Regulation of Autogenous Vaccines

| By | Vaccines, Veterinary drugs
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Antimicrobial resistance to medicinal products for human use and veterinary medicinal products is a growing health problem in the European Union and worldwide. The use of antimicrobial medicinal products that are used in animals may accelerate the emergence and spread of resistant micro-organisms and may compromise the effective use of the already limited number of existing antimicrobial medicinal products to treat human infections. Strengthening the prudent use of antimicrobial medicinal products to in the European Union has resulted in an increasing interest in the use of autogenous vaccines.

WHAT ARE AUTOGENOUS VACCINES FOR VETERINARY USE?

Autogenous vaccine for veterinary use is a vaccine prepared using microorganisms which have been isolated from the same infected animal to which it is then administered.

Today, global manufacturers of veterinary medicinal products provide autogenous vaccines for livestock farms around the world.

BENEFITS OF AUTOGENOUS VACCINES

The pluses of autogenous vaccines

Prevent rather than cure:

  • limit disease occurrence;
  • deal with multi-resistant bacteria.

This is the function of every vaccine; the development of bacterial resistance has abolished the option of antibiotic treatment.

Contribute to public health:

  • reduce excretion of the microbial toxins that cause infection;
  • limit the use of anti-infective agents;

The food-processing industry has a duty to protect consumer health.

Provide solutions where there are no vaccines:

  • vaccinate as a matter of urgency in the case of emerging diseases;
  • propose solutions for diseases described as “minor” and for species designated as “secondary”.

The time and cost involved in developing a commercial vaccine are sometimes incompatible with the demands of those working on the ground and of the target markets.

Obtain specific immunity:

  • fight against vaccination failure.

Antigenic variability within the same bacterial species, within the same serotype even, is such that total protection is often unpredictable when the vaccine antigen differs from the aggressor.

Reduce the costs of production:

  • limit the number of vaccine interventions by combining several valencies;
  • develop innovative pharmaceutical forms that reduce human interventions.

The cost of handling the animals and the resulting inconveniences for those involved as well as the stress caused to the animals themselves demand a commitment to simplify plans for prophylaxis. The number of injections can be reduced by combining several valencies. Excellent protection can be obtained in some cases with a single administration by developing high-performance adjuvants. Autogenous vaccines adapted to oral administration can be used in certain indications [1].

PROCESS FOR DEVELOPING AUTOGENOUS VACCINES

The veterinarian takes a sample, either from a sick animal or during an autopsy, which he sends to a diagnostic laboratory for culture. In the laboratory, the pathogenic agent is isolated, identified and serotyped using reagents produced by the manufacturer of veterinary medicinal products. The veterinarian then orders the manufacture of an autogenous vaccine from the isolated strain which is then sent to the manufacturing company. The autogenous vaccine produced by manufacturing company in a few weeks depending on its composition, is supplied to the veterinarian who issues it to his client. Manufacturing company is also available to help veterinarians develop a vaccination program.

Through its products and services, manufacturing company can offer a complete and custom-made solution to the livestock sector and the veterinary profession.

Produced in state-of-the-art biotechnology facilities according to high standards of sterility, autogenous vaccines can be used in multiple indications and are intended for many animal species, ranging from livestock to pets [1].

REGULATION OF AUTOGENOUS VACCINES IN EU

Currently, there are no harmonized requirements for the manufacture, control and use of autogenous vaccines across the EU. National laws and/or legislation are different when they exist, and sometimes there is no specific legislation covering use and production of autogenous vaccines.

Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 “On the Community code relating to veterinary medicinal products” as amended regulates the manufacture, control, placing on the market, import, export, supply, use and pharmacovigilance of immunological veterinary medicinal products. It guarantees the quality of veterinary medicinal products manufactured within the Community by requiring compliance with Good Manufacturing Practice (GMP). Each veterinary medicinal product must be authorized before being placed on the market.

Autogenous vaccines are also defined in this Directive, but are excluded from its scope. The consequence of this exclusion is that autogenous vaccines are not regulated on a European level. Their quality, manufacture and use depend on the individual national legislation of each member state. Legislation for autogenous vaccines differs from member state to member state [2, 3].

The new provisions will apply from January 2022, when Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 “On veterinary medicinal products and repealing Directive 2001/82/EC” will effectively replace Directive 2001/82/EC. From this time, veterinary medicinal products will only be regulated by Regulation 2019/6.

A number of articles of this Regulation shall also apply to inactivated immunological veterinary medicinal products which are manufactured from pathogens and antigens obtained from an animal or animals in an epidemiological unit and used for the treatment of that animal or those animals in the same epidemiological unit or for the treatment of an animal or animals in a unit having a confirmed epidemiological link.

Without prejudice to the date of application of this Regulation, the obligations regarding certificates of Good Manufacturing Practice for inactivated immunological veterinary medicinal products which are manufactured from pathogens and antigens obtained from an animal or animals in an epidemiological unit and used for the treatment of that animal or those animals in the same epidemiological unit or for the treatment of an animal or animals in a unit having a confirmed epidemiological link shall only start to apply from the date of application of the implementing acts laying down specific measures on Good Manufacturing Practice for those medicinal products.

These special GMP-guidelines for autogenous vaccines however still need to be prepared [2, 4].

REGULATION OF AUTOGENOUS VACCINES IN FRANCE

In France, autogenous vaccines regulation is defined in the following documents

The Public Health Code (Code de la santé publique)

Article L5141-2: “Autogenous vaccines for veterinary use are defined as any immunological veterinary medicinal products manufactured for the purpose of producing active immunity from pathogenic organisms obtained from an animal or animals from the same herd that have been inactivated and used for the treatment of this animal or of animals from this herd”.

