Conditional Marketing Authorisation of ATMPs

Conditional marketing authorisation applications requires the applicant to provide several specific information. 

The conditional marketing authorisation procedure allows the approval of a medicinal product meets several criteria, including that the medicine fulfils an unmet medical need, and supports its availability to patients despite providing less comprehensive data than normally required. Medicinal products for human use are eligible if they are intended for treating, preventing or diagnosing seriously debilitating or life-threatening diseases, including rare diseases. 

Therefore, to be granted a conditional marketing authorisation, the applicant has to demonstrate its ability to provide comprehensive data post-authorisation, that the medicine fulfils an unmet medical need and that the benefit of the medicine's immediate availability to patients is greater than the risk inherent in the fact that additional data are still required, as well as that the benefit-risk balance of the medicine is positive. (Article 4 § 1 of Regulation (EC) No 507/2006) 

The conditional marketing authorisation granted is valid for one year, renewable annually, and can be converted into a standard marketing authorisation once the conditional marketing authorisation holder has achieved its specific obligations post-authorisation. 

Post-authorisation the applicant has also to fulfil specific obligations, such as to complete ongoing studies or conduct new studies, to confirm the medicine's benefit-risk balance remains positive.  

If the applicant does not fulfil its specific obligations or if new data provided show that the risk-benefit balance is no longer positive, the European Medicines Agency can suspend or revoke the conditional marketing authorisation to protect patients’ health. 

The conditional marketing authorisation is a regulatory tool to foster early patient access to new medicinal products that notably fulfil an unmet medical need despite less complete data provided.  

The European Medicines Agency provides guidance to applicants (more information here), statistics in its annual report, and has issued a report on ten years of experience at the European Medicines Agency to analyse and review its experience on conditional marketing authorisation granted between 2006 and 2016. 

The conditional marketing authorisation has also been used to accelerate the approval of safe and effective COVID-19 treatments and vaccines in the European Union. More information here. 

1/ Medicines eligible to conditional marketing authorisation

• Medicinal products which aim at the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases.
•  Medicinal products designated as orphan medicinal products.
• In emergency situations (e.g. pandemic), “a marketing authorisation for such medicinal products may be granted also where comprehensive pre-clinical or pharmaceutical data have not been supplied”.

(Article 14-a(1) of Regulation (EC) No 726/2004 current version with amendments and Recital 2 of Commission Regulation (EC) N° 507/2006)

2/ Criteria for conditional marketing authorisation to be granted

The following criteria shall be met:

• The medicine addresses an unmet medical need, i.e. “a condition for which there exists no satisfactory method of diagnosis, prevention or treatment authorised in the Union or, even if such a method exists, in relation to which the medicinal product concerned will be of major therapeutic advantage to those affected”.
• The risk-benefit balance of the medicinal product is favourable.
• The applicant is likely to be able to provide comprehensive data.
• The benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required.

In emergency situations, a conditional marketing authorisation may be granted, subject to the above requirements, also where comprehensive pre-clinical or pharmaceutical data have not been supplied.

(Article 14-a(1) to(3) of Regulation (EC) No 726/2004 current version with amendments and Article 4(1) of Commission Regulation (EC) N° 507/2006)

3/ Specific obligations under conditional marketing authorisation

Conditional marketing authorisation is subject to specific obligations that are reviewed annually by the European Medicines Agency.

 Those specific obligations are especially:

• to complete ongoing studies, or to conduct new studies, with a view to confirming that the risk-benefit balance is favourable.
• specific obligations may be imposed in relation to the collection of pharmacovigilance data.

Those specific obligations and, where appropriate, the timeframe for their completion shall be clearly specified in the conditions to the marketing authorisation. They are made publicly available by the European Medicines Agency as part of the European Public Assessment Report.

The summary of product characteristics and the package leaflet shall clearly mention that a conditional marketing authorisation for the medicinal product has been granted subject to specific obligations to be reviewed annually. The summary of product characteristics shall also contain the date on which the conditional authorisation is due for renewal.

 (Article 14-a(4) to(6) of Regulation (EC) No 726/2004 current version with amendments and Article 5 of Commission Regulation (EC) N° 507/2006)

4/ Procedure for conditional marketing authorisation application

4.1/ Early dialogue prior to submission

Early dialogue with the European Medicines Agency and other stakeholders (e.g. health technology assessment bodies) is strongly recommended by EMA.

Aim: To discuss with the EMA, especially rapporteurs of the CHMP, PRAC and CAT, for instance:

• whether a specific medicinal product being developed for a specific therapeutic indication falls within the category of products intended for the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases, and whether it could meet the unmet medical needs of patients.
• the development plan and the design of the intended studies (both the pre-authorisation studies and studies to be proposed as specific obligations for collection of remaining data after authorisation).

