Stakeholders have been notified of the EMA intention to expect a more stringent application of the current 2009 CHMP guideline on clock-stops on granting clock-stop extensions from July 2024.
This announcement follows the conclusion of an internal EMA initiative in which industry was not invited to participate, called GIREX (Group for Internal Rules for EXtension of Clock-stops): see slides 6 -12 in Topic 8 - Assuring the Network’s Sustainability.
The EMA was requested by the CHMP given the challenges of the long EMA review times, the implementation of the HTA Regulation and a response to capacity issues within the network.
Similarly, to the EMA recently tightening their approach on submission timings, this new stringency on Clock-Stop extensions aims at more predictability and more mature dossier expected at submission.
Expected Impact
- Since April 1st, 2024, all applicants are now asked to complete a dedicated template for the request of extension for clock stop and all requests should be duly justified.
- Starting 1 July 2024,the EMA will apply the 2009 Guideline on extension of clock stop more strictly resulting in:
- Strong justification needed to support a clock stop extension.
- No extension beyond 6 months will be accepted (apart for exceptional circumstances).
- Clock stop to solve problems evident prior to submission will not be granted*
- What would happen if a clock-stop extension is not granted? Applicant will have to make the best effort to answer (as feasible, clarification meeting can be requested to discuss strategy) within the standard clock-stop timings (3 month/1 month) OR withdraw OR ultimately CHMP will issue a negative opinion.
- What about shorter clock-stops – will these now be more accepted/usual? Sadly no. The high workload across the wider EU network and impact of submission predictability means rapporteurs may not be able to accept shorter clock stops. When volunteering to be rapporteurs, the NCA team plan for 3 months + 1 month clock stop by default for a new MAA.
EFPIA, via an ad hoc Regulatory Science Committee meeting (10 July 2024) will:
- Reflect/feedback on the expected impact of this news which will support the discussion on the broader strategy to be taken by EFPIA.
- There is a need to discuss what EFPIA’s strategy should be to navigate the different dialogues that cover assessment timings. Balancing between increased predictability/better capacity (EMA driver)/faster EU approvals, the GPL narrative (more flexibility in the Centralised procedures e.g., dynamic regulatory assessment, ERPs), the implementation of the HTA Regulation (EMA timetable impacts HTA processes) and proposals under the Cancer Pathways Initiative.
- RSC members will also be asked to endorse a detailed survey to EFPIA members to find out more about the origin of the long clock stops in EU (compared to other regions).
*Examples of an ‘immature’ dossier where extension will not be granted (shared by the EMA during the 12th industry stakeholder platform on the centralised procedure held on 19 June 2024)
- Failed primary endpoints and applicant submits with some positive secondary endpoints following some “stats gymnastics” reinforced by planned RWE to ‘in-fill’ gaps.
- Interim analysis with limited OS and only 2 months of follow-up data
- Initial submission where applicant is planning to submit additional data at Day 120 and this data/analysis is subsequently delayed.
- Limited number of patients (an example of 7 patients was given) / study still enrolling/single arm study.
- When EMA Guideline indicated confirmatory trial is needed and it is not included in the dossier
- Pre-submission meeting identified issues and dossier is nevertheless submitted.
- Inspection issue due to the Applicant (if due to HA, clock stop will be granted)
Document source: Presentation-Assuring-Networks-Sustainability-f-day-ema_en.pdf