Annual renewal of conditional marketing authorisations: questions and answers

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This page lists questions that marketing-authorisation holders (MAHs) may have on annual renewals of conditional marketing authorisations. It provides an overview of the European Medicines Agency's position on issues that are typically addressed in discussions or meetings with MAHs in the post-authorisation phase. Revised topics are marked 'New' or 'Rev.' upon publication.

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.

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1. How long is my conditional marketing authorisation valid? New March 2016

In accordance with Article 14 (7) of Regulation (EC) No 726/2004, a conditional marketing authorisation (MA) is valid for one year from the date of notification of the Commission Decision to the marketing authorisation holder (MAH), and is renewable, annually, upon application by the MAH.

The conditional MA validity period is expressed in Commission Decisions, as follows:

  • Initial MA: by reference to the date of notification of the Commission Decision to the MAH. Notification dates of the Commission Decision are published in the Official Journal and can also be found for each product in the Community Register published by the European Commission.
  • Renewal: By reference to the previous MA expiry date.

In order for a conditional marketing authorisation to remain valid, a renewal application has to be made annually (irrespective of whether the marketing authorisation is suspended).

The renewal decision will usually refer to the expiry date of the preceding marketing authorisation so that the renewed authorisation will be valid from the date of the previous expiry.

For further information on the ‘conditional’ marketing authorisations, see Q&A 50 of the pre-submission procedural guidance question "Could my application qualify for a conditional marketing authorisation?".

References

2. When shall I submit my annual renewal application? Rev. March 2016

According to the legislation, MAHs must apply for an annual renewal at least six months before the expiry date of the conditional MA.

In case a MAH does not submit a renewal application, the conditional MA will expire automatically.

Once a renewal application has been submitted within this deadline, the conditional marketing authorisation shall remain valid until a decision is adopted by the Commission in accordance with Article 10 of Regulation (EC) No 726/2004.

In order to ensure that the Commission Decision on the renewal application can be issued ideally before expiry of the conditional MA, MAHs should take into account the following principles when planning for their renewal submission:

  • The annual renewal application must be submitted at least 6 months before the MA expiry date. A submission of the annual renewal application more than 1 month in advance of the submission due date will not be accepted by the Agency.
  • The start of the evaluation process will be the nearest possible starting date, as published by the EMA in the "Human Medicines – Procedural Timetables / Submission dates".
  • The CHMP assessment process can take up to 90 days.
  • The Decision-Making Process (incl. Standing Committee consultation) for renewal procedures is 67 days.

In addition, as the quality of the annual renewal application will be key to ensure a timely start and finalisation of the annual renewal procedure, a pre-submission dialogue between MAHs and the Agency may be considered, approximately nine months in advance of MA expiry.

References

3. How shall I present my annual renewal application? Rev. August 2017

In order to allow the CHMP to confirm the benefit-risk balance of the medicinal product and to review the specific obligations and their timeframes for completion, annual renewal applications should be presented as indicated below, in accordance with the appropriate headings and numbering of the EU-eCTD format.

In order to ensure that annual renewal applications are complete and correct before submitting them to the Agency, it is strongly recommended to use the pre-submission checklist for annual renewal of conditional marketing authorisation applications.

Module 1

1.0 Cover letter1with the following documents attached:

  • List of all authorised product presentations for which renewal is sought in tabular format (following the template for Annex A to CHMP Opinion)

Note: In cases where the MAH does not wish to renew certain product presentations (e.g. a certain pharmaceutical form, strength or pack-size), this should be clearly indicated in the cover letter and they should not be included in the appended list.

  •  Chronological summary table of the Specific obligations (SOBs) and other conditions to the MA stating the following for each: description (scope), reference number (preferably SIAMED number), due date indicated in Annex II of the Product Information, date of submission and procedure within which the SOB was submitted (if appropriate), date when the obligation or condition has been resolved (if applicable), and the current status.
  • A present/proposed table listing any changes introduced to the product information (incl. any minor linguistic amendment introduced for each language), if applicable.
  • Advice provided by the Pre-submission query service and or Procedure Manager, if applicable.

The cover letter should also contain the template table to facilitate registration of the submission.

Note: The Cover Letter should be signed by the person designated as MAH contact with the EMA. The Annual Renewal application is not an opportunity to notify the Agency of changes in contact person, which should be notified separately (see dedicated question under section ‘Other post-authorisation activities: questions and answers’ of the EMA published guidance: “How do I notify the EMA of changes to my Contact Persons specified in the application form”.)


