United Kingdom

Veterinary Medicines Directorate
Woodham Lane
New Haw
Addlestone
Surrey KT15 3LS

NATIONAL PROCEDURE

PUBLICLY AVAILABLE ASSESSMENT REPORT FOR A PROPOSED VETERINARY HOMEOPATHIC REMEDY

Eurofit Intramammary Gel

Date Created: January 2018

1/9

Eurofit Intramammary Gel

Közép-Európai Állatorvosi Központ KftApplication for National Procedure

Publicly Available Assessment Report

MODULE 1

PROPOSED PRODUCT SUMMARY

Name, strength and pharmaceutical form / Eurofit Intramammary Gel
Applicant / Közép-Európai Állatorvosi Központ Kft
2051 Biatorbágy
Vendel Park
Tormásrét u. 12
Hungary
Homeopathic material(s) and potencies / Phytolacca decandra30C
Hepar Sulfur30C
Siliceae30C
Sepia officinalis30C
Thuya occidentalis30C
Calcarea phosphorica30C
Pulsatilla pratensis30C
Iodum30C
Cantharis vesicatoria9C
Phosphorus9C
Baptisia tinctoria9C
Echinacea angustifolia9C
Acidum nitricum9C
Phellandrium aquaticum9C
Arnica montana9C
Bryonia9C
Target species / Cattle

MODULE 2

PUBLIC ASSESSMENT REPORT

Legal basis of original application / Homeopathic
Date of conclusion of the procedure / 14th December 2017

I. SCIENTIFIC OVERVIEW

This was an application for a homeopathicremedy, Eurofit Intramammary Gel. The product was proposed for use in cattle, with no formal indications.

The proposed dose was one injector (30ml) into each quarter of the udder after each milking, (in the morning and in the evening),for 2-3 days.

Part 9 of Schedule 1 (Marketing Authorisations of the Veterinary Regulations 2013, paragraph 65 (1)), states that the procedure for registering a homeopathic product is the same procedure as that for granting a marketing authorisation for a non-homeopathic veterinary medicine, as shown in Part 3. However, no proof of efficacy is required.

In light of the overall data submitted, scientific discussion within the VMD, and subsequent referral to the VeterinaryProducts Committee, a negative opinion for Eurofit Intramammary Gel was adopted. The overall benefit:risk analysis was not in favour of acceptingtheregistration, and the application was refused.

REFUSAL REASON:

The product was deemed to have a negative benefit:risk balance for the target species, cattle. The introduction of a syringe into the udder sphincter was considered to be an unacceptable safety risk for the animal because pathogens could be introduced into the udder by this route of administration.Other quality and safety aspects of the product were considered resolvable, but these were not pursued further once the application was refused.

II.QUALITATIVE AND QUANTITATIVE PARTICULARS OF THE CONSTIUENTS

II.A.Composition

The product (a gel),containedthe following:

Stock Name / Grade / Dilution / Scale of Potency
Phytolacca decandra / MMH[1] / 30 / C
Hepar Sulfur / MMH / 30 / C
Siliceae / MMH / 30 / C
Sepia officinalis / MMH / 30 / C
Thuja occidentalis / MMH / 30 / C
Calcarea phosphorica / MMH / 30 / C
Pulsatilla pratensis / MMH / 30 / C
Iodum / MMH / 30 / C
Cantharis vesicatoria / MMH / 9 / C
Phosphorus / MMH / 9 / C
Baptisia tinctoria / MMH / 9 / C
Echinacea angustifolia / MMH / 9 / C
Acidum nitricum / MMH / 9 / C
Phellandrium aquaticum / MMH / 9 / C
Arnica montana / MMH / 9 / C
Bryonia / MMH / 9 / C
Other Substances
Diluent
Ethanol(as Ethanol (70% Solution)[2]
Inert Base
Sodium Alginate
Water for Injections

The container/closure system consists of an applicator formed from white HDPE, with a white LDPE cap. The applicator contains a pistonformed from white LDPE. The particulars of the containers and controls performed were provided and conformed to the regulation.The choice of the formulation and the absence of preservative were justified.

The product is established pharmaceutical form and its development is adequately described in accordance with the relevant European guidelines.

II.B.Description of the Manufacturing Method

The mother tinctures of the constituents of the product are provided by suppliers as 70% alcohol solutions, prepared from sterilised alcohol. From these tinctures, 29C and 8C potencies are produced by successive 1 in 100 dilutions in 70% sterilised ethanol. In the final dilution, water for injections is used as the diluent. 62.5 ml aliquots of the 29C and 8C potencies are mixed to form one litre of solution, which is mixed with 99 litres of water for injections and the gelling agent sodium alginate to produce the final 30C and 9C potencies presented in the product. The gel is then filled into intramammary syringes.

II.C.Control of Starting Materials

The homeopathic material contained multipleingredients described in the Materia Medica Homeopatica. The homeopathic materials were manufactured in accordance with theEuropean Pharmacopoeial (Ph.Eur) monograph 'Methods of preparation of homoeopathic stocks and potentisation'.The homeopathic material specifications were considered adequate to control the quality of the material.

