MIDD can ease pediatric & rare disease drug loss in Japan

2025年7月8日

“Drug loss” refers to drugs that are already approved in Europe and the United States but are not available in Japan. This blog will outline the scope of drug loss in Japan and explore how MIDD (model-informed drug development) can help mitigate this issue.

The issue of drug loss in Japan has gained attention in media outlets, reports, and academic papers. The 2024 “Survey of the Actual State of Drug Loss and the Construction of Solutions” illustrates this problem. Between 2016 and 2022, the US FDA approved 136 new drugs. At the same time, the European Medicines Agency (EMA) approved 86 drugs. As of 2022, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) had not approved 86 drugs from this cohort. Let’s take a deeper look at these drugs:

overseas companies developed 56,
47 were indicated for drugs to treat rare/orphan diseases,
and 37 were for pediatric use,
The majority of these drugs were not under development in Japan.¹

As of July 2023, 75 drugs currently under development or regulatory review in Europe or the US weren’t being developed in Japan. Thus, the severity of this problem continues to escalate.²

Figure 1: 60% of globally approved new drugs cannot be used in Japan.

(Reference: Daisk Tanaka、Regulatory updates in Japan, 12th Joint Conference of Taiwan and Japan on Medical Products Regulation, 7 October 2024)

Addressing Japan’s drug loss with Model-informed drug development

Japan’s lack of innovative treatment options for pediatric cancer and rare diseases is a big challenge. Certara is addressing this issue by advocating for greater utilization of MIDD. We are leveraging this technology to confer multiple benefits to our clients:

Biosimulation technology can help optimize clinical trial designs
We use MIDD to inform data integration and analysis to support critical decision-making
Our experts are coordinating these efforts with the PMDA.

Certara offers comprehensive development support using MIDD strategies for pediatric cancer and rare diseases, particularly in cases where randomized controlled trials (RCTs) are not feasible. This approach helps create an innovative MIDD ecosystem aimed at mitigating drug loss in Japan.³

MIDD, which includes Quantitative Systems Pharmacology (QSP) and Model-Based Meta-Analysis (MBMA), tailored for specific diseases, provides evidence-based treatment options for innovative modalities, such as multi-specific antibodies and CAR-T cell therapies^4,5,6, where the areas facing a serious drug loss problem. The PMDA actively promotes the use of MIDD in its review processes, and further expansion of its application is expected in the future.7

図2：Technology-enabled Model-informed Drug Development Ecosystem

(Reference: Rajesh Krishna, The Utility of Model-Informed Drug Development for Rare Diseases, 2022年5月20日 Blog, Certara | Model-Informed Drug Development for Rare Diseases)

Leveraging Certara's expertise to navigate European, US, and Japanese regulatory requirements

Certara’s services team has a proven track record of providing comprehensive support to pharmaceutical companies in areas such as strategy planning and regulatory submission preparation for FDA Orphan Drug Designation and EMA Orphan Medicinal Product Designation. As a result, we can provide optimal regulatory in plans that meet Japan’s unique requirements, accelerating the development and market launch of drugs for rare diseases.

Certara also has a proven track record of MIDD-based pediatric services worldwide for pediatric diseases. Based on our strategic support for the EMA’s Paediatric Investigation Plan, the FDA’s Initial Pediatric Study Plan (iPSP), and Project Optimus, we design development strategies to address the unmet needs of pediatric cancer patients and others.

We work with global pharmaceutical companies in multiple ways across the globe, covering all stages of development process from Investigational New Drug (IND) applications and Clinical Trial Applications (CTA) to Post-Marketing Surveillance (PMS) for drugs that have been approved in Europe and the United States but are yet to be launched in Japan.

Certara’s Japanese team has several Japanese consultants who work with experts from around the world to provide various consulting services to Japanese pharmaceutical companies and any companies considering applying for new drug approvals to the PMDA.

Summary

By utilizing the quantitative data generated by MIDD, we can engage in scientific discussions with global regulatory agencies including the FDA, EMA, and PMDA. We also prepare data and review scenarios for pre-submission meetings and advisory board responses. This approach aims to develop clinical plans and data sets that are more likely to meet the regulatory requirements set by health authorities in each country, which could help reduce the risk of drug loss in Japan.

If your team is considering a new drug application to the PMDA or would like to consult with a Japanese MIDD expert, please don’t hesitate to contact us. Additionally, for those interested in consulting services for rare diseases or pediatric patients, please refer to the list of therapeutic areas available on our website.

Learn more about MIDD and regulatory services for Pediatrics and Rare Diseases for PMDA submissions

Never give up your commercial success in the Japanese market. Our Japanese and global experts will solve your questions and concerns even for the most complex drugs.

Read a case study of the successful approval of orphan drug in Japan

参照文献

厚生労働省Press Release　令和６年度厚生労働科学特別研究事業「ドラッグ・ロスの実態調査と解決手段の構築」研究班の整理結果に関する公表、2025/3/31．

医薬品医療機器総合機構（PMDA）理事長　藤原康弘、ドラッグ・ロスに対するPMDAの取り組み、第35回抗悪性腫瘍薬開発フォーラム, 2024/02/17

Rajesh Krishna, The Utility of Model-Informed Drug Development for Rare Diseases, 2022年5月20日 Blog, Certara | Model-Informed Drug Development for Rare Diseases

Certara. 4 Ways That Mechanistic Modeling Accelerates Bispecific (and Multispecific) Antibody Drug Development. Blog, Sep 12, 2024.

Certara. Quantitative Systems Pharmacology (QSP) Modeling for Immunotherapy-induced Cytokine Release Syndrome. Blog 2024年8月20日 .

Fediuk et al. End‑to‑end application of model‑informed drug development for ertugliflozin… CPT: Pharmacometrics & Systems Pharmacology, 2021.

Hasegawa M, Kijima S. MIDD in Japan- Implementations, challenges and opportunities. Adv Drug Deliv Rev. 2025 May;220:115553. doi: 10.1016/j.addr.2025.115553. Epub 2025 Feb 28. PMID: 40024482.