1.3 Product Information (PI):

1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

  •  If no changes to the PI (SmPC, Annex II, outer/ inner labelling and Package Leaflet) are proposed by the MAH clear reference to it should be made in the cover letter. In addition, a ‘clean’ version of the latest PI in English has to be provided in Word format.
  • If changes to the PI are proposed as part of the Annual Renewal dossier, a version of the PI in English, highlighting the changes proposed by the MAH should be provided in the eCTD and in Word format. In addition, a ‘clean’ version of the PI should be provided as Word format.

Note: All other language versions are only to be submitted after adoption of the opinion (See also, “When do I have to submit revised product information? In all languages?”).

The Annexes submitted should only reflect the changes introduced by the Annual Renewal data. Any updates to the product information not resulting from data submitted as part of the Annual Renewal should be submitted by use of the appropriate procedure (see question 1.7). However, minor linguistic amendments to the texts could be accepted in addition to changes introduced based on the annual renewal data, but this should be clearly mentioned in the cover letter and list of such changes provided as an attachment to the cover letter.


1.4 Information about the Expert

1.4.1 Information about the Expert – Quality (incl. signature + CV) – if applicable

1.4.2 Information about the Expert – Non-Clinical (incl. signature + CV) – if applicable

1.4.3 Information about the Expert – Clinical (incl. Signature + CV)


1.8.2 Risk Management Plan

An RMP is not systematically required as part of the Annual renewal application. Two scenarios are possible:

  • If an update of the RMP is proposed by the MAH with the Annual renewal application, section 1.8.2 should contain the updated RMP (‘clean’ version). In this case, a version of the RMP, highlighting the changes proposed by the MAH should be provided in Word format.
  • Where no update to the RMP is to be implemented, an RMP update should not be included in the Annual renewal submission. In this case, the MAH should specify this in the cover letter and declare in the clinical overview that the current approved RMP does not require changes. Alternatively, if applicable, the MAH can state that an RMP update is being assessed in a procedure ongoing in parallel and no additional RMP changes are considered warranted.

Module 2

2.3Addendum toQuality Overall Summary

An Addendum to the Quality Overview is not systematically required as part of the annual renewal application. It should be provided only in case important new pharmaceutical data are available.

2.4 Addendum to Non-Clinical Overview

An Addendum to the Non-clinical Overview is not systematically required as part of the annual renewal application. It should be provided only in case important new non-clinical data are available.

2.5 Addendum to Clinical Overview

A critical discussion should be provided within the Addendum to the Clinical Overview. It should address the current benefit/risk balance for the product on the basis of the data generated in SOBs and taking into account any other safety/efficacy data (including PSUR data) accumulated since the granting of the MA. 

An Interim Report on the specific obligations should be included in a separate section in the clinical overview addendum, reflecting the situation as close as possible to the submission date. The interim report on the fulfilment of the specific obligations should include details for each specific obligation. The aim of this report is to inform about the status of fulfilment of specific obligationsand the impact of data generated on the benefit risk-balance of the product. If data from a specific obligation is due at the time of annual renewal submission and have not been yet submitted, it can be included in the annual renewal submission dossier. Final reporting of clinical trials should follow the conventional format of study reports (see ICH Topic E3 Note for guidance on structure and content of clinical study reports, CHMP/ICH/137/95). Clinical Summaries and Clinical Study Reports should not be included in section 2.5, but in the respective dedicated eCTD Sections, see below. One single report should be submitted for the product including all remaining specific obligations. The structure and contents of the interim report will vary depending on the type of study and available data. For further guidance on the contents of interim report on the specific obligations, please refer to the &quotCHMP guideline on the scientific application and the practical arrangements necessary to implement Commission Regulation (EC) No 507/2006 on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation (EC) No 726/2004&quot.

2.7 Clinical Summaries

Clinical summaries will generally need to be updated, as appropriate, when new clinical study reports are submitted.


Module 5

5.3.5 Reports of Efficacy and Safety Studies (as appropriate) submitted to fulfil SOBs:

5.3.5.1 Study Reports of Controlled Clinical Studies Pertinent to the Claimed Indication

5.3.5.2 Study Reports of Uncontrolled Clinical Studies

5.3.5.3 Reports of Analyses of Data from More Than One Study

5.3.5.4 Other Clinical Study Reports


1Please note that there is no application form available for annual renewals and that the application form for standard 5 year renewals available on the eSubmission web site is not applicable to annual renewals of conditional marketing authorisations and therefore cannot be used.

4. How and to whom shall I submit my annual renewal application? Rev. March 2016

How: The requirements for the submission of applications related to the centralised procedure are provided on the EMA website. Please refer to Other post-authorisation activities: questions and answers - "How and to whom shall I submit my application?".

To whom: To the EMA, CHMP, PRAC and CAT (when involved) members, submissions via the Common Repository only.

