ManufactureAuthorisations ofto authorisedmanufacture veterinary medicines and exempt products for small pet animals

You must applyobtain for a manufacturing authorisation (ManA) and comply with Good Manufacturing Practice (GMP) to manufacture:

• an authorisedunauthorised veterinary medicine
• a medicine marketed under Schedule 6 of the current Veterinary Medicines RegulationsRegulation (Exemptions(Exemption for Small Pet Animals)

If you wish to apply for an authorisation to manufacture:

• an extemporaneous preparation for administration to an animal under the prescribing cascade (a ‘special’)
• a veterinary autogenous vaccine
• a blood product for administration to non-food animals
• an equine stem cell product

go to the guidance on: Specific Manufacturing Authorisations.

ManufactureManufacturers of human and veterinary medicinesproducts

Where a site handles both human and veterinary medicines you should also refer to guidance published by the the Medicines and Healthcare products Regulatory Agency (MHRA)., Thewho MHRAalso publishespublish a register of sites authorised to manufacture both human and veterinary medicines.

ManufactureManufacturing ofAuthorisation an authorised veterinary medicine (ManA)(ManA)

You must holdbe a manufacturinga authorisationManA (ManA)holder to carry out any of the following manufacturing,manufacturing assembly or importationassembling activities infor relation to 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 (secondary packing) before the medicine is sold or supplied; this includes the over-labelling of medicines

• batch certification of a veterinary medicine manufactured at another site in the UK including contract manufactured products

• importing a veterinary medicine from a non-EU or non-EEAEuropean Economic Area (EEA) country and subsequently releasing the medicine to the market (batch certification and release)certification)

You do not need a ManA to: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 medicine 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

Requirements

Duties for ManA holders

of the ManA holder

You must comply (where appropriate to the manufacturing steps performed) with the following legal requirements relating to the manufacture,manufacture assembly and importationassembly of veterinary medicines:

• manufacture the veterinary medicine in accordance with its marketingMarketing authorisationAuthorisation (MA)(MA)
• ensure the services of a registered Qualified Person (QP)(QP) are continuously available
• possess a current goodGMP manufacturingcertificate practice (GMP) certificate issued by a UK or EEA member national competent authority and ensure the veterinary medicine is produced in accordance with GMPwith GMP
• ensure Quality Assurance (QA) and Quality Control (QC) systems are in place

• make evidence of any control testing performed in accordance with the product’s MA available to us, on request

• ensure the finished product is labelled with:
  1. its registered name, strength and pharmaceutical form
  2. its batch number
  3. its expiry date
  4. its storage requirements
  5. any warnings required for safe handling of the product
• ensure each batch of product manufactured is batch (QC) tested to confirm that it meets its required specification before being certified/released to the market by the QP
• ensure a representative sample of the finished product is retained and made available to us for testing upon request

Good Manufacturing Practice (GMP)

(GMP) Compliance

GMP isGMP 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 arefor GMP are defined in in Eudralex volume 4.

GMP requirements GMP requirements for active substances as starting materials

The active substance (also known as the activeActive pharmaceuticalPharmaceutical ingredientIngredient or API) must have been manufactured in accordance with with Eudralex Volume 4, Part II. However, the following materials are exempted from the full application of Part II:

• 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 APIs from suppliers registered on the MA tothe MA to manufacture the veterinary medicine.

The suitability of an API supplier must be evaluated by the ManA holderthe ManA holder prior to use. This is usually obtained by:

• supplier audit, and
• provision of a QP statementa QP statement certificate of GMPof GMP

Transmissible Spongiform Encephalopathy (TSE)

You must comply with the European Commission’sCommission document EMEA/410/01–Rev 2 Notes for guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via veterinary medicinal products.

Required Personnel

You must appoint the following personnel:

Qualified Person (QP)(QP)

The QP’sThe QP’s role isand toresponsibility ensureis thatdefined eachin batchEudralex ofVolume veterinary4, medicineChapter manufactured2 underand theirAnnex responsibly16.

At isleast manufacturedone andQP testedmust tobe checknamed iton complies with the Veterinaryauthorisation Medicines Regulations and meetsmust thebe specificationpermanently inand itscontinuous marketingat authorisation.the TheManA QP’sholder’s fulldisposal.

