Medical network - August 28, on August 25, the CFDA website on the quality of generic drugs and curative effect evaluation work related matters of consistency announcement no. 100 (2017), the file draft had the net for advice on June 9.
The quality of generic drugs and the evaluation of efficacy consistency were evaluated
Notice of matters concerned (no. 100 of 2017)
For the evaluation of generic drug quality and efficacy consistency evaluation (hereinafter referred to as "conformance assessment"), the relevant issues are hereby announced as follows:
One, for enterprises to choose reference preparations, the state food and drug supervision and administration bureau will put on the implementation of the general office of the state council about to carry out the quality of generic drugs and curative effect evaluation opinion consistency > announcement of relevant matters of no. 106 (2016) attached to 289 varieties of the original enterprise drug list and publish to the society, as a reference for enterprises to choose reference preparations.The list is divided into two categories, which are listed in China and are not listed in China.It is suggested that enterprises should select one of the following orders for filing:
(1) original pharmaceutical products: imported pharmaceutical products that have been examined and approved for production in China, and unimported raw drugs;
(2) in the case of the cessation of production of the original research enterprises, the choice of the United States, Japan or the eu may be allowed to go public and obtain the drug of the status of the reference preparation.
For the reference preparation of the state administration of food and drug administration, it is recommended that enterprises carry out their research according to the published reference preparations.Suspicious of the reference preparation has been released, but to the administration of state food and drug supervision and administration of drug approval center objection and explain the reasons, the administration of state food and drug supervision and management of the expert advisory committee meeting will be held in public deliberation, and public review result.
Article 2. The reference preparation for the record of the state administration of food and drug administration shall be disclosed to the public.For reference published by the state food and drug supervision and administration bureau not preparation varieties, by the state food and drug administration bureau organization expert advisory committee to discuss the difference after put forward the following opinions:
(1) it can be confirmed that the conditions of reference are in conformity with the parameters;
(2) doubtful;
(3) clearly not eligible.
For (2) (3) whether the two situations continue to be studied or re-selected for the reference preparation, the enterprise shall independently decide and assume the corresponding responsibilities.
Three, enterprise procurement from abroad by reference drug product, when submit consistency evaluation need to offer to buy vouchers, materials such as product packaging and specifications, or other appropriate method to prove the reference preparation is state enterprise products.Companies found that the use of reference drug product for counterfeit products, should terminate the ongoing research work, has been declared, should be timely to the administration of state food and drug supervision and administration of drug approval report center and has withdrawn his application for consistency evaluation, as the case from responsibility;When the regulatory authorities find that the products used by enterprises are counterfeit products, they shall timely notify relevant enterprises and terminate the examination and approval;The listed company shall revoke the approval document and publish the information to the public. The enterprise shall be obliged to make an explanation and investigate the case according to the circumstances.
Four, according to the general office of the state council on further reform and improve the pharmaceutical production circulation use policy several opinions (countries do hair [2017] no. 13), shall manage the records of bioequivalence test institutions.The bioequivalence test in conformance assessment can be carried out in the established clinical trial institutions, or in other qualified institutions.Bioequivalence test sponsors may employ a third party assessment ability according to the quality control standard for clinical trials (GCP) requirements to evaluate the bioequivalence trial institution.
Five, the bioequivalence test before you begin, the applicant shall be according to the state food and drug supervision and administration bureau on the announcement of information platform of drug clinical trials in the requirements of the project will test, the clinical test units, sample analysis, the information such as reference preparation in the center of the state administration of food and drug supervision and administration of drug approval drug clinical trial registration and information public platform.The provincial food and drug administration has stepped up the daily supervision of the clinical testing institutions and found that the problems have been reported to the food and drug administration of the state administration of food and drug administration for examination and verification.
Six, to meet the human bioequivalence test waiver guiding principles of varieties, and is not suitable for varieties of research in the human body, the state food and drug administration and the difference between cases, partial released varieties of specific directory;The enterprise may also apply to the state administration for food and drug administration for exemption from the application and explain the reasons. The state food and drug administration has decided whether to agree to a waiver after the demonstration.
