# Clinical data required for the approval of pediatric pharmaceuticals in Japan

## TL;DR

This study examines the clinical data and approval processes for pediatric drugs in Japan to identify factors that facilitate drug approvals.

## Contribution

The study provides insights into the types of clinical data and administrative incentives that support pediatric drug approvals in Japan.

## Key findings

- Extrapolation from non-Japanese children and Japanese adults is commonly used in approval reviews.
- Confirmatory studies in Japanese children were conducted for only 10 out of 171 analyzed products.
- Administrative incentives like orphan drug designation and Sakigake are frequently applied.

## Abstract

In Japan, the number of pharmaceuticals with pediatric indications is low, and some are approved only in Europe or the USA but not in Japan. As the approval review report by the Japanese health authority contains any detailed items considered for drug approval, this study aimed to analyze the review reports and elucidate data types that facilitate the approval of pediatric drugs in Japan.

We identified products approved in Japan, extracted relevant product- and review-related information, and summarized the characteristics of pediatric drug clinical data and drug approval procedures.

Among 625 products (approved 04/2019–02/2024), 171 with pediatric indications were analyzed. The approval review considered orphan drug designation for 56 products, public knowledge-based application for 16 products, mandatory post-marketing surveillance for 42 products, and investigator-initiated studies for 11 products.

For only 10 products, confirmatory studies were completed exclusively in Japanese children. Among the other 161 products, extrapolation from non-Japanese children and Japanese adults and/or older children was discussed for 93 and 100 products, respectively. Extrapolation-based reviews focused on ethnic and population factors and consistency of exposure dose, efficacy, and safety.

Statistical confirmation is not always necessary for approval. Administrative incentives are often applied, including for orphan drugs and Sakigake designation and public knowledge-based applications.

The appropriateness or sufficiency of the clinical data package can refer to the PMDA. By considering joining a multinational study and determining the required number of Japanese patients, a path toward the approval of pediatric drugs in Japan can be identified.