Withdrawn-product notification: questions and answers

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This page lists questions relating to marketing cessation, marketing suspension and withdrawals of medicinal products from the market and of marketing authorisations in the context of the implementation of Directive 2012/26/EU and Regulation (EU) No 1027/2012 amending the pharmaceutical legislation with respect to pharmacovigilance.

The aim of these amendments is to strengthen the European system for the monitoring of safe and effective use of medicinal products including communication and transparency on potential safety issues and to allow consideration of the need for action in different Member States or at EU level. Revised topics are marked 'New' or 'Rev.' upon publication.

A PDF version of the entire post-authorisation guidance is available:

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure

These questions and answers have been produced for guidance only and should be read in conjunction with the rules governing medicinal products in the European Union, volume 2, notice to applicants.

MAHs must in all cases comply with the requirements of Community legislation. Provisions that extend to Iceland, Liechtenstein and Norway by virtue of the European Economic Area agreement are outlined in the relevant sections of the text.

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1. Do I have to notify market cessation, withdrawal, suspension of my medicinal product / marketing authorisation? Rev. August 2014

Marketing Authorisation Holders (MAHs) have to notify to the competent authorities any of the following actions they intend to take:

  • Temporary or permanent cessation of marketing of a medicinal product;
  • Suspension of marketing of a medicinal product;
  • Withdrawal of a medicinal product from the market;
  • Request for the withdrawal of a marketing authorisation;
  • Non-application for the renewal of a marketing authorisation.

Hereafter the medicinal products affected by any of these actions will be referred to as “withdrawn products”.

Such notification on “withdrawn products” should be provided by MAHs when the action affects either a pharmaceutical form or strength of a medicinal product in at least one Member State.

When the action affects a presentation in at least one Member State, the MAH should report such action via other means in the context of the “sunset clause monitoring”:

  • For centrally authorised products, this should be done through the marketing status overview. (See section 20 “Marketing and cessation notification” of the Post-authorisation Guidance)
  • For nationally authorised product, this should be done according to national requirements of competent authorities of Member State(s).

However, when the action affects a presentation that may raise a public health concern, a notification should be made to the Agency through the dedicated mailbox withdrawnproducts@ema.europa.eu using the template cover letter and notification report table “Notification of withdrawn products”, and to the Member State(s) concerned as applicable. The MAH has to exercise his best judgement to determine when it is appropriate to notify such cessation.

Regarding the definition of “cessation of placing on the market”, please refer to section 20 “Marketing and cessation notification” of the Post-authorisation Guidance, Question 20.2 “What is the meaning of “cessation of placing on the market”?.

References


1 Directive 2012/26/EU of the European Parliament and of the Council of 25 October 2012 amending Directive 2001/83/EC as regards pharmacovigilance.
2 Regulation (EU) No 1027/2012 of the European Parliement and of the Council 25 October 2012 amending Regulation (EC) No 726/2004 as regards pharmacovigilance.

2. Which medicinal products are concerned? Rev. August 2014

The obligation for the notification of cessation of placing a medicinal product on the market, suspension of the marketing of a medicinal product, withdrawal of a medicinal product from the market, request for the withdrawal of a marketing authorisation and the non-application for the renewal of a marketing authorisation apply to both centrally and nationally authorised medicinal products (including those authorised through the mutual recognition and decentralised procedures).

For nationally authorised products, notification to the EMA should only take place if the reason for the aforementioned actions is related to efficacy, safety, quality or compliance issues as listed in Question 3 “What information should be included in my notification and to whom should I notify?”.

3. What information should be included in my notification and to whom should I notify? Rev. August 2014

The notification should clearly state the action intended to be taken by the MAH (see Question 1 “Do I have to notify market cessation, withdrawal, suspension of my medicinal product / marketing authorisation?”) and the reason for such action, in particular when these are based on any of the following grounds:

  • the medicine is harmful;
  • the medicine lacks therapeutic efficacy;
  • the risk-benefit balance of the medicine is not favourable;
  • the qualitative and quantitative composition of the medicine are not as declared;
  • the controls on the medicinal product and/or on the ingredients and the controls at an intermediate stage of the manufacturing process have not been carried out or if some other requirement or obligation relating to the grant of the manufacturing authorisation has not been fulfilled.

For centrally authorised medicinal products, MAHs have to notify the Agency.

For nationally authorised medicinal products, MAHs have to notify the competent authorities of the Member State(s) concerned. They also have to notify the Agency when the action is based on one of the grounds listed above. Otherwise the Agency should not be notified of such action.

MAHs are advised that where the action is due to efficacy, safety and/or quality related issues for which particular procedures are already established, the notification according to the present provisions is without prejudice to any other reporting obligations related to medicinal products (e.g. quality/compliance issues, Pharmacovigilance issues, etc.), as appropriate (see Questions 5 and 6 “How should I proceed for my notification for a centrally / nationally authorised medicinal products”).

Such notification is also without prejudice to reporting the marketing status overview for the centrally authorised medicinal products at presentation level and per Member State, as detailed in the section 20 “Marketing and cessation notification” of the Post-authorisation Guidance)

 

References

4. When shall the notification be made? Rev. August 2014

The MAH shall notify the competent authorities, other than in exceptional circumstances, no less than two months before the interruption in the placing on the market of the product. This applies to both temporary interruptions and permanent interruptions.

