On February 9, 2025, China's Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) released two new guidelines: the Guideline for Acceptance and Review of Chemical Drug Registration (Trial) and the Guideline for Acceptance and Review of Biological Product Registration (Trial). These guidelines, set to take effect on March 10, 2025, aim to streamline the drug registration process, enhance electronic submission requirements, and align with international standards.
Guideline for Acceptance and Review of Chemical Drug Registration (Trial)
This guideline provides detailed instructions for the registration of chemical drugs, specifying procedures, document requirements, key review points, and acceptance criteria. It applies to clinical trial applications and marketing authorization applications for chemical drugs classified under categories 1, 2, 3, 4, 5.1, and 5.2. Applicants must strictly adhere to the guideline’s requirements to ensure the completeness and compliance of their submissions, improving the likelihood of successful acceptance.
Key updates include:
1. Enhanced Digital Submission Requirements: eCTD format and online submission are supported. PDF documents must include electronic signatures, and clinical trial databases must be submitted electronically.
2. Patent Declaration Compliance: Applicants must align with China’s Listed Drug Patent Information Registration Platform and adhere to the Implementation Measures for the Mechanism for Early Settlement of Drug Patent Disputes.
3. Reference Drug Information: Applicant must submit clear documentation of the reference drug’s source, approval information, and purchase records.
4. Clinical Trial Data: It is required to submit clinical trial progress reports, Development Safety Update Reports (DSUR), and Suspected Unexpected Serious Adverse Reactions (SUSAR) reports.
5. Simplified Foreign Document Certification: Documents conforming to WHO formats or the Convention Abolishing the Requirement of Legalization for Foreign Public Documents are exempt from notarization.
6. Refined Format Review Criteria: New provisions clarify electronic signature requirements, document validity, and exemption criteria for generic drug applications under specific conditions.
7. Upgraded Self-Inspection Checklist: Companies must submit manufacturing process validation reports, compliance verification for electronic signatures, and safety assessments for clinical trials.
8. Special Drug Management: The guideline prohibits outsourcing the production of compound preparations containing narcotic or psychotropic substances.
9. Drug-Device Combination Products: Medical device components must be submitted separately on CD-ROM.
Guideline for Acceptance and Review of Biological Product Registration (Trial)
This guideline outlines the requirements for the registration of biological products, including preventive and therapeutic biologics and in vitro diagnostic reagents managed as biological products. It details the acceptance and review procedures, document requirements, key review points, and acceptance criteria.
Key updates include:
1. New electronic submission requirements: PDF files must be electronically signed by the applicant or registration agent; electronic documents can be submitted via online transmission methods, such as eCTD or CD-ROM.
2. Clear submission routes for biosimilar pharmaceutical documentation: Quality assessments for biosimilarity must now be provided under section 3.2.R.6, "Other Documents."
3. Flexible Submission Pathways for Emerging Therapies: Pharmaceutical research data can be submitted under either the drug substance or drug product modules based on product characteristics, with non-applicable items marked as “Not Applicable.”
4. Enhanced Feedback Mechanism: Companies that have engaged in prior regulatory discussions must submit relevant communication records, official responses, and provide point-by-point replies to the feedback received.
5. Upgraded Patent Management: Biosimilars must reference publicly listed patents on China’s Drug Patent Information Registration Platform and submit patent declarations via the drug business application system.
6. Simplified Foreign Document Certification Process: Proof documents conforming to WHO standards are exempt from notarization, while those from treaty signatory countries require only an attached certification.
7. Strengthened Manufacturing Controls: A new requirement mandates that marketing authorization applications include records of at least three consecutive batches at the proposed commercial scale.
8. Defined Format Review Timelines: Previously unspecified, the new guidelines establish a five-day deadline for format review.
