Recent crises involving adulterated and contaminated drugs and pharmaceutical ingredients have raised the profile of FDA's ongoing campaign. Janet Woodcock, director of FDA's Center for Drug Evaluation and Research (CDER), has championed these initiatives for years, and they remain top priorities for her.
Woodcock and leaders of CDER's Office of Pharmaceutical Science (OPS) are counting on industry to implement sophisticated quality testing and production methods to help monitor thousands of products that are quickly shipped around the world. A series of standards developed by the International Conference on Harmonization (ICH) describes how, on a global basis, process understanding and control should be based on sound science and quality risk management.Manufacturers, for their part, have been hearing speeches about QbD and design space for nearly a decade. Now they are looking for evidence that investment in quality systems and processes will improve the efficiency of the application-review and approval process, ease the burden of plant inspections, and rationalize the postapproval drug-monitoring system.
Nasr believes that quality risk management has become sufficiently accepted around the world to define a systematic approach to pharmaceutical development and manufacturing. QbD can provide cost savings and improved systems for manufacturers, as well as efficient regulatory oversight by FDA and other authorities, Nasr said at the Pharmaceutical Technology "Quality and Process Excellence" conference in July 2008. QbD helps manufacturers overcome real-world challenges by supporting a formalized approach to quality risk management that improves product design, increases process understanding, encourages continual improvement, and better uses modern manufacturing and analytical technologies. By adopting modern manufacturing methods to ensure quality, manufacturers also can enhance efficiency and reduce costs.
Flexible regulatory oversight is an added benefit for companies that adopt QbD approaches. Nasr explained that by establishing a design space based on pro-duct characteristics and performance, a manufacturer may gain leeway to reduce end-product release testing and to make process improvements without further regulatory review.
Another potential reward for manufacturers that use QbD is relaxed requirements governing postapproval manufacturing changes. FDA has developed a guidance to spell out opportunities for reduced oversight of certain low-risk chemistry, manufacturing, and controls (CMC) changes. The agency's plan outlines more than 40 categories of changes that could be downgraded to allow manufacturers to report such actions in annual reports instead of filing changes-being-effected supplemental applications. Many of the reductions essentially involve administrative changes that do not need extensive CMC review, Nasr explained. Simplified reporting may apply to changes involving the following elements: