Veterinary medicinal products containing toltrazuril to be administered orally to chickens - referral

Current status

European Commission final decision

Overview

On 14 July 2022, the European Medicines Agency (the Agency) completed a review of the safety of oral veterinary medicines containing toltrazuril for use in chickens. The Agency’s Committee for Veterinary Medicinal Products (CVMP) concluded that the benefits of these veterinary medicines continue to outweigh their risks but that risk mitigation measures should be taken to assure consumer safety, including the amendment of the restriction period before the onset of lay. The restriction period is the time between the administration of a medicine and the start of the laying period in which chickens must not be treated.

What is toltrazuril?

Toltrazuril is an antiparasitic medicine which interferes with the enzymes needed by coccidian parasites to produce energy. As a result it is able to kill the parasites at all stages of their development and prevent the symptoms of coccidiosis and the spread of infection. Coccidiosis is usually a mild disease but it can be serious in young animals. It is spread by ingestion of the parasite’s eggs in a contaminated environment and the main symptom is diarrhoea.

Toltrazuril is only used in veterinary medicine and is usually given to chickens, turkeys and other species in their water. The products included in this procedure were limited to veterinary medicines containing toltrazuril which are given to chickens. They are available in Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Slovak Republic, Slovenia, Spain and the United Kingdom.

Why were oral veterinary medicines containing toltrazuril reviewed?

The Dutch veterinary medicines authority received a report concerning the use of a toltrazuril product in the Netherlands in young laying chickens to treat an infection with Eimeria brunetti, one of the coccidian parasites, causing illness and mortality. The Dutch Inspection Unit requested a check for residues (the marker residue being toltrazuril sulfone, also known as ponazuril) before eggs could enter the food chain. The results demonstrated that the marker residue could be identified in treated layers up to 96 days after treatment.

The product information of a number of veterinary medicines authorised in the European Union indicates a restriction period of 4 weeks before the onset of lay, during which oral veterinary medicines containing toltrazuril must not be used in chickens. Due to the long retention of toltrazuril in eggs from treated birds, the Dutch authority considered that the restriction periods in the European Union might not be adequate to ensure consumer safety.

Consequently, the Dutch authority asked the CVMP to carry out an assessment of the benefit-risk balance of oral veterinary medicines containing toltrazuril for use in chickens and to issue an opinion on whether the marketing authorisations for these medicines should be maintained, varied, suspended or revoked across the European Union.

Which data has the CVMP reviewed?

No proprietary data relating to residue kinetics of toltrazuril in chicken eggs following oral administration were provided by the concerned companies. The CVMP reviewed data from published literature, an unpublished report provided by a European Reference Laboratory, pharmacovigilance data and proposals for risk mitigation measures provided by the concerned marketing authorisation holders.

What are the conclusions of the CVMP?

Based on the evaluation of the currently available data and the scientific discussion within the Committee, the CVMP concluded that the restriction periods in which chickens must not be treated with these medicines before the onset of lay should be amended, to provide assurance for consumer safety.

The full changes made to the product information are detailed in Annex III of the CVMP opinion under 'All documents'. 

The European Commission issued a decision on 9 November 2022.

Questions and answers on the review of oral veterinary medicines containing toltrazuril for use in chickens

Reference Number: EMA/709204/2022

Key facts

About this medicine

• Approved name:
  Veterinary medicinal products containing toltrazuril to be administered orally to chickens
• International non-proprietary name (INN) or common name:
  toltrazuril

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/V/A/144
• Type:
  Article 35

  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.

• Authorisation model:
  Nationally authorised product(s)

Key dates and outcomes

• Opinion date:
  14/07/2022
• EC decision date:
  09/11/2022

All documents

European Commission final decision

Veterinary medicinal products containing toltrazuril to be administered orally to chickens – Article 35 referral – Annex I, II, III

Questions and answers on the review of oral veterinary medicines containing toltrazuril for use in chickens

Reference Number: EMA/709204/2022

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)