Good afternoon, gentlemen and Deputy Upton. The Irish Medicines Board is pleased to appear before the committee to answer questions relating to the proposed animal remedies regulations and the method of supply of intramammary antibiotics and vaccines. I should point out that the IMB is not party to the details, nor involved in the drafting, of the new proposed regulations. Such a regulation may be under consideration by the Department of Agriculture and Food, but we are not aware of the detail of any legislative proposals. We are, however, aware of the European Union review of the medicines legislation, which is currently under discussion at a working group of the Council and which was debated by the European Parliament late last year. We have not been directly involved in those discussions, although we had been engaged in consultations with the Department on the proposals. We also produced, in 1999, a report on the availability of intramammary antibiotics for the Minister for Agriculture, Food and Rural Development.
The IMB made a written submission to this committee on 11 October 2000 and we appeared before the committee to discuss the same subject on 20 February last year. We note, of course, that membership of this committee has changed and we think, therefore, that it is important to explain once again the specific mission and role of the board in relation to the licensing of veterinary medicines and vaccines.
With the indulgence of the committee I will state that the mission of the board is to protect and enhance human and animal health through the regulation of human and veterinary medicinal products. In evaluating applications for product authorisations, the IMB considers the quality, safety and efficacy of the product, including any risks for the user of the product, for the animal itself, for the consumer or for the environment. All of this is defined by European and national legislation. Each application is considered on its merits, but the IMB, in keeping with its policy of transparency as outlined in its service charter, has elaborated policies in relation to the method of supply of all veterinary medicines and, since we were given responsibility for them in 2000, the evaluation of veterinary vaccines. On the last two occasions I communicated the details of those policies to this committee. I will paraphrase and say that the committee is aware that while the board is a competent authority for human and veterinary medicines, it is not a competent authority for the licensing of veterinary vaccines, which are regulated by the Department of Agriculture and Food but on which products, since 1999, the IMB conducts an evaluation of quality, safety and efficacy on its behalf.
Much of the national policy on veterinary medicine stems from EU policy and legislation. The committee will be aware that EU scientific policy on veterinary medicines is principally established by the European Medicines Evaluation Agency, which is composed of scientific experts from EU member states. This body also licenses veterinary medicines and vaccines which qualify for a central or community-wide authorisation. Among the conditions of all product authorisations is that the method of supply should be defined. As I explained the last time I was before the committee, in accordance with the requirements of EU Directive 2001/82/EC, the availability of a veterinary medicine or product containing a new drug substance must generally be restricted to prescription. This directive also states that a prescription should be required for medicines intended for treatments which require a precise prior diagnosis or for which special precautions are necessary to avoid any unnecessary risk to the animal, the user, the consumer or the environment.
The European Commission has stated that in its opinion most, if not all, anthelmintic wormers for veterinary use, as well as vaccines, deserve the status of requiring a veterinary prescription. A proposal that all veterinary medicines used in food-producing animals be subject to prescription-only status is contained in the European reform proposals. In so far as national applications for product licenses and other policies on the quality, safety and efficacy of veterinary medicines are permitted, the IMB policy is established by independent experts of its scientific committee, which in the case of veterinary medicines is the Advisory Committee for Veterinary Medicines. The experts of the ACVM are appointed by the Minister for Health and Children and they come from various scientific backgrounds, including veterinary medicine, pharmacy, pharmacology, toxicology, immunology, clinical practice, livestock and equine research and other specialist disciplines. As necessary, the ACVM consults with other interested parties and stakeholders or establishes a working group of external experts, members of its own committee and specialists before finalising policies which are not already covered by EU regulations, directives, guidelines and position papers. In the case of intramammary products, this was indeed the procedure we followed.
I will turn for a moment to the IMB policy on intramammary medicines. It is important to restate that the conclusions and recommendations contained in the 1999 report remain relevant today. These conclusions were as follows: ideally, in order to ensure prudent use of intramammary antibacterials, a mastitis control programme should be in existence at farm level. This programme should contain the following elements: application of the recognised principles for mastitis control and prevention; good record keeping by the farmer; regular bacteriological and resistance monitoring of each herd in the programme; regular visits by the attending veterinary surgeon to advise on optimum methods of control and to monitor antibacterial usage; and, in the case of dairy cows, the monitoring of milk somatic cell counts and regular maintenance of the milking machine.
The ultimate goal for responsible use of intramammary antibacterials is that they should only be used when scientifically justified, they should be subject to veterinary prescription control and their use should be conditional on the existence and operation of a satisfactory mastitis control programme. The report noted that these goals were not provided for under existing legislation and considered several options for the supply of intramammaries, including the maintenance of the status quo, to restrict antibiotics to pharmacy sale or prescription control or to provide for an alternative method of supply. The report, which is available on the IMB website, www.imb.ie, outlines the merits and weaknesses of the various options for the supply of intramammaries. Importantly, the report acknowledges that existing prescription requirements, which require a veterinary surgeon to examine the animal or animals in question immediately prior to the supply or prescription of a medicine, would be untenable and, in any event, that any such control system needed to be combined with a mastitis control programme such as is defined in the report. The characteristics of such a programme were defined in the report and were undertaken after consultation with experts, including those from the Department of Agriculture and Food and experts from Teagasc.
