Notifying a change of marketing status

• In accordance with Article 13(4) of Regulation (EC) No 726/2004, Marketing Authorisation Holders are required to inform EMA of the date(s) of actual marketing of their centrally-authorised product on the Union Market.
• The actual marketing corresponds to the “placing on the market” which is defined in Chapter 1 of volume 2A of the Notice to Applicants as the date of release into the distribution chain i.e. out of the direct control of the Marketing Authorisation Holder. This also applies to the placing on the market following a marketing cessation.

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.

References

• Article 13(4) of Regulation (EC) No 726/2004
• Article 23a of Directive 2001/83/EC, as amended
• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2A

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.

References

• Article 13(4) of Regulation (EC) No 726/2004
• Article 23a of Directive 2001/83/EC, as amended
• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2A

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.

• The actual marketing of a centrally-authorised medicinal product (CAP) shall be reported to the Agency per presentation and per Member State (see question What is the meaning of “actual marketing” / “placing on the market”? ). Of note, for centrally authorised medicinal products, presentation corresponds to pack-size.
• MAHs shall also report to the Agency any marketing cessation (temporary/permanent) of their medicinal product per presentation and per Member State. This also includes the withdrawal of a medicinal product from the EU market, or any decision to withdraw or suspend the marketing authorisation or not to apply for the renewal of a marketing authorisation. The MAH should specify the reasons for such action and particularly if this is solely based on a commercial decision or related to any of the reasons listed in Articles 116 and 117 of Directive 2001/83/EC (e.g. quality, efficacy, safety reasons). When the marketing cessation or withdrawal is due to reasons listed in Articles 116 and 117 (e.g. due to the presence of nitrosamine impurities), MAHs should also notify the EMA of actions undertaken in third countries.

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:

• 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).
• 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.
• When reporting a marketing cessation, MAHs will be asked to clarify whether they anticipate a risk of shortage. MAHs should provide such information to the best of their knowledge at time of reporting a marketing cessation. This information will not replace existing processes to report shortages to EMA. This is only intended to facilitate dissemination of the information within EMA and EU Network.
• 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 and provide a copy of the letter to the Product Lead, Product mailbox, Withdrawn product mailbox, Rapporteurs and CHMP Chair. (See question How should I request the withdrawal of my central marketing authorisation?)
• For medicinal products authorised in a paediatric indication and for which the MAH has benefited from rewards or incentives under the paediatric regulations, the MAH should inform the Product Lead, Product mailbox, Rapporteurs of its intention to discontinue the placing on the market of the product (see question When to report the marketing status overview of centrally-authorised products to the Agency?) explaining the actions they are undertaking to ensure the medicinal product remains available to EU paediatric patients (e.g. transfer of a marketing authorisation, informed consent), in accordance with Article 35 of Regulation (EC) No 1901/2006. See question Is there an obligation to market a medicine which is authorised for a paediatric indication, following completion of an agreed paediatric investigation plan, and the product has already been marketed with other indications?

References

• Article 13(4) of Regulation (EC) No 726/2004
• Articles 116 and 117 of Directive 2001/83/EC
• Article 35 of Regulation (EC) No 1901/2006
• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2A.

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:

