FDA's "critical path" initiative to help streamline R&D costs and product development schedules is positioning the agency to eventually seek grant-making authority from Congress.

While FDA's ¹ March 16 report furthers several concepts already advanced by Commissioner Mark McClellan, the scope and ambition of the "critical path" statement gives the agency an enhanced role in prioritizing medical product research.

"Although there are numerous public and private groups with expertise to develop solutions, we believe that FDA is ideally positioned to bring together the stakeholders to identify and address the most significant problems," the report states.

"FDA will make internal changes to intensify its ability to surface crucial issues and to support high-priority critical path research efforts."

The nature of that support - whether strictly scientific or financial - remains to be seen; at the very least, the initiative hints at an historic convergence with the National Institutes of Health in planning translational research projects.

With rising healthcare expenditures and a burgeoning academic research pipeline - NIH's fiscal 2003 budget is approximately $28 bil. - FDA's expanded vision of its own responsibilities is timely.

In September, NIH Director Elias Zerhouni, MD, unveiled a "roadmap" intended to speed commercial-ization of agency-funded discoveries (² Also see "Interdisciplinary Teams Focused On Imaging Research Needed – NIH Director" - Medtech Insight, 8 March, 2004., p. 11).

The FDA report cites the roadmap with various bench-to-bedside initiatives such as the National Cancer Institute's centers of excellence; the Frederick, Md. bioscience nonprofit MdBIO; the European Organization for the Treatment of Cancer; and the UK national translational cancer research network.

FDA's renewed focus on what the report calls "downstream development concerns" ultimately may sway legislators to designate translational research funds to FDA. The agency is understood to be considering whether to appeal for grant-making authority from Congress in a future budget cycle (³ Also see "Imaging Technologies Tagged For FDA Drug Development Initiative" - Medtech Insight, 2 February, 2004., p. 7).

Further, by staking its unique claim to promulgate industry "best practices," including clinical and technical standards, FDA is asserting its institutional knowledge in comparison with other federal agencies.

"Few other groups of physicians and scientists are positioned to see so much of the broad picture," FDA writes. "Industry scientists encounter these problems in terms of their own product portfolios, but often lack cross-cutting information about an entire product area."

As an example of FDA "overcoming clinical trial hurdles" within the bioimaging industry, the agency notes that it proposed a four-arm, 40,000-patient study comparing digital with film mammography.

Because no single firm was able or willing to enroll such high patient numbers, FDA suggested that four companies each sponsor a 10,000-patient study, using a common protocol. That study, currently in one-year follow-up, is being conducted by the National Cancer Institute.

Digital mammography devices from GE Medical Systems, Hologic, Fischer Imaging and Fuji are being evaluated in the trial (⁴ Also see "Digital Mammography Firms May Meet FDA Requirements Through NCI Trial" - Medtech Insight, 5 March, 2001., p. 11).

More recently, to expedite imaging product applications, FDA and the National Institute of Biomedical Imaging & Bioengineering signed an agreement to co-sponsor a Laboratory for the Assessment of Medical Imaging Systems (⁵ Also see "NIH, FDA Team Up To Develop Imaging Methodologies; NIBIB Puts In $400,000" - Medtech Insight, 23 February, 2004., p. 5).

FDA also claims "characterization and manufacturing" know-how among its nearly exclusive credentials.

"The industrialization challenges posed by the demands of physical product design, characterization, scale-up and manufacturing are often little understood outside of FDA and the pharmaceutical and device manufacturing communities," the report notes.

As an example of FDA's accomplishments in this area, the agency cites a blood glucose monitor "uniform testing protocol" developed with reference materials from the Commerce Department's National Institute of Standards & Technology.

FDA also notes that in consort with the Centers for Disease Control & Prevention and industry, it enabled "difficult-to-obtain standards and samples" to facilitate West Nile Virus nucleic acid blood donor screening.

According to FDA, similar research with public and private partners will generate a "toolkit" to inject predictability and cost-effectiveness into the product development process.

Assays, standards, computer modeling techniques, biomarkers and surrogate clinical trial endpoints are listed as research tools that can speed commercial-ization of technologies.

The agency will hold a series of public events - including an April 22 FDA Science Board meeting - to explore "national critical path opportunities" to assist industry R&D.

The science board meeting will be the first with University of Texas System Executive Vice Chancellor for Health Affairs Kenneth Shine, MD, as chairman. Shine, a former president of the Institute of Medicine, joined as a panel member last year.

In addition to critical path research opportunities, the meeting will consider FDA's obesity initiative.

Among critical path research tools, "additional charac-terization procedures and standards for expanded stem cell and other cellular products, bioengineered tissues, and implanted drug-device combinations (e.g., drug-eluting stents) are urgently needed," the report says.

The development of coronary stent compressibility test standards and predictive software to gauge the effects of device design changes are two specific goals that FDA envisions.

Stent testing standards "will decrease the likelihood of failed designs and allow smaller clinical trial programs," the report states.

Similarly, FDA scientists "report an urgent need for predictive software to model the human effects of design changes for rapidly evolving devices."

"We believe that such software may be attainable with a concentrated effort, by assembling currently available data and identifying existing data gaps," FDA notes.

The report was requested by Deputy Commissioner Lester Crawford and McClellan, soon to take the helm at the Centers for Medicare & Medicaid Services.

Former Center for Drug Evaluation & Research Director Janet Woodcock, who is on a six-month detail to the commissioner's office as head of the Cross-Center Initiatives Taskforce, prepared the report with the therapeutic center directors.

In general, the report seeks to reverse a decline in submissions across all medical product sectors.

"In the case of medical devices, current capacity for technological innovation has outstripped the ability to assess performance in patients, resulting in prolonged delays between design and use," FDA notes.

During a March 16 teleconference, Centers for Devices & Radiological Health Director David Feigal described a recent drop in PMA submissions, "down the last two years by about 20%."

"There were about four years when we were running about 70 applications per year, and that dropped down into the 50s. There were some areas where we have not seen the same sorts of reductions, but they are not as often in the areas where we see the most innovative products," Feigal said.

The center director previewed the critical path initiative during AdvaMed's annual meeting in Scottsdale, Ariz. March 6 (⁶ Also see "CDRH Review Culture To Change As Consultant Use Becomes Routine – Feigal" - Medtech Insight, 15 March, 2004., p. 9).

Segments of the critical path include: prototype design or discovery; preclinical development; clinical development; and FDA filing/approval and launch preparation.

McClellan added: "There certainly are a lot of applications under development - for example, engineered tissues and the like, but we are not yet seeing applications for those products to the agency."

"It's still either at the basic research phase or earlier on in the development process," he noted.

The Office of Device Evaluation's FY 2003 annual report shows that 54 original PMAs were submitted that year, a slight increase over the 49 in FY 2002. By contrast, in FY 2001, 71 PMAs were submitted. The FY 2003 report also shows a 22% decrease in the number of investigational device exemption submissions to CDRH (⁷ Also see "ODE Annual Report Shows Faster PMA Reviews, Fewer IDE Submissions" - Medtech Insight, 2 February, 2004., p. 6).

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