VM3: Antimicrobials; the new rules, their impact and consequences

Key points:

• The Veterinary Regulation 2019/6 established new provisions and obligations for antimicrobials in veterinary medicines. Work on implementing regulations and guidelines is ongoing to further specify their use and restrictions.
• A systematic approach, based on strict scientific evidence, is the basis for objective recommendations and restrictions regarding the prohibition of use of certain antimicrobials in animals.
• Systematic, science-based monitoring of antimicrobial consumption and resistance in the EU confirms the effectiveness of the measures already implemented over the last years under the “One Health” concept.

Barbara Freischem gave an overview of how the EMA’s scientific advice on the list of antimicrobials to be reserved for human use was developed. This was a mandate that the EMA had received from the European Commission to prepare the legal basis for measures to control antimicrobial resistance.

A complete ban on the use of certain antimicrobials in animal health is thereby recognised as the strictest measure that can be applied to reserve their efficacy for human use. Due to time pressure, this work took place in parallel with the actual elaboration of the criteria to designate antimicrobials as reserved for human use. More than thirty experts with backgrounds ranging from microbiology to clinical aspects in human and veterinary medicine and expertise in infectious diseases were involved.

The group successfully managed the challenge of evaluating a large number of different antivirals, antifungals, antiprotozoals and antibacterial classes and subclasses, with different levels of evidence and applicable legislation. This first ever systematic review was based on the best scientific evidence available and followed a strictly scientific approach against three criteria laid out in Delegated Regulation 2021/1760: A) human importance, B) potential for transmission of antimicrobial resistance (AMR) and C) non-essential need for animal health.

A complete ban on the use of certain antimicrobials in animal health is thereby recognised as the strictest measure that can be applied to reserve their efficacy for human use

Only those substances or groups that met all three criteria were finally recommended to be designated as reserved for human use. Overall, the advice recommended twelve antibiotic classes, five antibiotic substances and eighteen antiviral substances to be reserved for humans. Based on this advice and after feedback from various regulatory bodies and the public on the draft legislative proposal, the Implementing Regulation 2022/1255 was adopted in a record time of less than five months.

Helen Jukes gave an update on the implementation of the CVMP Strategy on Antimicrobials 2021 to 2025. CVMP’s activities cover six areas: to authorise antimicrobial veterinary medicinal products, to maintain the effectiveness of authorised antimicrobials, to support their responsible use to encourage the development of new antimicrobials and alternatives, to advise on AMR risks to public health and finally to support EU-wide and global collaboration on the topic.

To date, CVMP has reviewed the SPCs of fifteen authorised antimicrobial products for their alignment with the new definitions and conditions of “prophylactic use” as laid out in the new Regulation. Mostly minor discrepancies have been found. It is for further discussion now with the Commission and EMA how any changes to the SPCs will be implemented.

In order to be in alignment with the update of definitions in the veterinary regulations, several related guidelines such as the ”Demonstration of Efficacy for antimicrobial VMPs” or the “Efficacy studies for intramammary products for cattle” have to be updated as well. The public consultation on a concept paper on a guideline on post authorisation studies for antimicrobials will open in January 2023. The guideline should address the circumstances and type of data that would be required for such studies.

The work on a list of candidate products for a dose review and potential adjustment for established veterinary antibiotics had to be postponed due to workload. Work is ongoing on the reflection paper on the extended data protection period when demonstrating a reduction of AMR, and a scientific advice on a list of products not to be used under the cascade or under certain conditions.

Further interventions will be necessary because there are still important differences in the antimicrobial consumption between different countries and high levels of AMR

Pierre-Alexandre Beloeil explained the EFSA monitoring of antimicrobial consumption and resistance in the EU MS as part of the EU actions to fight AMR. The monitoring is based on harmonised technical specifications across Europe in terms of the testing methods, the substances tested, the interpretation criteria and the sampling designs, with regular training and confirmatory testing in all reference laboratories. With a view on public health, the monitoring is performed in indicator food-borne bacteria in healthy food-producing animals and, since 2021, in bacteria from imported fresh meat from third countries.

Since 2014, when the monitoring programme started, an impressive amount of data from all MS has been collected, which allows for a scientific evaluation of trends and variations among reporting countries.

It is encouraging to see that there have been statistically significant trends of decreased AMR in many countries over in recent years. Also, the mean antimicrobial consumption in food producing animals has decreased significantly between 2014 and 2018. The available data confirm the positive association between antimicrobial consumption and resistance in both humans and food-producing animals. Hence, the measures taken to reduce the use of antimicrobials in food-producing animals have indeed been effective.

Further interventions will be necessary because there are still important differences in antimicrobial consumption between different countries, and high levels of AMR reported. There is an ongoing need to promote the prudent use of antimicrobials and the control and prevention of infection in both humans and food-producing animals under the concept of “One Health”.