To roleplace andproducts responsibilitieson arethe definedGB in Eudralexmarket, VolumeQPs 4,can Chapterbe 2located andanywhere. AnnexFrom 16.

AtJanuary least2021, one QP mustto beplace namedproducts on the authorisationNorthern andIreland mustmarket, beQPs permanentlymust andlive continuouslyin atNI the ManA holder’sor disposal.the EEA.

QPs must meet specific educational and vocational requirementsrequirements. andThey beare ausually memberexpected ofto onebe members of the following professional bodies: the Royal SocietyPharmaceutical ofSociety, Chemistry, the Royal Society of Biology,Chemistry the Royal Pharmaceutical Society or registered with the PharmaceuticalRoyal Society of NorthernBiology. Ireland. These professional bodies jointly undertake assessment of the candidate’s eligibility on our behalf.

QPs mustExceptionally, complywe withcan the QP Code of Practice.

Exceptionally Appointed QPs

We may exceptionally appoint someone as a QP whoa isQP noton a memberrestricted ofnamed-site onebasis ofonly.

QPs themust professionalcomply bodieswith butthe onlyQP forCode aof specificPractice. siteGuidance andon athe specificprofessional product;duties and providedresponsibilities thatof we are satisfied that the personQP hasis thein educationalEudralex qualificationsVolume and4 practicalAnnex experience to carry out the QP’s duties.16.

Production Manager

Your ManA applicationYour mustManA alsoapplication must nominate a suitably qualified Production Manager. Their role and responsibilities are defined in Eudralex Volume 4, Chapter 2.2.

Head of Quality Control

Your ManA applicationYour mustManA alsoapplication must nominate a suitably qualified Head of Quality Control (QC). The Head of QC cannot be the same person as the Production Manager but they may also be the QP.the QP. Their role and responsibilities are defined in Eudralex Volume 4, Chapter 2.2.

Batch certification

We forcan release

Youissue maya applyManA forsolely a ManA solelyto authorise the holder to certify and release batches of products for which they hold the MA where the medicine has been manufactured by a thirdcontract party manufacturer.

The QP namedThe QP named on a ManA granteda ManA granted solely for the purpose of batch certification for release may either take responsibility for all manufacturing stages conducted by the thirdcontract party manufacturer or may take account of confirmation from the thirdconfirmation party’sof QP that the batch hasby been manufactured in compliance with the product’scontract MAmanufacturer’s andQP. theUltimate requirementsresponsibilty of GMP. However, ultimate responsibility for batch certification of the batch for release to market lies with the certifying QP.

Veterinarycertifying medicines manufactured outside the UK must be imported via a ManA holder’s site and also batch (QC) tested, QP certified and released. In the case of importation from a country with which the UK has a formal agreement which includes mutual recognition of batch (QC) testing, the importing ManA holder’s QP may accept the batch testing carried out in the other country..

Record-keeping requirements

The record requirements are defined in regulation 21 of the Veterinary Medicines RegulationsRegulation. 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; anddate
• in the case of supply, the name and address of the recipientrecipient, where supplied
• all certification provided by the QP relatedthe QP related to the batch

All records and certificates must be kept for at least 5 years from the date that the batch is placed on the market.market or one year after the expiry of the batch whichever is longer.

Export

Exporting fromoutside of the UK

Veterinary medicines manufactured in the UK should be produced to the same standards irrespective of where they will be used. If you are manufacturing medicines in the UK exclusively for export you need a ManA and must holdcomply a ManA andwith GMP.

We will inspect your manufacturing site to ensure you comply with GMP.with GMP.

Manufacture of medicinesproducts marketed under the ExemptionsExemption for Small Pet Animals (SAM)

Medicines manufactured under Schedule 6 of the Veterinary Medicines Regulations (Exemptions(the Exemption for Small Pet Animals) must comply with GMP andwith GMP and be manufactured by the holder of a ManA or a Small Animal Medicines manufacturing authorisation (SAM) issued under under:

• Schedule 2 of the Veterinary Medicines Regulations 2013 as it has effect in Northern Ireland and Great Britain or:
  • fora sitescertificate issued by the competent authority (sites in EU, Australia, Canada, New Zealand and Switzerland,Switzerland)
  • a ancertificate authorisation issued by the relevantSecretary competentof authority;State or
  • for(sites sites in all other countries,countries)

  There approvalare fromno restrictions on the Secretaryretail supply within the UK of State

products manufactured under the exemption but they may only be wholesale supplied by the holder of a Wholesale Dealer Authorisation (WDA).

