Abstract

Keywords

Directive 2001/28/EC, veterinary medicinal products, autogenous vaccines, new regulation of the European Parliament and of the Council Regulation (EU) 2019/6 on veterinary medicinal products

Introduction

On 25/26th September 2017 a joint workshop titled “Autogenous Vaccines and Their Role in Animal Health Strategies”, organized by the International Alliance for Biological Standardization and the University of Gent, discussed the legal situation of autogenous vaccines in Europe in comparison to registered veterinary medicinal products. Representatives of the animal health industry and national authorities as well as the European Commission desired changes to the current legislation for veterinary medicinal products, based on experience with respect to the functioning of the veterinary medicines market, administrative burdens for registered products, scientific progress and protection of animal and public health.

In contrast to registered vaccines, autogenous vaccines are always inactivated and only allowed to be used locally, on one holding under exceptional circumstances, when a registered vaccine against an indication in a target animal is not available. The market for autogenous vaccines therefore is rather small, but their fast availability allows the veterinarian to quickly respond to new diseases or to diseases, against which no registered product is available. Batches of autogenous vaccines are rather small as they are herd and customer specific products.

Legal Situation of AV in Europe

Commission Directive 2001/82/EC as amended regulates the manufacture, control, placing on the market, import, export, supply, use and pharmacovigilance of veterinary immunologicals. It guarantees the quality of veterinary medicinal products manufactured within the Community by requiring compliance with good manufacturing practice. Each veterinary medicinal product must be authorized before being placed on the market.

Autogenous vaccines (AV) are also defined in this Directive 1), but are excluded from its scope. The consequence of this exclusion is that AVs 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.

In Germany the Animal Vaccines Act of 2006 (TierImpfVO 2006) requires that manufacturers of AV have a manufacturing authorization, issued only after inspection by the local authorities responsible for GMP. All batches manufactured must be notified to the authority responsible for GMP and includes the identity of the prescribing veterinarian, the operation of destination, target species and quantity supplied. In addition the German federal states have published a so-called “Question and Answer Paper” which includes recommendations for manufacturers and users of veterinary autogenous vaccines. However, the recommendations are not legally binding. A vaccine registration procedure including dossier evaluation for AV is currently not required in Germany. Some EU-member states hardly have any equivalent regulations. Most extensively regulated are autogenous vaccines in the United Kingdom.

Legal Situation in the UK

AVs are regulated in the Veterinary Medicines Regulation 2013 as amended. Manufacturers and their product intended to be placed on the market must be authorized by providing to the Veterinary Medicines Directorate (VMD) an application dossier that includes detailed quality documentation. Further manufacturers must either provide a GMP-certificate or ask the VMD for an inspection of the production and quality control facilities as part of the approval procedure. The need and use of autogenous vaccines in preference to UK authorized products must be soundly justified by a UK veterinarian.

Although mainly bacterial autogenous vaccines are used, also viral vaccines can be licensed. As the first manufacturer Vaxxinova GmbH in Cuxhaven received the license for the manufacture and use of autogenous Fowl-Adenovirus vaccine in the UK in 2015. Testing of viral isolates for extraneous agents as specified in the European Pharmacopoeia using validated methods is self-explanatory.

The mentioned UK-regulations on one hand seem to be a significant administrative burden to AV-manufacturers and veterinarians aiming to use AV in emergency situations. The consideration of the nature of the animal production industry on the other hand allows vaccine applications within larger epidemiological units and the use of the same isolate to produce further batches of vaccine on a quality risk basis. Each batch of vaccine must be tested for safety on-site on a small number of animals, before release of product. Adverse Reactions are notified to the Secretary of State within 15 days of learning the reaction. An overview of the requirements within some EU-countries is summarized in table 1.

Steps towards Harmonization in Europe

The “Recommendations for the manufacture, control and use of inactivated autogenous veterinary vaccines within the EEA” issued by the veterinary Coordination Group for Mutual recognition and Decentralised Procedures (20th March 2017) were a first step on European level to harmonize standards for autogenous vaccines. However these are currently not legally binding unless member states individually have included principles like these in their national law (e.g. the UK, Denmark, Hungary).

In a second step the conclusions of the Gent workshop were directly forwarded to the European Commission and included in a compromise “Proposal for a Regulation on veterinary medicinal products” by the European Parliament and the Council of the European Union on 5 June 2018. The new Regulation came into force in Jan 2019.