For frequently asked questions concerning technical issues, China Center for Drug Evaluation (CDE) releases corresponding answers on its website. For further enquiries about drug registration, please contact BaiPharm for professional help.

This article covers the Q&As on the first two topics. Q&As on other topics will be released soon. Please stay tuned.

1. The Submission and Acceptance of Drug Registration Applications;

2. Clinical trials

3. Bioequivalence (BE) Study

4. Selection of Reference Listed Drugs

5. Quality and Therapeutic Equivalence Evaluation for Generic Drugs

6. R&D Requirements for Biological Products

7. Associated Review and Approval of APIs, Excipients, and Packaging Materials

8. Administration and Requirements for Variations

9. Others

Part 1. The Submission and Acceptance of Drug Registration Applications

Q1: According to CDE\’s Notice of Adjusting the Acceptance Methods and the Application Document Requirements During COVID-19 Pandemic, should the applicant submit electronic application documents if the submission is after Feb. 7, 2022?

A1: If the applicant has submitted application documents in paper before Feb. 7, 2022, CDE will review the paper documents. If the registration application is found to be deficient in format review, the applicant should submit the supplemental documents in paper in due time according to Article 85 of the Administrative Measures for Drug Registration.

If submitted after Feb. 7, 2022, only application documents in the electronic form will be accepted.

Q2: What differences are there between electronic submission and submission in eCTD format?

A2: According to National Medical Products Administration (NMPA)\’s Announcement on Adopting the eCTD Format for Drug Application (No. 119 Announcement in 2021), only marketing authorization applications for class 1 chemical drugs, class 5.1 chemical drugs, class 1 therapeutic biological products, and class 1 prophylactic biological products can be submitted in eCTD format.

The Notice of Adjusting the Acceptance Methods and the Application Document Requirements During COVID-19 Pandemic applies to all drug applications accepted by NMPA.

Please don\’t mix up the two submission methods that are different in application scope and in technical requirements for compact disks.

Related Article: China to Accept eCTD Format for Marketing Authorization Applications for Specific Classes of Drugs; China Chemical Drug Registration Classification

Q3: Does the applicant need to submit the compact disk for drug registration inspection if the drug application is accepted after Feb. 7, 2022?

A3: If the applicant has submitted electronic documents in the compact disks according to the Notice of Adjusting the Acceptance Methods and the Application Document Requirements During COVID-19 Pandemic, it doesn\’t need to submit the documents or an additional compact disk for drug registration inspection.

But if the applicant submitted application documents in paper, it needs to submit the documents and an additional compact disk for drug registration inspection.

Q4: When the overseas originator drug or Chinese-domestically manufactured originator drug has been listed as a reference listed drug (RLD) but unavailable to the drug applicant, the drug applicant can choose the originator drug not imported to China as the RLD. In such a situation, can the applicant\’s generic drug be classified as a class 4 chemical drug?

A4: If the indication of the generic drug in the marketing authorization application is the same with the indication of the originator drug approved in China, the generic drug can be classified as a class 4 chemical drug for its application.

Q5: For a chemical drug marketed in China, how to submit the application for adding an indication approved in China and another indication approved overseas but not in China?

A5: To add an indication already approved in China, the applicant should submit a supplemental application.

To add an indication approved overseas but not yet in China, the applicant should submit the clinical trial application and the marketing authorization application according to NMPA\’s Announcement on Chemical Drug Registration Classification and Application Document Requirements (No. 44 Announcement in 2020).

Q6: Can the applicant directly submit a marketing authorization application for a generic chemical drug?

A6: The appendix two to CDE\’s Notice of Guidance for the Acceptance of Chemical Drug Registration Applications (Trial) (No. 10 in 2020) stipulates that if after evaluation, a generic drug applicant is considered with no need or incapable to apply for clinical trials, and the applicant meets the conditions for clinical trial exemption, the applicant can directly propose marketing authorization for the generic drug and should specify the situation under \”Other Items for Special Statement\” in the application form.

