New Notice from NMPA (No. 56 Notice of 2019)

Jul. 23, 2019

No. 56 order of 2019 by NMPA--Carry out on 16th July, 2019.

Part 1, General Requirements:

1. The use of APIs, Excipients and packaging materials must meet the requirements of formulations, which mainly includes quality, safety and function. Registrants of APIs, Excipients and packaging materials registers joint review and approval information on registration platform, formulation applicants use the registration information to do joint application. If the registrants of APIs, Excipients and packaging materials cannot register the information on the platform for special reasons, then the formulation applicants can submit the research documents of APIs, Excipients and packaging materials along with the formulation application.

2. Registrant of APIs, Excipients and packaging materials is responsible for the maintenance of registration information as well as the veracity and integrality of registration documents. Domestic APIs, Excipients and packaging materials suppliers shall register its own products on the platform as APIs, Excipients and packaging materials registrants. Overseas APIs, Excipients and packaging materials suppliers shall authorize its Chinese branch company or Chinese agent to do the registration,the registration documents should be in Chinese, overseas suppliers and its agency organization shall be responsible for the veracity and integrality jointly.

3. Applicants of formulation shall provide registration number of APIs, Excipients and packaging materials and letter of authorization from APIs, Excipients and packaging materials registrants.

4. Formulation applicants or MAHs undertake the entity responsibilities of drug quality, to audit GMP of APIs, Excipients and packaging materials suppliers to make sure they meet the drug requirements according to the related requirements.

5. The supervisory department shall take the responsibility for keeping confidentiality of the technical data submitted by the registrant of the original and auxiliary package and the technical information of the registration platform. The registration platform only discloses the registration status identification (A or I), registration number, variety name, enterprise name (agency name), manufacture address, original drug approval document number (if any) and validity period of original approval certificate (if any) of the registered varieties, product source, specification, update date and other necessary information.

Part 2, Product registration management

6. The APIs, Excipients and packaging materials registrant shall register on the platform according to the technical requirements of the registration data and obtain the registration number. Among them, the drug production license for the corresponding production scope should be obtained before the registration of API. In addition, the registration shall be conducted in accordance with the requirements of the Notice of the former China food and drug administration on the issuance of information requirements for classification declaration of new registration of chemical drugs (trial) (no. 80 order of 2016). Registration of excipients and packaging materials shall be conducted in accordance with the data requirements in annex 1 and annex 2 of this announcement. The technical requirements for registration data shall be constantly improved in accordance with industrial development and scientific and technological progress, and shall be duly updated and published by center for drug evaluation of NMPA (hereinafter referred to as CDE).

7. The application for registration of Drug product trigger the registered APIs, Excipients and packaging materials. When the Drug product is approved, it means that the related APIs, Excipients and packaging materials have passed the technical review, and the registration platform is marked as "A"; Not pass the technical review or not trigger with the registration of Drug products is marked as “I”.

8. In addition to the APIs, Excipients and packaging materials that are prohibited to be used, eliminated or cancelled by the state, the CDE shall transfer the relevant information to the registration platform and give the registration number, with the registration status marked as "A" :

(1) APIs whose expiry date of the approval certificate is no earlier than November 27, 2017;

(2) The API that has been accepted and completed the review and approval, includes  the API technology transfer application reviewed by the province FDA in accordance with document no. 38 [2013] of the state food and drug administration;

(3) The medicinal excipients and packaging materials that have been accepted and completed for review.

(4) Medicinal excipients that have obtained approval documents;

(5) Drug packaging materials whose validity date of approval certificate expires no earlier than August 10, 2016.

The registrant of the API, Excipients and Packaging materials should register all the requested documents to the registration platform, in accordance with the requirements of the registration information in this announcement, provide additional research documents on the registration platform, improve the registration information, and submit a letter of commitment for the consistency of the documents (promising that the technical documents submitted in the registration platform are consistent with the technical documents approved).

9. For generic or import the API which had used in the formulation marketed of China market, the API DMF can be reviewed independently after the registrant get the registration No. If pass the review and get the approval the status will be marked as â€œA” on the website, if not then “I”. The review & approval time limit and requirements shall be implemented in accordance with the current drug registration administration regulation and other relevant provisions.

10. For excipients that have been used in food and drugs for a long time and the safety has been well recognized, registration can be avoided (the list can be found on annex 3). The update list for these excipients will be update by CDE. And CDE has the right to require additional technical information if CDE believes it is necessary. The list will be updated by CDE accordingly.

11. Administrative license for excipients and packaging materials has been cancelled, and platform registration is free of charge. API is still an administrative license, and relevant requirements for platform registration technology review shall be implemented in accordance with current provisions and standards.

