China Rare Disease Drugs Clinical Pharmacology Research Technical Guidelines – Draft for Comments

China rare disease drugs clinical pharmacology research technical guidelines have been drafted for comments by the Center for Drug Evaluation (CDE) on October 12, 2024. This draft aims to support pharmaceutical companies in navigating the unique complexities of rare disease drug development. Rare diseases often come with distinct hurdles, including limited patient populations, variability in disease characteristics, and early-onset in childhood. To strengthen the guidance, the CDE encourages stakeholders to provide feedback.

Given the specialized nature of rare disease drug development, these guidelines offer structured guidance across four main areas: general considerations, study design principles, key drug types, and communication with regulatory authorities.

Key Areas of Focus

1. Strategic Flexibility in Clinical Pharmacology Requirements The CDE’s guidelines reflect a flexible approach to rare disease drug approval by permitting certain clinical pharmacology studies to be conducted post-market in cases where pre-market data is difficult to obtain. This adjustment provides an advantage to pharmaceutical companies, allowing them to expedite drug availability for rare disease patients without compromising safety standards. This flexibility highlights China’s balanced approach to regulatory oversight and patient access.
2. Utilizing Model-Informed Drug Development (MIDD) The guidelines strongly endorse MIDD as a critical tool for rare disease drug development, helping to overcome data scarcity and optimize study design. MIDD can support data extrapolation when patient populations are limited, enabling more robust predictions without requiring large sample sizes. Companies are encouraged to consider MIDD as an essential component of their clinical strategy, using it to bridge gaps in clinical data.
3. Early-Stage China-Based Research for Global Drugs For global companies developing rare disease drugs, the guidelines encourage early-stage research in China, especially for diseases with a substantial patient base locally. This approach allows for early access to Chinese patient data, benefiting both local and international drug development. It also aligns with China’s regulatory intent to integrate domestic data into the global development landscape, creating an avenue for accelerated approval.
4. Leveraging Real-World Data and Cross-Study Insights Recognizing the limitations of traditional clinical trials, the guidelines encourage companies to incorporate real-world and cross-study data into clinical research. This data can enhance study designs, especially where patient numbers are limited, and support a richer, more reliable evidence base for rare disease drugs.
5. Addressing Study Design Challenges Unique to Rare Diseases Rare disease trials face distinct challenges due to limited patient numbers and variability in disease expression. The guidelines provide specific guidance on designing studies to account for these challenges:
   • Study Population: A “general to specific” approach is recommended, progressing from non-clinical and healthy subject studies to rare disease patient trials, including pediatric studies.
   • Sample Size Optimization: Given limited patient pools, sample sizes should be planned with MIDD support to ensure statistical relevance.
   • Dosing Regimen and Genetic Factors: Dose selection should consider genetic variability and polymorphisms, with post-market studies advised for further validation.
   • Pharmacodynamic Indicators: Biomarkers are critical for rare disease drugs, serving as potential surrogate endpoints for accelerated approval where validated.

Tailored Approaches for Different Drug Types

The clinical pharmacology needs of rare disease drugs vary widely based on drug type, properties, and mechanisms of action. Below is a summary of the CDE’s recommendations by drug class:

• Gene Therapy Drugs: Often indicated for genetic disorders, gene therapy should undergo dose-escalation studies pre-market to confirm optimal dosing, with further studies to assess safety and efficacy in pediatric populations. Pre- and post-market pharmacokinetic/pharmacodynamic (PK/PD) assessments are encouraged.
• Cell Therapy Drugs: Due to unique factors like immune variability, cell therapies require specialized pharmacology studies. Modeling and simulation techniques are recommended to assess safety and efficacy.
• Small Molecule Drugs: These drugs should follow standard clinical pharmacology requirements, with necessary pre-market studies for PK, food effects, and QT safety. Non-critical studies may be completed post-market if they do not impact safety or efficacy.
• Other Drug Types (Antibodies, ADCs, Peptides): Pharmacology studies for these drugs should adhere to existing guidelines relevant to each category, addressing the unique characteristics of each drug type.

How to Submit Your Comments

Feedback and suggestions can be submitted to the CDE by emailing official feedback to wangyzh@cde.org.cn and majy@cde.org.cn by November 12, 2024.

Further information

China’s Rare Disease Drugs Clinical Pharmacology Research Technical Guidelines signal a forward-thinking, adaptive regulatory approach that balances patient access with rigorous scientific standards. For companies navigating the rare disease landscape, the guideline’s flexibility, strategic use of MIDD, and openness to real-world data offer valuable pathways to advance drug development. This draft also underscores China’s commitment to playing an active role in global rare disease drug research.

Read the original CDE announcement on China Rare Disease Drugs Clinical Pharmacology Research Technical Guidelines – draft for comments.

For more information on how these guidelines might impact your development process, contact us to learn about our specialized drug registration and filing services in China.

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