Veterinary Medicines Directorate
Woodham Lane, New Haw
Addlestone, Surrey
KT15 3LS
United Kingdom
Tel: +44 (0)1932 336911
Fax: +44 (0)1932 336618
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APPLICATION FOR AN EXCEPTIONAL MARKETING AUTHORISATION
An incomplete application form may delay the application process.
If submitting in hard-copy, please use block capitals.
Further guidance about this application type is available on GOV.UK.
Delete as appropriate:
This is an applications for a LIMITED MARKETING AUTHORISATION or PROVISIONAL
MARKETING AUTHORISATION
SECTION 1 – ADMINISTRATIVE DETAILS
1.
Proposed product name in the UK:
2.
Registered Company Number:
3.
Name and Address of Proposed Authorisation Holder:
Company Name:
Address:
4.
Contact Details for this Application:
Name:
Email Address:
5.
Invoice Details: Email address of where the invoice should be sent to.
Email Address:
6.
e-Issuing Details: Email address of where the authorisation documentation
should be sent to (if different from 4. above).
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
Email Address:
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
SECTION […] – DECLARATION
I apply for the application as described above. I confirm that the information given in support of this
application is correct at the time of submission.
Signature
Job Title
Name in
Date
BLOCK LETTERS
If any information provided in this application is later found to be false or incorrect, the
Secretary of State may suspend or revoke the authorisation.
1.
MRL status (only for food producing species)
When the veterinary medicinal product is intended for use in food-producing animals,
please provide the following information as available at the time of submission of the
application1.
Maximum Residue Limits (MRL) according to Council Regulation (EEC) No 470/2009
has been published in the Official Journal of the European Communities:
Substance(s)
MRL status
Species
Target
tissue(s)
Remarks
OJ date of publication
Application for a Maximum Residue Limit has been made to the EMEA:
Substance(s)
Date of submission
Species
Remarks
1All
substances contained in the product are subject to this requirement if they are pharmacologically
active in the dose in which they are administered to the animal. Excipients not included in any of the
Annexes of Council Regulation (EEC) No 470/2009 should also be listed and an appropriate justification
given.
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
2.1
Marketing authorisation holder/Contact persons/Company
2.1.1 Proposed marketing authorisation holder/person legally responsible for
placing the product on the market in the Community:
(Company) Name:
Address:
Country:
Telephone:
Telefax:
Email:
Attach proof of establishment of the applicant in the EEA (Annex 3.3)
2.1.2 Person/company authorised for communication on behalf of the applicant
during the procedure in the Community:
Name:
Company name:
Address:
Country:
Telephone:
Telefax:
Email:
If different to 2.1.1 above,
attach letter of authorisation (Annex 3.4)
2.1.3 Container, closure and administration device(s), including description of
material from which it is constructed. (use current list of standard terms –
European Pharmacopoeia)
2.1.4 Qualified person in the EEA for Pharmacovigilance
Name:
Company name:
Address:
Country:
24 hr telephone:
Telefax:
Email:
Attach C.V. of qualified person (Annex 3.5). See also Annex – point 3.14
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
2.2
Manufacturers
Note: ALL manufacturing and control sites mentioned throughout the whole
dossier MUST be consistent regarding their names, detailed addresses
and activities.
2.2.1 Authorised manufacturer(s) (or importer) responsible for batch release in
the EEA in accordance with Article 55 and Article 53 of Directive
2001/82/EC (as shown in the package leaflet and where applicable in the
labelling or Annex II of the Commission Decision):
Company Name:
Address:
Country:
Telephone:
Telefax:
Email:
Manufacturing Authorisation number:
Attach copy of manufacturing authorisation(s) (Annex 3.6)
For Vaccines :
Details of the state laboratory or laboratory designated for that purpose
(OMCL) where the official batch protocol review (Article 81 of Directive
2001/82/EC) or the official control authority batch release (Article 82 of
Directive 2001/82/EC) takes place.
