Can The FDA Support Biomedical Innovation? New Report Shows Doubt

By Trisha Gladd, Editor, Life Science Connect

In 2007, the FDA Science Board, an advisory board to the FDA Commissioner, was tasked with assessing whether or not the FDA is equipped to support current and future regulatory needs as they relate to medicine and food. This group of experts from a wide range of backgrounds created a report based on their findings, “FDA Science and Mission at Risk.” Overall, they concluded that, at that time, the FDA did not have the scientific foundation necessary to meet its regulatory responsibilities.   

At the request of the commissioner, the committee met again six years later to evaluate three principal areas deemed crucial to the agency’s ability to “carry out its scientific mission.” Additionally, the Science Board also reviewed progress made since 2007. While there were several positive findings, the new report indicated there are both new areas of concern in regard to the agency’s ability to support biomedical innovations as well as ones that were never properly addressed.

What Were The Concerns In 2007?

After completing its analysis in 2007, the FDA Science Board concluded that the agency suffered from deficiencies that would not allow it to meet its existing regulatory responsibilities as well as any that could emerge as the market progressed. In the report, the Science Board identified two sources for this deficiency:  

• The demands on the FDA have soared due to the extraordinary advance of scientific discoveries, the complexity of the new products, and claims submitted to FDA for pre-market review and approval, the emergence of challenging safety problems, and the globalization of the industries that FDA regulates. ƒ
• The resources have not increased in proportion to the demands. The result is that the scientific demands on the Agency far exceed its capacity to respond. This imbalance is imposing a significant risk to the integrity of the food, drug, cosmetic and device regulatory system, and hence the safety of the public.

Overall, the most significant conclusions were:

• FDA could not fulfill its mission, due to a weak scientific base and inadequate scientific workforce
• A disparity between FDA’s responsibilities and resources seriously threatened the Agency’s ability to perform its mission
• FDA did not have the capacity to ensure the safety of the nation’s food supply
• FDA’s ability to ensure the rapid entry onto the market of life-saving new medical therapies – especially those resulting from new and emerging technologies – was highly doubtful.

Recommendations were made to address these; however, in a concluding statement, the report called out the FDA’s ability to follow through with change by stating that “recommendations of excellent FDA reviews are seldom followed.” Based on this, the authors urged that the agency offer a comprehensive plan to address the issues outlined in the report and to present that plan to the Science Board.

Fast Forward To 2015

Six years after the release of the “FDA Science and Mission at Risk” report, a subcommittee was created by the Science Board called the Science Looking Forward Committee. Its responsibility was to assess the progress of the FDA since the 2007 report. Additionally, the commissioner also requested that the subcommittee look at three specific areas:

1. How FDA can meet emerging and future trends in science and technology
2. How FDA can better use collaborations to advance its mission
3. How FDA can support a culture of scientific excellence and creativity

Last week, the Science Looking Forward Committee outlined its findings in a report entitled “Mission Possible: How FDA Can Move at the Speed of Science.” First, the report noted several positive changes that had occurred as a result of the 2007 report. These included:

• Creation of the Office of the Chief Scientist
• New statutory authority from Congress that not only improves FDA’s ability to tackle public health problems but also increases Agency responsibilities related to regulating cigarette and tobacco products, food safety, compounding pharmacies, and biosimilars
• Initiatives across FDA programs to deal with important new and emerging technologies, such as (but not limited to) stem cells, 3-D printing, predictive toxicology, genome sequencing and computer simulation
• A Precision Medicine Initiative with the National Institutes of Health (NIH) to revolutionize personalized medicine
• Advances in regulatory science that promote the lifecycle approach to regulation for both approvals and the postmarket evaluation of the benefit-risk profile of drugs, devices, and biologics during their entire time on the market
• Increased focus on active postmarket surveillance
• Increased funding that enabled the FDA to increase its capabilities in several areas
• Intra-Agency initiatives and extramural programs and partnerships that enabled FDA to meet the eight scientific priorities identified in the Agency’s Strategic Plan for Advancing Regulatory Science in 2011 (and a ninth priority area, Strengthening the Global Product Safety Net, added in 2013)

However, it states that “the Subcommittee notes with concern that medical product and food manufacturing quality control procedures have not kept pace with the advances being made in research and product development, and that more research is needed in such areas as product design, manufacture, and quality assurance.” It recognized the steep price tag associated with bringing a new drug to market and that, overall, the FDA must be able to move at the speed of today’s science, in order to fulfill its mission and obligations.

A Look Ahead

For this reason, the subcommittee made the following recommendations, in order to support and stimulate biomedical innovation:

• Facilitate the qualification of biomarkers, including surrogate endpoints, where appropriate, for the evaluation of new therapies, especially for conditions that have no effective treatments, such as Alzheimer’s. Encourage additional research on new biomarkers to ensure their clinical validity and work on providing guidance on how new biomarkers can be qualified as surrogate endpoints.
• Encourage and facilitate the development of clinical trial networks and “master protocols,” especially in the areas of oncology and antimicrobial therapy, to expedite clinical trials and reduce their costs. The current process of designing a new clinical trial for every new product – at great cost in time and resources – should, where practical, be replaced by the use of trial networks and master protocols. FDA should provide technical assistance and regulatory advice to developers of “master protocols.”
• Expand the use of “Bayesian” designs and “adaptive” methods in clinical trial development, which allow developers of medical products to build more flexible clinical trials and thus improve the chances of obtaining dispositive data for a new product approval.
• Expand the Sentinel Initiative to provide “real-time” safety data and to evaluate the effects of major safety warnings or label changes on the use of drugs in the population; enhance and expand national medical device surveillance efforts by leveraging Sentinel and using unique device identifiers.
• Establish obtaining ongoing access to external experts in emerging technologies to help accelerate approvals, before Advisory Committee meetings.
• Evaluate, use, and perform risk-based safety assessments of emerging technologies, such as nanotechnology, which could benefit public health and regulatory science.

Other recommendations were made in regard to product manufacturing and quality, including expanding the use of DNA technology as well as appropriate analytical methods for assessing of products made using nanotechnology. It also called for preparing for the evaluation of the production of biosimilars, equipping field staff with novel technologies, and using other new technologies to monitor trends and mechanisms of antibiotic resistance.

Finally, the report concludes with a plea that the FDA rises up to these challenges, in order to be a significant contributor to the U.S. leadership in science. Without doing so, our industry and nation will continue to face the same risks it did when these issues were brought to light in the 2007 report eight years ago.  

So, what do you think? Is the FDA equipped to deal with the rate at which science is moving today? If not, where should their focus be? I'd love to hear your thoughts in the comments section below!