On Jan. 11, 2023, China Center for Drug Evaluation (CDE) released 10 Q&As, including nine questions on the electronic submission of drug applications and one on the application of overseas drugs for China’s marketing authorization.
Related: China Requires Electronic Submission of All Drug Registration Application Documents from Jan. 1, 2023
ChemLinked BaiPharm Portal translated the Q&As for your reference. In case of any discrepancies between the English translation and the original Chinese text, the original shall prevail.
Q1: Does the applicant have to submit application documents in paper if the application was accepted by CDE after format review, and the application was received by CDE before China National Medical Products Administration (NMPA)’s Announcement on Implementing Electronic Submission of Drug Registration Applications took effect on Jan. 1, 2023? For example, the application was signed for by CDE on Dec. 30, 2022, and was accepted on Jan. 6, 2023.
A1: The applicant is required to submit the paper documents to CDE within five workdays after acceptance according to the Announcement on CDE’s Adjustment of the Work Pattern for Application Acceptance and the Requirements for Receiving Drug Registration Application Documents During the COVID-19 Epidemic, to avoid hobbling CDE to complete the technical review on schedule.
For applications submitted on or after Jan. 1, 2023, applicants shall follow the Announcement on Implementing Electronic Submission of Drug Registration Applications.
Q2: What does “the supplemental documents during the review” refer to in the Announcement on Implementing Electronic Submission of Drug Applications and the Announcement on the Requirements for the Electronic Submission of Drug Registration Applications?
A2: It refers to the supplemental documents, stability study documents, and renewed certification documents that are submitted during the review.
Q3: After electronic submission is required for all drug applications, in what form should the stability study documents be submitted during the review?
A3: According to the Announcement on the Requirements Relevant to the Electronic Submission of Drug Registration Applications, such documents shall be submitted as follows.
Acceptance of Drug Application
Documents Submitted During the Review
Before Jan. 1, 2023
On or after Jan. 1, 2023
In compact disks
Q4: As the electronic submission has been required since Jan. 1, 2023, does the applicant still need to fill in the information relevant to paper documents, e.g., the number of paper document packages in the self-review form?
A4: The applicant can indicate “not applicable” at the corresponding information item.
Q5: What documents do the electronic documents for the administrative permission of acceptance include?
A5: It mainly includes:
- the letter of signing and receiving the application (meaning the application dossier has been received by technical experts at CDE);
- the acceptance notice (meaning the application is deemed complete in the preliminary review and permitted to enter the subsequent review);
- the fee-paying notice for administrative permission (requiring the applicant to finish the payment);
- the deficiency letter (meaning the application documents are deficient, thus CDE requires the applicant to submit the documents that are complete and correct);
- the testing notice (requiring the applicant to apply for drug testing);
- the rejection letter (meaning the application is rejected by CDE);
- the receipt notice (meaning the application has been received by CDE’s mail office), etc.
Q6: As the electronic submission of applications is required from Jan. 1, 2023, does the applicant need to include its legal representative’s digital signature in the drug registration application form?
A6: CDE allows both methods:
1) the legal representative of the applicant signs the hard copy of drug registration application form, and then scanned the signed form to get a PDF document;
2) the applicant adds the legal representative’s digital signature to the electronic drug registration application form.
Q7: Before submitting the application dossier, how should the applicant fill in and submit the application-related information (e.g., express mail information) via the Applicant’s Window (CDE’s online channel for applicants to submit information)?
A7: From Jan. 1, 2023, CDE stopped using email@example.com as the mail address.
Before submitting the application dossier, the applicant should fill in and submit the application-related information (e.g., express mail information) at the “Online Booking for Dossier Submission” Module in the Applicant’s Window on CDE’s website. If the dossier is organized according to the electronic common technical document (eCTD) format, the applicant should indicate “eCTD” in the note.
Q8: What are the requirements for the number of compact disks containing the documents submitted by the applicant?