Part 3, registration information of API, Excipients and Packaging materials usage and management.

12. If the research documents in the registration platform cannot meet the needs of the related review requirements during the joint review with formulation, the CDE may require the applicant of drug products or the relevant registrant of API, Exicipients and packaging materials to supplement the documents. The way to submit the supplementary information shall be clarified by the CDE in the notice of supplement.

13. If the API is marked "A", it indicates that the API has passed the review and is approved. API registrants can print approval documents, specifications and labels etc. on the registration platform for GMP inspection and import customs clearance etc.

For APIs without platform registration and submitting research documents together with drug formulation registration application dossiers, regulatory authorities shall mark relevant information of APIs in drug formulation approval documents, which can be used for GMP inspection and import customs clearance of APIs. etc.

14. The GMP inspection procedures and requirements for API manufacturers shall be implemented in accordance with relevant provisions of existing laws and regulations. After passing the GMP inspection, the registration information shall be updated on the registration platform.

15. If there is any technical change in the API marked "A", an application for change shall be submitted in accordance with the relevant provisions of the current drug registration administration and implemented after approval. Other changes of API, excipients and packaging materials shall be updated in time on the registration platform and summarized in the annual report submitted in the first quarter of each year.

16. When the APIs, excipients and packing materials are changed, the registrant of the APIs, excipients and packing materials shall take the initiative to carry out research, timely notify the relevant Drug Products manufacturing enterprises (drug market approval holders), and timely update the registration information, which shall be reflected in the annual report also.

Upon receipt of the above notice, pharmaceutical Drug Products (drug market approval holders) shall promptly evaluate or study the impact of the corresponding changes on the quality of Drug Products. If the changes affect the quality of Drug Products, they shall apply for supplementary applications. 

17. For the approved Drug Products, if change API, Excipients, packing materials and change the vendors of API, Excipients, packing materials, should carried out the studies according to the related guidelines, eg. Technical guidelines for research on the changes of approved Drug Products (one), Technical guidelines for research on process change of approved Drug Products, Technical guidelines for research on the changes of approved traditional Chinese medicine (one), Technical guidelines for research on the changes of approved biological products etc. And carry out in accordance with the current drug registration administration regulation. 

18. If an overseas supplier of API, Excipients, packing materials changes its registration agency, it shall submit relevant documents and materials to make the change.

Part 4, supervision and administration

19. The province (district, city) FDA should perform the marketed administration as the drug products for the API which the registration status is “A”, and carry out the Drug GMP inspection.

20. The province (district, city) FDA should strengthen the supervision and inspection of Drug products production enterprises (drug marketing license holders, MAH) within the administrative region. Supervise and urge the Drug products production enterprises (drug marketing license holders, MAH) to take the responsibility for auditing the vendors of API, Excipients, packing materials.

Enterprises producing Excipients and packaging materials with the pharmaceutical production license shall continue to be managed according to the original administrative requirements, and the site information shall be registered according to the requirements of this announcement after the expiration of the license.

21. According to the registration information, the Province (District, City) FDA shall strengthen supervision and extended inspection on the suppliers of excipients and packaging materials. If quality problems are found in the production of excipients and packaging materials, it shall deal with them in a timely manner according to laws and regulations, and require formulation manufacturers (MA holders) not to use relevant products, and carry out evaluation and disposal of listed products. The extended inspection shall be organized and carried out by the provincial NPMA where the formulation manufactures (MA holders) located. The local provincial FDA shall organize and carry out joint inspection for the daily inspection of the suppliers of pharmaceutical excipients and packaging materials.

On-site inspection of pharmaceutical excipients shall be carried out with reference to the “Pharmaceutical excipients GMP” (No.120 order of NMPA [2006]). On-site inspection of packaging materials shall be conducted by referring to the general rules for on-site inspection of pharmaceutical packaging materials, which is attached to the measures for management methods of packaging materials and containers in direct contact with drugs (Previous No.13 order of NMPA). The Province (District, City) FDA drug administration can further improve relevant technical specifications and standards according to regulatory needs, and promote the steady improvement of the quality of excipients and packaging materials.

NMPA will revise relevant standards in due course according to the implementation of supervision and inspection and the needs in each province.

22. The APIs, excipients and packaging materials developed, produced, imported and used within the territory of the People's Republic of China are applicable to the requirements of this announcement.

23. This announcement should be carried out since the 15th Aug 2019. In case of any discrepancy between the relevant documents of the excipients and packaging materials and the requirements of this announcement, this announcement shall prevail. The circular on the requirements for declaration of excipients and packaging materials (trial) (no. 155 2016) issued by the NMPA shall be annulled at the same time.

Hereby notice!