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Published byChina Center for Food and Drug International Exchange & Servier (Tianjin) Pharmaceutical Co., Ltd.
CHINA FOOD AND DRUG NEWSLETTER
施维雅(天津）制药有限公司
中国食品药品国际交流中心
2016. Volume7
国家食品药品监督管理总局发布《仿制药质量和疗效一致性评价工作程序》
为规范仿制药质量和疗效一致性评价工
作，根据《国务院办公厅关于开展仿制药质量
和疗效一致性评价的意见》（国办发〔2016〕8号）的有关要求，2016年5月25日，国家食品
药品监督管理总局发布《关于发布仿制药质量
和疗效一致性评价工作程序的公告》（2016年第105号）。内容如下：
仿制药质量和疗效一致性评价工作程序
为贯彻落实国务院办公厅《关于开展仿制
药质量和疗效一致性评价的意见》（国办发
〔2016〕8号），规范仿制药质量和疗效一致
性评价工作申报流程，特制定本工作程序。
一、评价品种名单的发布
国家食品药品监督管理总局发布开展仿制
药质量和疗效一致性评价（以下简称一致性评
价）的品种名单。药品生产企业按照国家食品
药品监督管理总局发布的品种名单，对所生产
的仿制药品开展一致性评价研究。
二、企业开展一致性评价研究
药品生产企业是开展一致性评价的主体。
对仿制药品（包括进口仿制药品），应参照
《普通口服固体制剂参比制剂选择和确定指导
原则》（国家食品药品监督管理总局公告2016年第61号），选择参比制剂，以参比制剂为对
照药品全面深入地开展比对研究。参比制剂需
履行备案程序的，按照《仿制药质量和疗效一
致性评价参比制剂备案与推荐程序》（国家食
品药品监督管理总局公告2016年第99号）执
行。仿制药品需开展生物等效性研究的，按照
《关于化学药生物等效性试验实行备案管理的
公告》（国家食品药品监督管理总局公告2015年第257号）进行备案。
对为开展一致性评价而变更处方、工艺
等已获批准事项的仿制药品（包括进口仿制药
品），应参照《药品注册管理办法》的有关要
To regulate the conformance evaluation of the quality and efficacy of generic drugs, according to the relevant requirements of the Opinions of the State Council General Office on Carrying out Conformance Evaluation of the Quality and Efficacy of Generic Drugs (State Council General Office [2016] No. 8), CFDA released on May 25, 2016 the Announcement on the Issuance of Work Procedures for Conformance Evaluation of the Quality and Efficacy of Generic Drugs (Announcement No. 105, 2016). The full text reads as follows:
Work Procedures for Conformance Evaluation of the Quality and Efficacy
of Generic Drugs
With a view to implementing the Opinions of the State Council General Office on Carrying out Conformance Evaluation of the Quality and Efficacy of Generic Drugs (State Council General Office [2016] No. 8), and regulating the applications and work procedures for conformance evaluation of the quality and efficacy of generic drugs, Work Procedures for Conformance Evaluation of the Quality and Efficacy of Generic Drugs (The Work Procedures for short) are hereby formulated.
I. Release of the list of varieties for evaluation
CFDA shall release the list of generic drugs for conformance evaluation of the quality and efficacy (hereinafter referred to as conformance evaluation). Pharmaceutical
manufacturers shall perform conformance evaluat ion of their generic drugs in accordance with the CFDA list.
II. Conformance evaluation by enterprises
Drug manufacturers are the main body for carrying out conformance evaluation. For generic drugs (including imported generic drugs), the selection of reference formulations should refer to the Technical Guidelines for Selection and Determination of Reference Formulation for Ordinary Oral Dosage Forms (CFDA Announcement No. 61, 2016) to carry out comprehensive and in-depth study. Reference formulations requiring record filing shall be subject to the Procedures for Filing and Recommendation of Reference Formulations for Conformance Evaluation of the Quality and Efficacy of Generic Drugs (CFDA Announcement No. 99, 2016). Generic drugs requiring bioequivalence studies shall be subject to record filing according to Announcement on Implementing Record Management for Bioequivalence Studies of Chemical Drugs (CFDA Announcement No. 257, 2015).
For generic drugs (including import generic drugs) that changed the prescription, production process and other approved issues to carry out conformance evaluation, the applicant should refer to the Provisions f o r D r u g R e g i s t r a t i o n t o s u b m i t a supplementary application in accordance with these Procedures. Other supplementary application shall be submitted in accordance with relevant provisions of the Provisions for Drug Registration.
