PUBLIC RELEASE SUMMARY on the Evaluation of the New Active Monepantel in the Product Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep APVMA Product Number 62752 JUNE 2010 © Commonwealth of Australia 2010 This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part may be reproduced without permission from the Australian Pesticides & Veterinary Medicines Authority. Requests and inquiries concerning reproduction and rights can be made to: The Manager, Public Affairs Australian Pesticides and Veterinary Medicines Authority PO Box 6182 KINGSTON ACT 2604 Australia Email: [email protected] This document is published by the APVMA. In referencing this document the APVMA should be cited as both author and publisher. ISSN: 1443-1335 Website: This publication is available from the APVMA website: http://www.apvma.gov.au Comments and enquiries may be directed to: Contact Officer Veterinary Medicines Program Australian Pesticides & Veterinary Medicines Authority PO Box 6182 KINGSTON ACT 2604 Australia Telephone: +61 2 6210 4700 Fax: +61 2 6210 4776 Email: #[email protected] CONTENTS iii CONTENTS PREFACE V About this document v Making a submission v Further information vi 1 INTRODUCTION 1 2 CHEMISTRY AND MANUFACTURE 2 2.1 ACTIVE CONSTITUENT 2 2.2 PRODUCT 3 2.3 RECOMMENDATION 3 3 TOXICOLOGICAL ASSESSMENT 5 3.1 EVALUATION OF TOXICOLOGY 5 3.2 PUBLIC HEALTH STANDARDS 9 4 RESIDUES ASSESSMENT 10 4.1 INTRODUCTION 10 4.2 DATA PROVIDED 10 4.3 EVALUATION SUMMARY 10 4.4 CONCLUSIONS AND RECOMMENDATIONS 15 5 ASSESSMENT OF OVERSEAS TRADE ASPECTS OF RESIDUES IN FOOD 17 6 OCCUPATIONAL HEALTH AND SAFETY ASSESSMENT 20 6.1 HEALTH HAZARDS 20 6.2 FORMULATION, PACKAGING, TRANSPORT, STORAGE AND RETAILING 20 6.3 USE PATTERN 20 6.4 EXPOSURE DURING USE 20 6.5 EXPOSURE DURING RE-ENTRY 21 6.6 RECOMMENDATIONS FOR SAFE USE 21 6.7 CONCLUSION 21 7 ENVIRONMENTAL ASSESSMENT 22 7.1 INTRODUCTION 22 7.2 ENVIRONMENTAL CHEMISTRY AND FATE 22 7.3 ENVIRONMENTAL EFFECTS 23 7.4 PREDICTION OF ENVIRONMENTAL RISK 24 7.5 CONCLUSION 25 iv PUBLIC RELEASE SUMMARY – [PRODUCT NAME] 8 EFFICACY AND SAFETY ASSESSMENT 27 8.1 EVALUATION OF EFFICACY DATA 27 8.2 EVALUATION OF TARGET ANIMAL SAFETY DATA 29 8.3 CONCLUSIONS 31 9 LABELLING REQUIREMENTS 32 ABBREVIATIONS 75 GLOSSARY 78 REFERENCES 79 LIST OF TABLES Table 1: The Limits of Quantification (LOQs) and Limits of Detection (LODs) for the analytical method 12 Table 2: MRL Standard - Table 1 Amendments 16 Table 3: MRL Standard – Table 3 Amendments 16 Table 4: Comparison of the recommended Australian and overseas monepantel MRLs/tolerances 18 PREFACE v PREFACE The Australian Pesticides and Veterinary Medicines Authority (APVMA) is an independent statutory authority with responsibility for assessing and approving agricultural and veterinary chemical products prior to their sale and use in Australia. In undertaking this task, the APVMA works in close cooperation with advisory agencies, including the Department of Health and Aging, Office of Chemical Safety and Environmental Health (OCSEH), Department of the Environment, Water, Heritage and the Arts (DEWHA), and State Departments of Primary Industry. The APVMA has a policy of encouraging openness and transparency in its activities and of seeking community involvement in decision making. Part of that process is the publication of public release summaries for all products containing new active ingredients. The information and technical data required by the APVMA to assess the safety of new chemical products and the methods of assessment must be undertaken according to accepted scientific principles. Details are outlined in the APVMA’s publication Vet MORAG: Manual of Requirements and Guidelines. This Public Release Summary is intended as a brief overview of the assessment that has been completed by the APVMA and its advisory agencies. It has been deliberately presented in a manner that is likely to be informative to the widest possible audience thereby encouraging public comment. About this document This is a Public Release Summary. It indicates that the Australian Pesticides and Veterinary Medicines Authority (APVMA) is considering an application for registration of an agricultural or veterinary chemical. It provides a summary of the APVMA’s assessment. Comment is sought from industry groups and stakeholders on the information contained within this document. Making a submission In accordance with sections 12 and 13 of the Agvet Code, the APVMA invites any person to submit a relevant written submission as to whether the application for registration of Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep should be granted. Submissions should relate only to matters that the APVMA is required by legislation to take into account