Circular of the General Administration of the people's Republic of China on the implementation of the opinions of the general office of the State Council on the evaluation of the consistency of quality and efficacy of generic drugs (2016 No. 106)

Source: CFDA 2016-05-27 in order to implement the opinions of the general office of the State Council on the evaluation of the quality and efficacy of generic drugs (GBF [2016] No 8) and improve the quality of generic drugs, The relevant matters are hereby announced as follows: 1 Evaluation object and implementation stage (1) generic drugs approved for listing before the implementation of new registration and classification of chemical drugs, including domestic generic drugs, imported generic drugs and original research drugs, shall be subject to consistency evaluation (II) in principle, consistency evaluation shall be completed by the end of 2018 for the chemical generic oral solid preparations (attachments) approved for marketing before October 1, 2007 and listed in the national essential drugs catalogue (2012 Edition) （3） For the chemical generic oral solid preparations other than those mentioned in paragraph (2) above, the enterprise may organize the consistency evaluation on its own; after the first product passes the consistency evaluation, the enterprise will not accept the application for the same product consistency evaluation of other drug manufacturers three years later 2 Selection and determination of reference preparations (4) the drug manufacturer shall select the reference preparations according to the guiding principles for selection and determination of reference preparations of general oral solid preparations (Announcement No 61, 2016 of the State Food and Drug Administration) for the varieties to be evaluated for consistency (V) pharmaceutical manufacturers shall, in accordance with the procedures for filing and recommendation of reference preparations for conformity assessment of quality and efficacy of generic drugs (Announcement No 99, 2016 of the State Food and Drug Administration), file the selected reference preparations with the office for conformity assessment of quality of generic drugs of the State Food and Drug Administration (hereinafter referred to as the office for conformity assessment) The industry association may recommend the reference preparation to the consistency evaluation office, and the original research drug manufacturer and internationally recognized same drug manufacturer may apply for the reference preparation to the consistency evaluation office The office of conformity evaluation actively publicizes the filing, recommendation and application information of the reference preparation to the public The food and drug administration shall publish the recommended and determined reference preparations in a timely manner, and drug manufacturers shall, in principle, select the published reference preparations for consistency evaluation (6) if the enterprise cannot find and determine the reference preparation, the drug manufacturer shall carry out the clinical effectiveness test 3 Research content of consistency evaluation (7) in the process of consistency evaluation, pharmaceutical manufacturers must take reference preparations as a control, and comprehensively and deeply carry out comparative research It includes the comparative study of main pharmaceutical indexes such as prescription, quality standard, crystal form, particle size and impurities, and the comparative study of dissolution curve of solid preparations, so as to improve the success rate of bioequivalence test in vivo, and provide the basis for listing the characteristic dissolution curve of drugs in the corresponding quality standard The drug manufacturer shall declare the varieties that conform to the guiding principles for exemption of bioequivalence test of human body (Circular No 87 of food and Drug Administration in 2016), and the consistency evaluation office shall organize the review and publish the results, allowing the drug manufacturer to adopt the method of in vitro dissolution test for consistency evaluation   （8） The varieties for carrying out bioequivalence test shall be put on record in accordance with the procedures specified in the announcement on the filing management of bioequivalence test of chemical drugs (Announcement No 257, 2015 of the food and Drug Administration), and in accordance with the technical guidelines for the study of bioequivalence of chemical drugs in human body with pharmacokinetic parameters as the end point evaluation index (general food and Drug Administration) Bureau Circular No 61, 2016) and other relevant requirements （9） For the varieties of non reference preparations that need to be tested for clinical effectiveness, two situations shall be distinguished: (1) if the prescription and process are unchanged, the records shall be made according to the requirements of the consistency evaluation office, and the test research shall be carried out according to the corresponding requirements of the guiding principles for clinical trials of drugs; (2) if the approved prescription and process are changed, the drug injection shall be applied Relevant requirements of the supplementary application of the measures for volume management shall be tested and studied IV procedures for consistency evaluation （10） After the completion of the consistency evaluation study, pharmaceutical manufacturers shall declare in accordance with the procedures for the consistency evaluation of quality and efficacy of generic drugs (Announcement No 105, 2016 of the State Food and Drug Administration): (1) the provincial food and drug administration shall be responsible for the reception of the consistency evaluation data and the acceptance of relevant supplementary application data within the administrative region of the bank Organize the on-site inspection of development and production, and take three batches of continuous production samples on site and send them to the designated drug inspection agency for review and inspection Upon completion of the above work, the provincial food and drug administration shall summarize and submit it to the consistency evaluation office (2) Imported generic drugs shall be accepted by the administrative service acceptance and complaint reporting center of the food and Drug Administration (hereinafter referred to as the acceptance and Reporting Center), and the application materials shall be subject to formal review, and the enterprise shall be notified to send three batches of samples to the designated drug inspection agency for review and inspection Upon completion of the above work, the acceptance and Reporting Center shall summarize and submit it to the consistency evaluation office   （11） The acceptance and Reporting Center shall be responsible for the acceptance of the application materials of the drugs produced and listed in the same production line in China and approved for listing in the EU, the US or Japan; the consistency evaluation office shall notify the drug review center of the food and Drug Administration (hereinafter referred to as the drug review center) to review the application materials of the original listing at home and abroad, and notify the food and drug administration The food and drug audit and Inspection Center (hereinafter referred to as the inspection center) shall inspect the production site It is deemed to pass the conformity assessment after being reviewed and approved by the conformity assessment office (12) for generic drugs that have been approved to be listed in the European Union, the United States or Japan, domestic drug manufacturers shall apply for generic drug registration according to the relevant requirements of the announcement on the issuance of the work plan for the reform of chemical drug registration and classification (Announcement No 51, 2016 of the food and Drug Administration), which shall be reviewed by the drug Audit Center, and shall be deemed to have passed the consistency evaluation after being approved to be listed V the principle of territoriality is not applicable to the recheck and inspection of conformity assessment samples In principle, the review inspection of the same variety shall be conducted by the same drug inspection institution designated by the food and Drug Administration (the list shall be published separately); the review inspection of supplementary application samples shall be carried out in accordance with the above principles For the varieties that are not assigned to recheck and test drug inspection institutions, the enterprise shall submit relevant application to the consistency evaluation office before submitting the application materials, and the consistency evaluation office shall submit the list of recheck and test drug inspection institutions to the food and Drug Administration for approval before implementation (14) the verification center shall be responsible for the overall organization and coordination of the verification of the authenticity, standardization and integrity of clinical research data such as bioequivalence test and clinical effectiveness test Among them, the clinical research data of domestic generic drugs submitted by the applicant shall be checked by the provincial food and Drug Administration and spot checked by the verification center; the domestic clinical research data of imported generic drugs submitted by the applicant shall be checked by the verification center; the foreign clinical research data of imported generic drugs submitted by the applicant shall be spot checked by the verification center The conformity assessment office can inform the verification center to carry out causal verification according to the problems found in the technical review of conformity assessment Vi safeguard measures (15) the consistency evaluation office of the food and drug administration is responsible for the consistency evaluation Organize experts to review and determine the reference preparation; evaluate the consistency evaluation data submitted by the enterprise; and provide consultation and guidance on relevant policies and work procedures It is also responsible for organizing the drug audit center to provide consultation and guidance on the technical requirements of bioequivalence test and clinical effectiveness test; organizing the audit center to provide consultation and guidance on the technical requirements of the production site inspection, development site inspection and clinical verification; organizing the China food and Drug Inspection Institute and the drug inspection institutions responsible for the review and inspection to provide consultation and guidance on the technical requirements of the production site inspection, development site inspection and clinical verification Consult and guide the technical requirements of variety review and inspection (16) the consistency evaluation office shall organize the establishment of an expert committee, covering pharmacy, clinical medicine, pharmacoeconomics, statistics, law, etc The expert committee is responsible for providing advisory opinions on the selection of evaluation varieties, the review of reference preparations, the evaluation of varieties, etc of the consistency evaluation office; reviewing the results of selection of reference preparations and the evaluation of varieties; and providing decision-making advisory opinions on the overall deployment of consistency evaluation, major policies and key technical issues (XVII) the State Food and Drug Administration and the China food and drug inspection and Research Institute set up the information column of "generic drug consistency evaluation" on the portal website, released the progress of consistency evaluation work in a timely manner, disclosed dynamic information such as reference preparation filing, variety declaration, acceptance, etc., comprehensively guided and standardized enterprises to carry out consistency evaluation work The consistency evaluation office will speed up the establishment of a special information work platform to carry out information-based management of work processes to ensure the openness and transparency of the consistency evaluation work (XVIII) each provincial food and drug administration shall, in accordance with the requirements of this announcement, supervise the consistency evaluation of drug manufacturing enterprises in the administrative region, and implement the work of data acceptance, on-site verification and sampling inspection, data collection and submission It is hereby announced Appendix: list of generic drug conformity assessment varieties to be completed by the end of 2018, food and drug administration, May 25, 2016