The monitoring of marketing status of medicinal products aims to increase communication and transparency on availability of medicinal products across the Union and potential safety issues and to allow consideration on the need for action in different Member States or at EU level.
A PDF version of the entire post-authorisation guidance is available:
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.
See also:
For centrally-authorised medicinal products “marketed” means that at least one presentation of the medicinal product is at least marketed in one Member State of the Union.
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In accordance with Article 13(4) of Regulation (EC) No 726/2004, Marketing Authorisation Holders are required to inform EMA if their centrally-authorised product ceases to be placed on the market of a Member State, either temporarily or permanently.
By analogy to the placing on the market, the “cessation of placing on the market” or “marketing cessation” is defined in the general principles outlined in the Chapter 1 of volume 2A of the Notice to Applicants as the “cessation of release into the distribution chain” with the consequence that the concerned product may no longer be available for the supply to the patients.
The date of marketing cessation shall be the date of the last release into the distribution chain.
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Monitoring the marketing status of medicinal products in the EU allow for the application of Article 24(4) to (6) of Directive 2001/83/EC and Article 14(4) to (6) of Regulation (EC) No 726/2004 (“monitoring of the sunset clause” (See also Q&A on Sunset clause monitoring).
This marketing status reporting also aims to increase transparency on availability of medicinal products across the Union and to enable EMA and National Competent Authorities to consider the need for action in different Member States or at EU level to protect Public Health.
In case of a temporary marketing cessation, the anticipated reintroduction date needs to be provided.
MAHs are advised that when cessation/suspension/withdrawal is due to efficacy, safety and/or quality related issues for which already particular procedures are established, reporting of such cessation in IRIS is without prejudice to applying the other specific related procedures (e.g. quality defect, pharmacovigilance reporting, etc.), in parallel, as appropriate:
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The so-called marketing status overview refers to the picture of the marketing situation of a specific medicinal product, at one time point of the product life-cycle, per presentation and per Member State. As of July 2021, the EMA is using the IRIS database to collect the marketing status notifications for centrally-authorised products and to provide an up-to-date overview to the EU Member States. (see question How to report marketing status updates to the Agency for CAPs?)
MAHs should inform the Agency of the marketing status of their centrally authorised medicinal product(s), at the time of the initial placing on the market and for any subsequent changes in marketing status (i.e. temporary marketing cessation, reintroduction on the EU market or permanent cessation), for each presentation and in each Member State, according to the timelines given hereafter:
Since the IRIS database is intended to be kept up-to-date with the marketing status of centrally authorised medicinal products, it is no longer needed to provide an annual update to the Agency at the time of anniversary of the Commission Decision on the central marketing authorisation. However an overview of the marketing status of medicinal products is still expected to be provided within PSUR and renewal applications.
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EMA used to receive notifications of placing on the market, marketing cessations and withdrawn product notifications by email.
As of end of July 2021, EMA requests MAHs of centrally-authorised products (CAPs) to submit their marketing status notifications via the IRIS platform.
- For authorised CAPs not yet marketed in any EU/EEA MS, MAHs should report the initial placing on the market of relevant presentations and any subsequent marketing status updates directly via the IRIS platform.
- For authorised CAPS already marketed in at least one EU/EEA MS, MAHs will progressively upload the marketing status of their CAPs in IRIS during a 9-months transition period (baseline data). Whilst it is allowed to report changes to the marketing status of their CAPs via the existing process (emails) during the transition period, once the baseline data have been submitted in IRIS, reporting of changes to the marketing status should continue in IRIS.
How to report marketing status updates via IRIS (new process that can be used as of end of July 2021)
There are 3 possibilities to report updates on marketing status for a medicinal product:
This function allows to report the same change in marketing status affecting one or more presentations of a CAP in one or more MS (e.g. placing on the market of 3 presentations in 5 Member States on the same day).
This function enables to report several different changes in marketing status affecting one or multiple presentations in one or multiple MS, by uploading an excel spreadsheet (e.g. placing on the market of presentation B in CZ, AT and NL + marketing cessation of presentation A in IT on different dates).