The report, therefore, proposed that a new control system, less restrictive than that required currently under prescription control but under the responsibility of a veterinary surgeon and linked to a herd health or mastitis control programme, should be instituted for medicines used in lactating cows. In the case of intramammary medicines for dry cows, the report also proposed a new, similar control system, based on an informed choice of the antibiotic and linked to a properly established and audited herd health or mastitis control programme on the farm.
Amongst the several recommendations of the report, it is important to highlight that the legislation governing the supply of intramammary medicines, including aspects of animal remedies regulations and poisons regulations and health board considerations, should be consolidated under the Animal Remedies Act under the aegis of the Department of Agriculture and Food, that a monitoring system for antibacterial resistance should be fully developed, and that legislative action should be taken to eliminate inducements, particularly financial inducements, that might encourage the inappropriate supply of antibiotics, including intramammary antibiotics. A weakness in the current system is that a farmer can be pointed in a certain direction on the choice of antibiotics on the basis of special offers or incentives. He may be offered combinations of therapy where a single substance might be most appropriate.
The report considered two major concerns related to the supply of intramammary antibiotics, including the risk to the consumer of residues remaining in animal tissues and produce and the emergence of drug-resistant strains of bacterial pathogens and the consequences of such resistance for animal and human use. I will focus on anti-microbial resistance because I have previously addressed residues in the consumer supply chain before the committee.
Of these two, most recent interest has been in the area of antibiotic resistance, which is an increasing and global problem. The primary impact of resistance is treatment failure, which causes an increase in morbidity and mortality and hence prolonged suffering of infected animals. A report by the Scientific Steering Committee of the European Commission in May 1999 acknowledged that in many European countries penicillin can no longer be used in the treatment of mastitis since B-lactamase producing staphylococcus aureus strains are common. It is important, however, to acknowledge that antibacterial resistance presents a major threat not just to animal health because it reduces the effectiveness of antibiotic treatment in animals, but also to humans. Drug resistance can prolong infectivity, thus increasing the risk of transmission of the infection and of resistant bacteria to other animals within a herd and to the environment, as well as a risk of transfer of resistant zoonotic pathogens which cause disease in humans. A further risk of antibacterial resistance in animals is that of selection of antibacterial resistance bacteria which are not pathogenic for man, but which may transfer their resistance via plasmids to human commensal and pathogenic bacteria. These bacteria, now with resistance, may later cause resistant disease in humans. Human and animal bacteria inhabit an environmental pool in which resistant bacteria, and genes transferring antibiotic resistance between bacteria, are inextricably intertwined and antibiotic resistance readily crosses the species boundaries.
The two factors which influence the spread of resistance in this manner are the selection pressure exerted by antibiotic use and the ease by which resistant organisms are able to spread between people or animals by cross-infection. Pressure from the animal health industry and from the farming industry to allow continued, ready access to intramammary medicines containing antibiotics without a meaningful and prudent prescribing policy means there is considerable potential for misuse and over-use of antibiotics which is recognised as a contributory factor to antibiotic resistance. To quote from the conclusion of the UK's House of Lords Select Committee on Science and Technology into the Resistance to Antibiotics in 1998, "antimicrobial resistance is here to stay; but action or inaction now, not only by Government but by everyone with a stake in public health, will have a real impact on the public health legacy which we pass on to the next generation." Calls for prudent use have also been made by other international scientific committees. Some of the conclusions of the Scientific Steering Committee of the European Commission are worthy of note in this context. It concluded that all available evidence points to an inexorable increase in the prevalence of drug resistance among bacteria which has paralleled the expansion of their antimicrobial use in all spheres.
This requires urgent attention by Governments and by all users of antimicrobials. It also concluded that although much scientific information is available, not all aspects of the development of antimicrobial resistance are well understood. To obtain robust evidence which might confirm and quantify the relationship between modes and extent of antimicrobial usage and the prevalence of resistance would probably take several years. To wait for incontrovertible evidence before taking action would be to miss an important opportunity for intervention.
The aim of interventions commenced now is to prevent antimicrobial resistance from becoming an even greater problem and to preserve the utility of the antimicrobials currently available. Action should be taken promptly to reduce the overall use of antimicrobials in a balanced way in all areas - human medicine, veterinary medicine, animal production and plant protection. This should involve improved disease preventative measures, elimination of unnecessary and improper use of antimicrobials, improving the effective use of antimicrobials currently available based on more precise diagnosis of the infectious agent, and on monitoring of antimicrobial resistance and control of antimicrobial usage.