Compliance with the Ph. Eur was demonstrated for 70% ethanol. Appropriate certificates of analysis were provided.

The packaging used was supported by satisfactory specifications and technical drawings, accompanied by suitable declarations of conformity with Ph. Eur and food contact use requirements.

II.C.4. Substances of Biological Origin

There are no substances within the scope of the TSE Guideline present or used in the manufacture of this product.

II.D.Control Tests Carried Out at Intermediate Stages of the Manufacturing Process

Not applicable.

II.E.Control Tests on the Finished Product

The finished product specification included tests on the finished product for: appearance, sodium alginate identity and content, extractable volume, pH, sterility and proof of absence of lead. Acceptable sterility data had not been provided at the time of refusal.

II.F.Stability

Stability data on the homeopathic materialswere not provided in accordance with applicable European guidelinesat the time of refusal.

III.SAFETY AND RESIDUES DOCUMENTATION (PHARMACO-TOXICOLOGICAL)

III.ASafetyDocumentation

Pharmacological Studies

No pharmacological data are required for applications for homeopathic remedies.

Toxicological Studies

There is no requirement for the provision of toxicological data for active substances in a Homeopathic Remedy Registration. However, a user risk assessment was required for the gel matrix, which was formed from sodium alginate and water for injections. (See User Safety).

Studies of Other Effects

Studies on eye and skin irritation tests,(performed in rabbits),were provided.

Eye irritation test

The test was performed on five rabbits fed on a normal diet and acclimatised to laboratory conditions. GLP[3]-compliance was not established.Results of the administration of the product to one eye of each animal, (the other eye was not treated in order to act as a negative control), showed minor, non-persistent reddening of the conjunctival mucosa. A warning was added to the user safety warnings in the proposed product literature:

  • This product may cause slight irritation if accidental eye contact occurs. If such contact occurs, wash eye thoroughly with cold water.

Skin irritation test

The test was performed on five rabbits fed on a normal diet and acclimatised to laboratory conditions. GLP-compliance was not established.

Results of the administration of the product to the pinna of the ear of each animal suggested, along with the results of the eye irritation test, that the product was not corrosive to skin.

Microbiological Studies

In vitro studies

Details of a ‘yoghurt test’, performed in accordance with CSN 570530 were provided. This test was performed on milk from animals treated with the proposed product, on order to observe any adverse effect on fermented milk. Ten milk samples from ten treated udder quarters were taken from ten cows, which were exhibiting general symptoms of infection/soreness in the udder. Milk samples were taken after the second milking following the last application of the product. Applications were performed for three days over six milkings.

User Safety

A user risk assessment was provided for the gel matrix. It was not considered likely that that the proposed product would pose an unacceptable risk to people administering the product to animals. However, the applicant’s proposed warnings and precautions as listed on the product literature were notconsidered adequate to ensure safety to users of the product, and amendments were proposed as follows:

  • Those with known hypersensitivity (allergy) to sodium alginate should avoid contact with this product.
  • This product may cause slight irritation if accidental eye contact occurs. If such contact occurs, wash eyes thoroughly with cold water.
  • Wash any exposed skin immediately after use.

Environmental Safety

No Environmental Risk Assessment is required for homeopathic remedies. However, the applicant provided an environmental impact statement, in which it was stated that because of the very low level of active substances present in the product, there would be no impact on the environment. This was accepted.

III.B.2Residues documentation

The applicant hasprovided proof that all substances included in the homeopathic remedy are suitable for use in food-producing animals under Regulation 37/2010.

Residue Studies

No residues data are required for applications for homeopathic remedies.

MRLs

The applicant demonstrated that all the constituents of the product had either entries in Table 1 of Regulation 37/2010, (which shows all approved maximum residues limits), or were on the CVMP’s ‘out-of-scope’ list. There were no consumer safety issues identified.

Withdrawal Periods

Meat and offal: Zero days.

Milk: Zero hours.

IV.CLINICAL DOCUMENTATION

Although no proof of efficacy is required for homeopathic preparations, safety issues in relation to the product administrator and the target animal are carefully considered. Because the product is placed within the udder sphincter, introducing the possibility of contamination into the teat quarter from environmental pathogens, the benefit/risk assessment for this product was considered to be negative.

VOVERALL CONCLUSION AND BENEFIT– RISK ASSESSMENT

The data submitted in the dossier demonstrate that the benefit/risk profile of the product not favourableand the application has been refused.

MODULE 4

POST-AUTHORISATION ASSESSMENTS

As the application was refused, there are no post-authorisation assessments.

VMD/L4/LicApps/TEMP/136/C1/9

[1] Materia Medica Homeopatica

[2] Prepared from Ethanol (96 per cent) Ph.Eur. 01/2015:1317 and Water for Injections Ph.Eur.

[3]GLP – Good Laboratory Practice.