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 Advanced Therapy Medicinal Products.
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 Advanced Therapy Medicinal Products, one of whose characteristics is to be innovative.
Accelerated Assessment Applicant: The people or pharmaceutical company applying to reduce the EMA’s 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 responsible for the scientific assessment of Advanced Therapy Medicinal Products 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): The accelerated assessment application to reduce the EMA timeframe to review a marketing authorisation application is conducted by the Committee for Medicinal Products for Human Use, the EMA's main scientific assessment committee for medicinal products for human use, notably responsible for the assessment of marketing authorisation applications under the centralised procedure.
Committee for Advanced Therapies (CAT) is the European Medicines Agency's committee responsible for assessing the quality, safety and efficacy of Advanced Therapy Medicinal Products. The CAT is notably in charge of preparing a draft opinion on each Advanced Therapy Medicinal Product application submitted to support the final recommendation of the Committee for Medicinal Products for Human Use.
Pharmacovigilance Risk Assessment Committee (PRAC) is the European Medicines Agency'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 Advanced Medicinal Therapy Products’ marketing authorisation applications though providing advice to the Committee for Medicinal Products for Human Use.
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 Committee for Medicinal Products for Human Use will reduce the application processing time from 210 to 150 days (excluding clock stops). For Advanced Therapy Medicinal Products, 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.
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 Committee for Advanced Therapies. 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 European Medicines Agency to shorten the centralised procedure review period of a marketing authorisation applicant 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 European Medicines Agency and the Committee for Medicinal Products for Human Use are the entry points for an accelerated assessment procedure application providing scientific support, advices and guidelines to secure an earlier access of the medicinal products, including Advanced Therapy Medicinal Products, to patients.
It also 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).
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 European Medicines Agency, 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 European Medicines Agency’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.
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 European Medicines Agency, 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 Good Manufacturing Practice.
The European Medicines Agency 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 safety and the benefit-risk balance of the medicinal product, and if necessary to take regulatory actions to protect public health.
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 interestfrom the point of view of public health and in particular from theviewpoint 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.
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
The scope of this guideline is to provide applicants with guidance on the accelerated assessmentrequest and the practical arrangements necessary to implement the legal provisions on the acceleratedassessment procedure.
This document provides a non-exhaustive overview of the potential pre-defined factors that can be used for the selection of marketing authorisation applications to be part of a programme of routine inspections and non-exhaustive overview of potential triggers that can be detected at the different stages of the assessment process and that can help the assessor to decide on the need for “for cause” inspections and be used to prepare an inspection.