Organizations press FDA on updated breakpoints
February 2023—The CAP and three other organizations told the FDA in a Jan. 6 letter they are increasingly concerned that it is not recognizing updated antimicrobial susceptibility interpretive criteria, or breakpoints, in a sufficiently timely manner.
The American Society for Microbiology, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, and the CAP said in the letter that a “clear path forward” is needed for breakpoint updates as well as for “‘bug/drug’ combinations that are routinely tested and reported” using Clinical and Laboratory Standards Institute breakpoints and for which there are no FDA breakpoints.
They told John Farley, MD, MPH, director of the FDA Office of Infectious Diseases, that in the absence of an FDA-recognized breakpoint, laboratories have to either apply off-label testing or use grandfathered tests, which in many cases are obsolete.
The testing and reporting of daptomycin for Enterococcus faecium is an example of a challenge the groups cited. The FDA approved it at a dose of up to 6 mg/kg/d for Staphylococcus aureus and 4 mg/kg/d for E. faecalis. It was never approved for the treatment of infections caused by E. faecium, “largely because there were insufficient cases in registration trials to set a breakpoint,” the groups write.
“Yet, as time has evolved, a primary clinical use of daptomycin is for the treatment of E. faecium infections, and recent PK/PD data have shown that doses of 8–10 mg/kg/d are needed for clinical success. However, this regimen is only effective for isolates with MICs below 8 mcg/mL, requiring susceptibility testing. In cases such as these,” they write, “effective treatments for resistant organisms can be found through an off-label use of a drug, but are hampered by the lack of testing options, leading clinicians to prescribe ‘in the dark.’”
When Congress passed the 21st Century Cures Act in 2016, it included language aimed at improving the update process, but the groups say they are concerned there hasn’t been a significant increase in the FDA Center for Drug Evaluation and Research’s acceptance of current, updated breakpoints.
Thermo Fisher, AstraZeneca to develop companion diagnostic for Tagrisso
Thermo Fisher Scientific is working with AstraZeneca to develop a solid tissue and blood-based companion diagnostic test for Tagrisso (osimertinib).
The test will help identify patients with non-small cell lung cancer who may be eligible for treatment with Tagrisso by identifying tumors that exhibit EGFR alterations including exon 21 L858R mutations, exon 19 deletions, or T790M mutations. Thermo Fisher says the collaboration will leverage the Oncomine Dx Express Test on the Genexus Dx System.
Digital pathology codes
The CAP has made available online information related to the 13 category III digital pathology codes that became effective Jan. 1. Each code and its descriptor is provided, along with answers to multiple frequently asked questions, among them: Do the codes have reimbursement rates attached? Do they have both TC and -26 components? Visit https://capatholo.gy/3HcLy2u.