When you need an Animal Test Certificate
You need an Animal Test Certificate (ATC) to carry out a veterinary field trial with a Veterinary Medicinal Product (VMP) under development or a VMP used outside of the terms of its marketing authorisation.
EU Directive 2001/82 defines a veterinary medicinal product as: (a) any substance or combination of substances presented as having properties for treating or preventing disease in animals; or (b) any substance or combination of substances which may be used in or administered to animals with a view either to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.
You must submit an application for an ATC to the VMD.
An ATC permits:
the use of a veterinary medicine outside of the terms of its marketing authorisation (MA) during a veterinary field trial (‘off label’ VMP use) or the administration of an unauthorised VMP, e.g. in a clinical trial for a potential MA application
the procurement and supply of that VMP
the import of any VMP specified in the certificate in accordance with the conditions
produce from treated animals to enter the food chain if appropriate
Assessment
Before an ATC can be granted a benefit: risk assessment for administration of the medicine will be conducted based on submitted data. Adequate safeguards must be provided to ensure the safety of participating animals, users, consumers and the environment (where applicable). In addition, field trial protocols will be reviewed for compliance with Good Clinical Practice (GCP). All trials must be carried out in compliance with UK animal welfare legislation.
A veterinary field trial will assess the safety and/or efficacy of a VMP under conditions of field use and will usually be conducted in client-owned animals. Assessment of the field safety and/or efficacy of a product may include, for example, taking a blood sample prior to the administration of a veterinary medicine to establish a baseline for parameters. Also, subsequent sampling at key points following administration of the veterinary medicine to monitor these parameters where justified. It is also anticipated that the test product will be compared with a control, so a field trial may include a group of animals designated as positive controls and treated with either an existing medicine or an established procedure, or a group of animals designated as negative controls and treated with a placebo.
An ATC may not be required in the following cases:
field trials involving food-supplements (‘nutraceuticals’) that are not VMPs or other non-medicinal therapies such as surgical interventions
field trials carried out by a veterinary surgeon where the veterinary medicine under investigation will be administered in accordance with the Summary of Product Characteristics (SPC) or the product will be administered in accordance with the provisions of “the cascade”. For further information, refer to The Cascade: Prescribing unauthorised medicines.
An ATC is not required for a Home Office licensed study including laboratory studies of a VMP conducted in animals that have been declared as not to enter the food chain where that study is authorised in full under the appropriate Home Office licence. However, should you intend for the produce from animals treated during a Home Office licensed study to enter the food chain an ATC will be required, whether treated with an unauthorised VMP or a VMP used ‘off label’.
Further information on how investigations are regulated under Home Office licences is available from the Home Office Animal (Scientific Procedures) Inspectorate.
Number of trials and products per ATC
Each trial requires a separate ATC as it should normally only investigate one therapeutic indication in a single species. Exceptions to this include trials of ectoparasiticides, endectocides, or multivalent vaccines.
A trial may involve more than one product if:
the second product is a placebo, or a positive control which is authorised for that species and indication in at least one EU or European Economic Area (EEA) Member State. A human product may be used as a control product where its use is well supported by literature references and there is no suitable authorised veterinary medicine
the products are of the same pharmaceutical form and contain the same ingredients, but differ in strength or dosage of the active or inactive ingredients
for vaccines the products differ only in the inclusion or exclusion of particular antigens under investigation
the products are of two or more dilutions of either the same allergen extract or mixture of allergen extracts used for desensitisation therapy; or the products used for in-vivo diagnosis of an allergy are manufactured by the same method from closely related substances, e.g. pollen
more than one product is expected to be required to produce therapeutic efficacy such as sedative or analgesic combinations or allergens
Types of ATC applications
ATCs are divided into three types according to the complexity of the trial. For further information on which type you may need please refer to
Annex A - What type of ATC do I need?
