Download Measure 15 of the French EcoAntibio Plan: autovaccines

Measure 15 of the French EcoAntibio Plan: autovaccines for
ruminants are re-approved in France
Autovaccines have been banned in ruminants in France since 2001 following the socalled ‘mad cow’ disease crisis, for fear that the material collected from an infected
animal could transmit prion disease. Since 2011, their return has been announced
under the national EcoAntibio Plan (measure 15) in order to reduce antibiotic use in
diseases that might be prevented by autovaccination. They are now officially approved
again since February 1st 2017, with a few minor restrictions on the nature of samples
(see table). French autovaccine manufacturers (Biovac, Filavie, Labocea) are
required to update the list of pathogens against which they are able to prepare
autovaccines in order to include pathogenic bacteria of ruminants. The list has been
validated by the National veterinary medicines agency (ANMV).
The French Official Journal of 31 January 2017 published two orders signed on 14 November
2016 reapproving autovaccines in ruminants. These orders put an end to a fifteen-year ban on
autovaccines in these species, due to a possible risk of transmission of transmissible subacute
spongiform encephalopathies (TSSEs).
The return of autovaccines was eagerly awaited. Because they were already mentioned late
2011 under measure 15 of the national EcoAntibio Plan 2012-2016. The French Health and
Food Safety Agency (Anses) also gave two favourable opinions on the return of the
autovaccines, in 2013 and in 2016.
However, veterinarians can only prescribe autovaccines as a last resort under the cascade, i.e.
only in the absence of efficacious vaccines authorised in France (or, if needs be, with a
marketing authorisation in another European country if the vaccine has obtained an import
licence for France).
A positive list of authorised samples
To avoid the risk of transmitting TSSE, autovaccines can only be based on material listed in
the table below. Other origins are therefore excluded.
Authorised material for bovine
autovaccines
 Milk
 Blood
 Urine
 Faeces
 Lungs and broncho-alveolar liquid
 Pus
 Placenta
 Synovial fluid
 Liver
 Intestines
 Spleen
 Lymph nodes
 Lacrimal swab
 Central nervous system of cattle under
twelve months of age.
 Animals without nervous signs (unless
their origin is known and 'guaranteed'
Authorised material for autovaccines
for sheep or goats
 Milk
 Blood
 Urine
 Faeces
 Central nervous system from sheep or
goats under three months of age.
 Any material if the genotype of the
animals sampled indicates 'a resistance
to TSSEs', with the exception of the
central nervous system of goats or
sheep over three months of age.

Animals without nervous signs (unless
their origin is known and 'guaranteed'
and excludes a TSE).
and excludes a TSE).
According to the 2016 Anses opinion, the material that may be used for the preparation of
autovaccines for cattle are 'mainly and by decreasing order of frequency':
 Milk (against mastitis),
 Lungs and broncho-alveolar liquid (against respiratory diseases),
 Faecal material (against digestive infections),
 Pus,
 Placenta and lochia.
All these materials are therefore allowed for the manufacturing of autovaccines.
For sheep and goats the restrictions on material are a little more complicated than for cattle. In
practice, in the case of mastitis, autovaccines are authorised on the basis of milk of all animals.
However, a proven 'TSSE-resistant' genotype is required for the collection of pus, lymph
nodes and placenta.
Veterinary certification of collected material
In order to ensure the respect of these requirements, the veterinarian performing the sampling
must complete a form of which the template is shown in the annex of the order.
This document mentions:
 The origin of the sample: species, age, gender, identification number and above all, type
of material, and for goats and sheep, the result of genotyping.
 Farm address.
 Veterinarian's address and signature.
'This document should accompany the sample to the manufacturer of the autovaccines', who
must keep it for 5 years. 'A copy should also be kept in the farm register for 5 years.'
There is no obligation for the veterinarian to keep a second copy.
Single-species bacterial autovaccines
Three further restrictions that do not pose any particular problems are:
1. Only autovaccines based on bacteria are permitted. Antiviral or antiparasitic autovaccines
for ruminants are therefore prohibited. In practice, the national veterinary medicines
agency (Anses-ANMV), which confirms the list of pathogens that may be included in
autovaccines, has never accepted the addition of viruses, even for non-ruminant species.
However, the legal definition of autovaccines does not, a priori, prohibit autovaccines if
they are inactivated.
2. Autovaccines for ruminants can only be administered to animals of the same farm as the
sample - that is part of the definition of autovaccines - and only to ruminants of the same
species. For example, in a mixed cattle-sheep or sheep-goat farm, if an autovaccine is
manufactured on the basis of a sample taken from sheep, this 'sheep' autovaccine cannot
be used in cattle or goats from the same farm, but only in sheep.
3. Autovaccines can only be administered by injection (subcutaneous or intramuscular) or by
mouth. Since autovaccines are inactivated, they are generally administered by SC or IM
route and not by mouth.
The control of Anses on autovaccine manufacturers
Autovaccine manufacturers are approved by the National veterinary medicines agency
(Anses-ANMV) for renewable periods of five years, on the basis of competencies of the
qualified person in charge (a veterinarian or a pharmacist) and of the equipment. An order of
6 March 2008 provides details of the good manufacturing practices for autovaccines required
of the manufacturers. It has now been slightly amended to provide for autovaccines for
ruminants.
The approval of the manufacturers includes the list of pathogens against which they are
allowed to prepare autovaccines. For manufacturers who wish to prepare autovaccines for
cattle, sheep or goats, the list should be updated to include pathogenic bacteria for these
species. The production of an autovaccine takes several weeks.
For the production of ruminant autovaccines, the following is required:
 At least eight passages in liquid or solid medium, while 'minimising the sample for each
passage' and using single-use material,
 The use of raw material complying with the monograph of the European Pharmacopoeia
on the risk of TSE, except, of course, the bacterium isolated from the sample.
Among the approved manufacturers, Biovac, recently acquired by Ceva, prepares
autovaccines for all animal species. Filavie belongs to the Grimaud group and is more
specialised in the poultry, rabbit and pig sectors. The Côtes-d'Armor departmental laboratory,
Labocea 22, mainly produces autovaccines for poultry and pigs. Finally, the Ille-et-Vilaine
laboratory, Labocea 35, no longer seems to produce them.
Sources:
Order of 14 November 2016 concerning the preparation of autovaccines for veterinary use in
ruminants (OJ of 31/01/2017). Document in French
https://www.legifrance.gouv.fr/affichTexte.do?cidTexte=JORFTEXT000033956149&dateTe
xte=&categorieLien=id
Order of 14 November 2016, amending the Order of 6 March 2008 concerning the good
manufacturing practices of autovaccines for veterinary use (OJ of 31/01/2017). Document in
French
https://www.legifrance.gouv.fr/affichTexte.do?cidTexte=JORFTEXT000033956145&dateTe
xte=&categorieLien=id
Opinion and report of Anses on the risk assessment, in particular of the transmission of prions,
in case of the authorisation of the use of autovaccines in ruminants (May 2016). Document to
be downloaded (pdf, in French):
https://www.anses.fr/fr/system/files/SABA2013SA0231.pdf
Regulation on autovaccines (in French). Articles R. 5141-129 to D. 5141-142 of the French
Public Health code.