The European Union recently introduced the so-called ‘veterinary medicines’ package. With the aim of promoting public health as well as animal health and welfare. Through industry harmonization, stimulating innovation, combating antibiotic resistance (AMR). The ABC of the new rules in Regulations (EU) 4, 5, 6 of 2019.
Antibiotic resistance (AMR), global health crisis
The emergence and increasing prevalence globally of antibiotic-resistant microorganisms (Antimicrobial Resistance, AMR) – and especially those that resist at least three classes of antibiotics (Multiple Drug Resistance, MDR) – constitutes today, According to the World Health Organization, one of the most serious threats to the health of the planet’s populations. 700,000 people die each year worldwide from bacterial infections that antibiotics can no longer treat. (1)
The post-antibiotic era-in which infections once considered trivial can have serious complications and even kill-is the reality in which we live today. Due to the lack of therapeutic alternatives to treat an increasing number of infections caused by bacteria, parasites, viruses, and fungi. Examples include the MDR strains of Salmonella, which we have already discussed, andMethicillin-resistant Staphylococcus aureus (MRSA). Which has caused, throughout the European Union, infections that are very difficult to treat.
AMR, health crisis in EU and Italy
Infections with multidrug-resistant bacteria cause more than 33,000 deaths each year in the EU and European Economic Area (Iceland, Norway, Liechtenstein. See note 2) alone. With an epidemiological impact comparable to the sum of influenza, tuberculosis and HIV/AIDS. And an overall annual cost-in terms of public health and productivity losses-estimated at about 1.5 billion euros in the EU alone. The figures in the latest report by theEuropean Centre for Disease Prevention and Control (ECDC), published in November 2019, show signs of improvement in some member states, including Italy. But the overall average consumption of antibiotics remains stable.
‘Unfortunately, our country holds the sad record in the European context of antibiotic resistance mortality. In fact, of the 33,000 deaths that occur in Europe each year from infections caused by antibiotic-resistant bacteria, more than 10,000 are in Italy’ (Annalisa Pantosti, AR-ISS Surveillance Manager).
In Italy, the situation is among the worst. Second only to Cyprus for antibiotic use in animal husbandry, the data show a high percentage of resistant isolated bacteria, higher than many other states. The incidence of carbapenemase-resistant Klebsiella pneumoniae strain, for example, increased from 1.3 percent to 33.5 percent between 2006 and 2015, combined resistance (third-generation cephalosporin, fluoroquinolones, and aminoglycosides) from 2.6 percent to 29.7 percent. (3)
‘One Health’
Antimicrobial resistance develops when microorganisms misreplicate, that is, exchange resistant traits. And inappropriate and excessive use of antimicrobials accelerates the emergence of resistant bacterial strains. Therefore, the abuse must be addressed:
– in the treatment of people, as recently pointed out by the Italian Medicines Agency (Aifa) itself,
– In animal husbandry. Where-as seen in recent examples on salmon aquaculture in Scotland and sea bream and sea bass aquaculture in Greece-the use of antibiotics is an improper reaction to diseases that result from environmental factors. (4)
‘One Health’
is the key concept-expressed in the latest European Action Plan to Combat AMR, adopted in 2017. With the idea of addressing human, animal and environmental health with a holistic, unified or otherwise synergistic approach. (5) Not forgetting that to date, food-producing animals consume two-thirds of the antimicrobials consumed in the EU. (6)
Animal welfare in turn is a ‘preventive measure in itself (…) as it helps to reduce the risk of animals contracting diseases and, consequently, limits the use of antimicrobials and allows for often higher production results‘. (7) However, this ‘measure’ still lacks an integrated and coherent from stable to table rule system.
EU, the ‘veterinary medicines’ package
The ‘veterinary medicines’ package moves from a realization, AMR constitutes ‘a global public health risk that impacts society as a whole and requires intersectoral, urgent and coordinated actions consistent with the One Health approach.’ (8). The existing framework is therefore being revised, (9) with a triad of regulations:
– reg. 2019/4, ‘on the manufacture, placing on the market and use of medicated feed‘,
– reg. 2019/5 ‘laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (EMA)‘
– Reg. 2019/6, ‘relating to veterinary medicinal products‘.
Reg. EU 2019/6, veterinary medicinal products
Reg. EU 2019/6, which we have already written about, comes into effect on 28.1.22. Despite the desire to reduce the reckless use of antimicrobials, the legislature’s priorities include fostering a single market for veterinary medicines by encouraging research, innovation and competitiveness. This simplifies the introduction of new drugs (particularly for ‘minor species’) and the replacement of drugs that have become ineffective, reducing the associated bureaucratic burden.
Measures to combat AMR apply to the entire supply chain, starting from the procedures for authorization of veterinary medicines, the way they are administered, labeling and advertising, data collection and pharmacovigilance system, to distribution and sale including online. Details follow.
Authorizations and limits of use
The framework for authorization of veterinary medicines is revised, in reg. 2019/6, with the aim of reducing administrative burdens and ensuring a level playing field for all applications. The centralized and national procedures are supplemented by a decentralized authorization procedure valid in several member states and special procedures for mutual recognition. The permits, still with a five-year term, will have unlimited time extension.
To mitigate the misuse of antimicrobials, their systematic use is prohibited, as well as those aimed at compensating for hygienic deficiencies, inadequate husbandry practices, lack of care, and poor herd management. The use of antimicrobial drugs in animals for the purpose of promoting growth or increasing productivity (as is still the practice in Canada and the US) is also prohibited.
Both prophylactic (before clinical signs of disease occur) and metaphylactic (i.e., treatment of a group of animals on which signs of infection occur) use of antimicrobials are restricted. (10) Veterinary prescription for prophylaxis and metaphylaxis must always be justified, and the latter must be preceded by diagnosis of the infectious disease.