(PDF, 75.2KB, 2 pages)
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The Type A or B procedures are appropriate for pharmaceutical companies wishing to generate data to support an application for an MA for a veterinary medicine. You will be required to confirm that the trial will be carried out in accordance with the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) Topic 9: Guideline on Good Clinical Practices.
Trials conducted under a Type S ATC should, where possible, be conducted in accordance with GCP. As these trials are specifically intended for small scale non-commercial research trials conducted by vets this may not be possible in all situations. To ensure robust study design and appropriate consideration of how to reduce, refine and replace the use of animals, the work should be subjected to an ethical review and conducted to recognised quality standards for published research, such as the Defra Joint Code of Practice for Research (JCoPR) March 2012. On completion it is expected that the work will be reported in compliance with the principles set out in the “Animal Research: Reporting In Vivo Experiments (ARRIVE)” Guideline (Kilkenny et al (2010))”.
Type A
This procedure is used where the product is already authorised as a human or veterinary medicine in the EU or EEA and is either:
an immunological product and the field trial is to be conducted in species included in the existing marketing authorisation, or
a pharmaceutical product and
the trial is to be conducted in companion animals, or
the trial is to be conducted in food-producing species and the existing MA is for the same species and the same or similar dosing regimen and method of administration
Type B
This procedure is used if the product does not meet the criteria set out for Type A.
Type S
This procedure is used for small-scale non-commercial trials involving no more than 50 animals. More than 50 animals may be used where justified for meaningful statistical analyses as part of the trial design in the product treatment group. These are carried out by researchers or practicing vets investigating the safety and/or efficacy of human or veterinary pharmaceutical products that are authorised in the EU, EEA, USA, Canada, Japan, New Zealand or Australia.
If you wish to use an immunological product that is not subject of a valid MA in the EU or EEA, contact the VMD before submitting an application under the Type S procedure.
You should contact the MA holder of the product before undertaking any trials using that product.
How to apply
Prior to submission
You are welcome to contact the VMD to discuss your proposed application. If you wish to arrange a meeting, please email: postmaster@vmd.defra.gsi.gov.uk and include ‘Request to arrange a company meeting’ in the subject line.
You must contact the VMD for advice prior to submission for applications involving veterinary medicines containing or consisting of genetically modified (GM) organisms. A medicinal trial in animals involving the deliberate release of genetically modified organisms into the environment requires both an ATC and consent granted by the Secretary of State for the Environment; a Part B experimental release under Directive 2001/18/EC. The GM Team of Defra is the UK Competent Authority implementing that Directive.
Consent for the Part B release is required before a trial may start. This may take up to 90 calendar days with the addition of any clock stops if information is needed from the applicant so you will need to apply well ahead of the ATC application.
Submission
You can submit your application electronically, or in hard-copy. More details can be found on the Submission of an application for an animal medicine licence page
Application Form
Application forms are available on the Apply to run a clinical trial using an animal medicine page.
Supporting Data
Do not submit any data or information that have not been asked for; doing so will delay the application process.
The data and documents required in support of an application for an ATC are listed in the application forms.
You must provide an explanation of the purpose of the proposed trial.
Evidence of an ethics committee approval should be provided, if available.
Data to support target animal safety are required for all applications except Type A where there is an existing EU authorisation for the same species using the same indications and dose regimen.
Reference to laboratory efficacy or challenge studies may be necessary.
Applicants may make cross-references to relevant studies in the dossier of an authorised veterinary medicine, which is held by the VMD and to which you have a right of access.
Trials to be conducted under an ATC obtained via a Type B procedure must comply with the latest version of the joint Committee for Proprietary (Human) Medicinal Products / Committee for Veterinary Medicinal Products guideline on, ‘Minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products’ – EMEA/410/01. You must provide relevant information including a signed declaration in the appropriate format together with a Certificate of Suitability.
The VMD will not approve trial protocols, except to ensure that safety issues are adequately addressed. The applicant must ensure that the results of trials carried out under ATCs will be appropriate for any subsequent applications for an MA.
Consent form
A blank example owner consent form must be submitted as part of an ATC application.
