I. Title: Import Drug Registration
II. Approval items: Approval for clinical trials of import (including from Hong Kong, Macao and Taiwan) traditional Chinese medicine (TCM) and natural medicinal products, which are classified in accordance with Annex I of the "Provisions for Drug Registration", namely:
Registration Category 1: an active ingredient obtained from plant, animal or mineral materials and its preparations that have not been marketed in China.
Registration Category 2: a newly-discovered Chinese crude drug and its preparations.
Registration Category 3: a new substitute for Chinese crude drug.
Registration Category 4: a new part for medicinal use from a currently-used Chinese crude drug and its preparations.
Registration Category 5: active fraction(s) extracted from plant, animal or mineral materials and its preparations that have not been marketed in China.
Registration Category 6: a combination preparation of TCM or natural medicinal product, which has not been marketed in China.
Registration Category 7: a preparation with changed administration route of a marketed TCM or natural medicinal product.
Registration Category 8: a preparation with changed dosage form of a marketed TCM or natural medicinal product.
Registration Category 9: generic TCMs or natural medicinal products.
III. Legal basis: "Drug Administration Law of the People’s Republic of China," "Regulations for Implementation of the Drug Administration Law of the People’s Republic of China," "Provisions for Drug Registration"
Review and approval fee for import drugs: RMB 45, 300 Yuan
Charging basis: "Notice of the State Planning Commission and the Ministry of Finance on the Adjustment of Fees for Drug Review, Approval and Tests" [J.J.G. (1995) No.340]
V. Limit of Approval: No limit for approvals
VI. List of application documents:
"Application Form for Registration of Import Drugs"
(A) General information:
1. Name of drug;
2. Approval documents;
3. Objective and rationale for the study;
4. Summary and evaluation of study results;
5. A draft of insert sheet, notes to the draft and the latest literatures;
6. Draft of the designed package and label;
(B) Files of pharmaceutical study:
7. Summary of pharmaceutical data;
8. Source and identification of medicinal materials;
9. Description on medicinal materials in terms of its ecological habitat, growth characteristics, morphological description, cultivation or plantation (breeding), on-site processing, and processing method, etc.;
10. A draft of Chinese crude drug standard and its notes to the draft, reference standards and other relevant information;
11. Plant or mineral specimen. The plant specimen should include flower, fruit and seed etc.;
12. Data of manufacturing process, process validation, and literatures; and source of excipients and their quality specifications;
13. Experimental data of the chemical constituents and relevant literatures;
14. Data of the quality study and relevant literatures;
15. A draft of drug standard and its notes to the draft, reference standards and relevant information;
16. Testing reports for product samples;
17. Data and literatures of product stability study;
18. Rationale for selection and specifications of immediate packaging material and container.
(C) Files of pharmacology and toxicology:
19. Summary of pharmacology and toxicology study.
20. Data and literatures of primary pharmacodynamics.
21. Data and literatures of general pharmacology.
22. Data and literatures of acute toxicity.
23. Data and literatures of chronic toxicity.
24. Data and literatures of special safety testing associated with topical or systemic drug administration, including anaphylaxis (local, systemic, and photosensitive toxicity), hemolysis and local irritability (vessels, skin, mucous, and muscle, etc.), and drug dependence, etc.
25. Data and literatures of genotoxicity.
26. Data and literatures of reproductive toxicity.
27. Data and literatures of carcinogenicity.
28. Data and literatures of animal pharmacokinetics.
(D) Files of clinical trials:
29. Summary of clinical trials.
30. The plan and protocol of clinical trials.
31. The clinical investigator brochure.
32. A draft of Informed Consent, and approval letter of Ethics Committee.
33. Clinical trials reports.
Specific requirements for the above application documents are detailed in Annex I of the "Provisions for Drug Registration".
VII. Requirements for application dossier:
(A) General requirements for the dossier:
1. The first page of the dossier is a list of application documents, which shall be arranged in order as per Annex I of the "Provisions for Drug Registration" (SFDA Order No. 28). Each document shall indicate on its cover: drug name, document item number, item name, and name, phone number and address of contacting person of the applicant.
2. All documents in the dossier shall be printed or copied in A4 size paper. The content shall be complete, standardized, clear, without alteration, and the data are real and reliable.
3. The documents shall be put in portfolio envelope(s), on which the application classification, registration category, drug name, the envelope number of set X, the total number of envelopes of the set, original or copy, the contact person, phone number and the name of registration application agent shall be indicated.
4. Two sets of complete application dossier (at least one set is in the original) shall be submitted for registration application, and one set of review documents in hard copy. Four application forms (1 in the original and 3 in hard copy) shall be separately put into each set of dossier (the original application form and a hard copy shall be put in the set of the dossier in the original).