Name:
Address:
Country:
Telephone:
Telefax:
Email:
2.2.2 Contact person in the EEA for product defects and recalls
Name:
Address:
Country:
24hr contact telephone number:
Telefax:
Email:
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
2.2.3 Batch control/Testing arrangements
Site(s) in EEA or in countries where an MRA or other Community
arrangements apply where batch control/testing takes place (if different
from 2.2.1) as required by Article 55 of Directive 2001/82/EC:
Name of the Company:
Address:
Country:
Telephone:
Telefax:
Email:
Brief description of control test carried out by the laboratory(ies) concerned:
2.2.4 Manufacturer(s) of the veterinary medicinal product and site(s) of
manufacture:
(Note: including manufacturing sites of any diluent/solvent presented in a
separate container but forming part of the veterinary medicinal product)
Name:
Company name:
Address:
Country:
Telephone:
Telefax:
Email:
Brief description of
form/assembler, etc.:
functions
performed
by
manufacturer
of
dosage
If the manufacturing site is in the EEA
Manufacturing authorisation number (under Article 44 of Directive
2001/82/EC):
Attach manufacturing authorisations required under Article 44 of
Directive 2001/82/EC (Annex 3.6)
Name of qualified person:
(if not mentioned in manufacturing authorisation)
If the manufacturing site is outside the EEA,
Where MRA or other Community arrangements apply, attach equivalent of
manufacturing authorisation (Annex 3.6)
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
Has the site been inspected for GMP Compliance by an EEA authority or by
an authority of countries where Mutual Recognition Agreements (MRA) or
other community arrangements apply within the terms of the agreement?
No
Yes
If yes, please provide in Annex 3.7 for each site a statement from the
competent authority which carried out the inspection, including:
- last GMP inspection date
- name of competent authority which carried out the inspection
- category of products and activities inspected
- outcome:
GMP compliant:
No
Yes
Has the site been inspected for GMP Compliance by any other authority
including those of countries where MRA or other Community arrangements
apply but not within the respective territory?
No
Yes
If yes, please provide summary information in Annex 3.7
including:
- last GMP inspection date (yyyy-mm-dd)
- name of competent authority which carried out the inspection
- categories of products and activities inspected
- outcome:
Positive
Negative
2.2.5 Manufacturer(s) of the active substance(s) and site(s) of manufacture
Note: All manufacturing sites involved in the manufacturing process of each
source of active substance should be listed. Brokers or supplier details
alone are not acceptable. For biotech products include all sites of storage
of master and working cell bank and preparation of working cell banks.
Substance:
Name:
Address:
Country:
Telephone:
Telefax:
Email:
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
For each active substance, attach a declaration from the Qualified Person
of the manufacturing authorisation holder(s) in Section 2.2.3 and from the
Qualified Person of the manufacturing authorisation holder(s) listed in
Section 2.2.4 where the active substance is used as a starting material that
the active substance manufacturer(s)1 referred to in Section 2.2.5 operate in
compliance with the detailed guidelines on good manufacturing practice for
starting materials.
Has a Ph.Eur. Certificate of suitability been issued for the active substance(s):
No
Yes
If yes,
- substance:
- name of the manufacturer:
- reference number:
- date of last update (yyyy-mm-dd):
Provide copy in Annex 3.8
- Is an Active Substance Master File (ASMF) to be used for the active
substance(s) reference/original?
No
Yes
If yes,
- substance:
- name of the manufacturer:
- reference number for EMEA / competent authority:
- date of submission (yyyy-mm-dd):
- date of last update (yyyy-mm-dd):
-
attach letter of access for Community/Member State authorities where the
application is made (see “European ASMF procedure for active ingredients)
(Annex 3.8)
-
attach copy of written confirmation from the manufacturer of the active
substance to inform the applicant in case of modification of the
manufacturing process or specifications according to Annex I of Directive
2001/82/EC (Annex 3.9)
1
According to Article 50a of Directive 2001/82/EC, manufacture includes complete or partial manufacture,
import, dividing up, packaging or presentation prior to its incorporation into a veterinary medicinal product,
including re-packaging or re-labelling as carried out by a distributor.
