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Review and issuance of Registration certificate for import of pharmaceutical excipients (incl. from Hong Kong, Macao and Taiwan)
2013-12-06

I. Project name: Registration of pharmaceutical excipients


II. Content of licensing: Review and issuance of Registration certificates for import (incl. from Hong Kong, Macao and Taiwan) of pharmaceutical excipients

III. Legal basis: "Drug Administration Law of the People's Republic," "Regulations for Implementation of Drug Administration Law", "Notice on the Issuance of Requirements for Registration Application of Pharmaceutical Excipients" (SFDA Department of drug registration [2005] letter No.61)

IV. Charges: RMB 45300yuan.
Charging basis: "Notice of the National Development and Reform 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 Registration of Imported Drugs”
(I) Summary data
1. Pharmaceutical excipients’ name (including the official name, chemical name, English name, Pinyin, etc.) and basis for nomenclature.
2. Proof documents.
(1) Proof documents, notarized documents and Chinese translations issued by drug regulatory authorities of the country or region of origin to permit the marketing and sales of pharmaceutical excipients and to prove the GMP-compliance of the manufacturers as well as the DMF of APIs
(2) For applications performed by overseas pharmaceutical excipients manufacturers’ Permanent Representative in China, the applicant should provide a copy of the "Registration certificate of permanent Chinese representative offices of foreign enterprises ".
(3) For entrustment of Chinese agencies engaged in application, Overseas manufacturer of pharmaceutical excipients shall provide the commission documents, notarized documents and their Chinese translations, as well as copies of Chinese agencies’ "Business License"
(4) Statement of the patents status and patent ownership of the products, or prescription and technology used in the production, as well as non-infringement assurance.
3. Project rationale and basis. The overview shall cover domestic and foreign R & D, sale and related literature, the production, and the application in formulations.
4. Summary and evaluation of major findings. Includes a summary of the main research findings and a comprehensive evaluation of the applied products’ safety, effectiveness, quality control and other aspects.
5. Package inserts ample, drafting instructions and the latest references. Product manual, including pharmaceutical excipients’ name, chemical structure or formula, usage, precautions, packaging (specifications, contents), etc., shall specify the validity period and be clearly marked with the words of "pharmaceutical excipients".
6. Packaging, label design proofs.


(II) Pharmaceutical Research Data
7. Pharmaceutical research data and overview. Including synthesis process, prescription screening, structure confirmation, quality research and quality standards development, stability studies and test data, literature review at home and abroad.
8. Production process research data and literature. Including the preparation process, chemical reaction formula, starting materials and organic solvent, the reaction conditions (temperature, pressure, time, catalyst, etc.) and operating procedures, refining methods, main physical and chemical constants and the cumulative results of periodic data, clearly defined feeding amount and the yield, impurities or other intermediate products that may be generated or introduced in the process, specification standards of the chemical raw material; the sources and scientific names of animal, plant, and mineral materials If the preparation process differs from that of the primary reference, the basis for modification should be made.
9. Test data and literature for confirmation of chemical structure or components.
10. Test data and literature for quality research. Including physical and chemical constants, purity test, contents determination, methodology verification and accumulated results of periodic data.
11. Compatibility test data and literature Associated with drugs.
12. Drug standards and the drafting instructions, and standard substance or reference substance. Quality standards should meet the format requirements of the current version of "Chinese Pharmacopoeia", and use its terminology and units of measurement. The products and concentration of all reagents, test solutions, buffer solutions, titration solutions, etc. should be those recorded in the current version of "Chinese Pharmacopoeia", and discrepancies should be described in detail. Additional information shall be attached for Standard substance or reference substance to describe the source, physical and chemical constants, purity, contents, determination methods and other data.
13. Inspection report for three consecutive batches of samples. self-test report for the applied product samples.
14. Test data and literature for stability studies. Including the stability testing of pharmaceutical excipients in direct contact with the packaging materials jointly with containers.
15. Selection basis and quality standards for packaging materials and pharmaceutical excipients indirect contact with drugs.


(III) Pharmacology and toxicology research data
16. Review of pharmacology and toxicology research data.
17. Pharmacodynamics test data and literature of the drugs intended to be applied.
18. Test data and literature in general pharmacology studies.
19. Acute toxicity test data and literature.
20. Long-term toxicity test data and literature.
21. Special safety test study and literature for allergy (topical, systemic and light-sensitive toxicity), hemolysis and local (blood vessels, skin, mucous membranes, muscle, etc.) irritation etc. that are mainly related to local and systemic administration of drugs.
22. Carcinogenicity test data and literature.
23. Reproductive toxicity test data and literature.
24. Carcinogenicity test data and literature.


