This category of veterinary medicinal product has a derogation from the prior marketing authorisation requirement (Article L.5141-5). 

Its preparation and use are strictly regulated by the rules. 

Its limitation period forms part of the cascade (Article L.5143-4, Article R.5141-141). 

Its preparation is subject to prior authorisation by Anses (CSP Article L.5141-12). It is issued to a person or a body for premises where the activities are actually carried out under the responsibility of a qualified person, veterinary or pharmacist, with professional experience in the field of immunology or manufacture of medicinal products. It shall be issued for a period of five years, renewable for a period of five years, on the basis of a descriptive file and after an administrative and technical enquiry. It mentions the pathogens by animal species of destination for which it is issued (CSP Articles R.5141-130 to 133).

Establishments for the preparation of autovaccines for veterinary use are veterinary pharmaceutical establishments subject to an authorisation issued by the ANMV. They must operate in accordance with the rules laid down in the Code de la Santé Publique and the Good Practice for the Preparation of Autovaccines for Veterinary Use (Ministerial Decree of 6 March 2008 (PDF), as amended by the Order of 14 November 2016 (PDF), published in the Official Journal on 31 January 2017).

The authorisation may be varied, suspended for a maximum of one year or withdrawn if there is a risk to public health, non-compliance with the rules or when a vaccine obtains a marketing authorisation for one of the pathogen pairs — destination species considered (CSP Article R.5141-136).  

The rules prohibit in principle the preparation of autovaccine for a combination pathogen/animal species for which a vaccine has a marketing authorisation in France (Article L.5143-4).

However, it allows companies with an authorisation to prepare autovaccines to apply for a derogation in the event of therapeutic insufficiency declared by the prescribing veterinarian to Antwerp (Anses) or technical impossibility to use this duly justified vaccine. The use of a self-vaccine is then the second intention. The derogation, valid for breeding and the combination pathogen/animal species concerned, shall be limited to 18 months, renewable upon written request.

The holder of an authorisation for the preparation of a veterinary autovaccine may give up autovaccines only to the veterinarian prescribing the holding concerned or to any other veterinarian who has declared the same place of business as that veterinarian (CSP Article R.5141-141).  

A Guide of Good Practice for the Prescription of Vaccines for Veterinary Use (GBPPA), drawn up by SNGTV, is available online to all veterinarians registered in the Association on the SNGTV website.

The link is: sngtv.org/— section “Veterinary medicine/Vaccines, autovaccines”.

The conditions for the preparation of autovaccines for veterinary use for ruminants are set out in the Orders of 14 November 2016 published in the Official Journal on 31 January 2017.

Statements of therapeutic failures are to be made by teledeclaration at the following address : pro.anses.fr/notificationMV 

To access the thematic file

The Order of 14 November 2016 on the preparation of autovaccines for veterinary use intended for ruminants, published on 31 January 2017, authorises the use of autovaccines in ruminants under certain conditions to ensure health safety.

Following the Anses opinion of May 2016 on “risk assessment, in particular prion transmission, in case of authorisation of the use of autovaccines in ruminants (PDF)”, the ministries wanted to lift part of the ban on preparing and prescribing autovaccines in ruminants. Two orders were published in the Official Journal on 31/01/2017, one repealing the Order of 2 December 2003 prohibiting autovaccines in ruminants, the other amending the Order of 6 March 2008 on good practice in the preparation of autovaccines for veterinary use .

The prescription of bacterial autovaccines in ruminants and their preparation by authorised laboratories becomes possible in the absence of authorised vaccines available, or where the latter have been subject to declarations of inefficiencies supported by a pharmacovigilance declaration.

The Anses report concluded that the likelihood of transmission of the prion via the use of autovaccines in ruminants was almost zero provided that several precautions were taken in relation to samples taken on farm, bacterial isolations, preparation and administration of those autovaccines. These arrangements correspond to those taken into account in the risk assessment and have been translated into legislation to ensure a high level of safety. 

Bacterial autovaccines in ruminants can only be administered via oral, intra-muscular and subcutaneous routes. Other routes of administration present a higher risk of prion transmission or have not been considered in the referral.  

