Medical Device Daily Washington Editor

WASHINGTON - The FDA's Critical Path Initiative, or CPI, may do wonders for new drug development, but its impact on the number of medical device and diagnostics developed and approved is less certain.

This month's publication of the Critical Path Opportunities Report detailed the areas in which the agency hopes to see substantial progress in the near term, but devices and diagnostics seem destined to play a somewhat peripheral role.

According to the Critical Path FAQ on the agency's web site, product development is currently based on tools that are “badly outdated,“ which calls for an upgrade of four elements of product evaluation, namely animal models of human disease, biomarkers of physiological reaction to therapeutic efforts, clinical trial design and quality assessment technology.

The FDA insists its aim is not to take “sole responsibility“ for nudging industry down this path, but that it is taking the lead because “it is the only entity capable of creating the focus necessary for this task.“

The running problems with drug innovation are well known.

According to the Center for Medicines Research , the number of new molecular entities cleared by FDA fell to a 10-year low of 26 in 2003. The high-water mark for that decade came in 1997, when more than 40 new molecular entities made it through the approval process and into the marketplace.

The FDA made the case that the sheer cost of getting a new drug to market is part of the slowdown, citing a report by Windover's In Vivo: The Business Medicine Report that shows that the investment required for one successful drug launch has jumped from an average of $1.1 billion between 1995 and 2000 to $1.7 billion between 2000 and 2003, an increase of roughly 55%.

In contrast, in the device arena, the FDA received a steadier number of premarket approval (PMA) submissions between 1993 and 2004, with 40 and 51 submissions, respectively, and a peak of 71 PMAs in 2001. Comparable data on 510(k) filings was not available.

According to the agency's press release last week that accompanied the Critical Path documents, the FDA is pinning much of its hopes on “a new generation of predictive biomarkers [that] would dramatically improve the efficiency of product development“ and identify safety problems prior to marketing. In that release, FDA's Deputy Commissioner of Operations Janet Woodcock, MD, who also is the director of the CPI, added that another aim of the CPI is “development of new types of clinical trials that will produce better data faster.“

Despite the emphasis on drug development, the Critical Path Opportunities List (a separate publication from the Critical Path Opportunities Report) may offer a glimmer of hope for some in the device/diagnostics industry as well.

Firms in the cardiovascular market may find encouragement in a discussion of improved trials and data development stemming from FDA's interest in “a statistical model for qualifying late loss in lumen diameter as a surrogate measure for drug eluting stent trials.“ Biomarkers that indicate cardiovascular disease are also an area of the agency's interest.

Makers of imaging technologies and agents were not left out.

Performance standards for novel imaging displays were mentioned in the report, as were the use of medical imaging to assist in product development and in detection of markers in several classes of disease states, including heart disease, arthritis, neurocognitive disorders and cancer.

The agency also expressed a keen interest in development of computerized modeling of device performance that would require the corollary development of a “rigorous model of specific aspects of human physiology,“ especially for pediatric applications.

To date, reaction from industry is cautious at best.

Richard Frank, MD, PhD, vice president of clinical and medical strategy for GE Healthcare (Waukesha, Wisconsin),said in an e-mail response to Medical Device Daily that while the effort to boost the use of biomarkers for drug development may feed demand for existing diagnostic and imaging technology, the resulting demand would most likely be “small, relative to clinical use,“ and that “the effort necessary to support such applications is greater because pharmaceutical and biologics innovators always want a customized approach to accommodate their specific product.“

As for the likelihood that device makers would be spurred to create new device and diagnostic technologies as a result of the emphasis on biomarkers (as well as CDER's recent interest in pre-production drug substance and drug product development data under the so-called 21st Century Quality Initiative), Frank said that this might be the case, “but only if there is co-development“ of such technology by drug and device firms.

Mark Leahey, executive director of the Medical Device Manufacturers Association (Washington), told MDD that while the association appreciates “the need to ensure that new products are developed,“ it nonetheless feels that “the focus should also be on the premarket review process as well.“