I. Project name: Imported Drug Registration
II. Content of licensing: Verification and issuance of registration certificates for imported TCM and natural medicine (incl. from Hong Kong, Macao and Taiwan), their classification follows the 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 currently-used Chinese crude drugs and their 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," "Regulations for Implementation of the Drug Administration Law,” and “Provisions for Drug Registration”
Review and approval fee for imported drugs: RMB45,300yuan.
For registration applications after the completion of clinical trials, since the application for clinical trials of imported drugs has been charged, therefore, the application is free of charge.
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. Quantity restrictions: No quantity limit for the licensing
VI. List of application dossiers:
"Application Form for the Registration of Imported Drugs”
(I) General information:
1 Drug name.
2 Proof documents.
3 Project rationale and basis.
4 Summary and evaluation of major findings.
5 Package inserts sample, drafting instructions and the latest references.
6 Packaging and label design samples.
(II) Pharmaceutical research information:
7 Overview of pharmaceutical research data.
8. Sources and identification basis for Chinese crude drugs.
9. Ecological environment, growth characteristics, morphological description, planting or cultivation (culture) technology, producing and processing methods for medicinal herbs.
10. Standard draft and the drafting instructions for Chinese crude drugs and provide pharmaceutical reference materials and relevant information.
11. Provide plant and mineral specimens; plant specimens should include flowers, fruits and seeds etc.
12. Research data, verification data and literature for production process, and the source and quality standards of excipients.
13. Testing data and literature studies of chemical ingredients.
14. Testing data and literature data for quality research.
15. Standard draft and drafting instructions for drugs, and provide reference material of drugs and related information.
16. The sample inspection report.
17. Testing data and literature for drug stability studies.
18. Rationale for selection and specifications of immediate packaging material and container.
(III) Pharmacology and toxicology research data:
19. Review of pharmacology and toxicology research data.
20. Main pharmacodynamic testing data and literature.
21. Testing data and literature in general pharmacology studies.
22. Acute toxicity testing data and literature.
23. Long-term toxicity testing data and literature.
24. Special safety testing data and literature of allergy (topical, systemic and light-sensitive toxicity), hemolysis and local (blood vessels, skin, mucous membranes, muscle, etc.) irritation, dependency studies, etc., which are mainly related to local and systemic administration of drugs.
25. Genotoxicity testing data and literature.
26. Reproductive toxicity testing data and literature.
27. Carcinogenicity testing data and literature.
28. Animal pharmacokinetic studies and literature.
(IV) Clinical trials data:
29. Overview of clinical trial data.
30. Clinical trial plans and protocols.
31. Clinical investigator's brochures.
32. A draft of Informed Consent, Ethics Committee’s approval letters.
33. Clinical trial reports.
Specific requirements for the above application dossiers are detailed in Annex I of the “Provisions for Drug Registration”.
VII. Requirements for application dossiers:
(I) General requirements for application dossiers:
1. The first page of the dossiers shall be a directory for application items, which shall be arranged in order as per Annex I of the “Provisions for Drug Registration” (SFDA Order No. 28). Each dossier shall indicate on its cover: the name of the drug and application item, document item number, and the name, phone number and address of contact person and 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 must be 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 in 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 dossiers (at least one set is in the original) and one set of review documents in hard copy shall be submitted for registration application, according to previous practices and actual situation. 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 signed & sealed by its domestic agent.
6. When mailing or submitting the application dossiers, 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.
(II) Specific requirements for application dossiers:
1. The "Application Form for the Registration of Imported Drug" should be filled in an accurate and standardized manner in line with the requirements of explanatory notes:
(1) Drug Registration Category: fill in as per the corresponding article Annex I of the “Provisions for Drug Registration” (SFDA Order No. 28).
(2) Additional application: other applications can be raised at the same time, such as exemption from clinical trials, non-prescription drugs, etc.
(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. Multiple package volumes and sizes of non-injectable formulations like agents, oral solutions, granules, ointments, eye drops, and pastes with the same drug formulations shall be subject to uniform management according to different packaging sizes, and filled in one application form.
(5) The applicant: on the application form, organization 1 and organization 2 refer to information of overseas licensed providers and production plant, these two items cannot be left blank. Except for the applicants in Hong Kong, Macao and Taiwan regions, the business name, address, etc. should be filled in English; Organization 3 refers to the information for overseas packaging plants which should be completed in accordance with the actual situation. Except for the applicants in Hong Kong, Macao and Taiwan regions, the business name, address, etc. should be filled in English; the relevant information of domestic agencies should be filled in Chinese.
