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Accelerated Assessment of ATMPs

Introduction

Any company wishing to market Advanced Therapy Medicinal Products (ATMPs) within the European Union must hold a marketing authorisation issued by the European Commission. 

Different options are offered by the European Union for being granted a marketing authorisation through specific regulatory mechanisms to facilitate early patient access to medicinal products, including ATMPs, while maintaining a high assessment of the quality of these medicines, and of their safety and efficacy regarding the benefit-risk balance. 

The accelerated assessment is a procedural tool to reduce the centralised procedure review period of a marketing authorisation applicant from 210 to a maximum of 150 days, excluding clock stops. An applicant may request an accelerated assessment for medicinal products if they are of major public health interest, in particular from the viewpoint of therapeutic innovation. The request shall be duly substantiated and its acceptance will be decided by the Committee for Medicinal Products for Human Use (CHMP). (Article 14 § 9 of Regulation (EC) No 726/2004). Nevertheless, the decision on accelerated assessment has no impact on the future CHMP opinion on whether a marketing authorisation should be granted. 

The accelerated assessment is particularly adapted to ATMPs, one of whose characteristics is to be innovative (Fig. 1). 

Accelerated Assessment procedures of authorised ATMPs
Fig. 1. Accelerated Assessment procedures of authorised ATMPs. Out of the 26 authorised ATMPs, 6 (23%) benefited from an Accelerated Assessment Procedure (3 from the standard MA procedure* and 3 from the conditional MA procedure).*The assessment of Skysona started under the Accelerated Assessment procedure, and it was then reverted to the standard timetable. It was counted among the standard procedures only. 

 

Main Actors

Accelerated Assessment Applicant: The people or pharmaceutical company applying to reduce the CHMP timeframe to review a marketing authorisation application for a medicinal product expected to be of major public health interest. If the CHMP accepts the accelerated assessment request of the applicant, the timeframe for the evaluation will be reduced from 210 to 150 days. 

European Medicines Agency: The European Medicines Agency (EMA) is an agency of the European Union whose goal is to protect and promote human and animal health. The agency is notably responsible for the scientific assessment of ATMPs to be marketed within the European Union and the European Economic Area, including in the context of Accelerated Assessment applications. 

Committee for Medicinal Products for Human Use (CHMP) at the EMA: The accelerated assessment application to reduce the EMA timeframe to review a marketing authorisation application is conducted by the CHMP, the EMA's main scientific assessment committee for medicinal products for human use, . The CHMP is responsible for the assessment of the Marketing Authorisation Application on a scientific basis, and for the adoption of an opinion on whether the medicinal product should be authorised or not. Such opinion is sent to the European Commission which will decide on granting or not the marketing authorisation. The CHMP is composed by one member appointed by each of the European Union Member States and European Economic Area countries plus Iceland and Norway, and up to five scientific experts.

More information on CHMP, including notably:

Committee for Advanced Therapies (CAT) at the EMA: The CAT is mainly responsible for preparing a draft opinion on the quality, safety and efficacy of each ATMP Marketing Authorisation Application, before final opinion by the CHMP as regards as the scientific assessment of a marketing authorisation application. The CAT also participates in the procedure of certification of quality and non-clinical data for small and medium-sized enterprises developing ATMPs, the provision of scientific recommendations on the classification of ATMPs, as well as any other activity requiring expertise on ATMPs. The CAT is composed by 5 members (and alternates) of the CHMP coming from five Member States, one member and one alternate appointed by each other EU Member State, one member and one alternate appointed by their respective Member States from the EEA/EFTA, two members and two alternates representing clinicians and appointed by the European Commission, and two members and two alternates representing patients’ associations and appointed by the European Commission.

More information on CAT, including notably :

Pharmacovigilance Risk Assessment Committee (PRAC) at the EMA: The PRAC is the EMA’s committee responsible for assessing and monitoring the safety of human medicines. The PRAC is responsible for all aspects of the risk management of medicinal products and for the assessment of the risk management plan provided by the applicant. The PRAC is notably involved in the assessment of ATMPs’ marketing authorisation applications though providing advices to the CHMP. The PRAC is composed of a chair, one member and one alternate member appointed by each of the EU Member States, one member and one alternate member appointed by each of the EEA/EFTA States, six members appointed by the European Commission to ensure the availability of the relevant expertise, one member and one alternate representing healthcare professionals and appointed by the European Commission, and one member and one alternate representing patients’ organisations and appointed by the European Commission.

More information on PRAC, including notably:

Definitions

Marketing Authorisation following accelerated assessment: The marketing authorisation following accelerated assessment is one of the European Union’s regulatory mechanisms to facilitate earlier market and patient access to innovative treatments of major public interest. It means that the decision of marketing authorisation has been taken after an accelerated scientific assessment conducted by the EMA. 

