Assessment of the official national insurance coverage of regenerative medical products for ophthalmic diseases in Japan following regulatory approval.

INTRODUCTION

Recently, significant progress has been made in the field of regenerative medicine in Japan for the treatment of ophthalmic diseases, with a notable emphasis placed on clinical research and practical applications, and in 2014, one significant development was the initiation of the world's first clinical research using iPS cells for age-related macular degeneration. In addition, three regenerative medical products for the treatment of limbal stem cell deficiency, a rare and intractable ocular surface disease, have recently been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) under the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act). In order to expedite the practical implementation of regenerative medicine, the PMD Act presented a new category for regenerative medical products alongside the two categories that currently exist (i.e., 'pharmaceutical products' and 'medical devices'). However, within the current official Japanese national insurance coverage plan, there is no category designated for 'regenerative medical products'. Although the approval system for regenerative medical products differs from country to country (i.e., the United States Food and Drug Administration (U.S. FDA), the European Medicines Agency (EMA), etc.), in Japan, they are approved by the Japanese MHLW and PMDA. When manufacturers seek newly approved regenerative medical products in Japan to be incorporated within those listed in the Japanese national insurance coverage plan, the products are classified as either 'pharmaceutical products' or 'medical devices' and are reviewed by the Central Social Insurance Medical Council ("Chuikyo", in Japanese) of the Japanese MHLW. Although the responsibility for applying for regulatory approval and insurance coverage lies with the manufacturer, as the developer who conducted the clinical study and the investigator-initiated clinical trial for two ophthalmic regenerative medical products (i.e., Sakracy® and Vyznova®), we perceived that the period from regulatory approval to insurance coverage listing for these two products was longer than for other ophthalmic regenerative medical products. These experiences became the research question and the focus was on ophthalmic regenerative medical products, with the rationale behind this submission being that the dissemination of our experience will be of benefit to all clinical researchers and manufacturers. Hence, the purpose of this present study was to investigate the insurance coverage of regenerative medical products for ophthalmic diseases in Japan from the aspect of specific coverage-related categories.

METHODS

In this study, we investigated newly approved regenerative medical products for ophthalmic diseases in Japan after the Revised Pharmaceutical Affairs Act came into effect in 2014. The insurance coverage categories (i.e., 'pharmaceutical products' or 'medical devices') of each product and the period from regulatory approval to insurance coverage listing were examined based on publicly available materials from the Japanese MHLW.

RESULTS

As of the end of 2024, five products are included on the insurance coverage list. The period for Luxturna Injection® (Novartis Pharma), categorized as a pharmaceutical product, to be included was 65 days, which was within the standard administrative processing time for pharmaceutical products, (i.e., 60 days or less, yet no later than 90 days), while the elapsed periods for Nepic® and Ocural® (Japan Tissue Engineering), Sakracy® (CynosBio), and Vyznova® (Aurion Biotech Japan), which are categorized as medical devices, were 74, 173, 224, and 534 days, respectively. The periods for Sakracy® and Vyznova® exceeded the standard administrative processing time for medical devices, which in principle ranges from 5 to 6 months. Moreover, the elapsed period of time from regulatory approval to insurance coverage listing for Vyznova® was more than twice as long as that which occurred for Sakracy®.

CONCLUSIONS

Regenerative medical products categorized as medical devices are required to undergo a review process conducted by the Technical Committee for Insurance Materials on Medical Devices of the Japanese Central Social Insurance Medical Council. Our findings suggest that both manufacturers and regulatory authorities need to revise the Technical Committee's strategy from the aspect of putting regenerative medical products into practical clinical use in Japan.