D. Bouchard

French Agency for Food, Environmental, and Occupational Health and Safety, National Agency for Veterinary Medicinal Products, Fougères, France

The European One Health Action Plan against Antimicrobial Resistance (AMR), adopted in 2017, recognizing the burden of AMR has defined a framework for concrete actions, some of which were ratified as measures during the regulatory revision related to medicated feed and veterinary drugs which came into force in 2022 (Regulation 2019/4 and 2019/6, respectively). The fight against AMR is one key objective of these revisions affecting all antimicrobials.

Regulation 2019/4 on the market and use of medicated feed: After the ban in the EU in 2006 of the use of antibiotics as feed additives for growth promotion, the revision of the regulation on medicated feed identified that cross-contamination of non-target feed (not intended to contain a specific active substance) with antimicrobials is a risk that need to be assessed and mitigated. To this aim, the EFSA published in 2021 a scientific risk assessment report on the maximum levels of cross-contaminations for 24 antimicrobials substances. In addition, an important measure is the prohibition of the prophylactic use of medicated feed containing antimicrobial veterinary medicinal products (VMPs). Thus, prophylaxis claims for antimicrobial VMPs intended for incorporation into feed are no more compliant with legislation.

Regulation 2019/6 on veterinary medicinal products: Measures on marketing authorization procedures (Articles 8; 36; 37): The risk of antimicrobial resistance is now included in the marketing authorization (MA) procedure as part of the benefit–risk balance of VMPs. It may lead to refusals or the possibility to request post-MA studies or monitoring. Documentation on the direct or indirect risks to public or animal health or to the environment of use of the antimicrobial VMP in animals shall be submitted for food-producing animals and for companion animals. Importantly, as part of new requirements, resistance in the environment shall now be addressed.

Measures on use of antimicrobials (Articles 37; 105; 107): VMPs containing antimicrobials are now subject to compulsory veterinary prescription. The prescription must specify the appropriate warnings and advice for the proper use of these drugs. This prescription has a very limited period of validity; the delivery of VMPs must take place within 5 days of the issuance of the prescription. The regulations also recognize the need to reserve certain last-resort antimicrobials for human use to treat life-threatening infections. The European Commission adopted a list of antimicrobials or groups of antimicrobials reserved for treatment in humans on July 19, 2022, in Implementing Regulation (EU) 2022/1255. The inclusion of an antimicrobial on this list will mean the prohibition of its use in animals, including within the framework of the cascade (outside the terms of the MA). Regulation (EU) 2019/6 introduces important provisions regarding the use of antimicrobial products for “prophylaxis” and “metaphylaxis”. Indeed, prophylaxis can now only take place in exceptional cases. The administration of the VMP should concern only individual animal (for antibiotics) or a restricted number of animals (for others antimicrobials) when the risk of infection is very high and the consequences are likely to be severe. The use of VMPs for metaphylactic purposes is only possible if the risk of spreading an infection or an infectious disease in the group of animals is high and when no other suitable solution is available.

Measures on Animals or products of animal origin imported into the Union (Article 118): Considering the international dimension of AMR, the regulation specifies that operators from third countries wishing to export animals or products of animal origin to Europe must neither use VMPs antimicrobials to promote growth, increase yield, or use antimicrobial drugs reserved for the treatment of certain infections in humans, set out in article 37(5).

Measures on Collection of data on antimicrobial medicinal products used in animals (Article 57): Recognizing the need for more detailed and standardized data, the regulation introduces a requirement to collect and report use data by animal species. Initially on a voluntary basis, the new regulations make it mandatory to transmit data on the use of Antimicrobials to the EMA starting from 2024 for cattle, poultry and pigs, from 2027 for other species whose products are intended for human consumption (and including all horses) and from 2030 for companion animals.

Taken together, these provisions will support the EU Green Deal's farm-to-fork strategy goal of reducing global sales of antimicrobials for farm animals and aquaculture by 50% in the European Union by 2030.