This function allowsto report
How do I submit baseline data for already authorised CAP in IRIS?
For CAPS already marketed in at least one EU/EEA MS, MAHs should progressively upload the marketing status of their CAPs in IRIS during a 9-months transition period (baseline data). To upload the baseline data, the same options available to report marketing status updates can be used, i.e. single or bulk upload. For detailed information on how to perform the submission, see IRIS technical guidance (sections 6.1 and 6.2).
When submitting the baseline for the first time, the marketing status will appear in IRIS as ‘No data provided’.
Example: For product X, presentation 001 is currently in the market in ES and PT. Presentation 001 was first launched in ES on 01/01/1999 and in PT on 03/02/1999. By default the IRIS database reflects: “No data provided” for all presentations in all EU/EEA MS.
Report for 001 Statues: Marketed. ”Date of Marketing Status change” 01/01/1999 for ES and 03/02/1999 for PT. This will result in 01/01/1999 becoming the ”Date of initial placing in the market” in ES and 03/02/1999 becoming the ”Date of initial placing in the market” in PT.
In the exceptional situation where the launch date is unknown “01/01/1900” should be used.
Example: Presentation 002 of Product X was never marketed in any MS and is currently showing as ‘No data provided’. A Marketing Status change from ‘No data provided’ to ‘Never marketed’ should be submitted for presentation 002 for all MS. Date of Marketing Status change and Reason for Cessation can be left blank.
Example: Presentation 003 of Product X was first placed in the market in Austria on 01.03.1995 and is permanently ceased from 01.03.2021. The MAH should report as a single or bulk upload a change in Marketing status to ”Marketed” with ”Date of Marketing Status change” as 01.03.1995. Once this case is processed, the MAH should report a change of marketing status as ”Not Marketed” with ”Date of Marketing Status change” as 01.03.2021.
EMA has prepared a technical guidance to help MAHs to submit their marketing status updates via IRIS.
For any question regarding your IRIS submission please contact EMA Service Desk.
How to report marketing status updates via email (existing process to be discontinued from May 2022 for EU/EEA/UK(Northern Ireland))
During the 6-month transition period where IRIS is progressively being populated with marketing status data of CAPs, MAHs can continue to report the marketing status updates of their already marketed CAP via emails as per the existing process until the baseline data are submitted into IRIS:
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MAHs of nationally-authorised products (NAPs) are required to inform the relevant National Competent Authorities of the marketing status of their medicinal products as per the requirements of Articles 23a and 123 of Directive 2001/83/EC, as amended. 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.
MAHs of NAPs are also required to inform forthwith the EMA of any action taken by the holder, in a EU/EEA Member State or in a 3rd country,
when the reasons for such action are based on any of the grounds set out in Article 116 or Article 117(1) of Directive 2001/83/EC, as amended (e.g. related to efficacy, safety, quality and/or compliance issues)
Such 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.
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 should be done in parallel to the notification to the ESI mailbox (P-PV-emerging-safety-issue@ema.europa.eu).
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Click Withdrawn-product notification: questions and answers - MAH notification time to enlarge the image
As per the existing process, once the Agency receives a notification of a “withdrawn product” via email from a MAH whether this is for a centrally or nationally authorised medicinal product, the Agency forwards such notification to all Competent Authorities in the EEA without undue delay.
As of end of July 2021, EMA uses the IRIS database to collect marketing status updates in the different EU/EEA Member States including withdrawn product notifications for centrally-authorised products and this information will be accessible to the National Competent Authorities and the European Commission. Notifications of withdrawn products received by email for NAPs will continue to be forwarded to EEA Competent Authorities as per the existing process.
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The MAH should send by email a request for withdrawal of the marketing authorisation to the European Commission (SANTE-PHARMA-POLICY@ec.europa.eu and SANTE-PHARMACEUTICALS-DMP@ec.europa.eu) keeping in copy the EMA Product Lead, the CHMP/PRAC/CAT Rapporteurs (as applicable), Chairs and Vice chairs of relevant committees and the EMA withdrawn products mailbox (withdrawnproducts@ema.europa.eu).
