How to get a Specific Manufacturing Authorisation: Autogenous Vaccine (AVA), Non-Food Animal Blood Bank (NFABBA), or Equine Stem Cell Centre (ESCCA) (formerly in VMGN 15).
Guidance on how to get an Autogenous Vaccine Authorisation (AVA), Non-Food Animal Blood Bank Authorisation (NFABBA), or Equine Stem Cell Centre Authorisation (ESCCA) - collectively known as Specific Manufacturing Authorisations.
The manufacturing premises and the method of production must be the subject of a valid AVA for autogenous vaccines manufactured from pathogens or antigens obtained from an animal/s and used for the treatment of that animal and/or other animals within the same epidemiological unit or in the same rearing chain.
An AVA will only be granted if:
- the product has been inactivated. It is expected that most authorisations will relate to the manufacture of bacterial vaccines. Additional safeguards will be required in respect of most viral vaccines
- the VMD is satisfied that the production process will produce a consistent, safe product
- the premises are under the supervision of a person who has sufficient qualifications and experience to manufacture the product safely
- a veterinary surgeon has confirmed a need and fully justified the use of the AVA in preference to UK authorised products
Manufacturers of autogenous vaccines may apply for two different types of authorisation; AVA-I (Individual), or AVA-S (Standard).
An AVA-I covers the production of a single batch of product; an AVA-S covers the on-going production of the products specified in the authorisation.
Viral Autogenous Vaccines
In the case of viral autogenous vaccines there is a need for a technical framework to give assurance that the associated risks are suitably controlled and that the final vaccines are free from contamination.
The requirements for the authorisation of these types of vaccines are:
A Manufacturing standard such as a full GMP certificate or inspection from a VMD inspector. Where a viral vaccine is being produced at a GMP compliant site within the EU, the VMD retains the right to address specific manufacturing issues with the national competent authority and if necessary to carry out a site inspection. This is because although GMP requirements are harmonised, production is not conducted to a harmonised set of requirements such as extraneous agent testing and validation of inactivation kinetics.
Assurance that the vaccine is an autogenous vaccine, ie. the vaccine is manufactured from pathogens or antigens obtained from an animal/s and used for the treatment of that animal and/or other animals within the same epidemiological unit or in the same rearing chain. The nature of the animal production industry where the vaccine is intended to be used should be taken into account. The use of the same isolate to produce further batches of vaccine would be on a quality risk basis and tested to determine similarity.
Complete testing of cell seed to Pharmacopoeia European requirements.
Inactivation kinetics validation. This must cover the agent in the vaccine but also all possible sources of contamination from the isolate itself as well as potential sources of cross contamination. A risk assessment approach to those viruses which are not likely to be present can be conducted taking into account the geographical source of the isolate, the health status of the animals from which the isolate originated, other isolates handled in the plant and the range of extraneous agents testing of starting materials. A condition of authorisation would include the obligation to update this assessment and validation as appropriate, when any new isolates/starting materials are handled at the plant.
Extraneous testing of the final product to Pharmacopoeia European requirements where not justified by inactivation kinetics. It may be possible to have derogations on the degree of testing depending on the range of agents covered by the inactivation kinetics validation package and the risk assessment.
Batch safety test using a double dose of vaccine to be conducted on the site of use of the vaccine with satisfactory results before use of the vaccine batch in the entire group of animals.
Validation of any tests used for extraneous agents testing should be provided.
Blood Banks (NFABBA)
An NFABBA authorises the collection, storage and supply of blood for use in non-food producing animals to meet unforeseen or exceptional needs. The authorisation also permits the blood to be placed onto the market without the need for a Marketing Authorisation (MA) as long as no medicinal claims are made.
NFABBA holders must be established in the United Kingdom.
The storage and supply of blood constituents obtained by the physical separation of donor blood into different fractions within a closed-bag system is also acceptable under this scheme.
Any other means of production of blood products should only be done under a full Manufacturing Authorisation (ManA) and, or an MA.
An NFABBA will only be granted if the VMD is satisfied that:
- the welfare of the animals used in the collection of blood will be respected
- the production process will produce a consistent, safe product
- the blood bank is under the supervision of a veterinary surgeon, or a person that is suitably qualified to operate the blood bank
Stem Cells (ESCCA)
An ESCCA authorises premises in the UK used for the collection, storage, processing, production and administration of equine stem cells for use as an autologous treatment for non-food producing horses.
It covers manufacturers that operate a cryo-storage facility, or bank of equine derived stem cells, or manufacture stem cells derived products.
An ESCCA will only be granted if the VMD is satisfied that:
- the welfare of the animals used in the collection of equine stem cells will be respected
- the production process will produce a consistent, safe product
- the centre is under the supervision of a veterinary surgeon, or a person that is suitably qualified to operate the centre
With the exception of an AVA-I, an authorisation will be valid continuously subject to satisfactory re-inspection of the premises.
The frequency of the inspections will be risk-based and derived from the performance of the authorisation holder at the last inspection.
An AVA-I will be valid for one year from the date it was granted.
The single batch of vaccine covered by the AVA-I must be manufactured and placed on the market before the expiry of the authorisation.
You must submit a variation application to the VMD if you intend to make any changes to an authorisation that could impact upon the quality, safety or efficacy of the products manufactured.eg. registered personnel changes, premises alterations, change of site.
An AVA-I may not be varied. The holder of an AVA-I will be required to submit an application for a new authorisation if any of the details change.