There are no restrictions on the importation of products which fully comply with this exemption.

WeSee exemption for small pet animals guidance.

Manufacturers of extemporaneous preparations for use under the cascade (ManSA)

You need a ManSA to legally manufacture and supply unauthorised extemporaneous veterinary medicines (also known as ‘Specials’) which have been specifically prepared to the order of a veterinary surgeon for use in accordance with the cascade.

The same guidance broadly applies to ManSAs as for ManAs, although a marketing authorisation (MA) is not required.

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 issuebe necessary for an unauthorised pharmaceutical equivalent to be manufactured and supplied. This should a SAMtemporary measure and should not be taken as justification for long term prescription/supply.

Supply in these circumstances should cease as soon as is possible, following re-instatement of the authorised product.

You may only supply an extemporaneous product to a personveterinary whosurgeon employsif all the servicesfollowing apply:

• there is a genuine order from a veterinary surgeon registered in the UK
• the product is formulated in accordance with the veterinary surgeon’s requirements
• the product is for administration to an animal under the veterinary surgeon’s care on their direct personal responsibility

The order and distribution of extemporaneous products 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 by ManSA holders

Your ManSA manufacturing and assembly site and its operations will be inspected for compliance with the Veterinary Medicines Regulations (VMR) and the principles of GMP.

The VMR requires that manufacture or assembly is carried out under the supervision of appropriately qualified personnel, each of whom must be named on the ManSA. The personnel include:

• a person responsible for Quality Control (QC)
• a Production Manager
• a person responsible for release (PR)(PRR), rather than a QP,QP. providedThe wePRR aremay satisfiedalso be the QC or a nominated deputy

You must take adequate precautions to ensure that the product is of the quality required for its intended purpose and that personit hascomplies sufficientwith qualificationsany relevant pharmacopoeial monograph standards. Written records of manufacture, assembly and experiencesupply must be kept for 5 years and be made available to manufactureus 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 us 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.

Advertising extemporaneous products

You may advertise the services you provide and the different types of dosage forms that are available, for example capsules, syrups.

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. Further information can be found on the Advertise veterinary medicines legally guidance.

Requirements for testing extemporaneous products

You should conduct appropriate testing to ensure products meet in-house specifications. For a one-off unauthorised extemporaneous product, you must demonstrate consistency of manufacture. As a minimum there should be a standard procedure that can be validated even if the end product safely.itself cannot be. However, there should be confirmation of homogeneity if this is appropriate to the preparation.

For furthera information,one-off see guidanceunauthorised extemporaneous product, you should be able to provide justification for Exemptionsthe specified 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 more regularly prescribed extemporaneous products that may be stored for smalla petlength animals.of time waiting for orders, you should undertake real-time stability studies to justify the specified 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 may also be required.

Labelling and record keeping requirements

You must ensure that extemporaneous products are labelled with the following, together with any additional information required by the terms of the ManSA:

• 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 site
• 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

Wholesale supply

As the holder of a ManAa ManA, ManSA or SAM authorisation, 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 wholesalea dealer authorisation (WDA), see Veterinary medicine wholesale dealer’s authorisationWDA.

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 the medicine to:

  1. thea holder of a WDA relatinga WDA relating to those products
  2. thea holder of an authorisation granted by the competent authority of another country authorising the supply of those products by way of wholesale dealing
  3. a person who may legally retail supply the product or who may legally administer the product
• ensure the appropriate and continued supply of the veterinary medicine
• only sell, or offer for sale or supply, the veterinary medicine in accordance with an MA unlessan MA unless it is an exempt medicine or is distributed to another country where it can be legally used as an unlicensed veterinary medicine

ApplicationsInspection of Manufacturers

Sites that are the subject of a manufacturing application are subject to a pre-approval inspection. Once a manufacturing authorisation has been granted, the site facilities and processes will be routinely inspected on an ongoing basis. The re-inspection frequency is risk- based and will depend on the level of compliance with GMP found at the last inspection.

