Doxyprex 100mg Premix - referral

Current status

European Commission final decision

Overview

Doxyprex 100 mg premix presented in 5 kg, 20 kg and 25 kg bags containing 100 mg/g doxycycline base as hyclate. The product is authorised with the indication the treatment of swine respiratory disease caused by Pasteurella multocida, Bordetella bronchiseptica and Mycoplasma hyopneumoniae.

In December 2005, a Mutual Recognition Procedure (MRP) started with Spain acting as Reference Member State and ten Concerned Member States.

Germany could not agree to the granting a marketing authorisation and the matter was referred to the Co-ordination Group for Mutual Recognition and Decentralised Procedures, CMD(v), and subsequently to the Committee for Medicinal Products for Veterinary Use (CVMP). Germany considered that the product could represent a potential serious risk to animal health on the grounds that the efficacy had not been sufficiently substantiated.

The CVMP during its meeting of 21-22 June 2006 started a referral procedure under Article 33(4) of Directive 2001/82/EC, as amended, for Doxyprex 100 mg premix. The Marketing Authorisation Holder (MAH) was requested to substantiate the efficacy of the product.

The applicant provided a justification for submission of this application on a “well-established use” basis. Within the EU doxycycline-based premix products for pigs at recommended dose rates of 10mg/kg once daily for 5 days are stated as having been authorised since 1985. Similar products with 8 or 10 days treatment durations are also available within the EU. Annex I of Directive 2001/82/EC as amended by directive 2004/28/EC notes that post-marketing experience with other products containing the same constituents is of particular importance and applicants should put a special emphasis on this issue. Therefore, the CVMP considered that the reports mentioned above give favourable evidence for the safety and efficacy of doxycycline in general, but also for the specific final formulation as marketed in Spain.

The applicant submitted a scientific report on Porcine Respiratory Disease Complex (PRDC). In the pivotal clinical trial, the presence of P. multocida and B. bronchiseptica was clearly demonstrated in sick pigs, however, no post treatment sampling was done to show bacteriological cure. The applicant justifies that the presence of M. hyopneumoniae was not determined by bacteriological methodsbecause it was difficult to isolate at that time. The presence was assumed. The applicant providedevidence of efficacy of the active substance, doxycycline, against M. hyopneumoniae in pigs from published literature and from MIC studies. These are all references provided with the original submission. However, the CVMP considered that the fact that no post treatment bacteriological samples were taken mean that bacteriological cure cannot be assumed or claimed.

The CVMP recommended the granting of the marketing authorisation to Doxyprex 100 mg/g Premix for medicated feeding stuff for pigs for the following indication because a positive benefit/risk analysis has been demonstrated and no potential serious risk has been identified.

“For the treatment and prevention of porcine respiratory disease, caused by Pasteurella multocida andBordetella bronchiseptica, susceptible to doxycycline, when the disease has been diagnosed in the herd.”

A benefit-risk analysis could not be conducted due to the lack of pivotal evidence on clinical efficacy for the indication M. hyopneumoniae. Therefore, the recommendation is to remove this pathogen from the indications.

The CVMP Opinion was adopted on 14 February 2007 and the subsequent Commission Decision on 22 May 2007.

Opinion following an Article 33(4) referral for Doxyprex 100mg premix: Background information

AdoptedReference Number: EMEA/532206/2007- Rev.1

Key facts

About this medicine

• Approved name:
  Doxyprex 100mg Premix
• International non-proprietary name (INN) or common name:
  Doxycycline

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  CVMP/532206/07
• Type:
  Article 33

  Mutual-recognition and decentralised referral: initiated because of disagreement between Member States within the framework of the mutual-recognition or decentralised procedure.

Key dates and outcomes

• Opinion date:
  14/02/2007
• EC decision date:
  22/05/2007

All documents

Doxyprex 100mg Premix - Article 33 Referral - Annex I, II, III

Adopted

Opinion following an Article 33(4) referral for Doxyprex 100mg premix: Background information

AdoptedReference Number: EMEA/532206/2007- Rev.1

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)