Guidance on applying for an authorisation to manufacture veterinary medicines (ManA).
If you are manufacturing an authorised veterinary medicine you must comply with the Good Manufacturing Practice (GMP) standards and obtain a Manufacturing Authorisation (ManA) unless the medicine is manufacturerd under an excemption for small non-food producing pet animals.
If you manufacture both human and veterinary medicines you should also refer to guidance published by the Medicines and Healthcare products Regulatory Agency (MHRA).
Manufacturing Authorisation (ManA)
You must obtain a ManA if you carry out any of the following manufacturing or assembling activities for an authorised veterinary medicine:
any process carried out in the course of making the medicine except for dissolving or dispersing the product in, or diluting or mixing it with some other substance used as a vehicle for the purpose of administering it
enclosing the medicine in a container which is labelled before it is sold or supplied (primary packing)
labelling the container (where the medicine is already enclosed in the container in which it is to be sold or supplied ie secondary packing) before the medicine is sold or supplied; this includes the over-labelling of medicines
importing veterinary medicine from a non-EU or European Economic Area (EEA) country and subsequently releasing the medicine to the market (batch certification)
You do not have to obtain a ManA to:
prepare, divide up, change the packaging or presentation of a veterinary medicine where this is done solely for retail supply, by or under the supervision of a veterinary surgeon or pharmacist in a registered veterinary practice premises or pharmacy (except a pharmacist may not break the immediate packaging of sterile products)
manufacture a veterinary medicine based on radio-active isotopes
manufacture a veterinary medicines for administration for research purposes in accordance with an Animal Test Certificate (ATC) or a licence issued under the Animals (Scientific Procedures) Act (A(SP)A) 1986
Compliance with GMP and GDP
GMP is defined as the part of Quality Assurance which ensures that products are consistently produced and controlled in accordance with the quality standards appropriate to their intended use.
The principles and guidelines for GMP are defined in Eudralex volume 4.
Export to a third country
Veterinary medicines in the UK should be made to the same standards irrespective of where they will be used. If you are manufacturing medicines in the UK exclusively for export to a non-EU or EEA country you need a ManA.
The VMD’s GMP inspectors will inspect your manufacturing site to ensure you comply with the EU GMP principles.
The VMD can issue a ManA solely to authorise the holder to certify and release batches of products for which they hold the MA where the medicine has been manufactured by a contract manufacturer.
The Qualified Person (QP) named on the manufacturer’s authorisation granted solely for the purpose of batch certification may either take responsibility for all manufacturing stages conducted by the contract manufacturer or may take account of the confirmation of the batch by the contract manufacturer’s QP. Ultimate responsibilty for batch certification of the batch lies with the certifying QP.
Duties of the ManA holder
You must comply (where appropriate to the manufacturing steps performed) with the following legal requirements relating to the manufacture and assembly of veterinary medicines:
- manufacture the veterinary medicine in accordance with the Marketing Authorisation (MA)
- ensure the services of the registered QP(s) are continuously available
- possess a current EU GMP certificate and any veterinary medicine is produced in accordance with GMP
- ensure Quality Assurance (QA) and Quality Control (QC) systems are in place
- make evidence available on request of any control testing performed in accordance with the MA
- ensure the finished veterinary medicine product is labelled with:
- registered name, strength and pharmaceutical form
- batch number
- expiry date
- storage requirements
- any warnings required for safe handling of the product
- ensure a representative sample of the finished veterinary medicine is retained and made available for testing upon request from the competent authority
The record requirements are defined in the VMR. The records for each batch must include:
- the name of the product
- the quantity manufactured, assembled or supplied
- the date of manufacture, assembly or supply
- the batch number and expiry date
- the name and address of the recipient, where supplied
- all certification provided by the QP related to the batch
All records and certificates must be kept for at least five years from the date that the batch is placed on the market or one year after the expiry of the batch whichever is the longer.
Transmissible Spongiform Encephalopathy (TSE)
The ManA holder must comply with the European Commission document EMEA/410/01–Rev 2 Notes for guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via veterinary medicinal products.
GMP requirements for active substances as starting materials
The Active Substance or Active Pharmaceutical Ingredient (API) must have been manufactured in accordance with Eudralex Volume 4, Part II. However, the following materials are exempted from full application of Part II, which relates to active substances:
- ectoparasiticidal active substances for veterinary use
- substances that are used exclusively for topical application to the unbroken skin of animals and which are ectoparasiticidal, anti-bacterial or anti-fungal agents
You may only use API from suppliers registered on the MA to manufacture the veterinary medicine.
The suitability of an API supplier must be evaluated by the ManA holder prior to use. This is usually obtained by:
- supplier audit
- provision of a QP statement certificate of GMP
A ManA holder must appoint the following:
Qualified Person (QP)
At least one QP named on the authorisation. They must be available on a continuous basis and live in the EEA. The QP’s role and responsibility is defined in Eudralex Volume 4, Chapter 2 and Annex 16.