Inspection Process

Pre-approval inspection

Before issuing a ManA, ManSA or SAM authorisation, we will have carried out a successful pre-approval inspection of your site, and any site(s) where quality control testing or other activity is contracted to a third party unless that site has already been inspected by us or the MHRA.

Scheduled inspection

We will periodically inspect your site(s) basis based on risk, although inspections will normally take place at least every 3 years.

We may inspect production facilities in countries outside of the UK that we do not have a Mutual Recognition Agreement (MRA) with.

Process: pre-approval and scheduled inspections

We will agree with you an inspection date and share the main areas that will be covered during the inspection. This will help you prepare.

After the inspection, we will send you an inspection deficiency report within 30 days. You should respond to any deficiencies cited within 30 days of receiving it.

Once we are satisfied with your response we will issue a final GMP inspection report and a GMP certificate within 90 days following the end of the inspection.

GMP certificates are only issued to ManA and SAM holders, contract QC test sites and manufacturing facilities located outside the UK that we do not have an MRA with.

Application forms, process and fees

• Application form for Manufacturersvariation to manufacturers authorisation (MS Word Document, 96.593.6 KB)
• Application form for Variation to manufacturers specials authorisation (MS Word DocumentODT, 93.698.3 KB)
• Application form for Scheduleschedule 6 manufacturer (ODT, 81.6 KB)
• Application form for Exceptionallyvariation Appointedto QPmanufacturers special authorisation (ODT, 32.494.2 KB)
• Application form for VMD GMP Inspectors Declaration of Interest (PDF, 90.1 KB, 1 page)

Before completing an application for a ManAa orManA, SAM, please read the ‘Interpretation of the Union Format for Manufacturer/Importer Authorisation’ on pages 144-158 of the the Compilation of Community Procedures on Inspections and Exchange of Information - ECA Academy (gmp-compliance.org).

SubmitAn your application for a ManA ora SAM,ManA, togetherManSA withor aSAM Siteauthorisation Mastershould Filebe (SMF)accompanied by emaila to;Site inspections@vmd.gov.uk.Master File.

Alternatively,To youhelp mayus alsoto sendefficiently itprocess viayour ourcompleted Veterinaryapplication Medicinesplease Digitalemail Serviceit to; inspections@vmd.gov.uk.

Timelines

We will validate your application within 10 days of receivingreceipt it, provided you’ve submitted all required information.information Theis provided. This validation time will be extended if we request further information from you.

After validation we will conductcarry out the pre-authorisationpre-approval inspection of your site within 90 days.

Application

Inspectors refusalDeclarations andof appeal

Interest

We mayrequire refuseour toinspectors grantinvolved anwith authorisationGood orManufacturing mayPractice grant(GMP) aninspections authorisationto thatsign isa differentDeclaration of Interests (DoI) every year, to ensure that youthey applieddo for.not Inhave suchany casesfinancial weor willother notifyinterests youthat ofcould theaffect reasontheir impartiality. We publish their DoIs for transparency and howto yousupport canthe appealsharing of information with our decision.regulatory partners.

Fees

ThereThe areVMD feescharges a fee for:

• processing an application for a new manufacturing authorisation (ManA and SAM)
• athe pre-authorisationapproval inspection of each site and subsequent risk-based inspections
• anon-going annual feeand inspection fees
• processing a variation application for an existing manufacturing authorisation (ManA and SAM)
• issuing duplicate or multiple GMP Certificatesmultiple GMP Certificates

Fees applied to animal medicine authorisation applications are not refundable or transferable.

Validity

Application ofrefusal authorisations

and appeal

YourWe authorisationmay willrefuse beto validgrant continuouslyan subjectauthorisation toor satisfactorymay re-inspectiongrant ofan yourauthorisation manufacturingthat site.

Theis frequencydifferent ofthan inspectionsthat isapplied risk-basedfor. andIn derivedsuch fromcases thewe compliancewill findingsnotify you of the previousreason inspection.and how you can appeal our decision.

Variation,Powers Suspensionto andvary, Revocationsuspend ofor anrevoke Authorisationauthorisations

VoluntaryLength variationof (Change)validity

An authorisation is valid indefinitely as long as the authorisation holder complies with the VMR and GMP which will be confirmed by scheduled inspections.