Vii. The varieties of the original enterprises in China shall be differentiated according to the following situations:
Belongs to the public after, there was no big change, or after the listed larger change but by the review does not affect the quality and curative effect, by the state food and drug administration bureau after auditing and verification, listed in the directory reference preparations.
Belongs to the public after a major change is the same as the country of origin effect product quality differences, in the 30 days after the announcement by the enterprise report center of total bureau of national food and drug supervision and administration of drug approval, and issued a statement on its website, illustrate the differences and the reasons, and in accordance with the requirements for consistency evaluation.
8. The applicant shall evaluate whether to meet the requirements of the technical guidelines for the evaluation of the consistency of the existing consistency of the quality and efficacy of the pharmaceutical products.Achieved by way of assessment, the applicant may be proposed to the administration of state food and drug supervision and management from attending consistency evaluation of the application, the state food and drug administration management will be in accordance with the requirements for current consistency evaluation technique, the original registration filing data review, review its authenticity and integrity.If the request is not reached, the applicant shall make a consistent evaluation according to the requirements.The review is approved by consensus assessment.
The applicant can assess whether to meet the requirements of the technical guidelines for the evaluation of the current conformance assessment.Upon assessment, the applicant may apply to the national food and drug administration's drug review center for a standard review that is consistent with the quality and efficacy of the original drug.The examination and approval of the state administration of food and drug supervision and administration shall be assessed through consistency.
9. The approved drugs approved by Chinese enterprises in the eu, us or Japan are listed in China.
(a) in the European Union, the United States or Japan's approval of generic drugs already on the market in China and the production of using the same production line the same prescription, overseas listing applicants need to submit a declaration of bioequivalence research, pharmaceutical research, data and other technical data, by the state food and drug administration bureau, after review by regarded as the evaluation of consistency.
(2) in the European Union, the United States or Japan's approval of generic drugs have been used in China but different production line or prescription craft is not consistent, enterprise must, according to the requirement of the consistency evaluation to listed abroad to declare the prescription craft and bioequivalence research, pharmaceutical research, data and other technical data to submit application for change to the administration of state food and drug supervision and administration, after review by approving changes prescription craft, regarded as the evaluation of consistency.
(3) in the European Union, the United States or Japan but not listed in the territory of China, confirmed by clinical research age-neutral, overseas listing can be used to declare bioequivalence research, pharmaceutical research, data and other technical information to the state food and drug supervision and administration bureau to apply for listing;If ethnic differences may exist, corresponding clinical trials should be carried out.The evaluation through consistency evaluation.
(4) the above technical data, should be used to the European Union, the United States or Japan's regulators listing application complete research data, including pharmaceutical research data, bioequivalence test data, etc., shall conform to the requirements of the current Chinese technical guidelines and to accept the state food and drug administration supervision and spot checks.Revoke the certificate of approval for providing false documents, materials, samples or other means of deception to obtain drug approval documents.
The drug mentioned in the preceding paragraph includes the name of a controlled subsidiary that is manufactured in China for the purpose of establishing or acquiring a controlling subsidiary outside China.Enterprises established overseas by Chinese citizens who invest in or participate in stocks or shares, and their products produced overseas still apply for listing licenses in accordance with imported drugs.
Ten, the application, submit the consistency evaluation technology department or the pharmaceutical inspection institutions entrusted by the applicant belongs, review inspection report issued by third parties and other samples, one of the declaration data submitted to the state food and drug administration.The state administration of food and drug administration will publish a list of agencies with the ability to review drug quality.
11, total bureau of national food and drug supervision and administration of drug approval center set up the office of compliance, coordinate for inspection, sampling and review related links, improve the quality of the check, inspection and review and efficiency, guarantee the inspectors and review member application consistency evaluation according to the same standard of check and review.The review, inspection and inspection shall be carried out in accordance with the relevant provisions of the state administration of food and drug administration, and shall be recorded in the relevant archives.The staff of the review, verification and inspection shall be responsible for the relevant conclusions.
12. The applicant shall bear legal responsibility for the reliability of the reported information and relevant data.Drug approval process to report data authenticity problems found, shall not be approved, and by the deparment in conjunction with the food and drug administration of the state food and drug supervision and administration bureau audit inspection center for investigation in accordance with the law, revocation of the original drug approval number, shall be investigated for relevant legal responsibility.If there is a problem of integrity of the application, the applicant shall not approve it, and the applicant may re-declare it after completing it.