中文翻译：

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I11 | 欧盟抗微生物药物立法的演变：要实现的目标和对处方者的影响

D.布沙尔

法国食品、环境和职业健康与安全局，国家兽药产品局，法国富热尔

2017 年通过的《针对抗菌素耐药性 (AMR) 的欧洲统一健康行动计划》认识到 AMR 的负担，为具体行动制定了框架，其中一些在与药物饲料和兽药相关的监管修订期间被批准为措施于 2022 年生效（分别为条例 2019/4 和 2019/6）。抗击 AMR 是这些影响所有抗菌药物的修订的主要目标之一。

2019/4 号法规关于药物饲料的市场和使用：欧盟在 2006 年禁止使用抗生素作为饲料添加剂促进生长后，药物饲料法规的修订确定了非目标物的交叉污染含有抗菌剂的饲料（不打算含有特定的活性物质）是一种需要评估和减轻的风险。为此，EFSA 于 2021 年发布了一份关于 24 种抗菌物质交叉污染最高水平的科学风险评估报告。此外，一项重要措施是禁止预防性使用含有抗菌兽药产品（VMPs）的药物饲料。因此，旨在掺入饲料中的抗微生物 VMP 的预防声明不再符合法规。

关于兽药产品的第 2019/6 号条例：关于上市许可程序的措施（第 8 条；第 36 条；第 37 条）：抗菌素耐药性风险现在作为 VMP 收益风险平衡的一部分包含在上市许可 (MA) 程序中。这可能会导致拒绝或可能要求进行 MA 后研究或监测。对于食用动物和伴侣动物，应提交有关在动物中使用抗菌 VMP 对公众或动物健康或环境造成的直接或间接风险的文件。重要的是，作为新要求的一部分，现在应解决环境中的阻力问题。

使用抗微生物药物的措施（第 37 条；第 105 条；第 107 条）：含有抗菌剂的 VMP 现在必须接受强制兽医处方。处方必须指定适当的警告和正确使用这些药物的建议。这个处方的有效期非常有限；VMP 的交付必须在处方签发后 5 天内进行。法规还认识到需要保留某些最后的抗菌药物供人类使用，以治疗危及生命的感染。欧盟委员会于 2022 年 7 月 19 日在实施条例 (EU) 2022/1255 中通过了一份保留用于人类治疗的抗菌剂或抗菌剂组清单。将抗菌剂列入该清单将意味着禁止其在动物身上使用，包括在级联框架内（在 MA 条款之外）。法规 (EU) 2019/6 引入了关于使用抗菌产品进行“预防”和“后继反应”的重要规定。事实上，预防现在只能在特殊情况下进行。当感染风险非常高且后果可能很严重时，VMP 的管理应仅涉及个体动物（对于抗生素）或有限数量的动物（对于其他抗微生物药物）。仅当在动物群体中传播感染或传染病的风险很高并且没有其他合适的解决方案时，才可能将 VMP 用于后预防目的。当感染风险非常高且后果可能很严重时，VMP 的管理应仅涉及个体动物（对于抗生素）或有限数量的动物（对于其他抗微生物药物）。仅当在动物群体中传播感染或传染病的风险很高并且没有其他合适的解决方案时，才可能将 VMP 用于后预防目的。当感染风险非常高且后果可能很严重时，VMP 的管理应仅涉及个体动物（对于抗生素）或有限数量的动物（对于其他抗微生物药物）。仅当在动物群体中传播感染或传染病的风险很高并且没有其他合适的解决方案时，才可能将 VMP 用于后预防目的。

针对进口到欧盟的动物或动物源产品的措施（第 118 条）：考虑到 AMR 的国际层面，该法规规定希望向欧洲出口动物或动物源产品的第三国经营者不得使用 VMPs 抗菌剂来促进生长、增加产量或使用专为治疗人类某些感染而保留的抗微生物药物，如第 37 条第 (5) 款所述。

用于动物的抗微生物药物产品数据收集措施（第 57 条）：认识到需要更详细和标准化的数据，该法规引入了按动物物种收集和报告使用数据的要求。最初是在自愿的基础上，新法规强制要求从 2024 年开始向 EMA 传输有关牛、家禽和猪的抗生素使用数据，从 2027 年开始将其产品用于人类消费的其他物种（包括所有马） ) 以及从 2030 年开始的伴侣动物。

总而言之，这些条款将支持欧盟绿色协议的“从农场到餐桌”战略目标，即到 2030 年将欧盟用于农场动物和水产养殖的抗菌药物的全球销售额减少 50%。