QPs must meet specific educational and vocational requirements. They are usually expected to be members of the Royal Pharmaceutical Society, the Royal Society of Chemistry or the Society of Biology. These professional bodies jointly undertake assessment of the candidate’s eligibility on behalf of the VMD. Exceptionally, the VMD can appoint someone as a QP on a restricted named-site basis only.
QPs must comply with the QP Code of Practice. Guidance on the professional duties and responsibilities of the QP is in Eudralex Volume 4 Annex 6.
An applicant for a ManA must nominate a suitably qualified Head of Production. Their responsibilities are defined in Eudralex Volume 4, Chapter 2.
An applicant for a ManA must nominate a suitably qualified Head of Quality Control who is not also the Production Manager although they may also be the QP. Their responsibilities are defined in Eudralex Volume 4, Chapter 2.
Powers to vary, suspend or revoke
Length of validity
A ManA is valid indefinitely as long as the ManA holder complies with the law and passes regular inspections.
You must submit a variation application to the VMD if you intend to make any changes that could have an impact on the quality, safety or efficacy of the products manufactured (eg. registered personnel changes, premises alterations, change of site).
Suspension and revocation
The Secretary of State may vary, refuse, suspend, withdraw or revoke a ManA if:
- the holder has not complied with the VMR
- the holder has manufactured a type of veterinary medicine which is not authorised by the ManA
- the holder has produced a veterinary medicine outside the terms of the MA
- the holder has premises or equipment which is no longer suitable
- the registered QP is not fulfilling their duties
- it fails to comply with GMP
If the VMD considers that animal or public safety is at risk, it may suspend an authorisation with immediate effect for up to three months. The VMD may renew the suspension for further periods of up to three months.
Manufacture of Extemporaneous products (Specials) authorisation (ManSA)
You require a ManSA to legally manufacture and supply unauthorised extemporaneous veterinary medicines (known as Specials) which have been specifically prepared to the order of a veterinary surgeon for use in accordance with the prescribing cascade.
The same guidance as for ManAs applies to ManSAs, except for the requirements for a marketing authorisation (MA) and the full application of GMP applies in the case of sterile manufacture.
An unauthorised medicine which is a pharmaceutical equivalent of an available authorised medicine should not be placed on the market. A medicine should be regarded as a pharmaceutical equivalent if:
- it contains the same amount of the same active substance(s) or, for liquid dosage, forms the same concentration
- it is in the same dosage form
- it meets the same or comparable standards considered in the light of the clinical needs of the patient at the time of use of the medicine
An authorised veterinary medicine obtainable from normal distribution channels in a reasonable time should be considered available for use. If an otherwise suitable authorised product becomes unavailable, it may be necessary for an unauthorised pharmaceutical equivalent to be supplied. This should be seen as a temporary expedient and should not be taken as justification for long term supply.
Supply in these circumstances should cease as soon as is practicable, following re-instatement of the authorised product.
You may only supply a Special to a veterinary surgeon if all of the following apply:
- there is a genuine order from a veterinary surgeon registered in the UK
- the product is formulated in accordance with the vets requirements
- the product is for administration to an animal under the vets care on their direct personal responsibility
The order and distribution of Specials should be in response to a clinical need in specific animals. This should be a direct process between the prescribing vet and the manufacturer and they cannot be supplied via a third party such as a wholesale dealer.
All involved in the supply chain should be aware of the unauthorised status of the product. It should be clear from the product’s packaging that the product is unauthorised because there will be no MA number on it.
Manufacture and Assembly
The manufacturing and assembly site and its operations will be inspected for compliance with the law and the principles of GMP.
The law requires that manufacture or assembly is carried out under the supervision of appropriately qualified staff, including a named Quality Controller and a Production Manager named on the ManSA. However, a QP is not required to be named on a ManSA for release of a finished unauthorised product.
A person responsible for release must be named on the ManSA. This may be the Quality Controller or a nominated deputy. Adequate precautions should be taken to ensure the product is of the quality required for its intended purpose and that it complies with any relevant pharmacopoeial monograph standards. Written records of manufacture, assembly and supply must be kept for five years and be made available to the VMD on request.
You must comply with the European Commission’s Notes for guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via veterinary medicinal products.
Where possible GMP assured API should be used.
You must ensure that any information you provide to the VMD relating to the evaluation of the safety, quality or efficacy of any medicine which you import, handle, store or distribute is not false or misleading.
You may advertise the services you provide and the different types of dosage forms that are available, ie capsules, syrups, etc.
