FDA’s “Critical Path”: Microbiologists Cite Barriers To Developing Anti-Infectives

American Society for Microbiology calls for more flexibility in risk/benefit assessments. FDA also is “uniquely positioned” to establish more reliable predictors of toxicity through data mining, ASM says.

A lack of flexibility in assessing risk/benefit and unreliable predictors of toxicity are among the barriers to anti-infective drug development, the American Society for Microbiology says in comments on FDA's "Critical Path" initiative.

ASM also volunteers to co-host a forum with FDA to refine Critical Path priorities on "product development related to infectious agents."

Through the Critical Path initiative, the agency requested feedback on ways to identify and prioritize pressing medical product development problems and suggestions for "areas that provide the greatest opportunities for rapid improvement and public health benefits." The comment period closed July 30.

In its comments, ASM proposes the agency place a higher priority on harmonizing international guidelines and on flexibility "concerning the evidence necessary to demonstrate safety and efficacy, particularly as it relates to data required for different indications for the same infectious agent."

Noting "thousands of infants died outside the U.S. from rotavirus infection" after the Wyeth vaccine Rotashield was withdrawn following a "very small percentage of adverse events in the U.S.," ASM urges FDA to "give much more thought" to "the risk-benefit ratio of products and the acceptable level of risk and actual numbers of patients practical to demonstrate an acceptable level of risk."

Another major clinical research barrier is "lack of electronic medical records and easy access to data" essential for demonstrating the need for new antibiotics and to aid the tracking of antimicrobial resistance, ASM says.

Additionally, FDA is "uniquely positioned" to establish more reliable predictors of toxicity, another hurdle to antimicrobial development, through "data mining" and establishing pharmacogenomic relational databases, the society notes.

ASM suggests diagnostics approval should be integrated with drug approval "when relevant." This practice would serve to reduce inappropriate use of antibiotics and antivirals and slow development of resistance.

Moreover, "clear guidance should be established for development of diagnostics for infectious agents, including collection and processing of specimens."

ASM further says that as FDA begins to review "increased numbers of biologic products and vaccines and immunomodulators in relation to review of biothreat countermeasures" under the animal efficacy rule, the agency should mine aggregate data for lessons learned and share such information.

Referencing a March 2003 report from the Institute of Medicine - "Microbial Threats to Health: Emergence, Detection and Response" - ASM calls FDA's Critical Path initiative "very timely."

ASM notes the IoM report "declared antimicrobial and vaccine development to be in a state of crisis based upon the status of the current pipeline for both naturally occurring infectious agents" and "those that might be intentionally released."

ASM cautions FDA must take care in its planning "to identify gaps that are most relevant to speeding translation and not duplicative of those already ongoing" at the National Institutes of Health.

Noting the National Institute of Allergy & Infectious Diseases has received an increase of $1.7 bil. for the development of bioterrorism countermeasures, including antivirals, antibacterials, vaccines and diagnostics, ASM points out the current environment presents a "unique opportunity to change the status quo."

"Academic-based scientists funded by NIAID are focusing on broad aspects of product development, not only basic research," the association observes.

As "priorities are being established and a blueprint for action being developed," it is "extremely important that FDA be engaged not only with industry, but also [with] academia and government scientists," ASM says.

- Shirley Haley