Variations (Changes)

You must submit a variation application to us if the details of your ManAmanufacturing orauthorisation SAM change. There are 2 types of variation: administrative and scientific.

Administrative variations do not require assessment by an inspector. Examples include:

• change of company name/trading name
• change of owner
• change of site address (administrative rather than site location fore.g. example, postcode change)
• removal of a QP,a QP, QC, Production Manager or PRPRR (providing that there is more than one)
• removal of a named site
• removal of a product type

Scientific variations require assessment by an inspector and may also require an inspection. Examples include:

• addition of a new manufacturing activity
• addition of categories of products handled at the site
• addition of new site
• change of site location
• change or addition of QP,of QP, QC, Production Manager or PRPRR

Compulsory variation, Suspension and Revocationrevocation

WeThe VMD, acting on behalf of the Secretary of State, may vary,suspend, suspendvary or revoke youra ManAmanufacturing orauthorisation SAM if:

• youthe haveholder has not complied with the VMR
• youthe haveholder has manufactured a type of veterinary medicine which is not authorised by yourthe manufacturing authorisation
• youthe haveholder has produced a veterinary medicine outside the terms of its MAits MA
• yourthe holder has premises or equipment which is no longer suitable
• yourthe registered QP orregistered PRQP is not fulfilling their duties or has left the company
• youthe havemanufacturer failedfails to comply with GMPwith GMP

If we consider that animal or public safety is at risk, we may suspend youran authorisation with immediate effect for up to 3 months. We may also extendrenew the suspension for further periods if necessary.required.

In all cases, we willthe VMD will notify you of the reason for suspending,suspending varying or revoking your authorisation and how you can appeal the decision.

InspectionManufacture of Manufacturers

Pre-authorisationautogenous inspection

Beforevaccines, issuingequine a ManA orstem SAM,cell weproducts will normally carry out a pre-authorisation inspection of your site, and any site(s) where quality control testing or othernon-food activityanimal isblood contracted to a third party unless that site has already been inspected by us or the MHRA.

Scheduled inspection

products

WeTo willapply periodicallyfor inspect your site(s) based on risk and compliance, although inspections will normally take place at least every 3 years.

We may inspect production facilities in countries outside of the UK that we do not have a Mutual Recognition Agreement (MRA) with.

Process: pre-authorisation and scheduled inspections

We will agree with you an inspectionAutogenous dateVaccine andAuthorisation share(AVA), theNon-Food mainAnimal areasBlood thatBank willAuthorisation be(NFABBA) coveredor duringEquine theStem inspection.Cell ThisCentre willAuthorisation help(ESCCA) yougo prepare.

After the inspection, we will send you an inspection deficiency report within 30 days. You should respond to any deficiencies cited within 30 days of receiving it.

Once we are satisfied with your response, we will issue a final GMP inspection report and a GMP certificate within 90 days following the endApply offor theproduct inspection.

GMP certificatesauthorisations are only issued to ManA and SAM holders, contract QC test sites and manufacturing facilities located outside the UK that we do not have an MRA with.page.

RegisterRegisters

The register of ManA holders and SAM holders is available at:

• Register of Veterinary-Only GMP SitesVeterinary-Only GMP Sites and related ManAs

Inspectors

Register Declarations of Interest

WeVeterinary-Only requiremanufacturers our inspectors involved with GMP inspections to sign a Declaration of Interestsextemporaneous (DoI)preparations everyfor year,use tounder ensure that they do not have any financial or other interests that could affect their impartiality. Their DoIs are published below in the interestcascade of transparency and to support the sharing of information with our regulatory partners.

(ManSA)

Good

Register Manufacturing Practice: Inspectors’ Declarations of Interest

PDF,Specific 248Manufacturing KB,Authorisation 1Holders page

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Contact you use assistive technology (such as a screen reader) and need aVMD version

For ofapplication thisrelated documentissues incontact athe moreInspections accessibleAdministration format,Team pleaseby emailemail; postmaster@vmd.gov.ukinspections@vmd.gov.uk. Please tellor uscall; what01932 format you need. It will help us if you say what assistive technology you use.

Contact Us

You can email us at; inspections@vmd.gov.uk.336911.