The letter to the European Commission should cover the following points:
- Medicinal product concerned (name, EU number(s)…);
- The reason for the withdrawal of the marketing authorisation and whether or not it is based on the grounds provided in Articles 116 and 117 of Directive 2001/83/EC;
- The Member States where the product is currently marketed;
- The proposed effective date for the withdrawal of the MA. The withdrawal of the MA will become effective on the EC notification date by default (e.g. usually within two months of the MAH request), or by any date agreed with the European Commission and specified in the Commission decision withdrawing the marketing authorisation. The MAH is therefore invited to clarify in their request if they would like to suggest a withdrawal date more than the two-month after their request to withdraw the marketing authorisation.
- How the MAH will approach the continued use of any remaining product, as they will continue to be responsible for any remaining product on the market(s); The MAH should therefore ensure that any product remaining on the market has been produced according to current GMP standards and that the QP responsible for batch release remains fully responsible for any remaining product that may still be in the market, including continuous monitoring of any product defects. Further, the MAH should ensure that the Pharmacovigilance System is still fully active in monitoring any safety signals that may arise from the usage of the withdrawn product and that the QP responsible for Pharmacovigilance is still maintaining all responsibilities for the product (whilst stock remains).
- How and when the company plans to inform the public, doctors and pharmacists, as applicable;
- The therapeutic alternative available, if appropriate, and whether the planned withdrawal will allow physicians and patients adequate time to consider and transition to alternative therapies.
- For medicinal products authorised in a paediatric indication, the MAH should confirm whether Article 35 of Regulation (EC) No 1901/2006 would apply in their case and what actions they are undertaking to comply with the requirements of the Paediatric regulation to ensure the medicinal product remains available to EU paediatric patients.
Provided that the withdrawal is solely based on commercial reasons (i.e. the withdrawal of the marketing authorisation is not linked to underlying quality, safety, efficacy or benefit/risk issues), it is agreed at EU level that there is no need for batch recalls for CAPs, the medicinal product can remain on the EU market until expiry date. The MAH remains responsible for the batches on the market and for pharmacovigilance activities.
In parallel to the formal request made to the Commission, IRIS needs to be updated via the withdrawn product notification (see question “How to report marketing status updates to the Agency for CAPs?”)
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MAHs are also required to notify the EMA of any action taken outside the EEA to suspend the marketing of a medicinal product, to withdraw a medicinal product from the market, to request the withdrawal of a marketing authorisation or not to apply for the renewal of a marketing authorisation, when such action is based on any of the grounds set out in Article 116 or Article 117(1) (e.g. quality, safety or efficacy issue).
Such notification should continue to be made by email to withdrawnproducts@ema.europa.eu using the below templates
with the Product mailbox and EMA Product lead in copy.
It is planned that these notifications regarding non-EEA countries will be included into IRIS and the EMA will communicate when such function is developed.
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Currently, only information on withdrawn products are made public on the EMA website:
As of July 2021, EMA uses the IRIS database to collect an overview of the marketing status of centrally authorised products in the EU/EEA/UK(Northern Ireland) (at presentation level) Currently these marketing status data are only shared with the National Competent Authorities and the European Commission.
In the future, information on the availability of EU medicinal products might be made publicly available. The Agency will communicate in due course when such functionality becomes available.
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The so-called “sunset clause” is a provision leading to the cessation of the validity of the marketing authorisation if:
For centrally-authorised products, the European Commission may grant exemptions on public health grounds and in exceptional circumstances if duly justified.(See question How to request an exemption to the sunset clause provision for centrally-authorised products?)
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This provision applies prospectively to all centrally authorised medicinal products from the date of entry into force of the Regulation i.e. 20 November 2005.
Therefore, for centrally-authorised medicinal products for which a MA has been granted before 20 November 2005 and for which no presentation are marketed in the Union at this date, the three-year period which leads to cessation of the MA will start as of 20 November 2005.
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The marketing authorisation of a medicinal product will remain valid if at least one authorised presentation/pack-size is placed on the market in the Union (in at least one EU/EEA Member State).
