Abstract
While multiple regenerative medical products have been approved in Japan, many changes such as manufacturing process, manufacturing site, analytical procedures, specifications limit, and shelf life can occur through the post-approval lifecycle management. Particularly, cell therapy products using chimeric antigen receptor T cells have characteristics different from ordinary pharmaceutical products, and therefore, are required to take prompt regulatory actions related to changes. When regulatory actions related to changes are taken, notification of minor change or partial change application should be submitted. However, the standard review period for partial change application for regenerative medical products in Japan is 12 months, and it is difficult to say that regulatory actions related to changes can be taken promptly. On the other hand, in 2021, confirmation of a change protocol and a prior notification system for changes in accordance with the protocol (Post-Approval Change Management Protocol: PACMP) were introduced. Based on the protocol agreed with the regulatory authorities, this system allows planned changes to be made promptly upon notification when expected results are obtained. In this study, we investigated whether PACMP can be used to promptly take regulatory actions related to changes in cell therapy products. The results of the investigation showed that, compared with the partial change application, the use of PACMP may enable more rapid changes of about 10-11 months for shelf-life extension and about 4-5 months for addition of manufacturing site and manufacturing process changes. However, it was considered that it would be difficult to change the analytical procedure or specification limit rapidly using PACMP.