• The MAH should notify the Agency within 30 days of the placing on the market, including the reintroduction on the market (i.e. placing on the market following a marketing cessation) of a medicinal product within the Union (i.e. per presentation and per Member State).
• The MAH should notify the Agency at least 60 days in advance, of a marketing cessation (temporary or permanent) at Member State level - unless the marketing cessation/suspension/withdrawal is related to the grounds listed in Articles 116 and 117 of Directive 2001/83/EC (e.g. quality, efficacy, safety issues) in that case the Agency should be notified immediately. MAHs should also inform the Agency immediately of marketing cessations undertaken in third countries due to reasons covered in Articles 116 and 117 of Directive 2001/83/EC (e.g. quality, efficacy, safety issues).   
• The MAH should notify the Agency of their request to withdraw their central marketing authorisation at least 2 months in advance unless unforeseeable circumstances which may require an immediate notification (e.g. safety reasons). The update in IRIS would not replace the formal request to address to the European Commission (see question How should I request the withdrawal of my central marketing authorisation?). Of note, for medicinal products authorised in a paediatric indication and for which the MAH has benefited from rewards or incentives under the paediatric regulations, the MAH should inform the EMA of its intention to discontinue the placing on the market of the product at least 6 months before discontinuation. See question Is there an obligation to market a medicine which is authorised for a paediatric indication, following completion of an agreed paediatric investigation plan, and the product has already been marketed with other indications? 
• The MAH should notify the Agency of their intent not to apply for a renewal of their central marketing authorisation at time of expected submission (i.e. at least 9 months prior to MA expiry). Notification in IRIS would not replace the need to inform  the Product Lead in parallel (cc product mailbox).

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.  

References

• Article 13(4) of Regulation (EC) No 726/2004

• Article 23a of Directive 2001/83/EC, as amended
• Articles 116 and 117 of Directive 2001/83/EC
• Article 35 of Regulation (EC) No 1901/2006

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.

• Newly authorised CAPs will be added progressively to IRIS with a status “Never marketed” by default. The MAH will be required to notify all changes to marketing status using the platform.

• CAPs that were authorised prior to the launch of IRIS Marketing Status, will have their marketing status in IRIS as ‘No data provided’:

- 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:

• Marketing Status Notification (Single) 

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).

• Marketing Status notification (bulk upload)

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).

• Withdrawn product notifications (affecting all presentations in all MS):

This function allows to report

• A request for withdrawal of the central marketing authorisation of your product (This would not replace the formal request to send to the European Commission, see question How should I request the withdrawal of my central marketing authorisation?)
• a decision not to apply for the renewal of the marketing authorisation
• a permanent marketing cessation affecting all presentations of a medicinal product in all MS. Of note, if the marketing authorisation is not withdrawn, it will automatically expire after 3 years of non-marketing under the sunset clause provision (see Q&A on sunset clause provision).

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’.

• Presentations already on the market: status should be reported as ‘Marketed’ with the date of the initial placing in the market as ‘Date of Marketing Status change’. This will become the ‘Date of initial placing in the market’ once the submission is processed.

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.

• Presentations that have never been marketed in at least one Member State  A specific Marketing Status category has been added for products that have never been on the market. ‘Never marketed’ should be chosen from the list of Marketing Status options. Reason for Cessation and the Date of Marketing Status change can be left blank. For newly authorised products, the default status will already be ‘Never marketed’.

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.

• Presentations that were previously marketed and for which the MAH would like to report a (temporary or permanent) marketing cessation as the current marketing status report through IRIS, this needs to be done in two steps: the initial placing on the market needs to be reported first before the marketing cessation can be reported.

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:

• initial placing on the market in EU/EEA/UK(Northern Ireland) to be notified within 30 days to the mailbox marketingstatus@ema.europa.eu with the EMA Product Lead with the product mailbox in copy.

• marketing cessations or withdrawn product notifications (in EU/EEA/UK(Northern Ireland) to be notified to the Agency via the dedicated mailbox  withdrawnproducts@ema.europa.eu using the template cover letter and notification report table “Notification of withdrawn products”with the Product Lead, Product mailbox and the Rapporteur of the product in copy.
• Particular cases of Withdrawn product notifications related to Art 116 117 reasons (e.g. quality, efficacy, safety) in 3rd countries – please see question on “When and how to report to the Agency actions taken in 3rd countries?”

References

• Article 13(4) of Regulation (EC) No 726/2004, as amended
• Article 14b of Regulation (EC) No 726/2004, as amended
• Article 16(2) of Regulation (EC) No 726/2004, as amended
• Article 35 of Regulation (EC) No 1901/2006, as amended
• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2A

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,

• 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 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).

