Drug Master File system of China （Part 2）

Chapter 2 How to file DMF in China?

I have introduced something about the background, basic requirements of China DMF system in the previous article. This time, I am going to introduce the detail filing process.

1 DMF Filling Process
The DMF filing process for APIs, Excipients, and Packaging materials is essentially the same for all three. Based on current regulatory requirements, once the application documents are prepared, the applicant should create a report CD to be submitted to the CDE. The CDE will conduct an integrity review of the application documents. If the review is successful, the CDE will issue an acceptance notification. Otherwise, the CDE will issue a notice of supplementary to the applicant, who must address the required corrections, submit to CDE again, and then receive an acceptance notification from the CDE. The process is presented in below Figure 1.

2 DMF Technical Review Process
2.1 DMF Technical Review for APIs
After DMF filling of the APIs used in generic drugs or imported approved drug product, APIs can undergo either a Bundling Review process or a stand-alone review process. The registration status identifier for those that have been approved is “A,” while those that have not passed it are marked as “I”. Technical review processes for APIs are presented in Figure 2 and Figure 3. 

2.2 DMF Technical Review for Excipients/Package materials
Similar as the bundling review of APIs, the technical review process of excipients and packaging materials is shown in Figure 4.

3 China DMF Maintenance
The maintenance of DMF mainly includes the following three forms: supplementary applications, annual reports, and renewal applications. Among them, the supplementary applications and re-registration mainly relate to APIs, while annual reports are applicable to all categories of DMF filings. Considering the complex categories involved in supplementary applications for APIs, those contents will not be provided in detailed. A summary of several maintenance methods is shown in below Table 3.

Table 3 Summary of DMF Maintenance

4 Prospects
The review system connecting APIs, excipients, and packaging materials has been an important part of the reform of China’s drug review and approval system since 2015. Through the active exploration and joint efforts of regulatory authorities and the industry in recent years, a relatively complete DMF system related to drugs has been established. At the same time, there is an expectation of further regulatory optimization. For example, further optimization is needed for the protection measures of core confidential control documents of intermediates, intermediate platform technologies, and upstream intermediates of biological products. The risk-based management concept for Excipients and Packaging materials, such as broader exemption measures for the DMF filling of long-term use and safety-approved pharmaceutical excipients, awaits further optimization.