How:

• Through CHMP scientific advice, or protocol assistance for orphan medicines. (More information on EMA website here on Requesting scientific advice or protocol assistance from EMA).
• Through a pre-submission meeting: After having created an EMA account via the EMA Account Management portal; the MAA pre-submission interactions form (available here, at the bottom of section 2.9 under “references”) shall be filled in electronically and sent to the EMA, by raising a ticket via EMA Service Desk, using the Question option “Pre-Submission Phase Request”, followed by the sub-option “Pre-Submission Interactions”. (More information on the EMA Website, here section 2.9.).

4.2/ Submission of an application

When:

• Six to seven months before submission: to notify the EMA of the intention to submit an application and to include a statement on the intention to request a conditional marketing authorisation.
• At the time of marketing authorisation application: the applicant may present a request for a conditional marketing authorisation.

How:

• To indicate in the application form the grounds for a conditional marketing authorisation application and to include the corresponding justification in the section 1.5.5 of Module 1 of the dossier.

4.3/ Assessment of an application and granting of a conditional marketing authorisation

The Rapporteur, Co-Rapporteur and the other CHMP and CAT members will assess the justification and the data submitted for a conditional marketing authorisation for an Advanced Therapy Medicinal Product as part of the overall assessment of the application.

The assessment of the justification regarding the scope of conditional marketing authorisation will be reflected in the relevant assessment reports and in the final CHMP assessment report.

A conditional marketing authorisation may be requested by the applicant (before submission of a marketing authorisation application as strongly recommended by EMA, or together with the marketing authorisation application), or proposed by the CHMP (after having consulted with the applicant) during the assessment of the application.

The conditional marketing authorisation of an advanced therapy medicinal product is granted by the European Commission, based on the scientific assessment led by the CHMP and including the CAT within the EMA.

More information on the procedure for conditional marketing authorisation application in the CHMP 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, and on EMA website here section 1.9.

5/ Validity and renewal of conditional marketing authorisation

Conditional marketing authorisation is valid for one year, on a renewable basis.

(Article 14-a(7) of Regulation (EC) No 726/2004 current version with amendments)

After its period of validity of one year the conditional marketing authorisation may be renewed annually.

• Submission of the application for renewal:
  • To the European Medicines Agency,
  • At least six months before the expiry of the conditional marketing authorisation,
  • Together with an interim report on the fulfilment of the specific obligations to which it is subject.
• Assessment of the application for a renewal:
  • By the CHMP (and CAT for ATMPs) within the EMA,
  • On the basis that the risk-benefit balance is to be confirmed, taking into account the specific obligations contained in the authorisation and the timeframe for their fulfilment,
  • Including an opinion as to whether the specific obligations or their timeframes need to be retained or modified.
  • Final opinion of CHMP to be given within 90 days following receipt of a valid renewal application, and to be made publicly available.
• Decision on renewal:
  • Adopted by the European Commission,
  • Once a renewal application has been properly submitted, the conditional marketing authorisation shall remain valid until a decision is adopted by the European Commission.

More information on the renewal of conditional marketing authorisation in the CHMP 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.

6/ Conversion of conditional marketing authorisation into standard marketing authorisation (not subject to specific obligations)

When the specific obligations of the conditional marketing authorisation have been fulfilled, the European Commission may, following an application by the marketing authorisation holder, and after receiving a favourable opinion from the European Medicines Agency, grant a marketing authorisation not subject to specific obligations (i.e. “standard”), valid for five years and renewable.

More information on the granting of a marketing authorisation not subject to specific obligations in the CHMP 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

Early contacts with the European Medicines Agency before the submission of the conditional marketing authorisation application  

Any issues or questions related to the conditional marketing authorisation application can be discussed with the European Medicines Agency during the pre-submission phase as part of early contacts with regulators. Before submitting a marketing authorisation application, the applicant is encouraged to indicate to the EMA its intention to request a conditional marketing authorisation in its notification of intention. Discussions in advance and pre-submission meetings are organised to provide assistance and guidance to the applicant before finalising the conditional marketing authorisation application. 

Pursuant to Article 11 of Regulation (EC) No 507/2006, the EMA has developed and issued guidelines on scientific assessment and practical arrangements necessary to implement conditional marketing authorisation.        

Contacts with the European Medicines Agency during the assessment of the conditional marketing authorisation application  

During the validation phase of the application and the whole assessment process, the conditional marketing authorisation applicant will maintain regular contacts and interactions with the European Medicines Agency, in particular to provide any additional answers or supporting documentation needed. 

Contacts with the European Medicines Agency post-conditional marketing authorisation 

Post-authorisation the applicant has to fulfil specific obligations, such as to complete ongoing studies, conduct new studies, and generate comprehensive data to the European Medicines Agency to confirm the medicinal product's benefit-risk balance remains positive. 

Published: 17/01/2023

Last updated: 23/01/2024

Authors: 

Luc-Sylvain Gilbert, EuroGCT ELSI Legal Information Officer 

and Aurélie Mahalatchimy, EuroGCT WP4 Convenor, UMR 7318 DICE CERIC, Aix-Marseille University, CNRS, Aix-en-Provence- France

Reviewed by:

Under internal review by EuroGCT Commercialisation Working Group.