Post Authorisation steps
Your authorisation may be varied, refused, suspended or revoked if:
- you have not complied with the Veterinary Medicines Regulations (VMR)
- you have manufactured a Veterinary Medicinal Product (VMP) which is not covered by the authorisation
- you have produced a VMP outside the terms of the authorisation
- the premises or equipment are no longer suitable
Where it appears to the VMD that animal or public safety is at risk it may suspend an authorisation with immediate effect for a period of up to three months. This suspension may be renewed for further periods of up to three months if the VMD considers this necessary.
Obligations on holders
You are subject to a number of obligations in relation to the labelling of containers of autogenous vaccines, recordkeeping, and the reporting of adverse reactions. The requirements for each are outlined in the VMR.
Autogenous vaccines may not be released onto the market before a target animal safety test has been conducted on the premises on which it is intended to administer the vaccine.
Holders of an AVA-S are subject to batch release requirements. The VMD must be notified every time a batch of autogenous vaccine has been placed onto the market. It should be noted that a product may not be placed onto the market until a satisfactory on-farm safety test result has been achieved.
You are subject to a number of obligations in relation to the supply and administration of blood and blood constituents from a blood bank, labelling of containers of blood, record-keeping, and the reporting of adverse reactions. The requirements for each are outlined in the VMR.
You should ensure that the health and welfare of the donor animals is respected at all times. In setting up a blood bank it is expected that the animals used as donors will be rescue animals waiting for re-homing or pet animals, and that the blood donation procedure will not require animal sedation.
If the donor animals are kept in a colony for the specific purpose of blood donation, or the blood donations require sedation of the animal, then an application for a Home Office Licence under the Animals (Scientific Procedures) Act (ASPA) 1986 and an NFABBA from the VMD will be required.
Donor animals should be tested for the absence of certain diseases that may pose a potential risk to transfusion recipients. These tests should be conducted in accordance with veterinary guidelines or following an appropriate risk assessment to ensure that the risk of disease transmission to transfusion recipients is minimised.
Donor animals must be certified by the attending veterinary surgeon in relation to their health status at the time of donation.
Home Office and Royal College of Veterinary Surgeons (RCVS) best practice criteria are outlined in Criteria for Use of Blood Donors for NFABBAs.
You are subject to a number of obligations in relation to the supply and administration of stem cells, labelling of containers of stem cell products, record-keeping, and the reporting of adverse reactions. The requirements for each are outlined in the VMR.
You should ensure that the health and welfare of the horses is respected at all times.
Criteria for use of blood donors
The following criteria has been agreed with the Home Office and the RCVS.
- Donations should take place under the supervision of a veterinary surgeon in premises including but not limited to a veterinary practice, farm or specifically adapted vehicle that provide the appropriate standard of hygiene for the procedures being performed. In addition the appropriate emergency backup must be available should it be required.
- All donations should adhere to the strict procedures detailed in the company’s approved procedures.
- All donors should be uniquely identified and records kept of all donations to ensure that donors that present problems at donations can be identified and excluded from further donations where appropriate.
- Donors should donate at no greater frequency than 8 weekly intervals.
- Only donors that are in a good state of health will be able to donate.
The donor should be examined by a veterinary surgeon prior to blood collection to ensure the animal is in a good state of general health. The examining veterinary surgeon is responsible for ensuring blood is only taken from animals with no history of: - surgery - medical conditions - taking any medication
that could have a detrimental effect on the donor or subsequent recipient. The veterinary surgeon is responsible for ensuring no changes have taken place since the last donation that could have a detrimental effect on the donor or subsequent recipient.
- Animals that are pregnant or nursing are not permitted to be blood donors.
- Any blood product not used should be disposed of as waste material.
- The donor should be closely monitored during the donation process. After donating, measures should be taken to reduce risk of haematoma and infection.
- Donors should be clinically examined after donating and monitored for signs of adverse effects. First time donors should remain under observation for at least 30 minutes post donation and repeat donors for no less than 15 minutes post donation. Post donation instructions should be provided including contact details of an emergency veterinary surgeon in the event of a delayed adverse reaction.
Additional criteria for Dogs
- Only dogs that are in a good state of health, do not appear stressed, are compliant and settled and can be handled without excessive restraint will be able to donate.
- Dogs should never have travelled outside the UK and Ireland.
- Dogs must not be sedated to facilitate donations.
- The donor dog must weigh a minimum weight of 25kg at the initial donation to allow the collection of 450ml +/-10%. Subsequent donations may be taken from the donor dog weighing 5% less than the original bodyweight (ie an absolute maximum of 495mls can be taken from a dog which must weigh at least 23.75kg). The examining veterinary surgeon must take into account the donor’s breed, activity level and haematological levels by measuring packed cell volume and/or haemoglobin levels before allowing the donation to proceed.
Additional criteria for New World Camelids (Alpaca, Vicuna, Llama and Guanaco)
- Only donors that are in a good state of health will be able to donate, herd health information including known disease status should be reviewed.
- The camelid’s travel history should be documented; any camelid imported from outside of the UK and Ireland within 12 months should not be used as a donor.
- Camelids may be chemically restrained to facilitate the collection of blood as long as the veterinary surgeon deems that it is in the best interest of the camelid. When deciding this, the veterinary surgeon should take into account if other more suitable donors are available from the herd.
- Blood collected and the products produced from the blood should only be used within the herd where the donating camelid resides.
- The donor must weigh a minimum weight of 50kg at the initial donation to allow collection of 450ml +/-10%, the examining veterinary surgeon must take into account the donor’s species and activity level before allowing the donation to proceed, haematological levels by measuring packed cell volume and/or haemoglobin levels should be measured prior to or retrospective to the donation.
- Donors who have had chemical restraint must be closely monitored until the veterinary surgeon is confident that no adverse reaction has taken place and that the animal has fully recovered from sedation.