Informed consent is a documented process by which an owner, or owner’s agent, voluntarily confirms the owner’s willingness to allow their animal(s) to participate in a particular study, after having been informed of all aspects of the study that are relevant to the decision to participate. The consent form should be in easily understandable language (i.e. minimising and explaining medical jargon) for the owner and include at least the following:
the owner’s consent to the inclusion of their animals into the clinical trial
explanation that the owner understands:
the nature of the trial and the purpose of the treatment
that their animals are participating in a clinical trial using a medicine that has not been authorised or is being used ‘off-label’
if a negative control or placebo is being included that their animal may not receive treatment as part of the trial
they may withdraw their animal from the trial at any time without any prejudice for the future veterinary care of the animal
a statement from the vet concerned confirming that if the animal is not responding to treatment that they may treat the animal at any time to maintain appropriate level of veterinary care
confirmation that the owner has fully understood the consent form
Labelling
The requirements for product literature are set out in the Product Literature Standard (PLS).
A package leaflet will be required if there is insufficient space on the label to include all required text.
For already authorised veterinary medicines, you should use the approved labelling, but a small over label should indicate any amended directions / warnings, the ATC number, and the words, ‘Veterinary clinical trial use only’ to ensure accountability in line with GCP requirements.
As a general rule, the VMD will expect labels to contain the following minimum information in English:
the words “For veterinary clinical trial use only”
name or other designation of the product
quantity of product
any restrictions on use
expiry date and, if appropriate, in-use expiry date
directions for use specific to the trial including dosage, frequency, duration, method and route of administration
contra indications, warnings and precautions, and special instructions for handling and storing the product
instructions for disposal (in most cases, these should state that any unused product and containers should be returned to the trial sponsor)
if to be used in species used to produce food (including horses, rabbits and pigeons) either the specified withdrawal period or the words “Not to be used in animals for human consumption”
name and address of ATC holder and ATC number
the manufacturer’s batch number
a unique code/number identifying the individual container, where appropriate (e.g. where the identity of the products used in the trial are blinded)
For Type A or B procedures you should provide a draft label and package leaflet text with the application.
For Type S procedures you should submit a statement of user and target species safety warnings to appear on the label/leaflet, but otherwise it is your responsibility to ensure that the labelling/leaflets conform to requirements. Additional guidance on the warnings can be found in the annex of the application form.
A suggested pro-forma for labelling can be found on the Apply to run a clinical trial using an animal medicine page.
Validation
All applications are checked (validated) upon receipt.
It is up to you to identify and submit all the necessary information in support of your application. If the application is incomplete, it is likely to fail validation.
Assessment phase
Once the application has passed validation it will proceed into the assessment phase.
On approval of the application you will be sent a certificate verifying that the trial has been approved and this may be subject to a number of conditions that will be specified on the certificate.
Timescales
The timescales for dealing with ATC applications are as follows:
new Type A/S applications within 30 calendar days of receipt
new Type B applications within 50 calendar days of receipt
variations and renewals within 30 calendar days of receipt
ATC Type A, Type S, variations and renewals:
Validation
Validated within 5 days of receipt.
If the application is incomplete the application will either:
• fail validation and you will be asked to resubmit the application, or
• the validation clock will stop and you will be asked to provide the outstanding data. Once received the validation clock returns to 0
Initial assessment
Approved, refused or questions asked by day 15. Whatever the outcome you will be informed.
Applicant response
If questions asked, you should provide a full company response within 10 days from the date of the letter. The clock continues to run during this time.
If a response is not received by the deadline the application will be considered withdrawn.
Sign-off
Upon receipt of the response the VMD has up to the end of the 30 day timeframe to assess the response and either approve or refuse the application.
Issue
Following approval, authorisation documentation will be issued within 5 days of assessor sign-off.
ATC Type B:
Validation
Validated within 5 days of receipt.
