China's 2025 Biological Product Registration Guidelines: What International Manufacturers Need to Know

China’s Center for Drug Evaluation (CDE) has introduced significant regulatory updates affecting the registration of biological products. On February 9, 2025, the National Medical Products Administration (NMPA) released the "Biological Product Registration Acceptance Review Guidelines (Trial)" (Announcement No. 15 of 2025), which will take effect on March 10, 2025. These new guidelines standardize review processes for preventive and therapeutic biological products as well as in vitro diagnostic reagents, ensuring a more structured regulatory framework. International manufacturers planning to enter the Chinese market must comply with updated submission formats, enhanced compliance requirements, and revised approval pathways. Early preparation is crucial to avoid delays or rejections during the transition period.

What “Trial” Means for International Manufacturers?

The “trial” designation indicates that these guidelines are provisional and subject to adjustments based on industry feedback and regulatory observations during implementation. While binding, NMPA may refine requirements (e.g., submission formats, data thresholds) within 12–24 months before finalizing the rules. International companies should:

• Monitor quarterly updates from NMPA;
• Prepare for potential mid-term adjustments to documentation or processes;
• Engage in official feedback channels to influence future revisions.

Four Major Changes

1. Full Upgrade of Electronic Declaration

• Mandatory Requirement: All submission materials must be submitted in eCTD format, overseas documents require electronic signatures and notarization certification.
• Practical Impact: Enterprises that have not used compliant electronic declaration systems have an initial submission rejection rate of up to 40% (based on 2024 data);
• Response Recommendations: Use localized declaration software certified by CDE (such as Veeva) to ensure document structure and verification code compliance.

2. Strengthened Communication Exchange Mechanism

• Pre-submission Communication: Conditional approval and priority review applications require prior written consensus with CDE;
• Risk Points: Projects without a historical communication number or without a response to each comment will trigger a correction notice;
• Case Reference: A European vaccine company experienced a 6-month delay in its market application due to not updating communication records in time.

3. Good Manufacturing Practice (GMP) Compliance Enhancement

• Overseas Factories: Must provide GMP certificates in WHO format or additional certificates from contracting countries (no consular authentication required);
• Contract Manufacturing: Only "Class B/C" certificate-holding enterprises are allowed to contract manufacturing, and blood products and cell therapy products are prohibited from contracting;
• Data Connection: Process validation batch records must include at least three batches of intended market scale data, and compatibility of overseas clinical batches requires separate demonstration.

4. Patent Declaration and Infringement Risk Prevention

• Biosimilar Drugs: Mandatory requirement to compare with the patent information registration platform of marketed drugs in China, and make a declaration of patent status for each item;
• Legal Liability: Failure to submit a "non-infringement declaration" may face patent litigation leading to a pause in approval during the review period.

Impacts on International Manufacturers

The trial guidelines introduce both opportunities and challenges for international manufacturers:

1. Accelerated Pathways for High-Priority Products

• Priority Review: Products addressing unmet clinical needs (e.g., oncology, rare diseases) qualify for a 40% faster review cycle (6–8 months vs. 12–18 months).
• Conditional Approval: Allows market entry based on Phase II data for life-saving therapies, pending post-marketing studies.

2. Streamlined Submissions for Innovators

• Reduced Toxicology Requirements: Novel biologics with validated MOA (mechanism of action) may omit certain animal studies, cutting development costs by 20–30%.
• Cross-Border Data Acceptance: Non-Chinese clinical data (e.g., FDA/EMA filings) are admissible if supplemented with ethnic sensitivity analyses.

Further Information

To read the original NMPA announcement about the Biological Product Registration Acceptance Review Guidelines (Trial), please click here.

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