Lost in translation: differences in antimicrobial indication approval policies between the United States and Europe

Antimicrobials, like all drug products, are approved in the United States through the Food and Drug Administration (FDA) and in the European Union partly through the European Medicines Agency (EMEA). This article investigates the differences in approved indications between these 2 bodies for a series of antimicrobial agents approved during the past decade.

The antimicrobial compounds most recently approved for specific indications by both the FDA and EMEA were included in the study. Indications were recorded from the respective Web sites and compared. Differences in approved indications were considered major if one regulatory body approved an agent for treatment of a specific condition while the other did not, or if one regulatory body approved an agent only for prophylaxis while the other approved it also for treatment. Differences were considered minor when the 2 bodies approved an antimicrobial for the same condition or pathogen but with different details regarding specific clinical situations.

Thirteen antimicrobial compounds approved by both the FDA and EMEA were included in the study, namely anidulafungin, caspofungin, dapto-mycin, doripenem, ertapenem, linezolid, micafungin, posaconazole, quinupristin/dalfopristin, retapamulin, telithromycin, tigecycline, and voriconazole. Among these 13 agents, differences in approved indications between the United States and Europe were found to be major for 6 and minor for 6. Approved indications were the same for only 1 agent. Major differences were noted for doripenem, linezolid, micafungin, quinupristin/dalfopristin, posaconazole, and telithro-mycin. Examples of major differences include the following: linezolid has a US indication for vancomycin-resistant Enterococcus faecium infections, but no similar indication in Europe; micafungin is indicated for pediatric use in Europe but not in the United States; and use of posaconazole is primarily therapeutic in Europe but preventive in the United States. Minor differences were noted for anidulafungin, caspofungin, daptomycin, ertapenem, retapamulin, and voriconazole. As an example of a minor difference, daptomycin has different indications for Staphylococcus aureus bacteremia. Tigecycline was the only agent for which the FDA and EMEA had approved identical indications.

Differences in the indications for most antimicrobial agents were found between the United States and Europe. Because any approved indication can be viewed as scientific evidence, these differences may raise legal issues regarding the treatment of specific entities. To minimize these differences, coordination is needed between the FDA and EMEA regarding the procedures for approving indications.