The evaluation of medicines, step-by-step
The assessment of a marketing authorisation application for a new medicine takes up to 210 ‘active’ days. This active evaluation time is the time spent by EMA experts to evaluate the evidence provided by the applicant in support of a marketing authorisation application.
This time is interrupted by one or two ‘clock-stops’ during which the applicant prepares the answers to any questions raised by the CHMP. The maximum duration of a clock-stop depend on how long the applicant thinks it will take to respond, but must be agreed by the CHMP. The first clock-stop usually lasts 3 to 6 months and the second one 1 to 2 months.
Overall, the assessment of a new medicine usually lasts around a year.
Did you know..?
The assessment time may be reduced to 150 days instead of 210 days, if the medicine developer is granted accelerated assessment. This is possible for medicines considered of major interest for public health, for example those that target a condition for which there is no treatment option and that have the potential to address the unmet medical need.
1. Preparation of assessment reports
The CHMP rapporteur’s and co-rapporteur’s teams assess the evidence provided on the medicine and independently prepare their assessment reports, where they highlight any issues or concerns to be addressed by the applicant.
2. Inspection (if recommended)
At this stage the rapporteurs may recommend an inspection of the medicine’s manufacturing site, of the site of a non-clinical or clinical study or of the pharmacovigilance processes involved in the application. If this is endorsed by the committee, the inspection will be conducted by inspectors of the EU national agencies.
3. Assessment of risk management plan
In parallel, two members of EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) are appointed as rapporteur and co-rapporteur to assess the company’s proposed risk management plan (RMP), which describes the way important risks will be minimised or managed if the medicine is authorised and how more information will be obtained about the medicine's risks and uncertainties (e.g. through post-authorisation safety studies). This assessment is reviewed by all PRAC members.
4. Draft list of questions
Based on their initial evaluation, the CHMP rapporteur and co-rapporteur share their respective assessment reports with all the CHMP and PRAC members, together with a list of questions to be addressed by the applicant. The assessment of the risk management plan, which also contains questions for the applicant, is also shared with the CHMP and PRAC members.
5. Peer review: written comments
The CHMP peer reviewers also review the rapporteurs’ assessment reports and send their comments, after looking specifically at the way the two assessments were performed and ensure that the scientific argumentation is sound, clear and robust.
6. Peer review: meeting
Comments from all parties, i.e. the rapporteur and co-rapporteur teams, the other CHMP members, the PRAC members, and the CHMP peer reviewers are discussed during a ‘peer review’ meeting. This is a key point in the evaluation of a medicine where the initial viewpoints are integrated and consolidated. This will lead to a single assessment report which will comprise an overview of the assessment and a list of concerns and objections.
7. Final list of questions
The single assessment report is then discussed at the CHMP plenary meeting. As a result of these discussions, some differing views and issues may be resolved and new concerns may be raised and the report is updated accordingly. Following these discussions, the CHMP adopts the report, which represents a common position in light of the evidence and discussions to date and includes a list of questions to be addressed by the applicant.
8. EMA experts continue assessment and prepare more questions
The rapporteur and co-rapporteur evaluate the information sent by the applicant in response to the issues raised by the CHMP and include their analysis of the responses in an updated assessment report.
9. Further review and comments
As in the initial phase, the CHMP members review and comment on the updated assessment report.
10. Review by PRAC members
The updated assessment report is also reviewed and commented on by the PRAC members and discussed at a plenary meeting of the PRAC. The PRAC may at this stage request that the risk management plan include the conduct of safety studies after authorisation.
11. Updated assessment report and possible list of outstanding issues
Comments from the CHMP and PRAC members are consolidated and integrated into an updated assessment report which is discussed and adopted at a plenary meeting of the CHMP by day 180 of the active evaluation time. Most of the time, this report will include a new list of questions for the applicant, called the list of outstanding issues.
12. Oral explanation (if requested)
After the second clock-stop, an oral explanation in which the applicant directly addresses the committee can be requested either by the applicant or by the CHMP. It is usually organised when the CHMP still has major objections with the application. If this occurs, the applicant is asked to provide clarifications on the committee’s outstanding issues.
13. EMA may consult external experts, doctors and patients
The rapporteurs or any CHMP member may at this stage suggest consulting a working party for specific questions or that the committee call on additional experts, including patients and healthcare professionals, through a scientific advisory group or ad-hoc expert group meeting. This group will be asked to answer specific questions, usually in relation to the use of the medicine in clinical practice, and the chair of the group will report back to the committee on the outcome of the discussion.,/p>
14. Updated assessment report and risk management plan
Once the responses to the outstanding issues are received and possibly discussed during an oral explanation with the company, the CHMP rapporteur and co-rapporteur assess the revised information from the applicant and include their evaluation in an updated assessment report, as do the PRAC rapporteur and co-rapporteur in relation to the risk management plan.
15. Further review and comments
The updated assessment report is reviewed by the members of the two committees and discussed at the CHMP meeting.
16. Adoption of opinion
By day 210 of the active evaluation time at the latest, the CHMP will adopt an opinion on the application. The committee will make a recommendation on whether or not a medicine should be granted a marketing authorisation and, if so, under which conditions of use. The committee will also agree on the wording of the product information for healthcare professionals and patients (i.e. the SmPC, labelling and package leaflet) and on any additional data that the company is required to provide after the medicine’s authorisation.
17. Recording of any divergent opinions
Most of the time, the committee reaches decisions by consensus. If such a consensus cannot be reached, the committee’s final opinion will represent the majority view. The divergent opinions and the names of the members expressing them are attached to the opinion of the committee and mentioned in the meeting minutes. The divergent opinions are then published together with the public assessment report.
18. The developer can appeal
19. Appointment of different (co)-Rapporteurs
20. Examination of grounds for appeal
The re-examination looks only at the points raised by the applicant in the grounds for appeal and is based only on the scientific data available when the committee adopted the initial opinion – in other words, the applicant cannot bring in new evidence at this stage. The applicant may request that the committee consults a scientific advisory group in connection with the re-examination. If an expert group was already consulted during the initial evaluation, different experts will be involved in the re-examination.
21. Adoption of final opinion