5. How shall my annual renewal application be handled (timetable)? Rev. March 2016

The MAH should submit the annual renewal application by the recommended submission dates published on the EMA website and, in any case, no later than 6 months before the MA ceases to be valid.

The Agency will acknowledge receipt of a valid annual renewal application and shall start the procedure in accordance with the recommended starting dates published on the EMA website. The MAH will be informed of the adopted timetable at the start of the procedure.

The timetable for the scientific evaluation by the CHMP will be set in order to ideally allow the Commission Decision to be adopted before the expiry date of the marketing authorisation.

Full procedural detailed timetables are published as a generic calendar on the EMA website (see: submission deadlines and full procedural timetables).

The published timetables identify the start and finish dates of the procedures as well as other interim dates/milestones that occur during the procedure.

The renewal procedure will involve the CHMP Rapporteur as well as the PRAC Rapporteur who have been appointed for the medicinal product. In case of an advanced therapy medicinal product additional steps will be included to accommodate the lead assessment by Committee for Advanced Therapies. 

DAYACTION
D 1Start of procedure
D 30CHMP and PRAC Rapporteurs’ joint assessment report
D 35Comments from PRAC and CHMP members
D 39Updated CHMP and PRAC RApporteurs’ joint assessment report
D 46PRAC outcome
D 60Adoption of CHMP opinion and CHMP assessment report (or request for supplementary information without a clock stop)
D 66Submission of responses to request for supplementary information
D 75CHMP and PRAC Rapporteurs’ joint assessment report
D 76PRAC outcome
D 80Comments from CHMP members
D 83Updated CHMP and PRAC Rapporteurs’ joint assessment report
D 90Adoption of the CHMP Opinion
6. What fee do I have to pay for a renewal? New March 2013

There is no fee payable for the annual renewal of a conditional marketing authorisation.

References

7. Can other non-renewal specific changes be included in the annual renewal application? Rev. March 2016

None of the changes introduced at renewal should substitute for the MAH's obligation to update the marketing authorisation throughout the life of the product as data emerge.

In particular major changes to the product, such as the introduction of a new indication and quality changes such as an extension of shelf life, should not be modified through the annual renewal procedure but have to be submitted and assessed through the appropriate variation procedure.

Where there are adequate and objective reasons not to renew the marketing authorisation in its existing terms and changes are necessary to the SmPC, labelling and package leaflet arising from the renewal evaluation, the Marketing Authorisation Holder may submit additional information and/or change the product information as part of the annual renewal process to address the concerns raised. Such changes will not require a separate variation procedure.

Other issues arising from assessment of data required for the annual renewal and changes due to the revision of the product information in line with SmPC guideline, other relevant guidelines, or EMA/QRD Product Information Templates can be considered within the annual renewal procedure.

A present/proposed table clearly listing any changes introduced to the product information (incl. any minor linguistic amendment introduced for each language) should be attached to the cover letter.

8. How to handle other ongoing variation applications during the renewal procedure and what impact may ongoing procedures have on the renewal procedure? Rev. March 2016

Although MAHs are advised to avoid other procedures at the time of annual renewal, such situations cannot be excluded.

In case that an ongoing variation (Type IA/IB or Type II) affects the product information and is not yet finalised at the time of the submission of the annual renewal application, the last product information adopted/accepted by the EC/CHMP/EMA should be used in the submission of the annual renewal application.

If the variation procedure is finalised before or upon finalisation of the annual renewal procedure, the accepted/adopted variation changes should be reflected in the annual renewal product information.

In cases where any other ongoing procedure may affect the product information, the MAH is advised to contact the Agency in advance of the submission or finalisation of the procedure(s) concerned.

9. Do I have to submit mock-ups and specimens? Rev. March 2016

No mock-ups or specimens are required for the annual renewal of a conditional marketing authorisation. For details of when to submit mock-ups and specimens in the post-authorisation phase of your medicinal product, please refer to the revised checking process of mock-up and specimens information on the EMA web.

References

10 .When do I have to submit revised product information? In all languages? Rev. March 2016

In case the renewal application affects SmPC, Annex II, labelling and/or package leaflet, the revised product information Annexes must be submitted as follows:

At submission

Language 
EN (only)
  • As part of the eCTD
  • Word format (highlighted and clean)

English language (only): complete set of Annexes within the eCTD sequence and in Word format (clean and highlighted showing the changes proposed as part of the Annual Renewal).

Where no amendments to the product information are proposed by the MAH, only an electronic copy of the latest approved product information (full set of Annexes, ‘clean’) in English must be submitted to the Agency in Word format.