Medicines must be used within the terms of the marketing authorization. And yet the so-called ‘(prescription a) waterfall’ is introduced. That is, the possibility for veterinarians to prescribe other medicines, by way of exception, if no suitable authorized veterinary medicine is available. In exceptional cases, member states may authorize the use on their territory of veterinary medicines not authorized in the same country. With authority to establish ‘such procedures as they deem necessary‘ to implement these provisions.
Human and veterinary drugs, pharmacovigilance
The Commission will identify a list of medicines of critical importance for preventing or treating life-threatening infections in humans, the use of which in veterinary settings should be ruled out. TheEuropean Medicines Agency (EMA) has already ruled on the issue, pointing out that the drug will be restricted to human use only in extreme cases, that is, when no other action can be taken to preserve its efficacy. (11)
A system of active surveillance of pharmacovigilance data on veterinary medicines will have to be activated by the holders of the relevant authorizations. A dedicated pharmacovigilance database will be established for reporting and recording suspected adverse events.
Advertising and distribution
Advertising should promote the responsible use of the veterinary medicine by presenting it objectively through the description of the properties it possesses. It must not be misleading or lead to inappropriate use of the drug, nor confuse its role with those of feed or biocides. Antimicrobial veterinary drugs may not be distributed for promotional purposes, either in the form of samples or in any other form.
The retail sale of veterinary medicines online is expressly allowed, limited to non-prescription veterinary medicines. Antimicrobials can only be sold online if specially permitted by the member state and the member state has set up a ‘secure system‘ for their supply. However, online sales may only be authorized to persons established in the territory of the state and only within the state itself.
AMR and Sustainable Development Goals (SDGs)
The European Centre for Disease Prevention and Control (ECDC) highlighted that despite the reforms adopted, it is ‘clear that public health actions to address the situation remain insufficient.’ (12) The health problem-taking into account its complexity, cross-border dimension and high economic impact-extends far beyond the serious public health and animal health consequences anticipated so far, in Europe and worldwide.
The danger is such that it threatens-along with the climate emergency, malnutrition and obesity (identified as the top three factors in the Global Syndemic) – the survival of the human species. However, the Sustainable Development Goals (SDGs) in UN Agenda 2030 appear to lack due attention to animal health and welfare. Although many of them depend on it, such as the ‘Zero Hunger‘ goal (SDG 2), life under water and on land (SDGs 13 and 14) and clean water supply (SDG 6). Moreover, the European Commission and FAO have highlighted the need to consider animal welfare at the heart of sustainability. (13)
The United Nations Inter-Agency Expert Group (IAEG-SDGs) has therefore proposed to supplement the SDGs with a specific indicator related to AMR under SDG 3 ‘Health and well-being. ‘Reduce the rate of bloodstream infections due to selected antimicrobial organisms.’ (14) And the food chain, once again, has the responsibility to turn the problem into a solution.
Giulia Torre and Dario Dongo
Notes
(2) See ECDC (European Centre for Disease Prevention and Control) report, 6.11.18,
(3) See EMA, Sales of veterinary antimicrobial agents in 31 Euuropean countries in 2017. As well as the more recent ECDC report,
Antimicrobial consumption in the EU/EEA, annual epidemiological report for 2018,
v. ECDC
Country visit to Italy to discuss antimicrobial resistance issues.
, January 9-13, 2017.
(4) Farm animal husbandry is the sector with the highest inappropriate use and misuse of antimicrobials. See on this point ECDC/EFSA/EMA, 2017, ECDC/EFSA/EMA Second Joint Report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals. Joint Interagency Antimicrobial Consumption and Resistance Analysis. (JIACRA) Report, in EFSA Journal, 15(7), 4872
(5) European Commission, 2017, Communication from the Commission to the Council and the European Parliament, European “One Health” Action Plan against Antimicrobial Resistance, COM(2017) 339 final, Brussels.
(6) See Table 5 of the most recent JIACRA report (2017, ‘analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals‘, 2014 data)
(7) European Parliament, 2018, Joint motion for a resolution on animal welfare, the use of antimicrobial drugs, and the environmental impact of industrial broiler farming,
(8) See reg. EU 2019/6, recitals 9 and 41
(9) Dir. 2001/82/EC (Community code relating to veterinary medicinal products), reg. EC 726/04 ‘laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency‘
(10) In particular, antimicrobial drugs should not be used for prophylaxis except in exceptional cases, for administration to a single animal or a small number of animals when the risk of infection or infectious disease is very high and the consequences may be serious. In such cases, the use of antibiotic drugs for prophylaxis is limited to administration to a single animal only. Antimicrobial medicines may also be used for metaphylaxis only when the risk of the spread of an infection or infectious disease in the animal group is high and no suitable alternatives are available (EU Reg. 2019/6, Art. 117(3) and (4))
(11) There are three criteria for identifying such medicines reserved for human use:
– their utmost importance to human health,
– the low importance for animal health and
– The ability of the drug to pose, when used in animals, a significant risk of transferring antimicrobial resistance from animals to humans. V. EMA (2019). Advice on implementing measures under Article 37(4) of Regulation (EU) 2019/6 on veterinary medicinal products – Criteria for the designation of antimicrobials to be reserved for treatment of certain infections in humans,
(12) ECDC (2018). Surveillance of antimicrobial resistance in Europe,
(13) V. FAO (2014).
Animal Welfare at the Heart of Sustainability.
,
(14) The amendment will be proposed to the United Nations Statistics Commission in March 2020. IAEG-SDGs (2019). Proposals for Consideration in the Open Consultation for the 2020 Comprehensive Review.
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
Graduated in law, master in European Food Law, she deals with agro-food, veterinary and agricultural legislation. She is a PhD in agrisystem.