The marketing authorisation of a centrally authorised medicinal product includes the initial marketing authorisation and all variations (e.g. additional presentations) and extensions (e.g. new strengths, new pharmaceutical forms) authorised for this specific medicinal product. This notion has been applied since the beginning of the centralised procedure and is reflected in the way the EU numbers are allocated to a specific centrally authorised medicinal product and all its presentations.
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A three-year period without marketing of a medicinal product in the EEA can be encountered further to the granting of the marketing authorisation: when a medicinal product has never been marketed or, after marketing of a medicinal product has been completely stopped.
The term “no longer actually present on the market” should be understood in the same way as “ceases to be placed on the market”. Therefore, the sunset clause period in case of a complete marketing cessation of the product shall start from the last date of release into the distribution chain of the medicinal product. For definition and modalities of reporting of cessation, details are given in Marketing and cessation notification.
As of end of July 2021, the EMA uses the IRIS database to collect marketing status updates and monitor the sunset clause provision for centrally authorised medicinal products. This is done in view to notify the Commission when a three consecutive year period without marketing has elapsed and that the sunset clause provision should take effect.
The MAH should be aware of the timing with regard to the sunset clause period for their product in order to take any action, should they wish to retain their central marketing authorisation.
Please refer to the Q&A on marketing status updates and withdrawals for more information on the IRIS database and the reporting of actual marketing and marketing cessation.
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The determination of the start of the 3-year period from granting of the marketing authorisation should be the date when the medicinal product can be marketed by the marketing authorisation holder, taking into account, e.g. marketing protection and other protection rules which have to be respected.
For a medicinal product authorised after 20 November 2005 under the centralised procedure, the Commission Decision will, in most cases, initiate the monitoring of the sunset clause and trigger the 3-year period.
However, where data protection rules applies to reference products, the 3-year period for generic, hybrids and similar biological medicinal products will start as of the end of the 10 or 11-year of marketing protection period of the concerned reference medicinal product.
Furthermore, other protection rules might need to be respected. Such information is not known by the Agency. MAHs are therefore advised to inform the EMA Product Lead of the existence and if known, the expiry date of the other protection period(s) to be respected as appropriate. This should be notified within 60 days from the date of the granting of the MA.
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The following situations can lead to the start of the sunset clause period (“ON”):
At the time of the granting of the marketing authorisation, the medicinal product may not be immediately placed on the Community market. As a consequence, the sunset timer will start running from the granting of the marketing authorisation by the Commission or when the MAH can legally place the medicinal product on the market. (see also question 5 of this Q&A listing: "In case of a protection period to be respected before placing the medicinal product on the market, when will the sunset clause period start counting?")
The MAH is obliged to inform the Agency of any product cessation (see question 1 of the Marketing and cessation notification Q&A listing). When there is no longer any presentation of the medicinal product placed on the Community market, the sunset timer will start running from the last date of release into the distribution chain of the medicinal product.
The following situations lead to the stop of the sunset clause period (“OFF”):
The sunset timer will stop running at the time of the first placing on the market of one presentation in one Member State.
As soon as a medicinal product is again placed on the Community market after a temporary cessation, the sunset timer will stop running at this date.
As soon as an exemption is granted by the Commission for a medicinal product, the sunset timer will be stopped.
The Commission may grant exemptions from the application of the sunset clause on public health grounds and in exceptional circumstances.
Exemptions can apply at any time of the central marketing authorisation life cycle (i.e. at the time of the marketing authorisation, during the marketing authorisation life, or approaching the expiry of the sunset clause period) depending on the type of exemptions.
At submission stage the following exemptions might be applicable:
It will be up to the MAH to justify why an exemption should apply based on public health grounds and in exceptional circumstances.
A request for an exemption including a justification should be notified to the European Commission, Health and Food Safety Directorate-General, Unit B5 (SANTE-PHARMA-POLICY@ec.europa.eu) with the EMA product lead, product mailbox and marketingstatus@ema.europa.eu in copy. Each justification will be considered on a case-by-case basis.
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