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
2.3
List of materials of animal origin contained or used in the manufacturing
process of the veterinary medicinal product?
NONE
Name
Function*
AS EX R
Animal origin Other
susceptible to animal
TSE**
origin
Certificate of suitability for
TSE (state number)
1.
2.
3.
4.
etc.
* AS= active substance, EX=excipient (incl. starting materials used in the manufacture
of the active substance/excipient), R=reagent/culture medium (incl. those used in the
preparation of master and
working cell banks)
** as defined in section 2 (scope) of the Note for Guidance on minimising the risk of
transmitting animal spongiform encephalopathy agents via human and veterinary
medicinal products
If a Ph. Eur. Certificate of Suitability for TSE is available according to Resolution
AP/CSP (99)4 of the Council of Europe attach it in Annex 3.10
2.3.1 Does the veterinary medicinal product contain or consist of Genetically Modified
Organisms (GMOs) within the meaning of Directive 2001/18/EC ?
No
Yes
If yes, does the product comply with Directive 2001/18/EC ?
No
Yes
Attach a copy of any written consent(s) of the competent authorities to the
deliberate release into the environment of the GMOs for research and
development purposes where provided for by Part B of the above-mentioned
Directive (Annex 3.11)
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
3.
ANNEXED DOCUMENTS (WHERE APPROPRIATE)
3.0
Evidence that the product is intended for use in a Limited Market.
3.1
Evidence that the Provisional Marketing Authorisation criteria has been met.
3.2
Overall benefit: risk discussion for the proposed product.
3.3
Proof of establishment of the applicant in the EEA.
3.4
Letter of authorisation for communication on behalf of the applicant/MAH
3.5
Curriculum Vitae of the Qualified Person for Pharmacovigilance
3.6
Manufacturing Authorisation required under Article 44 of Directive 2001/82/EC (or
equivalent, outside of the EEA where MRA or other Community arrangements
apply). A reference to EudraGMP will suffice when available.
3.7
Statement (or GMP Certificate issued by an EEA inspectorate, when available) from
the competent authority which carried out the inspection of the manufacturing site(s)
(not older than 3 years). References to Eudra GMP will suffice when available.
Where applicable a summary of other GMP inspections performed in the last 2
years.
3.8
Letter(s) of access to Active Substance Master File(s) (Drug Master File(s)) or copy
of Ph. Eur. Certificate(s) of suitability
3.9
Copy of written confirmation from the manufacturer of the active substance to inform
the applicant in case of modification of the manufacturing process or specifications
according to Annex I of Directive 2001/82/EC.
3.10
Ph. Eur. Certificate(s) of suitability for TSE
3.11
Written consent(s) of the competent authorities regarding GMO release in the
environment.
3.12
Mock-ups of the proposed packaging, or text.
3.13
Detailed description of the Pharmacoviglance system.
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
ANNEX 1
The data requirements for an Exceptional MA are listed below.
Therapeutic Allergen Products
Therapeutic allergen products may qualify for consideration for an LMA. A case for
establishing that the proposed product falls within the definition of limited markets
should be presented with the application.
In some cases it is anticipated that the authorisation of bulk concentrated allergens will
be appropriate. These may then be used to formulate dosage forms for individual
animals on a case by case basis as extemporaneous preparations.
The inclusion of specific allergens in the application should be justified and its relevance
to the clinical situation in UK should be explained.
All relevant data available at the time of making the submission of the application for an
LMA should be included in the supporting data. As mentioned above, any gaps in the
quality, safety and efficacy data must not be critical to the safety of the product and it
must be possible to mitigate any risks to an acceptable level.
