Goals and objectives of the manufacturing unit are closely linked and consistent with corporate objectives and the site has a clear focus.
- Manufacturers have joint improvement programs with suppliers to increase performance.
- All potential bottleneck machines are identified and supplied with additional spare parts.
- For product and process transfers between different units or sites, standardized procedures exist that ensure a fast, stable and complied [probably should read “compliant” instead of “complied”] knowledge transfer.
- Charts showing the current performance status such as current scrap rates and current up times are posted on the shop floor and visible for everyone.
- The firm regularly surveys customers’ requirements.
- The firm ranks its suppliers and conducts supplier qualifications and audits.
Critically, a mature quality system should not be stagnant, nor should advice about the maturity of the quality system be considered in isolation. FDA wants industry to produce and report quality metrics, as discussed in prior blogposts (here, here, and here). Moreover, FDA encourages industry to aim for continuous improvement in manufacturing, laboratory, and quality systems.
So, back to corn pudding recipes. What my grandmother meant by “mature” was that corn that had stayed a long time on the stalk might be past its prime, if eaten on the cob, but was the best to use to make corn pudding. She didn’t recommend corn that had been picked days ago (“old” corn). As to whether the best corn pudding is made just with eggs, or with eggs and flour, that is a whole ’nother controversy (here).