China’s CDE Releases Two Guidelines on Rare Disease Drug Development

On July 30, 2025, China’s Center for Drug Evaluation (CDE) released two pivotal technical guidelines to support rare disease drug development:

No.25 of 2025: Technical Guidelines for Model-Informed Drug Development for Rare Diseases
No. 26 of 2025: Technical Guidelines for Clinical Pharmacology Studies of Drugs for Rare Diseases

Both guidelines are effective immediately and apply to chemical drugs and biologics, excluding traditional Chinese medicines.

Strategic Context

Rare disease drug development presents global challenges due to small patient populations, high disease heterogeneity, and geographic dispersion. These factors often make traditional randomized controlled trials infeasible. The new guidelines reflect China’s commitment to flexible, data-driven approaches aligned with international regulatory practices.

Guideline Overview

1. Model-Informed Drug Development (MIDD) - Guideline No. 25 of 2025

This guideline promotes the use of quantitative pharmacology to support decision-making in rare disease trials. Recommended modeling approaches include:

Population Pharmacokinetics (PopPK)
Physiologically Based Pharmacokinetics (PBPK)
Quantitative Systems Pharmacology (QSP)
Model-Based Meta-Analysis (MBMA)

These models help simulate drug behavior, predict exposure–response relationships, and extrapolate across populations. Sponsors are expected to submit:

Modeling objectives and rationale
Methodology and data sources
Key assumptions and validation strategy
Interpretation of results

Applications include dose optimization, population extrapolation, and predictive modeling for efficacy and safety.

2. Clinical Pharmacology – Guideline No. 26 of 2025

This guideline supports a case-by-case approach when traditional studies are impractical. It emphasizes:

Pharmacokinetics (PK): absorption, distribution, metabolism, excretion
Pharmacodynamics (PD): drug efficacy and safety
Biomarkers: for diagnosis, disease progression, and surrogate endpoints

Sponsors may tailor study designs based on molecular type (e.g., gene therapy, cell therapy), patient characteristics, and feasibility. If full pharmacology studies are not feasible pre-approval, a risk-based scientific justification is required.

3. Industry Impact

The guidelines provide a structured framework to accelerate innovation and improve regulatory predictability in China’s rare disease space.

Global Sponsor Advantage: MIDD enables sponsors to address data limitations and engage early with regulators, especially in gene and cell therapy programs.
Clinical Development Flexibility: Adaptive strategies, including post-approval studies and real-world data, support faster progression.
Technical and Regulatory Alignment: Clear planning for modeling, biomarker integration, and regulatory communication is essential as China shortens review timelines and expands digital submission requirements.

Further Information

Explore the official announcements on the 2025 technical guidelines for rare disease drug development from China’s Center for Drug Evaluation (CDE):

Model-Informed Drug Development (MIDD) – Guidance on leveraging modeling and simulation to optimize rare disease drug development.
Clinical Pharmacology Studies – Key considerations for designing and conducting pharmacology studies in rare disease populations.