United Kingdom
Veterinary Medicines Directorate
Woodham Lane
New Haw
Addlestone
Surrey KT15 3LS
DECENTRALISED PROCEDURE
PUBLICLY AVAILABLE ASSESSMENT REPORT FOR A VETERINARY
MEDICINAL PRODUCT
Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
MODULE 1
PRODUCT SUMMARY
EU Procedure number
UK/V/0382/001/DC
Name, strength and
pharmaceutical form
Ketosol 100 mg/ml Solution for Injection for
Horses, Cattle and Pigs
CP-Pharma GmbH
Ostlandring 13
31303 Burgdorf
Applicant
Germany
Active substance
Ketoprofen
ATC Vetcode
QM01AE03
Target species
Horses, Cattle, Pigs
Indication for use
Horses:
the alleviation of inflammation and pain
associated with musculoskeletal disorders
the alleviation of visceral pain associated with
colic.
Cattle:
the supportive treatment of parturient paresis
associated with calving
reducing the pyrexia and distress associated
with bacterial respiratory disease when used in
conjunction with an antimicrobial therapy as
appropriate
improving the recovery rate in acute clinical
mastitis, including acute endotoxin mastitis,
caused by gram negative microorganisms, in
conjunction with antimicrobial therapy
reducing oedema of the udder associated with
calving.
Pigs:
reducing the pyrexia and respiratory rate
associated with bacterial or viral respiratory
disease when used in conjunction with
antimicrobial therapy as appropriate
the supportive treatment of Mastitis Metritis
Agalactia Syndrome in sows, in conjunction with
antimicrobial therapy as appropriate.
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
MODULE 2
The Summary of Product Characteristics (SPC) for this product is available on
the Heads of Medicines Agencies (veterinary) (HMA(v)) website (www.hma.eu).
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
MODULE 3
PUBLIC ASSESSMENT REPORT
Legal basis of original
application
Generic application in accordance with Article
13 (1) of Directive 2001/82/EC as amended.
Date of completion of the
original decentralised
procedure
25 April 2012
Date product first authorised
in the Reference Member
State (MRP only)
Not applicable.
Concerned Member States for Austria, Belgium, Czech Republic, Denmark,
original procedure
France, Germany, Hungary, Ireland, Italy, The
Netherlands, Poland, Spain.
I. SCIENTIFIC OVERVIEW
This was an application for a generic product, for which the UK reference
product was Ketofen 10% Solution for Injection, authorised in February 1992.
The indication in horses is for the alleviation of inflammation and pain associated
with musculo-skeletal disorders, and for the alleviation of visceral pain
associated with colic. In cattle, the indication is for supportive treatment of
parturient paresis associated with calving, reduction of distress and pyrexia
associated with bacterial respiratory infections, when used in conjunction with
appropriate antimicrobial therapy, improvement of the recovery rate in acute
clinical mastitis, including acute endotoxin mastitis caused by Gram-negative
organisms, in conjunction with appropriate antimicrobial therapy, and the
reduction of oedema of the udder associated with calving. In pigs, the indication
is for the reduction of pyrexia and respiratory rate associated with bacterial or
viral respiratory disease, in conjunction with an appropriate antimicrobial
therapy, and the supportive treatment of Mastitis Metritus Agalactia Syndrome in
sows in conjunction with appropriate antimicrobial therapy.
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.1
The product is safe for the user, the consumer of foodstuffs from treated animals
and for the environment, when used as recommended. Suitable warnings and
precautions are indicated in the SPC. The efficacy of the product was
demonstrated according to the claims made in the SPC.
1
SPC – Summary of Product Characteristics.
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
The overall risk/benefit analysis is in favour of granting a marketing
authorisation.
II.
QUALITY ASPECTS
A.
Composition
The product contains 100 mg/ml ketoprofen and excipients benzyl alcohol, Larginine, citric acid monohydrate and water for injections.
The container/closure system consists of 50 ml and 100 ml amber glass vials
(Type II), with a chlorobutyl rubber stopper covered by an aluminium cap. The
vials are packed into cardboard boxes. The particulars of the containers and
controls performed are provided and conform to the regulation.
The choice of the formulation and the presence of preservative are justified. The
product is an established 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. Water is heated and L-arginine added. The
active substance is then added. After mixing and cooling, the remaining
excipients are added, and in-process control testing is carried out.
C.
Control of Starting Materials
The active substance is ketoprofen, an established active substance described
in the European Pharmacopoeia (Ph. Eur). Suitable CEP2 certificates were
provided. The active substance is manufactured in accordance with the
principles of good manufacturing practice.
The active substance specification is considered adequate to control the quality
of the material. Batch analytical data demonstrating compliance with this
specification have been provided. Tests include those for appearance, solubility
and impurities.
All excipients are monographed in the Ph. Eur, and are used frequently in
veterinary medicinal products.
2
CEP – Certificate of European Pharmacopoeia.
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
D.
