The U. S. Food and Drug Administration (FDA) announced a broad initiative to help make innovative medical technologies available sooner, and to reduce the costs of developing safe and effective medical products while maintaining FDA's traditional high standards of consumer protection. This is an FDA-wide initiative, involving all four of FDA's medical product review centers (drugs, biologics, devices, and veterinary medicine).
FDA intends to achieve this goal through new actions in three major areas:
Reducing the delays and avoidable product development costs by avoiding multiple cycles of FDA review when possible, through early communication and other steps to improve the quality of new product applications.
Improving the quality and efficiency of the review process, by adopting a quality systems approach to medical product reviews.
Facilitating new product development, by providing clearer up-to-date guidance for particular diseases and for emerging technologies.
The agency outlined its proposed actions in a detailed report, "Improving Innovation in Medical Technology: Beyond 2002." The report also summarized FDA's product review performance during 2002. Last year showed mixed results. Total products approved increased, including new treatments for hepatitis B and C and various cancers, new screening tests for HIV and hepatitis, new cardiac devices, and new antimicrobials for cattle and swine, and a chewable tablet for pain and inflammation in dogs. But last year also brought fewer marketing applications and longer total approval times in some significant product areas, including new molecular entities for drugs and for Class III medical devices (which FDA must review and approve before marketing). Approval times increased for priority new molecular entities for drugs and for some biologic applications, and decreased for some standard drug and biologic applications and for significant new animal drug applications.
"FDA approved a variety of important new medical products last year, and FDA largely met its user fee review goals," said FDA Commissioner Mark B. McClellan, M.D., Ph.D. "However, we also noted a decline in product applications from manufacturers in some key areas, which contributed to an increase in average and median review times. There is some evidence that this finding is a result of technology development becoming more costly, and reorienting to new areas as a result of breakthroughs in basic research. These results call for decisive action now, so that the trends of the future are not toward fewer products with higher development costs. FDA cannot control these trends, but we can take steps to help by making the drug development and our review processes more efficient and effective."
"Today's initiative seeks to establish regulatory standards and processes that reflect the latest biomedical and risk management science," Dr. McClellan added. "The quality systems approach and the specific guidance we envision should help establish an improved regulatory paradigm - one that will improve the development of innovative medical technology and reduce the costs of technology development, while maintaining FDA's traditional high standard of consumer protection."
Many of these FDA initiatives will be developed in collaboration with other government agencies and expert groups, particularly the National Institutes of Health. "The expanded biomedical research efforts supported by NIH are beginning to show up in the technology pipeline," said Elias Zerhouni, M.D., Director of the National Institutes of Health. "We applaud FDA's efforts to ensure that these new scientific findings are translated into therapies for patients as quickly and effectively as possible. We intend to work closely with FDA as they improve the regulatory pathways for development of these new products."
"We are highly supportive of this forward looking effort to accelerate the development of critical new drugs, especially cancer treatments and preventives, and deliver them to patients faster," stated Andrew C. von Eschenbach, M.D., Director of the National Cancer Institute. "We look forward to a very close working relationship with the FDA on these initiatives."
To address the problem of marketing delays and increasing product development and review costs, the agency will begin by analyzing the root causes of product approvals that require more than one review cycle. With the reauthorization of the Prescription Drug User Fee Act (PDUFA) and the enactment of the Medical Device User Fee Modernization Act (MDUFMA) in 2002, as well as the anticipated PDUFA appropriations for Fiscal Year 2003, FDA expects to move aggressively this year to install potential remedies for preventable cases of multiple-cycle review. These remedies include improving the quality and frequency of communications between FDA and sponsors of drugs, biological products, and medical devices, and implementing a continuous marketing application pilot project.
Because a review cycle takes time - for example, typically 6 months for a priority drug application and 10 months for a standard new drug application - and because a many products that are ultimately successful are not approved on the first cycle, avoiding multiple cycles where possible can lead to substantial improvements in product availability and cost. A recently published study by Tufts University showed that savings on the order of $100 million in development costs per approved drug could be realized by cutting total clinical development and regulatory review time by about 25 per cent, or by using better clinical screens to increase clinical success rates from the current 21.5 per cent, to between 25.2 per cent and 25.6 per cent. Improved communication and guidance could help product developers achieve such improvements by helping them design their clinical studies more effectively. Savings could be used by the sponsor to develop other innovations, and passed on to patients as lower product prices.
Rather than a change of standards, these efforts to reduce approval times and costs are geared to building excellence and predictability into the product development process so that the required scientific data are present in the marketing application the first time it is submitted.
"Improvement in the rate of single-cycle approval must result from better product development, not lower standards," said Dr. McClellan. "It should benefit patients and the general public health, by expediting the availability of new medical products whose efficacy and safety are well documented in a more time- and cost-efficient manner."
With respect to the second overall goal of this initiative, FDA will establish a continuous improvement/quality systems approach to medical product reviews across the agency. This approach will include such initiatives as enhanced reviewer training on good review practices, institution of peer review within the FDA review process, and further development of standards for the review process.
Such a system is expected to result in a more efficient review process and a better scientific and professional environment for FDA reviewers, as well as to foster FDA review divisions that are strong, well-integrated learning organizations focused on sharing knowledge and being more transparent internally and externally.
To achieve the third broad objective, FDA will support the development of new technologies by creating clearer guidance for product approvals in priority areas. These published guidances will be designed both to help innovators develop new products and high-quality successful marketing applications for particular diseases, and to improve the FDA review process for emerging technologies. To promote the availability of novel treatments for such important diseases as diabetes and obesity, FDA expects to create working groups that would draw experts from across the agency and from the broader community to create guidance for dealing with specific diseases. Manufacturers, disease associations, health professionals, FDA reviewers -- everyone with a stake in developing new treatments -- would then have a clearer understanding of key review questions, required scientific evidence and clinical endpoints to target for establishing efficacy in clinical trials, and what is expected in a new product application. As a result of this collaborative process, FDA expects that the required evidence and endpoints will accurately reflect the latest scientific knowledge.
In addition, FDA believes it can help speed potentially important emerging technologies to the market by reducing regulatory uncertainty and increasing the predictability of product development. Toward this end, FDA will clarify the regulatory pathways - pathways expected to cut across FDA's product centers - in three emerging areas of technology: cell and gene therapy, pharmacogenomics and novel drug delivery systems.