Collaborative Pilot Update

16 December 2022

Background

In July 2022, ICMRA initiated two pilot programs focusing on i) collaborative assessment of chemistry, manufacturing, and control (CMC) related post-approval changes (PACs) and ii) collaborative hybrid inspections to inform CMC assessment. In addition to maximising resources and facilitating more effective and efficient reviews, the overarching goal of each collaborative pilot is the identification of misalignments, differences, and potential areas for alignment or harmonization in assessment and inspection activities across participating regulatory regions in the context of manufacturing lifecycle management. A better understanding of areas of potential alignment and difference is an important first step to harmonising specific CMC- and inspection-related regulatory procedures to facilitate the timely implementation of appropriate regulatory actions across different regions. In the interests of transparency and openness, ICMRA will provide regular updates on the status of each collaborative pilot and include further information on the types of applications received and selected for each pilot to help industry take advantage of this opportunity to participate.

Selection Process

Industry were invited to submit applications to participate in each pilot based on criteria outlined in section 4 and section 7, respectively, of the PAC and hybrid inspection pilot implementation plans. Briefly, applications focusing on products intended for the treatment of patients with COVID-19, Breakthrough/PRIME/SAKIGAKE products, or products deemed medically necessary/critical medicine, with applications submitted to multiple regulatory authorities in parallel would be prioritised. Following each submission, representatives from ICMRA’s PQ KMS sub-working group tasked with operationalising the pilots evaluate each submission against the criteria described in the implementation plans and assess whether submissions are aligned with the overall goals and objectives for each pilot.

Successful Applications to Date

To date, two applications have been selected for the collaborative assessment pilot. Both applications include PACs for products deemed medically necessary or critical and intended for submission in at least two regulatory regions in parallel. The first pilot application includes post approval change management protocols (PACMP) covering the planned addition of a drug substance manufacturing site, drug product manufacturing site and QC testing site for a biological molecule and includes two participating regulatory agencies. The second pilot application relates to the submission of a PACMP for the addition of a new drug product manufacturing and testing site for a biological molecule, which includes 6 participating regulatory agencies (with two of them being an observer only). Both applications are expected to be completed in Q2 2023.

There has been one application to participate in the collaborative hybrid inspection pilot (CHIP). The ICMRA sub-working group is currently engaging with the Sponsor concerning their application.

Rationale for Not Currently Selecting Applications

The overall standard of each submission received to date has been thorough and of high quality, which is very much appreciated by all assessors from each regulatory agency. Each pilot aims to conduct three assessments or collaborative hybrid inspections over an anticipated duration of 1-1.5 years. Consequently, not all applications received could be selected to participate in the collaborative assessment pilot at this time. The rationale for declining certain applications includes submissions beyond the current scope of the pilots. Moreover, because FDA, EMA and PMDA are leading the development of a framework to support information sharing and coordination of each pilot, it is necessary that at least one of these agencies be included in an application. Therefore, any application that does not include one of these three regulatory agencies will likely be declined.

An additional reason for not selecting an application is due to a product having a national licence in several EU member states, rather than being centrally authorised through EMA. While not an exclusion criteria per se, the PQ KMS sub-working group considered that for collaborative assessment pilot applications which include the EU, involvement of the EMA is preferred. Other applications not selected included submissions for PACs where proposed updates had already been approved by some regulatory agencies, thus lessening the opportunity for further harmonisation of assessment or inspection activities across regions.

Next steps

The assessment of the two selected collaborative assessment pilots will proceed throughout Q1 and Q2 2023. The ICMRA Collaboration Pilots are actively soliciting additional applications from interested companies and would plan to accept a third pilot application in 2023, ideally starting in Q3. Interested parties are encouraged to continue to submit applications to the collaborative assessment and hybrid inspection pilots throughout Q1 and Q2 next year. Once all pilots are completed, it is planned to publish the findings on the ICMRA website, including lessons learned, best practices and standards, etc.