A8: From Jan. 1, 2023, for submitting a new drug registration application, the applicant should submit the compact disks according to the corresponding requirements as below:
One set of compact disks for review
Application dossier (including clinical trial database, if the database is applicable)
Required for all new applications for drug registration
One set of compact disks for inspection
Application dossier (including clinical trial database, if the database is applicable)
Required for new applications for drug registration (including applications for active pharmaceutical ingredients, and applications submitted in eCTD format);
Except applications for which inspections are not required, including
- application for drug clinical trial application;
- license renewal application for drugs manufactured outside China;
- supplemental application directly for administrative review and approval.
Other compact disks
(one set for each category of documents)
Documents on the verification of the drug’s generic name
Required for drug registration applications that involve the mentioned documents
Documents on clinical trial database
Documents on the review of the OTC drug’s suitability and medication package inserts
Compact disks containing the documents on the review of the OTC drug’s suitability and medication package inserts should also include the following documents:
Marketing authorization applications for chemical drugs and biological products
Module 1 and 2 documents in the application dossier
Marketing authorization application for traditional Chinese medicines (TCMs)
1) Administrative documents and drug information;
Q9: In terms of the compact disks for submitting different types of dossiers, what are the requirements for the sealing, jewel case cover, and file cover?
A9: The requirements are:
1. Sealing: the applicant should put the compact disks containing different categories of application dossiers into standardized hard jewel cases, and put the cases into file packets according to different drugs and application items.
2. Jewel case cover: the applicant should mark the following information on the cover.
- document category;
- application code / data verification code / acceptance code / filing code (all of the involved codes should be marked);
- the serial number of the compact disk among the disks in the whole set;
- the number of disks in the whole set.
3. File packet cover: the applicant should mark the following information on the cover.
- document category;
- application code / data verification code / acceptance code / filing code (all of the involved codes should be should be marked);
- drug name;
- applicant / registration agency’s name;
- the serial number of the packet among the packets in the whole set;
- the number of disks in the whole set;
- contact person and phone number, etc.
Q10: What should the applicant of an overseas drug pay attention to when collecting the drug quality standards according to the format required by the currently effective Chinese Pharmacopoeia 2020 Edition?
A10: CDE has discovered some issues in the application dossiers which are collected according to the format specified in the Chinese Pharmacopoeia 2020 Edition. The issues made it unfeasible to draw clear conclusions from the testing for drug registration.
To improve the services for drug applicants and the quality of the application dossiers, CDE advises applicants to pay attention to the following points:
(1) According to the regulations on testing for drug registration, the drug quality standards in the application should comply with the general technical requirements in the Chinese Pharmacopoeia. The specific format and standards should comply with the Chinese Pharmacopoeia.
In the application dossier submitted to CDE, the drug quality standards (for the verification) collected according to the currently-effective Chinese Pharmacopoeia 2020 Edition should be consistent with the standards submitted to the National Institutes for Food and Drug Control (NIFDC) for verification testing.
(2) The drug quality standards in the application shall be made according to the corresponding contents in the application dossier. The methods and limits used in the standards should be consistent with those in the application dossier.
For example, the following practice is not permitted: the sterility testing method in the application dossier is from the European Pharmacopoeia or the United States Pharmacopoeia and provided with corresponding methodological validation documents. However, the drug quality standard in the application is from the Chinese Pharmacopoeia without methodological validation. As a result, the testing for registration cannot come to a clear conclusion.
Besides, the format and the description of the drug quality standards should comply with the currently-effective Chinese Pharmacopoeia. The standards should be complete and comprehensive to avoid unclear testing conclusion caused by absent description of the method.
For example, the standards in the application may have the following flaws:
- not including the description of capsule filler’s characteristics;
- not including the specific methods for preparing the system suitability solution, sensitivity solution, reference solution, test solution, dissolution media, dissolution media, etc.
- not providing the device’s model number and/or complete test parameters;
- not using the international unified code for the units of measures, etc.
Also, the quality standards should be compiled and reviewed carefully to avoid human errors and writing errors. For example, the standard limit in the application should be 0.5% but is mistakenly written as 2.0%; the standards are mistakenly copied from those of another drug.