13. From the tenth working day after the publication of the announcement, the application for conformance evaluation shall be handled or received by the national food and drug administration administrative matters handling service and the complaint reporting center.
(a) belongs to change the prescription craft of generic drugs (including imported generic drugs), should refer to "drug registration management approach" (order no. 28) of the state food and drug administration of the relevant requirements, apply for supplement, indicate it in the application form special declaration matters "consistency evaluation application, prescription craft had a change".Domestic generics should comply with the declared data concerning the release chemicals generics oral solid preparation quality and curative effect evaluation declaration data consistency requirements (trial) notice "(the state food and drug supervision and administration bureau announcement no. 120 2016) data requirements.Imports of generic drugs can be submitted for submission as required by circular no. 120 of 2016;Can also be in accordance with international people use drug registration as prescribed by the technical coordination meeting (ICH) common technical document (CTD) outside the full set of technical data, the requirements of the notice no. 120 and 2016 "profile" and "evaluation" in vitro part submit declaration.
(2) belong to the unchanged prescription application process consistency evaluation, drug supplementary application form should be filled in, indicate it in the application form special declaration matters "consistency evaluation application, prescription process does not change".The declaration shall be in conformity with the requirements of paragraph (1) of this article or relevant notices and notices.
(3) listed on the approval of the European Union, the United States or Japan belongs to the production of generic drugs in China has been on the market in China and overseas listing is proposed and the production of the same production line the same prescription drug, drug supplementary application form should be filled in, indicate it in the application form special declaration matters "collinear production consistency evaluation application, production prescription craft have change" or "apply for collinear production consistency evaluation, production line of the prescription process does not change".The declaration shall comply with the relevant requirements of article 9 and subparagraph (1) of this article.
Active pharmaceutical ingredients, excipients, and could not provide a direct contact with drugs packaging material source of legal documents, which used active pharmaceutical ingredients, excipients, and packaging materials production enterprises come into direct contact with drugs shall be submitted to the active pharmaceutical ingredients, excipients and direct contact with drugs used packaging material has the legitimate use of the European Union, the United States or Japan statement (or by the agent enterprises to submit), and the reasons for can't provide the related technical documents.The pharmaceutical production enterprise shall submit relevant research materials.The explanation will be made public with the conclusion of the evaluation of conformance.
Administration (4) the state food and drug administrative matters to accept the service and complaint reporting center to sign for 5 days, the declaration data are in the form of censorship, in conformity with the requirements, accepted by the administration service and complaint reporting center issue a notice of acceptance (prescription process change) or receive notice (prescription process does not change);If it does not meet the requirements, it shall issue a notification of non-acceptance (the prescription process has changed) or not accept the notification (the prescription process has not changed) and explain the reasons;The information is not complete or not in accordance with the statutory form of the issuance of the notice of correction.
Upon acceptance, the state food and drug administration shall conduct a volume review of the enterprise's declaration data.Complete the volume within 45 days after meeting the requirements;If it does not meet the above requirements, it shall not be approved and shall give reasons.
Administration of state food and drug supervision and administration of drug approval center to establish a review has presented for inspection and sampling requirements, approved by the state administration of food and drug supervision and administration of the food and drug inspection center unified organization of research field, production scene or clinical trial data are for inspection or sampling.In case of inspection, the relevant inspection authorities shall be appointed.The inspection shall be completed within 60 days after the completion of the examination.
15. The pharmaceutical audit center of the state administration of food and drug administration has summarized the situation of inspection and sample inspection, and put forward a comprehensive review opinion on whether to pass the conformance evaluation.
The review shall generally be completed within 120 days after acceptance.If the applicant is required to supplement the information, the applicant should complete the supplementary information within 4 months.The time limit is not included in the time limit.
Through comprehensive evaluation, by the state administration of food and drug supervision and administration of approval document issued by the drug approval center announced that included into the catalogue of listed Chinese medicine ", allowing them to use "through consistency evaluation" logo, enjoys through consistency evaluation of relevant policies.
