EMA issues Concept Paper for Antimicrobial Resistance Risk Assessment Guideline

On 10 January, the European Medicines Agency published a concept paper for a guideline on antimicrobial resistance risk assessment, which is open  for public consultation until 30 April 2013.
Antimicrobial1 resistance (AMR) is an important issue to be addressed in applications for marketing authorisations of veterinary medicinal products (VMP) and related issues regarding animal pathogens must be discussed in the clinical part of the dossier. Important for the risks for the public health are not only the issues of antimicrobial residues, but also the risks from resistant bacteria in food (see Annex 1 of Directive 2001/82/EC).

Besides food borne risks there are also potential non-food risks to public health linked to use of antimicrobials in animals including companion animals. One example would be meticillin-resistant  Staphylococcus aureus (MRSA) which is a zoonosis that may spread via direct contact between animals and humans.
An antimicrobial risk assessment in the context of marketing authorisation applications for veterinary medicinal products involves several complicating factors:

  • The hazard is not the antimicrobial substance itself but a consequence of its use and the use of the VMP is one of several risk factors. Although use of antimicrobials is regarded a very important risk factor, it is nevertheless the case that there are other risk factors determining the risk to public health. As example livestock trade and poor hygiene which will increase spread of resistant bacteria between animals. Furthermore slaughter house practices will have impact on the risk for further spread to humans.
  • The hazard identification as described in GL27 (Guidance on the pre-approval information for registration of new veterinary medicinal products for food producing animals with respect to antimicrobial resistance) considers the resistant bacteria and resistance genes but does not take into consideration the consequences on human health such as severity of the resulting disease and availability of alternative treatments (the "hazard characterisation").
  • The risk cannot be fully quantified: The AMR related public health risks linked to the use of a certain VMP will be semi-quantifiable at best. The number of resistant bacteria will vary depending on what other risk factors are present. Furthermore, there is no parallel to the ADI-concept. It will not be possible to establish thresholds defining a certain "safe level" of resistant bacteria in the gastrointestinal tract.
  • It is not only de-novo development of resistance which is to be considered but also the amplification and spread of strains pre-existing before administration. Thus, the exposure scenarios need to consider not only the treated individual animal but must include assessment at population level.
  • There is no guideline detailing data requirements for the exposure assessment. Furthermore the exposure assessment will include different aspects like pre-harvest at individual level, pre-harvest at group level and post harvest factors.
  • The hazard identification and characterisation is substance/class dependent rather than product dependent. It is only the level of exposure of the active component that could differ between products containing the same antimicrobial agent
  • The company may suggest risk mitigation measures to minimise the risk, e.g. by adding warnings or contraindications to the summary of product characteristics or by restricting the target population for treatment. Therefore, the use of a tiered approach which allows refinements should be made possible.

Therefore, the risk assessment model to be applied will be complicated and also data sources other than data provided by applicants on the specific product (as requested in GL27) will be of importance for the assessment.

Read more about the related discussion and recommendations in the "Concept paper for a guideline on antimicrobial resistance risk assessment".

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