References

• Article 23a of Directive 2001/83/EC, as amended
• Article 123 of Directive 2001/83/EC, as amended

Click here 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.

References

• Article 14b of Regulation (EC) No 726/2004, as amended
• Article 123 of Directive 2001/83/EC, as amended

The MAH should send by email a request for withdrawal of the marketing authorisation to the European Commission (SANTE-PHARMA-POLICY@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?”)

References

• Article 13(4) of Regulation (EC) No 726/2004, as amended
• Article 14b of Regulation (EC) No 726/2004, as amended
• Article 16(2) of Regulation (EC) No 726/2004, as amended
• Article 35 of Regulation (EC) No 1901/2006, as amended

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 template cover letter and notification report table “Notification of withdrawn products” and 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.

References

• Article 123 (2b) of Directive 2001/83/EC
• Articles 116 and Article 117(1) of Directive 2001/83/EC

Currently, only information on withdrawn products are made public on the EMA website:

• The list of human medicinal products which have been withdrawn from the EU market (also referred as “list of withdrawn products”) is published every year on the EMA website. This list includes both centrally and nationally authorised medicinal products for which marketing authorisations have been refused, revoked or suspended in the Union, or whose supply has been prohibited or which have been withdrawn from the market due to grounds related to Article 116 and 117 (e.g. quality, efficacy or safety reasons). 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 referral procedure at European level).
• For centrally authorised products, the withdrawal or the expiry of the marketing authorisation is also made publicly available on the EPAR webpage of the medicinal product on the EMA website, together with the reason(s) for such action.

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.

References

• List of withdrawn medicinal products in accordance with Art. 123(4) of the Directive (1 January - 31 December 2022)
• Article 123(4) of Directive 2001/83/EC, as amended

Please refer to Q3.1 and 3.3 of the Q&A on Paediatric Investigation Plans [Paediatric investigation plans: questions and answers | European Medicines Agency (europa.eu)]

The so-called “sunset clause” is a provision leading to the cessation of the validity of the marketing authorisation if:

• the medicinal product is not placed on the market within three years of the authorisation being granted or,
• where a medicinal product previously placed on the market is no longer actually present on the market for three consecutive years.
• This provision applies to nationally-authorised products and centrally-authorised products.

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?)

References:

• Article 14(4-6) of Regulation (EC) No 726/2004
• Article 24(4-6) of Directive 2001/83/EC, as amended
• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2A

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.

References:

• Document published by the Commission on 10 October 2005 - Application of the "Sunset Clause" in the Review of the Pharmaceutical Legislation to Medicinal Products Authorised before Directives 2004/27/EC and 2004/28/EC and Regulation (EC) No 726/2004 start to apply
• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2

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.

References:

• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2A

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.

References:

• Article 13(4) and Article 14(4-6) of Regulation (EC) No 726/2004

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.

References:

• Chapter 1 (section 2.4.2), The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2A
• Summary record of the 58th meeting of the Pharmaceutical Committee (1st June 2005) – published on the Commission website on 10 October 2005,
• Article 14(11) of Regulation (EC) No 726/2004
• Article 10(1) of Directive 2001/83/EC, as amended

The following situations can lead to the start of the sunset clause period (“ON”):

• Granting of the Marketing authorisation

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?")

• A temporary or permanent cessation of placing on the market the medicinal product

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”):

• Initial placing on the Community market

The sunset timer will stop running at the time of the first placing on the market of one presentation in one Member State.

• At the re-placing on the market after a temporary cessation of the whole medicinal product

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.

• Exemption

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:

• Medicinal products to be used in emergency situations, in response to public health threats duly recognised either by the WHO or by the Union (Decision No 2119/98/EC).
• Antimicrobial medicinal products such as antibiotics, antivirals and immunologicals (for active and passive immunisation) aimed at the prevention and/or treatment of disease caused by bio-terror agents in response to an emergency public health need.

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.

References:

• Article 14(6) of Regulation (EC) No 726/2004