(IV) Clinical trial data
25. Summary of related clinical trial data at home and abroad.
26. Clinical research protocols and programs.
27. Clinical investigator's brochure.
28. Sample manuscript of Informed consent, ethics committee’s approved documents.
29. Clinical study report.
Specific requirements of the above application dossiers are detailed in the "letter on the issuance of requirements for registration application dossiers of pharmaceutical excipients" (SFDA Department of drug registration [2005] letter No.61).

VII. Requirements for application dossiers:
(I) General requirements for application dossiers:
1. The first page of the application dossiers should be the catalog for application items, which shall be arranged in order of the "letter on the issuance of requirements for registration application dossiers of pharmaceutical excipients". Each data shall indicate on the cover: pharmaceutical excipients name, data item number, item name, contact name, phone, and address of the applicant.
2. The dossiers should use A4 size paper for print or copy, the content should be complete, standardized and clear; shall not be altered, the data must be real and reliable.
3. The dossiers shall be loaded in portfolio in full set, the portfolio envelope shall indicate: Application classification, registration classification, pharmaceutical excipients name, the portfolio’s X Set, X envelope, original / copy, the contact person, telephone, registration application agency name.
4. Registration applications shall submit two sets of complete application dossiers (at least one set of the originals) and a set of summary data copy , 4 copies of Application form (1 original and 3 copies) , which shall be enclosed in each set of dossiers (the full set of original data should have 1 original Application form, and a copy of Application form).
5. "Application Form for the Registration of Imported Drug ": download from CFDA website (www.cfda.gov.cn) the offer procedures of drug registration application), fill in as required, save and print the document, which must be signed by overseas applicants, and stamped and signed by domestic agencies.
6. Along with the submission or mail of the application dossiers, their electronic version shall be sent to the Administrative Service Center by e-mail. e-mail address: slzx@cfda.gov.cn.
7. The data verification code of the electronic application forms should be consistent with paper application forms.
8. Foreign materials should 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: should be "pharmaceutical excipients."
(2) Application item: "for marketing."
(3) Formulation type: "non-preparation excipients."
(4) Specifications: separate specification and acceptance number shall be designated for pharmaceutical excipients with multiple specifications in registration application.
(5) Applicant: the entries of institution 1 and 2 on the application form refer to foreign licensed provider and manufacturer information, these two cannot be vacant. business name, address, etc. shall be filled in English, except for the applicants from Hong Kong, Macao and Taiwan regions; institution 3 refers to overseas packaging plant information, which should be completed in accordance with the actual situation, business name, address, etc. shall be filled in English, except for the applicants from Hong Kong, Macao and Taiwan regions; Items of domestic agencies must be filled in Chinese.
(6) The information on the Application form should be consistent with those provided in the proof documents.


2. Proof documents, notarized documents and Chinese translations issued by drug regulatory authorities of the country or region of origin to permit the marketing and sales of pharmaceutical excipients and to prove the GMP-compliance of the manufacturers as well as the DMF of APIs
(1) The proof documents issued by the drug administration authorities of the country or region of origin, which permit the marketing of the pharmaceutical excipients and prove the GMP compliance of the manufacturers of pharmaceutical excipients, shall meet the unified format specifications recommended by the World Health Organization.Files in other formats must be notarized by public notary organizations of the country of origin and certified by Chinese embassies and consulates in the country.
(2) If the excipient is not yet permitted for marketing in the country or region of origin, the applicant can provide the documents proving its marketing in other countries or regions, as well as the DMF (Drug Master File) information documents of APIs, notarized documents and Chinese translations, which shall be submitted to CFDA for approval. However, the documents proving GMP compliance of pharmaceutical excipients manufacturers must be provided by the pharmaceutical excipients regulatory institutions in country or region of origin.
(3) The applications for medicinal hollow capsules, gelatin capsules, and pharmaceutical gelatin derived from imported bovine pharmaceutical excipients are required to provide the proof documents of the sources and types of the main raw material for preparing capsules-gelatin, and provide government documents which prove the raw material were from BSE non-involved country.
(4) Government proof documents, certificates, and notarized documents shall not be opened without authorization.
(5) Itemized review should be conducted for major information of the exporting country, the importing country, pharmaceutical excipients name, specifications, marketing approval and sales status in the exporting country, licensed providers, manufacturers etc., which should be consistent with the corresponding information listed in the Application form.
(6) The documents provided shall be within the validity period (if any).


