United Kingdom
Veterinary Medicines Directorate
Woodham Lane
New Haw
Addlestone
Surrey KT15 3LS
NATIONAL PROCEDURE
PUBLICLY AVAILABLE ASSESSMENT REPORT FOR A VETERINARY
MEDICINAL PRODUCT
Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in
Dogs
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
MODULE 1
PRODUCT SUMMARY
Name, strength and
pharmaceutical form
Veterinary Allergenic Extracts for the Treatment of
Atopic Dermatitis in Dogs.
Composition of the Prescription Product
(personalized label) is performed by the trained
pharmacist and in accordance with the
prescription for the individual patient. Dilutions
of the extracts are calculated based on the
concentration of the individual extracts. Sterile
aqueous diluents are used to prepare dilutions.
Target potency per dose: 20,000 PNU/mL of each
individual extract.
Applicant
Greer Laboratories LTD.
89 High Street
Hadleigh
Ipswich
Suffolk
IP7 5EA
UK
Active substance(s)
Pollens, fungi, inhalants, epidermals and insects.
(See SPC1 for full details).
ATC Vetcode
Q107AS
Target species
Dogs
For the preparation of allergenic extracts to be used
in the treatment of allergen-specific canine atopic
dermatitis in dogs 9 months or older.
Indication for use
Treatment regimen should be based on an
established allergen specific IgE test.
This is a Limited Marketing Authorization. A full set
of supporting efficacy data is not available for this
product.
Further information on this product and its
supporting
data
can
be
found
on
http://www.vmd.gov.uk/ProductInformationDatabase/
1
SPC – Summary of Product Characteristics.
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
MODULE 2
The Summary of Product Characteristics (SPC) for this product is available on
the Veterinary Medicines Directorate website (www.vmd.defra.gov.uk)
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
MODULE 3
PUBLIC ASSESSMENT REPORT
Legal basis of original
application
Limited Marketing Authorisation. Authorised
under the European Medicines Agency (EMA)
guidelines for MUMS2/Limited Markets
I. SCIENTIFIC OVERVIEW
The product Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis
in Dogs is authorised under a Limited Marketing Authorisation, under European
Medicines Agency (EMA) guidelines for MUMS/Limited Markets. This type of
Marketing Authorisation is intended for use where limited numbers of a product
are expected to be sold, and where a need for a specific drug is required. Due
to the nature of the use of such drugs, a full dossier meeting all requirements for
the marketing of the drug is not required, provided that the safety, quality and
efficacy of the product can be supported by available data, and a favourable
benefit-risk profile is determined. There is a requirement for Periodic Safety
Update Reports (PSURs) to be submitted for annual reassessment of this
product. Moreover, results of any additional studies must be submitted to the
Veterinary Medicines Directorate (VMD).
The product is for the preparation of allergenic extracts, for use in the treatment
of allergen-specific canine atopic dermatitis in dogs of 9 months or older, which
have presented with sensitisation to environmental allergens. The allergens are
prepared as extracts to be diluted in sterile aqueous diluents by trained
pharmacists or by veterinarians. Canine atopic dermatitis (CAD) is an
inflammatory and pruritic allergy skin disease, arising from genetic
predisposition, which is characterised by the development of specific IgE
antibodies due to allergic response. The treatment regimen is therefore based
on an established allergen specific IgE test. The available allergen extracts are
multiple, (refer to the SPC for full details), and are derived from pollens, fungi,
inhalants, epidermals and insects. Allergen specific immunotherapy (ASIT) is
commonly used as a treatment for CAD, and indeed, is the only treatment
offering long-term remission for this condition. This form of treatment has been
available since the 1960’s, and there is therefore a large amount of published
data available. The prevalence of relevant data contributed to the authorisation
of this Limited Marketing Authorisation. This is the first application for an
authorisation for an allergen product in the United Kingdom.
The product is produced and controlled using validated methods and tests which
ensure the consistency of the product released on the market. It has been
shown that the product can be safely used in the target species, the slight
reactions observed are indicated in the SPC. The product is safe for the user,
and for the environment, when used as recommended. Suitable warnings and
2
MUMS – Minor Uses and Minor Species.
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
precautions are indicated in the SPC. The efficacy of the product was
demonstrated according to the claims made in the SPC. The overall benefit/risk
analysis is in favour of granting a marketing authorisation.
II.
QUALITY ASPECTS
A. Composition
The product contains various allergenic extracts and the excipients phenol,
sodium chloride, sodium bicarbonate and water for injections.
The container/closure system consists of the extracts supplied in volumes of 5
ml, 10 ml, 30ml, and 50 ml. The vials are manufactured from Type I European
Pharmacopoeia (Ph. Eur.), grade glass. The stoppers meet the requirements set
out in the Ph. Eur. for Type II stoppers, and the particulars of the containers and
the controls performed are provided, and conform to the regulation.
The presence of a preservative (phenol) is justified. The product is a novel
pharmaceutical form, and its development is adequately described in
accordance with the relevant European guidelines.
B.
Method of Preparation of the Product
The product is manufactured fully in accordance with the principles of good
manufacturing practice from a licensed manufacturing site. Process validation
data on the product have been presented in accordance with the relevant
European guidelines.
C.
Control of Starting Materials
The active substances are novel active substances of a biological origin, none of
which are described in the Ph. Eur. The active substances are manufactured in
accordance with the principles of good manufacturing practice.
Starting materials of biological and non-biological origin used in production
comply with appropriate specifications as appropriate, and are used are in
compliance with the relevant Ph. Eur. monographs and guidelines. The
materials are appropriately screened for the absence of extraneous agents,
according to appropriate guidelines. Any deviation from the guidelines was
adequately justified.