5. "Import Drug Registration Application Form": the drug registration application form submission program could be downloaded from CFDA website (www.cfda.gov.cn); the application form shall be filled in as required, printed and saved, and shall be signed by the overseas applicant, and stamped and signed by its domestic agent.
6. When mailing or submitting application dossier, the electronic version of the application form shall be sent to the following e-mail address dedicated for drug registration: email@example.com.
7. The data checking code on the electronic and paper application form should be identical.
8. Foreign language materials shall be translated into Chinese.
(B) Specific requirements for application documents:
1. The " Application Form for the Registration of Import Drugs" shall be filled in an accurate and standardized manner in line with the requirements of explanatory notes:
(1) Drug Registration Classification: fill in as per the corresponding articles in Annex I of "Provisions for Drug Registration" (SFDA Order No. 28).
(2) Additional application items: additional applications for reducing and exemption of clinical trials, OTC drugs, etc., can be raised at the same time.
(3) Specifications: where the drug for registration has multiple specifications, an acceptance number shall be designated for each specification in a separate application form.
(4) Packaging Specifications: multiple Packaging Specifications shall be filled in one application form. For non-injectable preparations such as mixture, oral solutions, granules, ointments, eye drops, paste and etc., when the formulations are not changed, and while their packing volumes, size, and etc. are different, they shall be treated according to different packaging specifications and filled in the same application form.
(5) The applicant: organization 1 and organization 2 on the application form refer to the information of the overseas licensee and production plant, and the two items cannot be left blank. Except for the applicants in Hong Kong, Macao and Taiwan regions, the enterprise name, address, etc. shall be filled in English. Organization 3 refers to the information for the overseas packaging plants and shall be completed in accordance with the actual situation. Except for the applicants in Hong Kong, Macao and Taiwan regions, the enterprise name, address, etc. shall be filled in English. Relevant information of domestic agents shall be filled in Chinese.
(6) The information on the application form shall be consistent with the approval documents as provided.
2. While there is a same product in monitoring period, the product as filed shall not apply for import registration.
3. Requirements for approval documents:
(1) Approval documents issued by relevant drug regulatory authority of the country or region of origin for marketing authorization and compliance with GMP, as well as their notarization documents; export certificate(s) issued by the competent authority for species of the exporting country.
① Shall be issued by relevant drug regulatory authority of the producing country or region (including the EU).
② The format of CPP (Certificate of a Pharmaceutical Product) shall be in line with the format recommended by WHO. While the format of approval documents issued by relevant drug regulatory authority of the country or region of origin for marketing authorization and compliance with GMP is not as recommended by WHO, the original copy of the notarization document(s) issued by the public notary office of the country of origin, and the certificate(s) issued by the Chinese Embassy in the country shall be simultaneously submitted.
③ The originals shall be provided. While hard copies are submitted, the original copy of notarization document(s) issued by the public notary office of the country of origin, and the original copy of the certificate(s) issued by the Chinese Embassy in the country shall be filed at the same time.
④ No government approval document(s), notarization document(s) and certification document(s) shall be unpacked without permission.
⑤ The key information of the documents shall be consistent with the corresponding information filled in the application form, such as the exporting country, importing country, drug name, product name (especially foreign trade name), specification, status of whether or not approved for marketing or already marketed in the exporting country, certificate holder, and manufacturer etc.
⑥ All approval documents as provided shall be within the validity period.
⑦ Where applying for international multi-center clinical study, GMP-compliance document(s) and the drug’s phase Ⅱ clinical trial approval document(s) issued by drug regulatory authority of the country or region of origin shall be provided.
(2) Where the registration affairs are attended by the permanent representative office in China of the overseas pharmaceutical manufacturer, a hard copy of "Registration Certificate of Overseas Enterprise Permanent Representative Office in China" shall be provided.
Where the application is attended by the Chinese agent entrusted by the overseas pharmaceutical manufacturer, the appointment document, notarization document and hard copy of the Chinese agent’s "Business License" shall be provided.
(3) Description of the patents in China and their ownership status of the drug for application, or its process formula, process procedures, indications, etc., as well as non-infringement statement to other patents.
(4) Hard copy of the approval document for the research project of narcotic drugs, psychotropic substances and toxic drugs.
(5) Hard copy of "Drug Packaging Materials and Containers Registration Certificate" or "Import Packaging Materials and Containers Registration Certificate" for packaging materials (or containers) in direct contact with the drug.
(6) The safety testing data shall be accompanied by the relevant certificate of Good Laboratory Practice (GLP), and the clinical study sample shall be accompanied by the relevant certificate of GMP.
(7) Other approval documents.