If the application is incomplete the application will either:
• fail validation and you will be asked to resubmit the application, or
• the validation clock will stop and you will be asked to provide the outstanding data. Once received the validation clock returns to 0
Initial assessment
Approved, refused or questions asked within 35 days. Whatever the outcome you will be informed.
Applicant response
If questions asked the clock will stop pending receipt of your response. You will be asked to provide a response within a given deadline.
If a response is not received by the deadline the application will be considered withdrawn.
Sign-off
Upon receipt of the response the clock restarts and the VMD has up to the end of the 50-day timeframe to assess the response and either approve or refuse the application.
Issue
Following approval, authorisation documentation will be issued within 5 days of assessor sign-off.
Fees
Once an application has passed validation, you will be sent an invoice for the fee.
For further information regarding fees, see the Fees charged for an application for animal test certificate (ATC) page.
Post authorisation steps
Validity of an ATC
During the validity of the ATC, if evidence becomes available which casts doubt on the safety, quality or efficacy of the product(s) involved, or which alters the benefit:risk assessment the VMD may revoke, suspend or compulsorily vary the certificate.
If the VMD becomes aware that an ATC holder has changed any of the approved specifications of the ATC without the prior approval of the VMD, the ATC will be suspended immediately. The suspension will remain in force until the changes have been approved, or the product is brought into line with the terms and conditions of the certificate.
Renewal of an ATC
An ATC is valid for two years. If the trial is not finished within this timeframe you may apply to renew the ATC. If an ATC is not renewed by the renewal date it will cease to be valid.
There is no formal application form for renewing an ATC.
For Type A and B: You should submit a letter via email requesting renewal of your ATC. The letter should include a justification of why it needs to be renewed, any variations made to the ATC, the ATC number, particulars of the progress of the trial, and a summary account of any adverse events noted.
For Type S: You should submit a letter via email requesting renewal of the Type S. The letter should include a justification of why it needs to be renewed and any adverse events noted.
Email: s.response@vmd.defra.gsi.gov.uk
The timescales for progressing a renewal are the same as those used for a new ATC using a Type A procedure.
For information about renewal fees, see the Fees charged for an application for animal test certificate (ATC) page.
Variation of an ATC
If you wish to make any changes to your ATC, you will need to submit an application to the VMD. The application form is available on the Apply to change an animal test certificate (ATC) page.
Only certain changes may be made by way of a variation (as listed in the application form). All other changes will require submission of a new application; however, where an existing UK trial is being modified, as long as the product formula, species and purpose of the trial remain the same, a Type A procedure will apply.
The timescales for progressing a variation are the same as those used for a new ATC using a Type A procedure.
It is recognised that some tests cannot be set up until an outbreak of a particular disease occurs. In these cases, an ATC may be issued for a maximum number of sites and animals, on the condition that you notify us of the test sites for the exact number of animals included at each site, as soon as they are known. There will be no charge for this.
For information about variation fees, see the Fees charged for an application for animal test certificate (ATC) page.
Pharmacovigilance
You are responsible for reporting adverse events to the VMD and must name a person responsible for pharmacovigilance in your application. This person, usually a vet, must have overall responsibility for investigating any suspected adverse events, monitoring them and, when necessary, reporting them to the VMD. You should ensure that they are notified promptly by the investigators of serious adverse events. Appropriate arrangements should be put in place to ensure that ‘blinding’ of products does not interfere with pharmacovigilance responsibilities.
Any serious adverse events, i.e. any reaction involving a human or which has caused increased mortality or serious ill health in treated animals or birth defects in the offspring of treated animals, to any substance used under an ATC must be reported to the VMD within 15 days. For further information on reporting adverse events, see the Veterinary Pharmacovigilance: your responsibilities page.
You should keep appropriate records of adverse events that may occur following administration of the test article, control or placebo including those which are not serious. A summary of all adverse events that occur during the trial will be required if the ATC is to be renewed. For studies conducted under GCP the study protocol should include procedures for observing, recording and reporting adverse events.
Contact us
Email: postmaster@vmd.defra.gsi.gov.uk