In livestock farming, autovaccine can only be given to the same ruminant species as that of the animal taken, so it is not possible in a farm composed of different ruminant species to administer a self-vaccine prepared from a sample from another ruminant species of the same farm, as the variability of heterogeneous infections has not been studied.

The matrices on which samples may be taken are subject to restrictions. Usable matrices are those studied in the context of the referral and for which an acceptable level of risk could be established. 

In cattle, the central nervous system from animals less than twelve months old, milk, blood, urine, faeces, lung and bronchoalveolar washing liquid, pus, placenta, joint liquid, liver, spleen, lymphatic nodes, intestines and tear swabs can be taken. 

In small ruminants, the central nervous system of animals less than three months old, milk, faeces, blood and urine may be taken. 

There are differences between the matrices that can be used in cattle on the one hand and sheep/goats on the other hand, linked to different levels of tissue infectivity in these species. 

The other matrices authorised in bovine animals could not be retained in small ruminants on the one hand because of levels of infectivity considered to be significant (e.g. Foetal annexes, lymphoid tissues) or by analogy with a tissue at risk (e.g. Presence of Gut Associated lymphatic Tissue (GALT) — and Bronchus Associated Lymphoid Tissue (BALT) respectively in intestines and bronches).

However, where the genotyping of the ovine/caprine animal taken establishes proven resistance to transmissible spongiform encephalopathies, all matrices except the central nervous system of animals over three months old may be taken. 

Article 3 (II) of the Order states that veterinary autovaccines from ovine or caprine animals whose genotyping indicates resistance to transmissible subacute spongiform encephalopathies may be prepared on the basis of samples taken from matrices other than the central nervous system of ovine or caprine animals more than three months old. 

Polymorphisms to codons 136 (A/V), 154 (R/H) and 171 (R, Q/H) of the PNRP gene have a major effect on sheep’s susceptibility to classical and atypical scrapie agents and BSE. Anses-ANMV considers that only the following alleles comply with Article 3 (II) of the Order of 14 November 2016 referred to above: ARR/ARR; ARR/AHQ; ARR/ARQ; RRC/VRQ

Polymorphisms to codon 222 of the PNRP gene have a major effect on the susceptibility of goats to classical scrapie agents ⁽¹⁾. Anses-ANMV considers that only the K222 allele (Lysine au codon 222) complies with Article 3 (II) of the Order.

In the form accompanying the sampling, the veterinarian must provide, in addition to the details of the holding, the species, sex, identification number and age of the animal taken, the matrix taken and also certify that the animals taken have not shown neurological signs or that they can be linked to a cause other than a TSE. 

Laboratories preparing autovaccines have obligations in addition to the rules currently in force and will have to apply to Anses-ANMV for amendment of their authorisation if they wish to prepare autovaccines for ruminants. These additional obligations are:

• complete at least 8 passages prior to the preparation of autovaccines or prior to storage of the strain to ensure sufficient dilution;
• use single-use equipment for these first 8 passages to ensure the absence of iatrogene transmission;
• use for the preparation of autovaccines of biological raw materials (other than bacteria) certified in accordance with the European Pharmacopoeia monographs to ensure that there is no cross-contamination, if derived from ruminants.

The Decree also lays down an obligation to include on the labelling of the self-vaccine ‘the name of the holding concerned by the exclusive use of this self-vaccine’ in addition to the provisions already in force in Article R.5141-139 of the Code de la Santé Publique. 

These new provisions, which make it possible to improve therapeutic arsenal in the absence of authorised vaccines available, are a step forward in the context of the reduction of antibiotic use and the search for alternatives. 

It should be noted that another Order of 2 December 2003 prohibiting the execution, supply, prescription, administration to animals, import and export of extemporaneous veterinary preparations and veterinary magistral preparations based on products of bovine, ovine or caprine origin is therefore still prohibited.

To access the thematic file

(1) Anses 2013-SA-0231, page 33/107 and EFSA’s Scientific Opinion EFSA-Q-2016-00268