【Pharmaceutical Affairs and Food Sanitation Council】Recurrence Prevention Measures for the SMA Drug Issue‐Including Pre-evaluation of Application Data

2020年12月18日 (金)

Approved by Pharmaceutical Affairs and Food Sanitation Council

On December 3, 2020, the Committee on Regenerative Medicine Products and Biotechnology, Pharmaceutical Affairs and Food Sanitation Council generally approved the recurrence preventive measures compiled by Novartis Pharma K.K. after the delay in the approval of its “Zolgensma Intravenous Infusion” indicated for the treatment of spinal muscular atrophy (SMA) due to its improper response. The measures have included prevention of data falsification through prior evaluation of assurance of reliability of application data.

Regarding this drug, inappropriate data manipulation was revealed in a part of the application data after filing of the marketing application. In addition, although the drug is subject to the Sakigake (Advance Review) Designation System, the marketing application was filed before making full use of the comprehensive evaluation consultation system at the Pharmaceuticals and Medical Devices Agency (PMDA), which was also viewed as a problem. Accordingly, the company and the government have been working on the detailed recurrence preventive measures.

Zolgensma had been developed by AveXis in the US which was acquired by Novartis in 2018. According to the report by Novartis Pharma K.K. in the recurrence prevention measures, however, Novartis failed to identify issues on reliability assurance in a timely manner since it had kept allowing the AveXis’s reliability assurance division even after the acquisition.

Novartis Pharma K.K. also mentioned that it lacked awareness of checking its own application data prepared abroad as the domestic corporation and lacked responsibility for filing in Japan.

Accordingly, the measures have included that the company as the domestic corporation is responsible for filing in Japan, conducts prior evaluation to ensure reliability assurance of application data, and reinforces the organization to enable fostering awareness of reliability assurance and taking appropriate actions.

Meanwhile, with regard to utilization of the PMDA’s consultation system, it was stated that both the domestic corporation and AveXis lacked understanding of the Sakigake (Advance Review) Designation System and had insufficient human resources. The report also mentioned that Novartis Pharma K.K. failed to accurately predict the impact when application was filed before completion of consultation and that the coordination with the headquarters in Switzerland was insufficient when a delay in responding to the review was identified.

In order to prevent the above, the domestic corporation would evaluate in advance that the response for a designated product is appropriate and the corporate organization would be changed so that the domestic corporation can directly make comments to the headquarters and request an integral solution.

Although no negative comments were made by the committee members about the recurrence prevention measures presented on the day, Novartis would modify insufficient descriptions in some parts. After the corrections approved by the committee, the MHLW has expressed its views that it would like to review the drug upon confirmation of proper implementation of preventive measures, in the case where the company requests the drug to be designated as Sakigake (Advance Review) Designation Product.