D.
Specific Measures concerning the Prevention of the Transmission
of Animal Spongiform Encephalopathies
Scientific data have been provided, and compliance with Annex 1of Directive
2001/82/EC has been satisfactorily demonstrated.
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
E.
Control tests during production
The tests performed during production are described and the results of
satisfactory tests, conforming to given specifications, are provided.
F.
Control Tests on the Finished Product
The tests performed on the final product conform to the relevant requirements
and any deviation from these requirements was justified. The tests include in
particular those for bulk sterility testing, preservatives effectiveness, (during
extract composition), and relative potency.
G.
Stability
Stability data on the active substances have been provided in accordance with
applicable European guidelines, demonstrating the stability of the active
substance when stored under the approved conditions. The in-use shelf-life of
the product is supported by the data provided.
H. Genetically Modified Organisms
Not applicable.
J.
Other Information
The shelf-life of the veterinary medicinal product is 12 months. The shelf-life of
mixtures prepared from the concentrated allergens should not extend beyond
the shortest shelf-life of the individual components used to prepare the product
to be administered. The product should be stored in a refrigerator (2oC to 8oC),
and must not be frozen.
III.
SAFETY ASSESSMENT
Assessment of safety for ASIT products is complicated by a number of factors.
Namely, the large numbers of possible allergens, determining the stage in the
treatment regime when the dog is most susceptible to allergens, the possible
prolonged treatment regime, the variable treatment which may be required, and
the frequency of dose and the dose amount which must be adjusted to the
individual animal. The atopic dog is considered as the most susceptible target
species, having already been sensitised. Possible threats to safe treatment are
local reactions, increased pruritus or other signs and anaphylactic reactions. All
relevant scenarios are addressed within the SPC.
Laboratory trials
Appropriate laboratory data were presented for this application. The safety of
the administration of one dose, an overdose and the repeated administration of
one dose in the target animal were demonstrated in an appropriate study.
Allergenic extracts, mimicking typical immunotherapeutic regimens that would be
supplied to dogs suffering from canine atopic dermatitis were employed in a
suitable study containing an appropriate number of dogs. Initially, serum testing
was performed in order to confirm that the animals were non-atopic, and then
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
the animals were acclimatised and monitored prior to allergen challenge. Dogs
were divided into groups by sex, and each group had a similar body weight. The
dogs were challenged with immunotherapy admixtures at various time points,
which reflected the average dosage schedule used in the treatment of allergic
patients. Volumes of initial and secondary doses reflected the maximum dose
that would be used in the treatment of such patients. Double doses were
employed at a later time point. Any adverse reactions were noted, and the slight
reactions at the injection site which may occur during treatment are cited in the
SPC. The investigation was performed according to the recommendations of
Directive 2001/82/EC as amended and the relevant guidelines, and it was noted
that only field studies in the sensitised dog would provide essentially realistic
information.
No investigation of any effect on reproductive performance was conducted; the
SPC therefore carries an appropriate warning. There were also data presented
with regard to any effect on immunological function, these omissions were
permissible under the MUMS guidelines, and suitable warnings are cited in the
SPC. No specific assessment of the interaction of this product with other
medicinal product was made, appropriate warnings are included in the SPC.
Field studies
A number of published references were provided for this section. These
references included what were considered to be major studies, (which had
involved the utilisation of the applicant’s product in trials), being presented. The
majority of data provided for this MUMS authorisation were provided via
laboratory studies, with supporting data demonstrating the safety of the
applicant’s product from published literature. This was considered acceptable for
this type of application.
Ecotoxicity
The applicant provided a first phase environmental risk assessment in
compliance with the relevant guideline which showed that no further assessment
was required. The assessment concluded that as the active substances are
allergenic compounds derived from natural sources and are unchanged proteins
or glycoproteins which are highly soluble in water, there is little risk to the
environment. In addition, there is no derivation from genetically modified
organisms, the product is produced aseptically, and doses are very small in
relation to what is already present in the environment. Warnings and precautions
as listed on the product literature are adequate to ensure safety to the
environment when the product is used as directed.
IV
CLINICAL ASSESSMENT (EFFICACY)
Clinical Studies
Laboratory Trials
No laboratory studies were presented. This was considered acceptable for this
type of application. Sufficient data from published literature were provided which
supported the efficacy of the product, when used as directed.
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
Field Trials
The applicant provided letters from UK veterinarians supporting use of the
product, which contributed to the benefit /risk evaluation for this Limited
Marketing Authorisation, and substituted for a lack of laboratory data and
controlled field studies. In addition, a number of published references were cited,
which included the effective use of the applicant’s product in the field.
V OVERALL CONCLUSION AND BENEFIT– RISK ASSESSMENT
The data submitted in the dossier demonstrate that when the product is used in
accordance with the Summary of Product Characteristics, the benefit/risk profile
for the target species is favourable and the quality and safety of the product for
humans and the environment is acceptable.
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Product Name: Veterinary Allergenic Extracts for the Treatment of Atopic Dermatitis in Dogs
Greer Laboratories Ltd
Application for National Procedure
Publicly Available Assessment Report
MODULE 4
POST-AUTHORISATION ASSESSMENTS
The SPC and package leaflet may be updated to include new information on the
quality, safety and efficacy of the veterinary medicinal product. The current SPC
is
available
on
the
Veterinary
Medicines
Directorate
website
(www.vmd.defra.gov.uk)
This section contains information on significant changes which have been made
after the original procedure which are important for the quality, safety or efficacy
of the product.
None
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