If changes are approved as part of the Annual Renewal, the following steps will apply:

After CHMP Opinion (Day +5)

In case the annual renewal results in changes to the SmPC, Annex II, labelling and/or package leaflet, the revised complete set of Annexes must be submitted as follows:

Language 
All EU languages (incl. EN, NO and IS)

Via Eudralink

  • Word format (highlighted)

All EU languages (incl. EN, NO and IS): complete set of Annexes in Word format (highlighted).

After Linguistic check (Day +25)

In case the annual renewal results in changes to the SmPC, Annex II, labelling and/or package leaflet, the revised complete set of Annexes must be submitted as follows:

Language 
All EU languages (incl. EN, NO and IS)

Via Eudralink

  • Word format (highlighted)
  • PDF format (clean)

All EU languages (incl. EN, NO and IS): complete set of Annexes in Word format (highlighted) and in PDF (clean).

Translations of the adopted product information in all EU languages (including English, Icelandic and Norwegian) are to be provided electronically (in one Eudralink package) to the Member States Contact Points for Translations by Day +5 with a copy to the EMA Product Shared Mailbox.

The revised Annex A, where applicable, is to be provided to the Agency as a separate word document in all EU languages (see point 1.12 below) and in pdf (clean).

References

11. When will the linguistic checking of the product information take place? Rev. March 2016

Translations of the adopted product information in all other EU languages (Including Icelandic and Norwegian) are to be provided electronically (in one Eudralink package) to the Member States Contact Points for Translations (list of members states contact points for translation) by Day +5 and copied to the EMA Procedure Assistant.

The following checks post-opinion will apply:

Check by

When

Who

Scope

QRD/ ‘Member State’

Day +5 to +19

Member States

Detailed review of (highlighted changes in) all translations

PIQ

Day +25 to +27

EMA

Review of implementation of Member States comments

Comments will be sent directly by the Member States to the MAH at the latest by Day +19, with a copy to the EMA Procedure Assistant.

The MAH will send the final translations with tracked changes, incorporating the Member States’ comments, electronically to the EMA Procedure Manager secretary by Day +25.

The Agency will check if all Member States’ comments have been implemented before sending the final translations to the Commission. In order to facilitate and accelerate the check of the implementation of the Member States’ comments, the applicant should indicate in QRD Form 2 for each language if all comments have been implemented or not. In the latter case, a justification should be provided for the appropriate language(s) stating why certain comments are not reflected in the final texts.

In case the Renewal affects only the Annex II, no or a shorter post-opinion translation timetable may be considered by the Agency on a case-by-case basis.

Following receipt of the final translations from the EMA, the Commission will start the 22-day Standing Committee consultation, addressing only legal and public health matters (which means in principle no further linguistic review).

The Commission Decision on the renewal will be issued after consultation of the Standing Committee, by Day +67.

References

12. What do I need to do if I do not want to renew the Marketing authorisation of certain product presentations or the entire product? Rev. March 2016

In cases where the MAH does not wish to renew certain product presentations (e.g. a certain pharmaceutical form, strength or pack-size) this should be clearly indicated in the cover letter (See also “How shall I present my renewal application”).

In case the MAH does not wish to renew the entire Marketing Authorisation (i.e. all presentations) a letter to this effect should be addressed to the Agency and the European Commission at the latest 6 months prior to the expiry of the concerned Marketing Authorisation, clearly and in detail stating if the marketing authorisation is surrendered for any reasons beyond purely commercial ones.

This is without prejudice of the MAH obligation to notify such action to the Agency according to the provisions set out in Article 14 (b) of Regulation (EU) No 726/2004. Please refer to the EMA questions and answers on Withdrawn product notification.

References

13. What do I need to do if all Specific Obligations have been complated? Rev. Mar 2016

Once the specific obligations have been fulfilled, the Committee may at any time adopt a recommendation for the granting of a marketing authorisation no longer subject to specific obligations. MAHs who consider that all Specific Obligations have been fulfilled should indicate this in the cover letter of the submission, in which final data from the last outstanding specific obligation is being submitted. This could be either within an annual renewal application or a variation, whichever is appropriate.

References

14. Will there be any publication on the outcome of my annual renewal application? Rev. March 2016

The EPAR (published on the EMA website) will be revised to implement the CHMP conclusions in relation to the renewal procedure.

Besides, the CHMP meeting highlights following each CHMP meeting gives information in its Annex on opinions in relation to renewal applications.

In case of an unfavourable opinion, recommending suspension or non-renewal of the MA, a Question and Answer (Q&A) document will be published by the Agency. This will include information and reasons for such an opinion. The information will be provided in lay language, so that it can be understandable for the general public.

References

15. Who should I contact if I have a question when preparing my application? Rev. August 2017

If you cannot find the answer to your question in the Q&A when preparing your application or during the procedure, please contact the procedure manager responsible for your product.

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