Q7: Will the acceptance documents relevant to chemical API (active pharmaceutical ingredient)\’s DMF (drug master files) filing be sent to the applicant?

A7: According to CDE\’s Notice of Adopting the Electronic Administrative Authorization Documents for Chemical APIs, applicants can print the acceptance documents via the \”Applicants\’ Window\” on CDE\’s website.

Q8: Should the applicant organize the chemical API filing documents according to the Notice of Chemical Drugs\’ New Registration Classification and Application Document Requirements (Trial) (No. 80 Announcement in 2016)?

A8: The applicant should conduct researches according to NMPA\’s Notice of Chemical Drug Registration Classification and Application Document Requirements and relevant technical guidelines.

It should organize the application documents with serial numbers according to the existing M4 Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use. The applicant can choose not to submit documents under the inapplicable items by marking them inapplicable, but need to specify the inapplicable reasons.

Q9: Can the applicant apply for adding a strength through generic drug marketing authorization application?

A9: No. According to Administrative Measures for Drug Registration and relevant regulations, the applicant should submit a supplemental application to add a strength.

Q10: How to apply for changing the dose, immune procedures, and target group of a marketed vaccine?

A10: According to NMPA\’s Biological Product Classification and Application Document Requirements (No. 43 Announcement in 2020), a vaccine with a changed dose and immune procedures belongs to class 2.5 improved vaccines, while a vaccine with a changed target group belongs to class 2.6 improved vaccines. To market a vaccine with these changes, the applicant should submit the clinical trial application and the marketing authorization application.

Q11: Is the applicant permitted to apply for license renewal earlier than six months before the oversea-manufactured drug\’s marketing authorization license gets expired?

A11: Yes, it is permitted.

Q12: How to continue with the drug application if the registration procedures have been terminated because the applicant fails to pay fees in time?

A12: According to NMPA\’s Announcement on New Standards for Drug Registration Fees (No. 75 Announcement in 2020), the registration procedures will be terminated if the drug applicant fails to pay fees accordingly. If the applicant intends to proceed with the application, it should re-submit the application according to the Administrative Measures for Drug Registration.

Q13: Can the applicant apply for priority review for a newly accepted application for a product manufactured on the same production line with another product, or a re-submitted application that has been withdrawn before?

A13: The applicant should refer to the Administrative Measures for Drug Registration for priority review scope and the Work Procedures for Priority Review of Drug Marketing Authorization Applications for priority review procedures.

Related Article: Expedited Programs for Drug Registration-3.3 Priority Review

Q14: How to apply for marketing authorization for the combination therapy of two or more new molecular entity drugs whose clinical trials have both/all been approved? Does the applicant need to re-submit the application documents previously submitted for each single drug?

A14: As each single drug has not been put on the market, the applicant should submit new clinical trial applications for each drug separately and link the applications together.

Overlapping documents in the combination therapy (except clinically-mixed drugs) application and single drug application can be exempted from submission.

However, the pharmacological and toxicological evaluation of the combination therapy should be combined with each single drug\’s data. Therefore, all single drugs\’ pharmacology and toxicology documents should be submitted.

Q15: How to determine the registration classification of a generic chemical drug whose originator drug was marketed in China, and the originator\’s multiple generic versions have been marketed in China?

A15: Considering that the finished dosage forms (originator and its generic versions) with the same API already have complete and sufficient safety and efficacy data on Chinese people, the generic chemical drug can be registered as a class 4 chemical drug.

Q16: Which is the registration classification for a new dosage form (505b2) approved by FDA and listed as RLD and RS (reference standard) in the Orange Book? Class 5.1 or class 5.2?

A16: According to current regulations, such a drug belongs to class 5.1 chemical drugs.

Part 2: Clinical Trial

Q1: Is it mandatory to submit manufacturing and testing standard procedures in the stage of applying for biological product clinical trial?

A1: No, it\’s not mandatory.

For more FAQs, please read them on BaiPharm.