Zinc oxide - referral

Current status

European Commission final decision

Overview

On 16 March 2017, the European Medicines Agency (the Agency) completed a review of the safety and effectiveness of veterinary medicinal products containing zinc oxide to be administered orally to food-producing species. The Agency's Committee for Medicinal Products for Veterinary Use (CVMP) concluded that the overall benefit-risk balance for veterinary medicinal products containing zinc oxide to be administered orally to pigs is negative, as the benefits of zinc oxide for the prevention of diarrhoea in pigs do not outweigh the risks for the environment.

The CVMP recommended the refusal of the granting of the marketing authorisations and the withdrawal of the existing marketing authorisations for veterinary medicinal products containing zinc oxide.

What is zinc oxide?

Zinc oxide is an inorganic compound and is known to be relatively poorly absorbed. Veterinary medicinal products containing zinc oxide are used for the treatment and/or prevention and control of post-weaning diarrhoea in piglets. Different indications and dosages are currently recommended, but zinc oxide is mainly used in the feed at a dosage of 100 mg per kg body weight per day for 14 consecutive days, which equates to 2500 ppm zinc in feed.

Why were orally-administered veterinary medicinal products containing zinc oxide reviewed?

In May 2015, following a referral procedure (EMEA/V/A/108) under Article 33(4) of Directive 2001/82/EC for Gutal 1000 g/kg premix for medicated feeding stuff for piglets1, the CVMP identified a risk to the environment due to accumulation of zinc. The CVMP considered that there is some uncertainty associated with the calculated risks for some environmental compartments and recommended various risk mitigation measures, which were anticipated to reduce the accumulation of zinc in the environment.

Nevertheless, in February 2016, due to remaining concerns related to the risk to the environment and the potential increase of prevalence of antibiotic resistant bacteria from the use of products containing zinc oxide, the Netherlands and France initiated a referral procedure under Article 35 of Directive 2001/82/EC for all orally-administered veterinary medicinal products containing zinc oxide and requested the CVMP to review all available data and to evaluate the overall benefit-risk balance of the products concerned.

Which data has the CVMP reviewed?

The applicants and marketing authorisation holders concerned by the referral procedure submitted proprietary data and scientific references on efficacy, antimicrobial resistance and environmental risk.

What are the conclusions of the CVMP?

Based on the evaluation of the currently-available data, the CVMP concluded that the overall benefit-risk balance for veterinary medicinal products containing zinc oxide to be administered orally to pigs is negative, as the benefits of zinc oxide for the prevention of diarrhoea in pigs do not outweigh the risks for the environment. The CVMP acknowledged that there is a risk of co-selection for resistance (the selection of multiple antimicrobial resistance genes by an antimicrobial) associated with the use of zinc oxide but that, at the present time, such risk is not quantifiable. Effective measures to manage the accumulation of zinc in the environment were not identified and, as a result, the CVMP recommended the refusal of the granting of the marketing authorisations and the withdrawal of the existing marketing authorisations for veterinary medicinal products containing zinc oxide.

The European Commission issued a decision on 26 June 2017 and Member States may defer the withdrawal of the marketing authorisations for up to five years from this date, if they consider that immediate action may have adverse impact in their territory given the lack of availability of alternatives and the change required in pig farming practices.

Zinc oxide Article-35 referral - Questions and answers on veterinary medicinal products containing zinc oxide to be administered orally to food-producing species

Reference Number: EMA/394961/2017 Summary:

Outcome of a referral procedure under Article 35 of Directive 2001/82/EC - EMEA/V/A/118

Key facts

About this medicine

• Approved name:
  Zinc oxide
• International non-proprietary name (INN) or common name:
  zinc oxide

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/V/A/118
• Type:
  Article 35 referrals (prior to January 2022)

  This type of referral is initiated in cases involving the interests of the Community or concerns relating to the protection of human or animal health or the environment.

Key dates and outcomes

• Opinion date:
  16/03/2017
• EC decision date:
  26/06/2017

All documents

European Commission final decision

Zinc oxide Article-35 referral - Annex I,II

Reference Number: EMEA/V/A/118

Zinc oxide Article-35 referral - Questions and answers on veterinary medicinal products containing zinc oxide to be administered orally to food-producing species

Reference Number: EMA/394961/2017 Summary:

Outcome of a referral procedure under Article 35 of Directive 2001/82/EC - EMEA/V/A/118

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)