Accelerated assessment: The maximum timeframe for the assessment of a standard marketing authorisation application under the Centralised procedure is 210 days to give an opinion (excluding clock stops). The acceptance of the accelerated assessment procedure application for a medicinal product of major interest for public health by the CHMP will reduce the application processing time from 210 to 150 days (excluding clock stops). For ATMPs, the 150-day timeframe is split into 2 phases of 120 + 30 days with a clock-stop up to 3 months for the submission of written answers allowed after day 120. 

More details on the accelerated assessment timetable here. 

Challenges

The first main challenge for the regulator, here the EMA, especially the CHMP, is to conduct the marketing authorisation review in 150 days instead of 210, even though another EMA’s Committee has to be involved in the case of ATMPs, the CAT. Moreover, it is necessary to anticipate and integrate routine Good Clinical Practice (GCP) and pre-approval Good Manufacturing Practice (GMP) inspections into the accelerated assessment procedure for the EMA to verify the GCP and GMP compliance of studies and manufacturers for applications for marketing authorisation in accordance with its legal obligation.  

The second main challenge is for the applicant to substantiate its request and justify the expected major interest for public health of the medicinal product particularly from the point of view of therapeutic innovation. As there is no definition of what constitutes major public health interest, it should be justified by the applicant on a case-by-case basis. The applicant can highlight the unmet needs addressed by the new medicinal product for maintaining and improving public health, a therapeutic innovation and treatment, or a major impact and added value on medical practice of the medicine regarding the introduction of new methods of therapy or the improvement of existing methods.  

In addition to the accelerated assessment request, a pre-submission request as well as information for early identification of a need for pre-authorisation GMP and/or GCP’s inspections are required from the applicant in order to accommodate the potentially needed inspection within the accelerated timetable.  

Opportunities and incentives

Accelerated assessment is a regulatory tool supported by the EMA to shorten the centralised procedure review period of a marketing authorisation application from 210 to a maximum of 150 days for medicinal products of major public health interest particularly from the point of view of therapeutic innovation. The EMA and the CHMP in particular, are the entry points for an accelerated assessment procedure. They provide scientific support, advice and guidelines to secure an earlier access of the medicinal products, including ATMPs, to patients.  

The EMA has in particular issued guideline on the scientific application and the practical arrangements necessary to implement the procedure for accelerated assessment pursuant to Article 14(9) of Regulation (EC) No 726/2004.  

The EMA provides templates for applicants submitting an accelerated assessment request regarding Pre-submission request (selecting scope for Accelerated Assessment), Applicant's justifications for accelerated assessment, Information required for early identification of a need for pre-authorisation GMP inspections, and Information required for early identification of a need for pre-authorisation GCP inspections. More information here (Section 2.8). 

Practical steps for ATMP accelerated assessment

1/ Eligibility to Accelerated Assessment procedure

  • ATMP Marketing authorisation application planned under the centralised procedure whose general steps are described under the ‘centralised procedure’ entry.
  • To justify the ATMP is of major public health interest: 
    • “major interest from the point of view of public health and in particular from the viewpoint of therapeutic innovation” (Article 14(9) of Regulation (EC) N° 726/2004)
    • “to meet, in particular the legitimate expectations of patients and to take account of the increasingly rapid progress of science and therapies” (Recital 33 of Regulation (EC) N° 726/2004)

2/ Requesting a pre-submission meeting at the EMA

EMA strongly recommends all applicants, notably the ones submitting a PRIME application, to request a pre-submission meeting six to seven months before submitting an accelerated assessment request.

  • Aim: To discuss with the EMA, especially rapporteurs of the CHMP, PRAC and CAT, the proposal for accelerated assessment, the data and risk management plan of the forthcoming marketing authorisation application.
  • How: 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 template, 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 can be found here in section 2.9.

3/ Submitting an Accelerated Assessment request to the EMA

Request should be submitted 3-2 months before submission of marketing authorisation application.

  • Aim: Upon CHMP acceptance of the request, to reduce the timeframe for the evaluation to 150 days (2 phases of 120+30 days of assessment for ATMPs) for medicinal product of major public health interest.
  • How: After having created an EMA account via the EMA Account Management portal; the pre-submission request, the applicant’s justifications for accelerated assessment as well as the information required for early identification of a need for pre-authorisation GCP and GMP inspections, should be sent using the EMA templates (available here, at the bottom of section 2.8 under “submission and assessment of the request”), by raising a ticket via EMA Service Desk, using the Question option “Pre-Submission Phase Request”, followed by sub-option “Accelerated Assessment”.

More information on the EMA website can be found here in section 2.8.