in deciding whether to grant the application. These grounds include occupational health and safety, chemistry and manufacture, residues, safety and first aid, environmental fate and toxicity, trade and efficacy. Submissions should state the grounds on which they are based. Comments received outside these grounds cannot be considered by the APVMA. vi PUBLIC RELEASE SUMMARY – ZOLVIX MONEPANTEL BROAD SPECTRUM ORAL ANTHELMINTIC FOR SHEEP Submissions must be received by the APVMA by close of business on Monday 5 July 2010 and be directed to the contact listed below. All submissions to the APVMA will be acknowledged in writing via email or by post. Relevant comments will be taken into account by the APVMA in deciding whether the product should be registered and in determining appropriate conditions of registration and product labelling. When making a submission please include: • Contact name • Company or Group name (if relevant) • Postal Address • Email Address (if available) • The date you made the submission. All personal and confidential commercial information (CCI)1 material contained in submissions will be treated confidentially. Written submissions on the APVMA’s proposal to grant the application for registration that relate to the grounds for registration should be addressed in writing to: Zuzanna Rajczyk Veterinary Medicines Program Australian Pesticides and Veterinary Medicines Authority PO Box 6182 Symonston ACT 2609 Phone: (02) 6210 4733 Fax: (02) 6210 4741 Email: [email protected] Further information Further information can be obtained via the contact details provided above. Further information on public release summaries can be found on the APVMA website: http://www.apvma.gov.au 1 A full definition of "confidential commercial information" is contained in the Agvet Code. INTRODUCTION 1 1 INTRODUCTION The Australian Pesticides and Veterinary Medicines Authority (APVMA) has before it an application from Novartis Animal Health Australasia Pty Ltd for registration of a new product, Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep, containing the new active constituent monepantel. This publication provides a summary of the data assessed and an outline of the regulatory considerations for the proposed registration of Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep. Internal parasites are a major problem in sheep in Australia. Anthelmintics are used to control worms in sheep, however development of resistance to the commonly used anthelmintics is becoming an increasing problem. Monepantel is a new amino-acetonitrile derivative (AAD) anthelmintic with a novel mode of action. It acts on a nematode-specific ACR-23 nicotinic acetylcholine receptor sub-unit. Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep is an oral drench that contains 25 mg/mL monepantel. The proposed use is for the treatment and control of AAD-sensitive strains of gastro-intestinal roundworms (nematodes), including macrocyclic lactone, benzimidazole (white), levamisole (clear) and morantel-resistant strains in sheep. The proposed dose rate is 2.5 mg monepantel/kg bodyweight (1 mL Zolvix/10 kg bodyweight). Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep is administered as a single treatment. If repeat treatments are necessary, sheep are not to be retreated less than 21 days after the last treatment and after 3 consecutive treatments, 115 days must elapse before treating again with Zolvix. Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep will be packaged in 0.25L, 0.5L, 1L, 2.5L, 5L and 10L containers. Zolvix Monepantel Broad Spectrum Oral Anthelmintic for Sheep is currently registered in New Zealand, Uruguay and 27 countries in the European Union. The APVMA seeks public comment on the product outlined in this document prior to the product being registered for use in Australia. The APVMA will consider all responses received during the public consultation period in deciding whether the product should be registered and in determining conditions of registration and product labelling. 2 PUBLIC RELEASE SUMMARY – ZOLVIX MONEPANTEL BROAD SPECTRUM ORAL ANTHELMINTIC FOR SHEEP 2 CHEMISTRY AND MANUFACTURE 2.1 ACTIVE CONSTITUENT Monepantel is a new active constituent and there is no compendial specification available. The Pharmaceutical Chemistry Section of the APVMA has evaluated the chemistry aspects of monepantel (manufacturing process, quality control procedures, batch analysis results and analytical methods). The chemical active constituent monepantel has the following properties: COMMON NAME (ISO): Monepantel (INN) CHEMICAL NAME: N-[(1S)-1-Cyano-2-(5-cyano-2-fluoromethylphenoxy)-1-methylethyl]-4- trifluoromethylsulfanylbenzamide CHIRALITY: The active substance has one