In 2000, the Committee for Veterinary Medicinal Products at the European Medicines Evaluation Agency called for prudent use policies in the EU which apply equally to all antibacterial medicines throughout the Union, including those licensed centrally as well as in member states. Calls for prescription control of all antibiotics used in human and veterinary medicine have also been made by the World Heath Organisation and the OlE. Contrary to the view of the Irish animal health industry group, the EU animal health industry group has stated that "antibiotic use should be subject to appropriate professional advice, including that of the veterinary surgeon where appropriate."
In preparing for the submission before the committee I took time to consult with my colleagues in the Department of Agriculture and Food. While robust national data on resistance in human and animal bacteria is difficult to obtain, there is anecdotal and scientific evidence nationally that antibacterial resistance is becoming problematic. Indeed, the IMB has been made aware through recent consultation with the Department of Agriculture and Food of a case where a farm had to be depopulated as a means of controlling resistance to staphyloccus infection - one of the commonest causes of mastitis in cattle. Furthermore, the IMB would question the scientific validity of mastitis control programmes which are operated currently by co-operatives under licence by the health boards, which are devoid of data on antibacterial resistance and which are not linked to a prudent use policy on the selection of the antibiotics used.
I turn now to the IMB's policy on the supply of veterinary vaccines. In the elaboration of their policy on vaccines, the Advisory Committee for Veterinary Medicine considered the following issues: whether the products present a particular risk to the animal, for example, it is possible that anaphylactic reactions may occur in the animal or in the person giving the product to the animals, or indeed there might be a zoonotic disease implication; whether the product may cause effects which affect any subsequent diagnostic test or disease eradication policy; whether special skill is necessary for the administration of the vaccine; whether there are any special contra-indications or precautions needed in administering the product; whether there are special or unusual conditions for the supply, storage and disposal of the products; whether there is a requirement for specific advice for safe and effective use of the product, for example, as part of a herd vaccination campaign to eradicate or prevent diseases, or whether the duration of immunity is limited or specific to a sub-category of animals; and whether the animal owner or farmer would have the necessary training, skill and expertise to diagnose the need for a particular vaccine and to administer it.
In these last two cases, it must be recognised that the efficacy of a vaccine relates to the specific antigenic properties of that product, the physiological and immune status of the animals, the expected disease challenge and the interactions between animal host and pathogen. The fact that many diseases in animals present clinical signs which are not unique to a particular infectious agent and that there may be variation in the antigenicity of microbes causing infectious disease requires the use of specific antigens in a vaccine. If the correct vaccine is not chosen or if it is used incorrectly, an immune response of the host to the organism causing the disease will not take place or the response will not be sufficient.
Other factors which also require consideration in the choice of vaccine are whether the suppression of the immune system is expected, for example, combinations of live attenuated vaccines or the impact of passive immunity on neonatal animals in particular. It is not the purpose of this submission to give a detailed lecture on vaccinology. Rather, the IMB wishes to share with the committee the considerations which must be taken into account when evaluating applications for the granting of a licence for vaccines. It must be recognised that animals vaccinated incorrectly, or with an unsuitable product, are not protected against the disease in question, and animal welfare could therefore be compromised.
Before formulating its policy on vaccines, the ACVM consulted widely and examined the policies in other EU member states and at the EMEA. All veterinary vaccines licensed by the EMEA for all animal species have been restricted to veterinary prescription. The IMB acknowledged that commercial considerations were outside the scope of its evaluation, which was based on scientific and animal welfare considerations. On the basis of the these considerations, the IMB agreed the following general principles for decisions on the appropriate method of supply of veterinary immunological products: vaccines for dogs and cats should be restricted to prescription only, likewise for horses; and vaccines for livestock, fish and poultry should be given the category "prescription only medicine [exempt]", as defined by the Animal Remedies Act, 1993. That means that they can either be prescribed by a veterinarian or given in person by a pharmacist.
In publicising its policy, the IMB wished to provide the animal health industry, the Department of Agriculture and Food and other stakeholders with clear policy guidance so that consistency between the categorisation of similar products can be achieved. However, I should emphasise that a case by case evaluation of each application is made before a final recommendation is made. The IMB fully recognises that it is the Department of Agriculture and Food who, as the competent authority for veterinary vaccines, will make the final determination on the recommendations from the IMB on the authorisations and that it may take other considerations into account. Indeed, the IMB understands that the Department of Agriculture and Food has already done so for a number of products.
The IMB is very conscious of its responsibilities in the protection of human and animal health. The regulation of medicines is founded and continues to be based on science and in law. While acknowledging the financial challenges which farmers face currently, the distribution of veterinary medicines should not be looked at purely from an economic viewpoint. Antibiotic misuse - using the wrong drugs or vaccines - is expected to have significant economic and animal welfare costs and caries a risk to public health. The regulation of veterinary medicines and food safety issues have become of paramount concern to consumers both within the EU and beyond. The principle that food is inherently safe has been questioned and the precautionary principle is expected to be applied in areas of uncertainty. The IMB hopes that this submission will help the committee in understanding its policies on the supply of vaccines and intramammary medicines.