Specific Measures concerning the Prevention of the Transmission
of Animal Spongiform Encephalopathies
A declaration demonstrating that the product complied with the latest version of
the CPMP/CVMP3 guideline was submitted, this was satisfactory.
E.
Control on intermediate products
Not applicable.
F.
Control Tests on the Finished Product
The finished product specification controls the relevant parameters for the
pharmaceutical form. The tests on the specification, and their limits, have been
justified and are considered appropriate to adequately control the quality of the
product. Satisfactory validation data for the analytical methods have been
provided. Batch analytical data from the proposed production site have been
provided demonstrating compliance with the specification. Tests include those
for appearance, pH, colour visible particles, relative density and index,
ketoprofen identification, and assay of specific excipients.
G.
Stability
Stability data on the active substance have been provided in accordance with
applicable European guidelines, demonstrating the stability of the active
substance when stored under the approved conditions.
H.
Genetically Modified Organisms
Not applicable.
J.
Other Information
The shelf-life of the product as packaged for sale is 30 months. Shelf-life after
first opening the vial is 28 days.
III.
SAFETY AND RESIDUES
TOXICOLOGICAL)
ASSESSMENT
(PHARMACO-
As this is a generic application according to Article 13, and bioequivalence with a
reference product has been demonstrated, results of pharmacological and
toxicological tests are not required.
Warnings and precautions as listed on the product literature are the same as
those of the reference product and are adequate to ensure safety of the product
to users, the environment and consumers.
CPMP – Committee for Proprietary Medicinal Products.
CVMP – Committee for Veterinary Medicinal Products.
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
III.A
Safety Testing
User Safety
The applicant has provided a user safety assessment in compliance with the
relevant guideline. Warnings and precautions as listed on the product literature
are adequate to ensure safety to users of the product. The warnings are the
same as those of the reference product.




In case of accidental self-injection seek medical advice and show the
package leaflet or the label to the physician.
People with known hypersensitivity to the active substance and/or benzyl
alcohol should avoid contact with the product.
Avoid splashes on the skin and eyes. Wash the affected area thoroughly
with water should this occur. If irritation persists seek medical advice.
Wash hands after use.
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 product will be used on individual animals or a small number
of animals in a herd.
Warnings and precautions as listed on the product literature are adequate to
ensure safety to the environment when the product is used as directed.
III.B
Residues documentation
Residue Studies
Additional residues studies were not required for this a, because the CVMP
recommended in an MRL summary report that ketoprofen products administered
to the proposed dosing schedule should have a 4-day withdrawal period in all
three indicated species. This was based on injection site residues studies.
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
MRLs
Substance
Marker
residue
Animal
species
Ketoprofen
N/A
Porcine
Equidae
Bovine
L-arginine
N/A
All
Benzyl Alcohol
N/A
All
Sodium Chloride
N/A
All
Citric Acid
Monohydrate
N/A
All
Water for Injections
N/A
All
MRLs
(µg/kg)
Target
tissues
None
required
Meat,
milk
None
required
None
required
None
required
None
required
None
required
Meat,
milk
Meat,
milk
Meat,
milk
Meat,
milk
Meat,
milk
Other provisions
The CVMP
recommends a 4-day
withdrawal period for
edible tissues.
For use as an excipient
only.
Withdrawal Periods
Horses, cattle and pigs must not be slaughtered for human consumption during
treatment. Animals may be slaughtered for human consumption only after the
following periods from the last treatment:
Cattle
meat and offal: following intravenous administration - 1 day
following intramuscular administration - 4 days
milk: zero hours
Pigs (meat and offal): 4 days
Horses (meat and offal): 1 day
Not to be used in mares producing milk for human consumption.
IV
CLINICAL ASSESSMENT (EFFICACY)
As this is a generic application according to Article 13, and bioequivalence with a
reference product has been demonstrated, efficacy studies are not required.
The efficacy claims for this product are equivalent to those of the reference
product.
IV.A Pre-Clinical Studies
As this is a generic application according to Article 13, and bioequivalence with a
reference product has been demonstrated, efficacy studies are not required.
The efficacy claims for this product are equivalent to those of the reference
product.
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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised Procedure
Publicly Available Assessment Report
IV.B
Clinical Studies
Laboratory Trials
As this is a generic application according to Article 13, and bioequivalence with a
reference product has been demonstrated, efficacy studies are not required.
The efficacy claims for this product are equivalent to those of the reference
product.
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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Ketosol 100 mg/ml Solution for Injection for Horses, Cattle and Pigs Application Number00043/2011
CP Pharma mbH
Application for Decentralised 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 Product Information Database of the Veterinary Medicines
Directorate website.
(www.gov.uk/check-animal-medicine-licensed)
The post-authorisation assessment (PAA) 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.
The PAA for this product is available on the Product Information Database of the
Veterinary Medicines Directorate website.
(www.gov.uk/check-animal-medicine-licensed)
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