The European Medicines Agency (EMA) has announced the release of a new draft guideline regarding the testing of veterinary antibiotics, with regulators saying the changes provide greater detail on their expectations for demonstrating efficacy relative to a targeted microorganism.
The guideline is in part intended to cut down on rates of increasing antimicrobial resistance, EMA wrote in an accompanying statement, with the theory being that ineffective drugs only serve to build up microbial resistance to drugs. "All [antimicrobial] use will inevitably select for antimicrobial resistance," EMA explained in the guidance. "Thus, it is vital that all unnecessary or inadequate use is avoided in order to prolong the time period during which the compounding in the proposed dose will remain effective."
The guideline is an update of one first released in 2003 and describes the preclinical and clinical data required to prove therapeutic efficacy in a given indication, as well as the recommended study designs to obtain said data.
EMA explains that four general considerations must be specifically addressed by companies when submitting a veterinary antimicrobial dossier for consideration:
- The drug's indication must be justified through data showing its effectiveness as resolving infections either in full or, in the case of multi-factorial diseases, in substantial part.
- The target population (e.g. animal species) should be well-defined and identifiable.
- Data obtained for the purposes of approval should utilize existing recommendations per appropriate use (e.g. fluoroquinolones should only be used in cases where other antimicrobials have failed).
- The dosing of the drug should be justified to avoid unnecessary exposure of the animal and its microorganisms to antimicrobials, and the minimum inhibitory concentration (MIC) should be indicated in the application.
Trials on the animals will generally test one or more of three possible claims: that a drug is effective at treating a microbe, that a drug is useful in preventing likely infection when a group is partially exposed to a microbe, and that a drug is useful in preventing disease in otherwise healthy animals. The second of these considerations, known as metaphylaxis claims, require a special assessment, requiring proof that a disease did not spread throughout a herd as much as it otherwise would have. EMA notes that this claim will only be accepted in addition to a treatment claim, and "never as a separate indication."
Other parts of the guideline go on to describe some of the more practical aspects of preparing an antimicrobial dossier, including explorations of the microbe's resistance qualities, the need for in vitro testing, pharmacokinetic and pharmacodynamic data, qualities and data required of clinical studies, and the summary of product characteristics.
The consultation on the guideline ends on 30 November 2013.
EMA: Guideline for the demonstration of efficacy for veterinary medicinal products containing antimicrobial substances