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‘Positive & Productive’ – US, EU Regulators On First Collaborative CMC Change Assessment

Executive Summary

An application to add new manufacturing and quality control sites for a oncology biologic was approved in the US and the EU on the same day, a move that was said to be “a significant accomplishment” in aligning the regulators in each region on the assessment process and timeline.

There has been a positive outcome from the first collaborative assessment by regulators taking part in an international pilot exploring how to make it easier for drug companies to make post-approval manufacturing changes in different countries and ensure the supply of critical medicines.

The assessment, which involved US and EU regulators evaluating an application to add new manufacturing and quality control sites for a oncology biologic, was completed under the four-month goal window for a standard manufacturing supplement assessment, and approval by both agencies was granted on the same day.

The collaborative assessment teams from the Food and Drug Administration and the European Medicines Agency had “a positive and productive experience,” the FDA said, adding that the coordination efforts by the regulators also received positive feedback from industry.

They produced a common set of “highly aligned” information requests and comments for the applicant.

The fact that the EU approved the submission on the same day as the FDA marks “a significant accomplishment in aligning FDA and EMA on the assessment process and timeline,” the FDA said, noting that Japan’s Pharmaceuticals and Medical Devices Agency served as an observer during the assessment.

The first experience with the collaborative approach, which is a project of the International Coalition of Medicines Regulatory Authorities, was announced by the FDA on 28 July, around a week after the ICMRA and industry held a workshop that included discussion on the initiative.  (Also see "All Eyes On International Pilots For Streamlining Regulatory Assessments & Inspections" - Pink Sheet, 13 Jul, 2023.)

Collaborative assessments are expected to help address the challenges involved with making post-approval chemistry, manufacturing and controls (CMC) changes.

“A single manufacturing change, even when critically important, can be complex and time-consuming to implement,” the FDA said. “Depending on the extent of the change, regulators may need to assess, inspect, and approve it. Because drug manufacturers often sell the same product in many countries, they must work with global regulators that have different expectations and review timelines for such changes.”

Collaborative assessments will avoid duplicative assessments for CMC-related post-approval changes, and could help ensure the supply of the medicine.

The FDA said that the ICMRA had so far accepted several proposals for the CMC changes pilot, which was launched last year, including the recently completed one (see sidebar). The other proposals cover different post-approval change scenarios from across the manufacturing lifecycle, including the transfer of quality control sites for a biologic, addition of a new drug active pharmaceutical ingredient manufacturing site, and addition of a new finished drug product manufacturing site.

Collaborative Hybrid Inspections

The CMC post-approval changes project is one of two pilots being conducted under the ICMRA’s  “pharmaceutical quality knowledge management system (PQ KMS)” initiative.

The other pilot focuses on hybrid inspections, which involves conducting a collaborative facility assessment using a combination of on-site inspection and remote assessment tools.

A regulator from one country will perform an on-site inspection, with regulators from one or more other countries remotely connecting at the same time. “The pilot aims to identify the best virtual platforms and information technology (ie, video) to facilitate concurrent on-site inspection and distant assessment,” the FDA explained. It will also develop protocols and reports for performing hybrid inspections to share with other ICMRA regions.

The hybrid inspection pilot has so far accepted two proposals, according to the FDA. One covers a pre-license inspection to support the drug substance manufacturing and quality control site transfer for a biologic, and the other covers a pre-approval inspection to support the addition of a drug manufacturing site.

“Together, these two pilots are working to identify best practices and standards in the quality assessments of CMC post-approval changes and the collaborative hybrid inspections that may be needed to support these assessments,” the FDA said. “The work accomplished through these pilots will also identify any differences and potential areas for future alignment or harmonization across regions.”

The ICRMA is expected to complete the pilots by early 2024.


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