(6) The information on the application form should be consistent with the proof documents as provided.
2. While there is a same product in observation period, the product as filed shall not apply for import registration.
3. Requirements for proof documents:
(1) Proof documents issued by relevant drug regulatory authority of the manufacturing country or region for marketing authorization and GMP-compliance, as well as their notarization documents; export certificate(s) issued by the biological species control authority of the exporting country. Proof documents issued by the manufacturing country or region
① shall be issued by drug administration departments of the manufacturing country or region (including the EU).
② The format of CPP (Certificate of a Pharmaceutical Product), which is issued by relevant drug regulatory authority of the manufacturing country or region for marketing authorization and GMP-compliance, shall be in line with the format recommended by WHO, if not so, 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 Government proof documents, notarial documents and certificates shall not 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 proof documents as provided must be within the validity period.
⑦ Application for international multi-center clinical study must provide GMP-compliance documents and proof of the drug’s Phase Ⅱ clinical trials issued by drug administration of the countries or regions of origin.
(2) Where a foreign manufacturer’s representative office in China deals with the registration issues, copies of Registration Certificate of Resident Office of Foreign Enterprise shall be provided.
Where a foreign manufacturer authorizes a domestic enterprise or agency for the registration issues, copies of the authorization letters with notarized documents and the Chinese translation as well as the Business License of the domestic enterprise or agency shall be provided.
(3) Description of the patents in China and their ownership status for drug for applications, or their prescription, technology, intended use, etc., as well as a statement of non-infringement to other patents.
(4) Copies of approval letters for research project of narcotic drugs, psychotropic substances and toxic drugs.
(5) Copies of "Drug packaging materials and containers registration certificate" or "Imported packaging materials and containers registration certificate" for packaging materials (or containers) in direct contact with the drugs.
(6) Safety testing data should provide the appropriate certificate of Good Laboratory Practice (GLP); clinical test samples should provide appropriate pharmaceutical GMP certificates.
(7) Other proof documents.
VIII. Application process diagram:
IX. Licensing 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 dossiers. Where the application dossier is within the functions of the administrative authority, the application dossiers 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.
(II) 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 and review the standards, and a time limit of 115 days for inspection of special drugs and vaccine products, the time frame for NIFDC inspection is in parallel with that for CFDA examination and CDE technical review, and the specific time frame is allocated as follows:
After receiving information and samples, NIFDC shall arrange drug control institutions to conduct registration test within five days. The competent drug control institutions shall complete the registration inspection within 60 days from the receipt of dossiers, samples and related standard substances and submit the report to NIFDC; the sample tests and re-review of drug standards for special drugs and vaccine products can be completed in 90 days. After receiving the registration test reports and imported drug registration standards, which have been reviewed, the technical review shall be carried out by experts within 20 days; if necessary, re-review shall be conducted as per the review comments.
(III) Technical review:
Along with drug registration, Administrative Acceptance Service Center shall transfer the application dossiers to CFDA Center for Drug Evaluation for overall technical review.
Registration Categories 1-7: CDE of CFDA shall complete the technical review within 150 days in accordance with the technical review principles (120 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 50 days (40 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.
(IV) Decision of administrative examination & approval:
After receiving CDE’s completed technical review data, CFDA shall make licensing 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 & approval, CFDA Administrative Acceptance Service Center shall deliver the decision to the applicants.
For disagreements of CFDA decision, the applicant can, prior to administrative reconsideration or administrative litigation, explain the reasons and apply for re-review to CFDA within 60 days from the date of receipt of the decision. The contents of the re-review shall be limited to only the original application items and the original application dossiers.
After receiving the application for re-review, CFDA shall make a decision 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 limits.
X. Commitment of time frame:
Registration Categories 1-7: The decision for administrative licensing shall be made within 170 days from the date of acceptance (140 days for products approved to enter into the special approval procedures); (Note: CFDA shall make the decision 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.)
Registration Categories 8-9: Starting from the date of acceptance, administrative licensing decision shall be made within 180 days (Note: CFDA shall make a decision for licensing 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.)
The above time frames do not encompass the time required for the applicants to supplement information and the re-review of supplementary information.
XI. License validity and renewal:
The CFDA-issued drug approval number, "Imported Drug Registration Certificate" or "Pharmaceutical Product Registration Certificate" shall be valid for five years. Upon expiry of these certificates, if the production or import is still necessary, the applicant shall apply for renewal within six months before expiry.
XII. Annual inspection or annual review of the license: 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 GUIDANCE counts on working days, excluding legal holidays