VIII. Application process diagram:
IX. Approval procedures:
After the application is filed to the Administrative Acceptance Service Center, and the application dossier submitted is in accordance with the list in VI of this Notice, the format examination shall be conducted by the work staff of the Center. Where the application item is not subject to administrative approval according to law, a decision of non-acceptance shall be notified to the applicant immediately. Where the application item is not within the functions of the administrative authority, a decision of non-acceptance shall be made immediately, and the applicant shall be informed to launch the application to relevant administrative authority. Where in the application dossier, there are errors that can be corrected on the spot, the applicant shall be allowed to make the corrections on the spot. Where the application dossier is incomplete or does not meet the statutory format, the applicant shall be informed of all the supplements and amendments to be made once and for all on the spot or within five days. If the applicant is not informed within the above-mentioned period, the application shall be deemed as accepted from date of receipt of application materials. Where the application dossier is within the functions of the administrative authority, the application materials are complete and comply with the statutory format, or where the applicant has submitted all supplements and amendments in accordance with the requirements of the administrative authority, the application for administrative approval shall be accepted.
(B) Drug registration inspection:
After the Administrative Acceptance Service Center accepting the application, CFDA shall inform NIFDC to conduct registration inspection, determine issues related to the approval or review, which shall be completed within 30 days from the date of acceptance.
NIFDC has a time limit of 85 days to test samples, review the standards, and a time of 115 days for inspection of special drugs and vaccine products. The time limit for NIFDC inspection is in parallel with that for CFDA format examination, and CDE technical review. The specific time frame is allocated as follows:
After receiving information and samples, NIFDC shall arrange drug control institution to conduct registration test within five days. After the receipt of data, samples and standard substances, drug control institutions who undertake import drug registration, shall complete the registration test within 60 days and submit the registration test reports to NIFDC; special drugs and vaccine products for sample testing and drugs standard review shall be completed in 90 days. After receiving the registration test reports and import drug registration standards having been reviewed, the technical review shall be carried out by experts within 20 days, if necessary, re-review shall be conduct as per review comments.
(C) Technical review:
Along with drug registration, Administrative Acceptance Service Center shall transfer the application materials to CDE, CFDA for overall technical review.
Registration Categories 1-7: CDE of CFDA shall complete the technical review within 90 days in accordance with the technical review principles (80 days for products approved of special approval process). After the completion of the technical review, the Notice for supplementary material should be issued to applicants failed to meet the technical review requirements of the CDE, who shall supplement the dossiers within four months, and CDE shall complete the review of the supplementary dossiers in no more than 30 days (20 days for products approved of special approval process).
Registration Categories 8-9: CDE shall complete the technical review within 160 days in accordance with relevant review principles, and issue the Notice for supplementary information to disqualified applications to require the applicants supplement the dossiers within four months, and CDE shall complete within no more than 53 days the review of the Supplementary Information.
(D) Decision of administrative examination and approval:
After receiving CDE’s completed technical review data, CFDA shall make approval decisions within 20 days. If a decision cannot be made within 20 days, and extension of 10 days can be granted with competent leader’s consent.
Within 10 days from the date of decision making of administrative examination and approval, CFDA Administrative Acceptance Service Center shall deliver the decision to the applicant.
With any objections to decisions made by CFDA, the applicant can fill in within 60 days upon receipt of the decision the "Application Form for Drug Registration Re-review" to apply for re-review and elaborate reasons, before the application for administrative reconsideration or an administrative lawsuit. The contents of the re-review shall be limited to only the original application items and the original application dossier.
After receiving the application for re-review, CFDA shall make a decision for re-review within 50 days and notify the applicant. If the original decision is maintained, CFDA shall no longer accept repeated application for re-review.
If the re-review requires technical re-review, CFDA should organize relevant professional and technical personnel to perform the re-review within the original application time limit.
X. Commitment of time frame:
Registration Categories 1-7: the decision for administrative examination and approval shall be made within 110 days from the date of acceptance (100 days for products allowed for special approval process) (Note: CFDA shall make approval decisions within 20 days, if not so, an extension of 10 days can be granted with the consent of competent leaders).
Registration Categories 8-9: the decision for administrative examination and approval shall be made within 180 days from the date of acceptance (Note: CFDA shall make approval decisions within 20 days, if not so, an extension of 10 days can be granted with the consent of competent leaders).
The above time frames do not encompass the time required for the applicant to supplement documents and the re-review of supplementary documents.
XI. Validity and renewal of approval:
After being approved, clinical trials of drugs should be implemented within three years. The original approval documents shall be automatically annulled for overdue implementation; under such cases, if the clinical trial still needs to be conducted, it shall be subject to re-application.
XII. Annual inspection or review of the approval: None
XIII. Authority of Implementation:
Implemented by: CFDA
Accepted at: CFDA Administrative Acceptance Service Center
XIV. Institutions for inquiries and complaints:
For inquiries: CFDA
For complaints: CFDA Bureau of Investigation and Enforcement, Department of Legal Affairs
Note: The time frame of this Notice counts on working days, excluding legal holidays