On 11 July 2007, France presented to the EMEA a referral under Article 35 of Directive 2001/82/EC, as amended, concerning Tribrissen Oral Paste for Horses (including associated names) and authorised products for which this product served as a reference product, containing trimethoprim and sulfadiazine as active ingredient.
France considered that the dosing regime of the product is not correct. It considered that this may lead to lack of efficacy and furthering resistance development in target pathogens, which could possibly lead to risks to human health where zoonotic bacteria are concerned.
The CVMP started the referral procedure during its meeting of 10-12 July 2007. The Marketing Authorisation Holders were requested in a list of questions to provide:
- Justification of the recommended dose for each of the indications claimed in relation to efficacy and potential selection of antimicrobial resistant bacteria.
- Part I Summary of the dossier, including the Summary of Product Characteristics, the expert reports and the quantitative and qualitative composition of the product;
- If applicable, Part IV Efficacy information, including information on pharmacokinetics, pharmacodynamics and anti-microbial resistance data.
- The Periodic Safety Update Reports for at least the last 3 years.
- Justification of the withdrawal period, in case the recommended dose should increase.
Marketing Authorisation Holders submitted written responses, defending the authorised dose of 1x30 mg/kg body weight per day for all indications but suggesting a higher dose may be required in the case of salmonellosis. Neither the Periodic Safety Update Reports of the products nor the literature presented included reports of lack of efficacy in the field. Having assessed the responses, the CVMP concluded that:
- The efficacy of a dose of 1x30 mg/kg body weight per day to be administered over a maximum period of 5 days has been substantiated for all indications, except for salmonellosis.
- There is no documented evidence of problems relating to lack of efficacy or any change in the resistance situation of the relevant target pathogens that would constitute a concern relating to animal or human health.
- No dose could be established for the treatment of salmonellosis.
- The use of the product should be based on susceptibility testing and take into account official and local antimicrobial policies.
- The established withdrawal periods are safe and can be retained.
The CVMP recommended varying the Marketing Authorisations of the concerned veterinary medicinal products in accordance with the conclusions where applicable.
The CVMP Opinion was adopted on 12 December 2007 and the subsequent Commission Decision on March 2008.
|International non-proprietary name (INN) or common name||
European Commission final decision
Community interest referral: initiated in cases involving the interests of the Community or concerns relating to the protection of human or animal health or the environment.
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Opinion following an Article 35 referral for veterinary medicinal products which contain the active substances trimethoprim and sulfadiazine: Background information (PDF/30.72 KB)Adopted
First published: 02/08/2008
Last updated: 02/08/2008
Tribrissen - Article 35 Referral - Annex I, II, III (PDF/66.09 KB)Adopted
First published: 10/10/2008
Last updated: 10/10/2008
Description of documents published
Please note that some of the listed documents apply only to certain procedures.
- Overview - lay-language summary of the stage of the procedure
- Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
- List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
- Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
- List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
- List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. veterinary healthcare professionals, farmers, academia) (if applicable)
- Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
- Scientific conclusions – scientific conclusions of CVMP
- Divergent positions – divergent positions of the CVMP members (if applicable)
- Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
- Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
- Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)