Regulatory Insights: Focus on China — New Provisions for Drug Registration in 2020
In this blog post, Guoliang Liu, director of China regulatory solutions, and Kelly Wang, associate director of China regulatory solutions, discuss the China “Provisions for Drug Registration” (Decree No. 27, “provisions” hereafter) issued on March 30, 2020. Sponsors of clinical trials and marketing authorization holders (MAHs) must adhere to the requirements set out in the new provisions as of July 1, 2020. This post will outline key aspects sponsors and MAHs should consider as these new regulations are implemented.
Overview of new provisions
The new provisions issued in March 2020 are the result of years of effort by the Chinese government to reform the pharmaceutical industry in China to encourage innovation, speed products to market and offer the benefits of new medicines to patients. Some process improvements described in the new provisions have already been implemented but had not been formalized into law until now. The new provisions are the first revision to the regulations issued by the National Medical Products Administration (NMPA) since October 2007.
The updated provisions supersede previous regulations and cover issues that exist in practice but were not addressed under the previous regulations. Following the release of the new provisions, accompanying interpretations and technical guidelines are expected to be issued before July 1.
These are the primary revisions as compared to the 2007 provisions:
Full implementation of the Marketing Authorization Holder (MAH) system
Previously only manufacturers could be the MAH for local products. Under the new provision, pharmaceutical companies or medical research institutions can be the MAH provided they have the capability to support the corresponding responsibilities. A regulatory framework of product quality assurance should be established to ensure safety, quality and efficacy of the products. The MAH shall manage the product throughout its life cycle, as well as conducting required post-marketing studies, and may contract a manufacturer to produce the product.
Optimized assessment and processes for Clinical Trial Application (CTA) approval
A number of changes regarding CTA approval were released and implemented in recent years; the new provisions consolidate these changes in a single regulation.
Key elements include:
- Sponsor is recommended to have pre-investigational new drug (pre-IND) consultation with NMPA for key issues before investigational new drug (IND) submission.
- CTA technical review timeline is standardized to 60 working days with tacit approval. This means the sponsor can initiate the study if there is no objection from NMPA within 60 working days.
- CTA amendment approval timeline is also standardized to 60 working days. It is unnecessary to obtain approval from NMPA for changes to the protocol, CMC and nonclinical that do not impact patient safety; instead such changes should be included in the annual Development Safety Update Report (DSUR). Interpretation of impact on patient safety is at the discretion of the sponsor. Consultation with the Centre for Drug Evaluation (CDE) is recommended in cases where the sponsor is unsure about potential patient safety impact.
- If safety problems, such as adverse events or other risks, are identified during a clinical study the sponsor shall promptly adjust the clinical trial plan, suspend or terminate the study and report to NMPA.
- Clinical studies must be registered in the CDE website (within 30 days of the IND application approval), and study results must be posted, as well.
Optimized assessment and processes for Marketing Authorization (MA) approval
After receiving an application, the NMPA will carry out the assessment, inspection and quality specification verification in parallel, rather than individually as occurred previously. This will shorten the review timeline significantly.
The on-site inspection will be determined on a risk basis, so it may not be necessary for every MA approval.
The provisions also describe the criteria and benefit for four accelerated pathways:
- Breakthrough medicines
- Conditional approval
- Priority review
- Special approval
These pathways aim to improve efficiency and shorten the registration process. They apply to clinically and urgently needed drugs in short supply, pediatric medicines, medicines for rare diseases, medicines for major infectious diseases, urgently needed vaccines for disease prevention and control and innovative vaccines.
Pre-MA meeting is required for priority review
The standard MA approval timeline has been changed to 200 working days from 150 working days; MA priority review timeline is now specified as 130 working days. For urgent medical need of orphan drugs that are approved in another country, the MA approval timeline is 70 working days. The timeline excludes any time needed for the sponsor to prepare the deficiency letter and any potential delays resulting from inspection and testing.
Optimized and simplified submissions for variations after MA approval
Variations are classified into three categories:
- Review and approve changes: These apply to major changes and NMPA-stipulated changes and should be submitted for approval before implementation
- Record changes: Submit to NMPA before implementing the change
- Report changes: Should be included in the annual report
Regulation of medicines throughout life cycle
The NMPA will strengthen supervision of medicines’ research and development, registration and post-marketing surveillance. It will also increase the monitoring of clinical and non-clinical research organizations and set requirements on drug safety files. The provisions stress streamlining of processes between drug registration and manufacturing authorization to ensure good manufacturing practice (GMP). The provisions will make transparent evaluation processes and decisions after inspection outcomes. Public surveillance and feedback are welcome.
Reinforced roles and responsibilities
The new provisions require fine-tuning of the roles and responsibilities of sponsors, MAHs and regulators. Data fraudulence and plagiarism shall be punished to maintain integrity and reputation of the pharmaceutical industry and encourage innovation. The punishment will not only apply to the company or organization, but also to the person deemed directly responsible.
Major step forward
These new provisions are a major step forward, importantly defining responsibilities and liabilities, and revising regulatory procedures for medicines regulation in China. In addition, the streamlined provisions more closely align regulations, processes and approval timelines with those of other ICH countries, particularly the requirements of the U.S. Food and Drug Administration and the European Medicines Agency. Marketing authorization holders should ensure the requirements are followed as of July 1, 2020, and implement requirements of accompanying guidance documents as they become available. The PPD™ clinical research business of Thermo Fisher Scientific will continue to provide services to current and future customers in line with these new provisions.