The allergenic active ingredients should be described in as much detail as possible and
this should include specifications and control methods relating to identity and purity of
the source material.
The production process for each allergen or group of allergens should be described
step by step with a flow chart, with an indication of when aseptic precautions are
introduced. Intermediate or bulk products in the process should be identified and the inprocess controls should be described.
In certain cases, data obtained with a representative allergen product may be
extrapolated to another, as long as a close relationship exists between their active
components. It may be necessary to sub-divide some groups into smaller families and
justification for this division should be provided.
Each family or subgroup of allergens must be described and tested separately.
Batch to batch consistency should be established by comparison with in-house
reference preparations using a number of biological and analytical methods.
Consistency of production must be documented on at least three production runs.
For stability data, the concept of the homologous groups may be applied and data
obtained on one member of the family may be extrapolated within the same family. A
shelf life longer than 12 months is only acceptable with stability studies obtained by
immunological or equivalent methods that can demonstrate allergenic activity
throughout the shelf life period.
The concept of the homologous groups may also be applied for the performance of
clinical trials.
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
Measurement of total allergenic activity of individual batches of each allergen extract
should be undertaken using validated immuno-assay methods.
Specific Data Requirements
You should provide the information set out in Volumes 6a and 6b of the European Notice to
Applicants and in Annex 1 of Directive 2001 / 82 / EC, as amended.
You should provide experts reports and an overall risk:benefit assessment.
For LMAs, you should provide justification that the proposed product falls within the
definition of limited markets. To do this, you may use the headings in the template
referenced in EMA paper, ‘EMA Guidance for Companies Requesting Classification as
MUMS / Limited Markets’ – EMA/CVMP/370663/2009.
Some data may be omitted from the application package in any section of the dossier;
however, these must not be critical to the safety of the product and it must be possible to
mitigate any risks to an acceptable level.
The following list includes examples of the type of data gaps that may be acceptable, but
these cannot be considered in isolation from other data gaps:
Quality
• Antimicrobial preservative efficacy and broached vial studies have not been
conducted, but the labels indicate the product should be used immediately
following first opening.
Safety
• Skin and eye toxicity data on the formulation are not available, but a
scientific evaluation can be made using available data on the active
substance(s) and excipients, such as Material Safety Data Sheets (MSDS),
published toxicity profiles (which may need to be purchased), or published
literature, to predict the potential for skin and eye irritation and skin
sensitisation and propose appropriate user warnings. The labels carry the
agreed user warnings.
• Residue depletion studies are not available, but a scientific evaluation can
be made using the pharmacokinetic data in the target species and the data
in the MRL summary report to predict the expected depletion of residues
and propose appropriate withdrawal periods or support “standard
withdrawal periods” (as defined in legislation) that include additional
“uncertainty factors” (usually in the form of additional days) to address the
absence of data. The labels clearly state the agreed withdrawal period and
that residue studies have not been performed and indicate what safety
margin (uncertainty factor) has been applied, where applicable.
Efficacy
• Pharmacokinetics, pharmacodynamics: new studies using the proposed
formulation in the target species are not available but the PK/PD profile of
the active substance is well described in published peer reviewed papers;
interspecies extrapolation may be acceptable if physiologically justified.
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015
• Safety: target species tolerance data using the proposed formulation are not
available but peer reviewed papers or published toxicology profiles are
available which characterise the margin of safety in the target species and
the proposed product contains excipients with well known safety profiles,
and field safety data for the final formulation are available for the proposed
dose.
• Field trial data are not available, but sufficient relevant data generated in
laboratory studies in the target species (using the final formulation to be
marketed) are available to indicate that the product is likely to work and to
indicate the dose regimen selected is appropriate. The labels indicate that
field trials have not been undertaken.
Author: HStenson
VMD/L4/Authorisations/030/C - #632499 – Revised May 2015