3. For application entrusted from Overseas pharmaceutical excipients manufacturers to Chinese agencies, the applicant shall provide the entrustment documents, notarized documents and Chinese translations, as well as the "Business license" of the Chinese agencies. For applications performed by overseas pharmaceutical excipients manufacturers’ Permanent Representative in China, the applicant should provide a copy of the "Registration certificate of permanent Chinese representative offices of foreign enterprises ".

VIII. Diagram of application procedures:

IX. Licensing procedures:
(I) Acceptance:
After the Application is made to the Administrative Service Center, and the application dossiers submitted in order listed in Article VI of this "TIPS", the work staff shall review the format. If the application items are not subject to administrative examination and approval according to law, the decision of non-acceptance shall be immediately made. If the application items are not within the purview of the executive authorities, the decision of non-acceptance shall be immediately made and the applicant shall be informed to apply to related administrative institutions; .If the application dossiers have errors that can be corrected on the spot, the applicant shall be allowed to correct on the sport; if the application dossiers are incomplete or do not meet the statutory form, the applicant should be informed in full to enrich or rectify the relevant contents on the spot or within five days. If they are not informed, the application dossiers shall be deemed accepted from date of receipt. If the application dossiers are within the scope of the administrative institutions, the application materials are complete and comply with the statutory form, or the applicant has submitted all application materials in accordance with the requirements of the administrative authorities for enrichment or correction, the application shall be accepted for administrative examination and approval.


(II) Drug registration inspection:
After the Administrative Service Center accepted the application, CFDA shall inform NIFDC of registration testing, approval decision or other affairs related to the review, which should be completed within 30 days from the date of acceptance.
NIFDC shall organize sample tests and standards review within a timeframe of 85 days, which is in parallel with CFDA inspection and CDE technical review, the specific timeframe is allocated as follows:
NIFDC shall designate related drug control institutions to conduct registration inspection within five days upon receipt of the application dossiers and samples. Drug control institutions undertaking the registration inspection for imported drugs shall complete the registration inspection within 60 days upon receipt of the application dossiers, samples and standard substances, and submit the drug registration inspection test report to NIFDC. After receiving the drug registration inspection test report and imported drug registration standards that have been reviewed, NIFDC shall organize experts to perform technical review within 20 days, and if necessary, re-review shall be conducted according to review comments.


(III) Technical review:
Along with the drug registration inspection, CFDA Administrative Service Center shall deliver the application data to CDE for technical review.
CDE shall complete the technical review in accordance with the related principles in 150 days (120 days for products allowed to enter the 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).


(IV) Administrative licensing decision:
After receiving the CDE technical review data, CFDA shall make the decision for licensing within20 days. If a decision cannot be made within 20 days, an extension of 10 days may be granted upon approval of competent CFDA leaders.


(V) Delivery:
Within 10 days from the date of decision making of administrative examination and approval, CFDA Administrative Service Center shall deliver the decision to the applicants.


(VI ) Re-review:
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 dossiers.
After receiving the application for re-review, CFDA shall make a decision for re-review within 50 days and notify the applicants. If the original decision is maintained, CFDA shall not accept the application for reconsideration again.
If the reconsideration needs a technical review, CFDA shall organize relevant professional and technical personnel to conduct the review according to the original application timeframe.

X. Commitment time frame:
And make a decision for administrative licensing within 170 days (140 days for products allowed to enter the special approval process) from the date of acceptance. (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.)
The above timeframe does not include the time for supplementary information and the corresponding review.

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. If production or import are still necessary upon expiry of the certificate, the applicant shall apply for renewal six months before the expiry.

XII. Authority of implementation:
Authority of implementation: CFDA
Location for acceptance: CFDA Administrative Service Center

XIII. Annual inspection or annual review of the license: None

XIV. Institutions for inquiries and complaints:
Inquiries: CFDA
Complaints: CFDA Bureau of Investigation and Enforcement, Department of Legal affairs
Note: The time frame of this TIPS counts on working days, excluding legal holidays

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