"Through conformance evaluation" is used to identify the drug labels and instructions of the drug through or through consistency evaluation.By and shall be regarded as by consistency evaluation of medicines, since the issued by the state food and drug supervision and management of administration, as of the date of approval documents can be used in the drug labels, specifications "by consistency evaluation" logo.The design, color and font of the logo must be consistent with the state administration of food and drug administration.The name of the drug is marked with a text form in the lower part of the label. (example: XXXX no. XX of XXXX).Logo should be integrated and drug use manual, label printing, such as label, instruction with narcotic drugs, psychotropic drugs, toxic drugs for medical use, radioactive pharmaceuticals, drugs for external use only, and over-the-counter medicines such as prescribed by the state special logo, the size of the logo size shall not exceed the mark of the provisions of the state.The name of the notice below shall be no more than half of the typeface used in the general name.Other requirements for drug use instructions and labels shall be in conformity with the provisions of drug instructions and labelling regulations issued by the original state food and drug administration.
17. Application for the consistency evaluation of the enterprise's declaration and the conclusion of the appraisal shall be made public.Varieties by consistency evaluation, and report to the public its product manuals, enterprises and bioequivalence test data, involving enterprise production process and its parameters, such as technical secrets, in accordance with the relevant provisions of the state food and drug supervision and management of administration.The specific standards shall be separately formulated by the pharmaceutical audit center of the state food and drug administration.For a variety that has not been assessed by consistency, the reasons for not passing will be stated in the release of the decision.
Article 18 the state food and drug administration administration of food and drug administration shall inform the enterprise of its failure to approve the review of the consistency evaluation and the conclusion of the comprehensive review.If the company has different opinions, it may apply for the meeting to communicate and submit the written opinions within 15 days from the date of publication (or notification of the applicant).The pharmaceutical evaluation center of the state food and drug administration shall, within 15 days upon receipt of the application, decide whether to convene the meeting and notify the applicant in writing.The applicant shall prepare a written opinion within 20 days prior to the meeting to serve the pharmaceutical audit center of the state food and drug administration.The drug evaluation center of the state food and drug administration shall hold a communication meeting within 20 days after receiving the written opinion of the applicant.
After the communication, the enterprise still has the objection, may apply to the state food and drug administration the general administration of food and drug administration to apply for the expert advisory committee meeting to hold the public demonstration.The drug evaluation center shall make a decision according to the expert's conclusion, which shall be submitted to the state administration for food and drug administration.The methods and procedures for the meeting of the expert advisory committee shall be carried out in accordance with the relevant provisions of the state administration of food and drug administration.
19. The production enterprises with the consistency evaluation of the variety of drugs shall reach more than 3, and shall no longer select the varieties that have not passed the conformance evaluation in the case of centralized procurement of drugs.
Due to less number of production enterprises through consistency evaluation and affect the market supply of basic drugs directory at the state, by the state food and drug administration bureau jointly with the relevant ministries and commissions issue list, encourage enterprises to apply for generic drugs research and development.The list of medicines will be dynamically adjusted according to the consistency of the varieties.
The state food and drug administration and encourage qualified marketing authorisation holder with the enterprise, will through consistency evaluation of pharmaceutical production entrust other enterprise production, to expand production, meet the market needs.
The staff of the food and drug administration shall have the obligation to keep confidential the technical secrets and trade secrets in the enterprise declaration documents as well as the review and inspection procedures of drugs.If there is evidence to prove that the food and drug regulatory staff divulges the technical secrets and trade secrets of the enterprise, it shall be dealt with in accordance with the regulations of the state administration of food and drug administration.If it is suspected of a crime, it shall be transferred to the judicial organ for criminal responsibility.The reviewers and inspectors who have been appointed to perform temporary work tasks shall, in accordance with the provisions of the agreement, be required to sign a confidentiality agreement.
21. The state administration of food and drug supervision and administration encourages all sectors of society to monitor the research and development and production behaviors of enterprises in conformity assessment, and to report violations of the law.Encourage all sectors of society to supervise drug review and inspection.The informants shall be kept confidential and shall be rewarded according to the relevant regulations.
The above working time shall be on weekdays.
Article 23. This notice shall be implemented since the date of promulgation. The relevant documents of the original publication shall be subject to the discrepancy between the relevant documents and the relevant documents.
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