You must not advertise or promote the specific substances that you can manufacture. However you may provide lists of active substances and formulations with prices to a veterinary surgeon but only on request.
You may also provide placebo samples to a veterinary surgeon enquiring about your services.
Requirements for testing
Testing should be done to ensure products meet in house specifications. For a one-off Special, you must demonstrate consistency of manufacture. As a minimum you should be a standard procedure that can be validated even if the end product itself cannot be. However, there should be confirmation of homogeneity if this is appropriate to the preparation.
For a one-off Special, there should be justification for the shelf life. Such products should have a short shelf-life to reflect the fact there are no data to substantiate the validity of the stated expiry date.
However, if you are producing a range of more common Specials and they are stored for a length of time waiting for orders, you should undertake real-time stability studies to justify the proposed shelf-life. Depending on the nature of the products being manufactured data may be required to support the proposed shelf-life and on-going stability studies in accordance with GMP principles.
Labelling and record keeping requirements
You must ensure that Specials are labelled with the following, together with any additional information required by the terms of the authorisation:
- the name of the veterinary surgeon who ordered the veterinary medicine
- a precise description of the veterinary medicine
- the date of production
- the name of the authorisation holder and the address of the authorised premises
- the expiry date
- any necessary warnings
- instructions for use
You must also keep the following records for at least 5 years:
- the name and address of the veterinary surgeon who ordered the medicine
- a precise description of the veterinary medicine
- the date of production
- the expiry date
- the date of supply to the veterinary surgeon
Applications are subject to a pre-approval inspection. The registered facilities and processes are then routinely inspected on an ongoing basis. The re-inspection frequency is risk- based and will depend on the level of compliance with the principles of GMP found at the last inspection.
Before issuing a ManA or ManSA, VMD inspectors will have carried out a successful pre-approval inspection your site including any site where quality control testing or other activity is contracted to a third party.
The VMD will inspect you on a periodic basis based on risk although inspections will take place at least every 33 months.
The VMD will inspect production facilities in non-EU or non-EEA countries that do not have a Mutual Recognition Agreement with the EU before issuing a GMP certificate.
Process: pre-approval and routine
The VMD inspector will agree an inspection date with you and issue anbefore the inspection detailing the main areas for inspection. You should look at this in preparing for inspections.
The VMD will issue anwithin 30 days of the inspection.
You should respond to any deficiencies in the report within 30 days of completing the inspection. You should respond to any deficiences in the report within 30 days.
Following a satisfactory response to the inspection deficiency report, the VMD will issue a finaland GMP certificate within 90 days of the last day of the inspection.
GMP certificates are only issued to ManA and Exemptions for Small Pet Animals registered facilities, contract QC test sites and to manufacturing facilities located outside the EEA .
As the holder of a ManA or ManSA, you may store and distribute any veterinary medicine manufactured or assembled in line with your authorisation. If you buy or store any other veterinary medicine to supply to a wholesale dealer or retailer, you must hold a wholesale dealer authorisation (WDA).
If you wholesale supply a veterinary medicine that you have manufactured or assembled, you must:
- comply with the principles of Good Distribution Practice (GDP)
- only distribute veterinary medicines that you manufacture to:
- a holder of a WDA relating to those products
- a holder of an authorisation granted by the competent authority of another EEA country authorising the supply of those products by way of wholesale dealing
- any person who may legally sell or supply these products for sale or who may legally administer those products
- ensure the appropriate and continued supply of the veterinary medicine that is manufactured or assembled
- sell, or offer for sale or supply, the veterinary medicine in accordance with an MA unless it is an exempt medicine or is distributed to another Member State (MS) where it can be legally used as an unlicensed veterinary medicine
- where the veterinary medicine is supplied to a person for retail sale or supply, you must enclose with the product:
- a document which makes it possible to ascertain the date supply took place
- the name and pharmaceutical form of the product supplied
- the quantity of the veterinary medicine supplied
- the names and addresses of the person or persons who supplied the medicine
As a ManA or ManSA holder you must also:
- inform the VMD of any proposed changes to be made to any personnel or processes registered in your authorisation
- provide information about the products manufactured under your authorisation to the VMD on request
- retain batch documentation and permit access to this documentation by the VMD on request
Apply for a Manufacturing Authorisation
The details of your ManA are published in the EudraGMP
The details of your ManSA are published in VMD’s own.
The details of approved specific manufacturing authorisations for AVAs are published in VMD’s AVA Register
The details of approved specific manufacturing authorisations for blood banks & stem cells are published in VMD’s Approved Specific Manufacturing Authorisations Register.
For a register of sites which manufacture both human and veterinary medicines you should refer to the guidance published by the Medicines and Healthcare products Regulatory Agency (MHRA).
For application related issues contact the Inspections Administration Team via email firstname.lastname@example.org or tel: 01932 336911.