FDA and the Antibiotic Breakpoint Updating Process

Abstract

We read with interest the Current Topics article prepared by Jeffrey L. Fox, “FDA reasserts authority over antibiotic breakpoint updating process,” in the May 2007 issue of Microbe (p. 222). We were disappointed that such an important article did not present a more balanced view of all stakeholders, including interviews with additional clinical microbiologists or clinicians including those specializing in infectious diseases. However, Fox accurately points out the key regulatory requirements of the Food and Drug Administration (FDA) and the patient safety benefits of regular updates to breakpoints in the face of emerging bacterial resistance. FDA and Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) share common interests in establishing breakpoints for interpretation of antimicrobial susceptibility tests. CLSI convened a special meeting in January, which included representatives from FDA, CDC, large and small pharmaceutical companies, diagnostic devices companies, clinical microbiologists, and infectious diseases clinicians from the United States and abroad, to discuss how CLSI and FDA can best work together on the issue of antibiotic susceptibility test interpretive breakpoints. The group recommended that CLSI publish the initial FDA breakpoints of newly approved antimicrobial agents following a brief presentation to CLSI by the drug's sponsor. If the CLSI Subcommittee on Antimicrobial Susceptibility Testing (AST) does not agree with the FDA breakpoints, the drug will not be included in the CLSI susceptibility testing publications. Further, CLSI would not propose any alterations of the FDA breakpoints for at least two years following approval of the official drug label. If, after that time, emerging resistance or other issues arise that suggest the need to revise the breakpoints, the subcommittee would review all relevant data to determine if a change would be warranted. These recommendations have been endorsed by CLSI's AST Subcommittee, Area Committee on Microbiology, and Board of Directors. This new approach should assuage the concerns of pharmaceutical companies that the FDA and CLSI breakpoints might differ for their new drugs. It should also better serve clinical microbiology laboratories and diagnostic device manufacturers because there will not be conflicting breakpoint recommendations for new drugs in the United States.