Article L5141-12: “The preparation of autogenous vaccines for veterinary use should be undertaken by a qualified person (personne qualifiée) or company or organization employing a qualified person who has obtained for this purpose a license issued by the French Agency for Food, Environmental and Occupational Health & Safety (l’Agence nationale chargée de la sécurité sanitaire de l’alimentation, de l’environnement et du travail – ANSES)” [1, 5].

Decree no. 2005-374 of 20 April 2005 about autogenous vaccines for veterinary use in amendment of the Public Health Code – regulatory part (Décret n° 2005-374 du 20 avril 2005 relatif aux autovaccins à usage vétérinaire et modifiant le code de la santé publique – partie réglementaire)

Article 5141-129: “The preparation of autogenous vaccines is undertaken under the responsibility of a qualified person who has obtained the license provided for in article L5141-12, …)”; “The qualified person is a pharmacist or veterinarian. …”; “The qualified person has undergone professional training or has professional experience in the domain of immunology or the manufacture of medicinal products. He or she exercises his or her functions personally. He or she monitors the activities involved in the preparation, storage, transport and monitoring of autogenous vaccines for veterinary use in accordance with Good Practice as defined by order of the ministers responsible for agriculture and health issued on the proposal of the general director of the French Agency for Food, Environmental and Occupational Health & Safety”.

Article R5141-141: “The holder of the permit provided for in article L5141-12 can supply an autogenous vaccine for veterinary use only to a prescribing veterinarian or to any other veterinarian who has given, on inclusion in the order, the same business address as defined in article R242-52 of Rural Code (Code rural)” [1, 6].

HARMONIZATION OF THE LEGAL FRAMEWORK FOR AUTOGENOUS VACCINES IN EU

EMAV – the Association of European Manufacturers of Autogenous Vaccines and Sera is representing the leading European producers of those medicinal products, such as AniCon Labor, Ceva Sante Animale, IDT Biologika, Vaxxinova, etc.

EMAV combines the interests of manufacturers of specific vaccines and sera for farm, companion and exotic animals, to promote the European harmonization process.

Members of EMAV are currently working under different national frameworks being in place for their site location. They would like to contribute their many years of experience to the process of harmonization, especially by developing the future GMP-standard, specific to autogenous vaccines [7].

AUTOGENOUS VACCINES IN RUSSIA

Today in Russia there is no regulation in the field of autogenous vaccines. First of all, the registration procedure for this type of vaccines is not spelled out in our legislation. Nevertheless, this direction could be of interest to both livestock farms and manufacturers of veterinary medicinal products.

“A promising area is the manufacturing of autogenous vaccines, the use of which is not yet regulated in Russia. The bottom line is that a microorganism that is local for a particular enterprise, for example, for a poultry farm, is cultivated, studied, and then the whole population is vaccinated. In Europe, autogenous vaccines are prepared according to EU regulation, they do not need to be registered, but can only be used in the enterprise where the microorganism is isolated. I think this direction has a good future, since an autogenous vaccine in a certain sense is an alternative to antibiotics, the use of which must be reduced”, – said recently Dmitry Lozovoy, director of the Federal Center for Animal Health (FGBI “ARRIAH”), in an interview with the federal branch newspaper “Veterinary Medicine and life” [8].

In certain situations, autogenous vaccines for veterinary use complying with basic quality and safety requirements can be a very useful tool in the animal health and welfare management in certain situations. In the Russian Federation, studying the experience of leading European manufacturers of veterinary medicinal products may be the first step in this direction.

Author: Konstantin Morozov, GMP Specialist of Ceva Sante Animale LLC

REFERENCES:

  1. Ceva Biovac. Autogenous Vaccines. URL: https://www.biovac.ceva.com/en/Autogenous-vaccines/Autogenous-Vaccines (дата обращения01.2020)
  2. Lohmann Tierzucht. Brigitte Othmar-Vielitz. Autogenous veterinary vaccines. URL: http://www.ltz.de/en/news/lohmann-information/2019-1/4_Autogenous_veterinary_vaccines.php (дата обращения01.2020)
  3. Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products. URL: https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:2001L0082:20090807:EN:PDF (дата обращения 22.01.2020)
  4. Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC (Text with EEA relevance). URL: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32019R0006&from=EN (дата обращения 22.01.2020)
  5. Code de la santé publique. URL: https://www.legifrance.gouv.fr/affichCode.do?cidTexte=LEGITEXT000006072665&dateTexte=20200109 (дата обращения 22.01.2020)
  6. Décret n° 2005-374 du 20 avril 2005 relatif aux autovaccins à usage vétérinaire et modifiant le code de la santé publique (partie réglementaire). URL: https://www.legifrance.gouv.fr/affichTexte.do?cidTexte=JORFTEXT000000448515&categorieLien=id (дата обращения 22.01.2020)
  7. Association of European Manufacturers of Autogenous Vaccines and Sera. Principles. URL: https://www.emav.be/en/pages/show/principles (дата обращения 22.01.2020)
  8. Ветеринария и жизнь. Курица или яйцо? Что нужно для выполнения планов по импортозамещению и экспорту продовольствия. URL: https://www.vetandlife.ru/vizh/mneniya/kuritsa-ili-yaytso-chto-nuzhno-dlya-vypo/ (дата обращения 22.01.2020)
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