Woodcock Pushes Advanced Drug Manufacturing Technologies
CDER director Janet Woodcock says “advanced manufacturing technologies” could reduce U.S. drug maker reliance on foreign-sourced active pharmaceutical ingredients (APIs) and thus “enable U.S.-based pharmaceutical manufacturing to regain its competitiveness with China and other foreign countries.” Testifying before a 10/30 House Energy and Commerce Subcommittee on Health hearing, Woodcock sounded alarms over the increasing number of API manufacturing sites in China and other countries and the U.S.’s reliance on foreign-sourced APIs, which exposes patients to potential supply shortages.
Woodcock told the hearing that FDA has been “working diligently in collaboration with industry and other federal agencies to ensure our reliance of foreign manufacturing does not pose a national security risk. While FDA cannot tell industry where they can and cannot manufacture APIs, we can work with industry to utilize new technologies and new manufacturing methods to further incentivize domestic production of drugs and APIs.”
Woodcock described advanced manufacturing as a “collective term for new medical product manufacturing technologies that can improve drug quality, address shortages of medicines, and speed time-to-market... Examples of some cross-cutting advanced manufacturing technologies include continuous manufacturing and 3D printing. Advanced manufacturing technology, which FDA supports through its Emerging Technology Program (ETP), has a smaller facility footprint, lower environmental impact, and more efficient use of human resources than traditional technology...”
Advanced manufacturing has been in use for years in the automotive, aerospace, and semiconductor sectors, and it is now just beginning to be used by pharmaceutical companies. For APIs and finished dosage form manufacturing, new technologies include “continuous manufacturing” in which products are produced as a continuous stream, as opposed to traditional batch manufacturing where breaks or stops exist between different processing steps, Woodcock told the hearing.
She said advanced manufacturing could also reduce quality issues that “trigger drug shortages or recalls.” For example, product quality can be controlled with modern automation and control systems and can be intensely monitored during production by using high-resolution analytics. “High technology, computer-controlled production facilities are better able to rapidly respond to changes in demand because they typically do not have the equipment scale-up issues associated with traditional methods and can be capable of seamlessly producing a variety of dosages and even dosage forms,” Woodcock said. Such platforms also have smaller footprints than traditional manufacturing platforms, and the equipment can be made portable so that it can be moved closer to markets, reducing shipping costs.
Woodcock said FDA is driving the move to advanced manufacturing under ETP, which encourages close collaboration with industry and other stakeholders early in the technology development process. “It provides subject matter experts and fosters coordination within CDER and FDA’s Office of Regulatory Affairs for precedent-setting issues regarding quality and good manufacturing practices,” she said. “Under this program, CDER has approved five drug applications utilizing continuous manufacturing for [finished dosage form] manufacturing, and the first application utilizing 3-D printing technologies. Currently, these drugs are being made in the U.S., and one drug is being made both in the U.S. and in the UK.”
Additionally, Woodcock said that advanced manufacturing technologies could pose some regulatory challenges because most regulations were developed based on traditional batch manufacturing methods under a unified pharmaceutical quality system. “As a result,” she said, “FDA has launched an effort to identify and implement needed changes in the regulatory structure. For example, new policy and regulatory topics related to emerging technologies include the management of data-rich environments, the evolving concepts of process validation for advanced manufacturing systems, and the regulatory oversight of post-approval changes for such systems. Furthermore, CDER, in collaboration with the Biomedical Advanced Research and Development Authority, is working on a strategy and new regulatory framework to develop and implement miniature, mobile manufacturing platforms (‘Pharmacy on Demand’) for manufacture of essential drugs near or at the point of care.”