Besides, the MAH shall notify the competent authorities forthwith of any action taken either in the EEA or in a third country to:

  • suspend the marketing of a medicinal product;
  • withdraw a medicinal product from the market;
  • request the withdrawal of a marketing authorisation;
  • not to apply for the renewal of a marketing authorisation.

The grounds for any of the (intended) actions above should be declared as indicated in this Q&A (see Question 5 “How should I proceed for my notification for a centrally authorised medicinal product?” and Question 6 “How should I proceed for my notification for a nationally authorised medicinal product?”)

MAH notification time


 

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References

5. How should I proceed for my notification for a centrally authorised medicinal product? Rev. August 2014

The MAH of a centrally authorised medicinal product should inform the Agency of the (intended) action together with the reasons if:

  • the action considered is taken in the EEA;
  • the action considered is taken in a third country and is related to efficacy, safety, quality and/ or compliance issues as listed in Question 3 “What information should be included in my notification and to whom should I notify?”..

The notification should be made to the Agency via the dedicated mailbox withdrawnproducts@ema.europa.eu by using the template cover letter and notification report table “Notification of withdrawn products”.

The EMA Product Lead and the Rapporteur of the product should always be kept informed.

Particular cases:

  • In case of an emerging safety issue1 (ESI), should the MAH decide to take any action with regards to the marketing of the medicinal product or to the marketing authorisation of this medicinal product, the notification of such action to the Agency according to the present provisions should be done in parallel to the notification to the ESI mailbox.
  • In case of a quality defect, should the MAH decide to take any action with regards to the marketing of the medicinal products or to the marketing authorisation of this medicinal products, the MAH should complete the published Defective Product Report Form, specifying in which countrie(s) the action(s) is/are taken and the anticipated date(s) as to when the medicinal product is no longer available on the market of the concerned countrie(s). The form should be sent to qdefect@ema.europa.eu as detailed in Notifying quality defects or products recalls. Please note that no separate notification to the EMA via the mailbox withdrawnproducts@ema.europa.eu is required.
  • In case of a voluntarily request from the MAH to withdraw a marketing authorisation, the MAH should send a letter to the European Commission to request a withdrawal of the marketing authorisation. The MAH should notify the Agency of such request to the Commission via the dedicated mailbox withdrawnproducts@ema.europa.eu by using the template cover letter and notification report table “Notification of withdrawn products”, and should copy the EMA EPL and the CHMP Chair. The MAH should attach to its notification a scanned copy of the letter addressed to the European Commission.

References


1An emerging safety issue (ESI) is defined as a new information on the safety or efficacy of the medicinal product in the post-authorisation phase used inside or outside the terms of its marketing authorisation which might influence the evaluation of its benefit-risk profile or have an impact on the public. An ESI may arise from any source including (but not limited to) a study (interventional or non-interventional), scientific or medical literature, signal detection activities, any routine activities performed by the MAH, or regulatory actions taken outside the EU.

6. How should I proceed for my notification for a nationally authorised medicinal product? Rev. December 2014

The MAH of a nationally authorised medicinal product (including those authorised through the mutual recognition and decentralised procedures) should inform the competent authorities of the Member states concerned of the (intended) action together with the reasons for such action if:

  • the action considered is taken in the EEA;
  • the action considered is taken in a third country and is related to efficacy, safety, quality and/or compliance issues as listed in Question 3 'What information should be included in my notification and to whom should I notify?'.

Notification to the competent authorities of the Member State(s) concerned should be submitted in accordance with the practices established at national level if applicable. Where national competent authorities have not provided particular instructions, the template cover letter and notification report table 'Notification of withdrawn products' should be used.

In addition, if the action is related to efficacy, safety, quality and/or compliance issues as listed in Question 3 'What information should be included in my notification and to whom should I notify?', the MAH of a nationally authorised medicinal product should also notify the Agency together with the reasons for such action, regardless of whether the action is going to be taken in the EEA or in a third country.

In case of an emerging safety issue (ESI), should the MAH decide to take any action with regards to the marketing of the medicinal product or to the marketing authorisation of this medicinal product, the notification of such action to the Agency according to the present provisions should be done in parallel to the notification to the ESI mailbox.

References

7. How will the Agency inform the Member States? Rev. August 2014

Once the Agency receives a notification of a “withdrawn product” from a MAH whether for a centrally or nationally authorised medicinal product, the Agency forwards such notification to all Competent Authorities in the EEA without undue delay.

 References

8. What will be the follow-up of my notification?

As part of the follow-up of the notified action, Member States and/or the Agency may request additional information from the MAH. Depending on the action taken and the grounds for such action, the appropriate regulatory procedure will be initiated where applicable.

9. Will the Agency publish the list of “withdrawn medicinal products”? Rev. August 2014

The Agency should annually make public a list of human medicinal products which have been withdrawn from the EU market. This includes both centrally and nationally authorised products for which marketing authorisations have been refused, revoked or suspended and products, whose supply has been prohibited or which have been withdrawn from the market.

The list specifies whether the action has been initiated by the Marketing Authorisation Holder or whether it was imposed by the Competent Authorities (e.g. following a review procedure at European level).

The EMA aims at publishing an updated list twice a year.

References

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