Interactions with regulators

Early contacts with the European Medicines Agency before the submission of an accelerated assessment request  

The applicant for an accelerated assessment procedure is strongly encouraged to have early discussions and contacts with the EMA, six to seven months before the submission of its request, to prepare the evaluation under accelerated assessment. Pre-submission meetings give the applicant the opportunity to meet the rapporteurs from the different EMA’s scientific committees, to present the content of the dossier for an accelerated assessment of the marketing authorisation and to obtain procedural and regulatory advice from the agency. 

To appreciate the eligibility of a medicinal product for an accelerated assessment procedure, the EMA has issued marketing authorisation pre-authorisation guidance and templates. (Section 2.8). 

Early contact with the EMA via the PRIME Procedure for Priority Medicines is particularly recommended before request of an accelerated assessment for an ATMP. 

Contacts with the European Medicines Agency during the accelerated assessment procedure  

During the validation phase of the application and the whole assessment process, the applicant for a marketing authorisation following accelerated assessment will maintain regular contacts and interactions with the EMA, in particular to provide any explanations, documentation and data needed. 

Contacts with the European Medicines Agency and national competent authority post- marketing authorisation following accelerated assessment 

Post-authorisation the applicant has to continue to monitor the safety and efficacy of its medicinal product on an ongoing basis in accordance with the European Union GMP.  

The EMA and the national competent authority will conduct regular inspections (on-site and samples analysis) during the five-years duration of the authorisation to monitor the quality, safety, efficacy, and the positive benefit-risk balance of the medicinal product, and if necessary to take regulatory actions to protect public health. 

European Union Legislation

Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (Text with EEA relevance), OJ L 136, 30.4.2004, p. 1-33, CELEX number: 32004R0726

European Union Guidance

EMA guidance documents

More information on the EMA website: Accelerated Assessment.

Relevant literature

  1. EMA Priority Medicines Scheme (PRIME): Will More Paying-for-Performance Agreements Be Needed Due to Immature Data? - Antoñanzas, F., C. A. Juárez-Castelló, and R. Rodríguez-Ibeas The European Journal of Health Economics, Vol. 19, No. 7 (09/2018): 905-907
  2. Accelerated Access to Innovative Medicines for Patients in Need - Baird, L G, R Banken, H-G Eichler, F B Kristensen, D K Lee, J C W Lim, R Lim, and al. Clinical Pharmacology & Therapeutics, Vol. 96, issue 5 (11/2014): 559-571
    1. Scientific abstract
  3. Overview of regulatory initiatives in the European Union to stimulate research and accelerate access to orphan drugs and other high medical need products - Baran-Kooiker, Aleksandra, Marcin Czech, and Coen Kooiker. Acta Poloniae Pharmaceutica - Drug Research, Vol. 76 No. 1 (2019): 3-17
    1. Scientific abstract
  4. Do the EMA accelerated assessment procedure and the FDA priority review ensure a therapeutic added value? 2006-2015: a cohort study - Boucaud-Maitre, Denis, and Jean-Jacques Altman. European Journal of Clinical Pharmacology (07/2016) 72: 1275-1281
    1. Scientific abstract
  5. Regulatory Affairs 101: Introduction to Expedited Regulatory Pathways - Cox, Erica M., Anita V. Edmund, Erica Kratz, Sarah H. Lockwood, and Aishwarya Shankar. Clinical and Translational Science (2020) 13: 451-461
    1. Scientific abstract 
  6. EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation - Detela, Giulia, and Anthony Lodge. Molecular Therapy: Methods & Clinical Development, Vol. 13 (06/2019): 205-232 
    1. Scientific abstract  
  7. Comparison of regulatory pathways for the approval of advanced therapies in the European Union and the United States - Iglesias-Lopez, Carolina, Mercè Obach, Antonio Vallano, and Antonia Agustí. Cytotherapy, 23 (2021): 261-274
    1. Scientific abstract
  8. Accelerated Access to Medicinal Products - Van Delm, Kaat European Pharmaceutical Law Review, Vol. 4, No 4 (2020): 192-206
    1. Scientific abstract
  9. An Overview of Cancer Drugs Approved through Expedited Approval Programs and Orphan Medicine Designation Globally between 2011 and 2020  - Wang, Shuhang, Qiuyan Yang, Lan Deng, Qi Lei, Yuqi Yang, Peiwen Ma, Yuxin Men, and al. Drug Discovery Today, Vol. 27, Issue 5, (05/2022): 1236-1250
    1. Scientific abstract

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Acknowledgements

Published: 17/01/2023

Last updated: 18/05/2024

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

The authors deeply thank Valentin Brunel for his support in the design of Figure 1. 

Reviewed by:

Under internal review by EuroGCT Commercialisation Working Group.

Research Pathways Overview

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