CFDA Issued Work Procedures for Conformance Evaluation of the Quality and Efficacy of Generic Drugs
2 CHINA FOOD AND DRUG NEWSLETTER
求，提出补充申请，按照本工作程序执
行。其他补充申请，按照《药品注册管理
办法》的有关规定执行。
三、资料的提交和申报
完成一致性评价研究后，国产仿制药
生产企业向企业所在地省级食品药品监督
管理部门提交和申报有关资料。未改变处
方工艺的，提交《仿制药质量和疗效一致
性评价申请表》、生产现场检查申请和研
究资料（四套，其中一套为原件）；改变
处方工艺的，参照药品注册补充申请的要
求，申报《药品补充申请表》、生产现场
检查申请和研究资料。已在中国上市的进
口仿制药品按照上述要求，向国家食品药
品监督管理总局行政事项受理服务和投诉
举报中心（以下简称受理中心）提交和申
报一致性评价有关资料。
四、资料的接收和受理
省级食品药品监督管理部门负责本
行政区域内一致性评价资料的接收和补充
申请资料的受理，并对申报资料进行形式
审查。符合要求的，出具一致性评价申请
接收通知书或补充申请受理通知书；不符
合要求的，出具一致性评价申请不予接收
通知书或补充申请不予受理通知书，并说
明理由。省级食品药品监督管理部门对申
报资料形式审查后，组织研制现场核查和
生产现场检查，现场抽取连续生产的三批
样品连同申报资料（一套，复印件）送国
家食品药品监督管理总局仿制药质量一致
性评价办公室（以下简称一致性评价办公
室）指定的药品检验机构进行复核检验。
受理中心负责进口仿制药品的一致
性评价资料的接收和补充申请资料的受
理，并对申报资料进行形式审查。符合要
求的，出具一致性评价申请接收通知书或
补充申请受理通知书；不符合要求的，出
具一致性评价申请不予接收通知书或补充
申请不予受理通知书，并说明理由。受理
中心对申报资料形式审查后，将申报资料
（一套，复印件）送国家食品药品监督管
理总局食品药品审核查验中心（以下简称
核查中心），由核查中心组织对进口仿制
药品境外研制现场和境外生产现场进行抽
查；将申报资料（一套，复印件）送一致
性评价办公室指定的药品检验机构，并通
知企业送三批样品至指定的药品检验机构
进行复核检验。
五、临床试验数据核查
对生物等效性试验和临床有效性试
验等临床研究数据的真实性、规范性和完
III. Submission of application dossiers
Upon completion of the conformance eva lua t ions , domes t ic gener ic d rug manufacturers shall submit the application dossiers to the competent provincial food and drug administration departments. For applications without any change in the manufacturing process, the applicant shall submit Application Form for Conformance Evaluation of the Quality and Efficacy of Generic Drugs, application dossiers for production site inspection, and study data (four copies, one of which being the original); for applications involving changes of the manufacturing process, the applicant shall, referring to the requirements for supplementary application for drug registration, submit the Supplementary Application Form for Drug Registration, application dossiers for production site inspection, and study data. For imported generic drugs that have been marketed in China, the applicant shall, in accordance with the above requirements, submitted conformance evaluation dossiers to CFDA Acceptance Center for Administrative Services and Complaints & Reports (hereinafter referred to as the Acceptance Center).
requirements, the Acceptance Center shall issue a Notice of Rejection with justification for such dec is ion . Af ter the formal inspection, the provincial food and drug administration departments shall organize the inspection of the R&D and production site, and perform on-site sampling of three consecutive batches of product, which are to be submitted together with the application dossiers (1 copy) to testing agencies designated by CFDA Office of Quality Conformance Evaluation of Generic Drugs (hereinafter referred to as the Conformance Evaluation Office) for inspection and verification.
The Acceptance Center shall be responsible fo r t he r ece ip t s and accep t ance o f conformance evaluation and supplementary application dossiers for imported generic drugs, as well as the formal inspection. For applications meeting the requirements, the Acceptance Center shal l issue a Notice of Acceptance of the conformance evaluation or supplementary application; for applications not meeting the requirements, the Acceptance Center shall issue a Notice of Rejection with justification for such decision. After the formal inspection, the Acceptance Center shall submit the application dossiers (1 copy) to CFDA Center for Food and Drug Inspection (hereinafter referred to as CFDI), who shall organize random inspection of the overseas R&D and production sites of imported generic drugs; CFDI shall submit the application dossiers (1 copy) to testing agencies designated by the Conformance Evaluation Office, and inform the manufacturer to send three consecutive batches of product samples to designated testing agencies for verification and inspection.
V. Review of the clinical trial data
CFDI shall be responsible for the overall organization and coordination of the review of the authenticity, compliance and integrity of the bioequivalence studies and clinical efficacy trials and other clinical study data. Wherein the clinical study data of domestic generic drugs submitted by the applicants shall be reviewed by the provincial food and drug administration departments, and
IV. Receipt and acceptance of application dossiers
The provincial food and drug administration departments shall be responsible for the receipt and acceptance of conformance evaluation and supplementary application dossiers, and perform formal inspection thereof. For applications meeting the requirements, the Acceptance Center shall issue a Notice of Acceptance of the conformance evaluation or supplementary application; for applications not meeting the
Volume VII 2016 3
整性的核查，由核查中心负责总体组织协
调。其中对申请人提交的国内仿制药品的
临床研究数据，由省级食品药品监督管理
部门进行核查，核查中心进行抽查；对申
请人提交的进口仿制药品的国内临床研究
数据，由核查中心进行核查；对申请人提
交的进口仿制药品的国外临床研究数据，
由核查中心进行抽查。一致性评价办公室
可根据一致性评价技术评审过程中发现的
问题，通知核查中心开展有因核查。
六、药品复核检验
承担一致性评价和补充申请复核检验
的药品检验机构，收到申报资料和三批样
品后进行复核检验，并将国内仿制药品的
复核检验结果报送药品生产企业所在地省
级食品药品监督管理部门；进口仿制药品
的复核检验结果报送受理中心。
七、资料汇总
各省级食品药品监督管理部门将形式
审查意见、研制现场核查报告、生产现场检
查报告、境内临床研究核查报告、复核检验
结果及申报资料进行汇总初审，并将初审
意见和相关资料送交一致性评价办公室。
受理中心对进口仿制药品的申报资
料进行形式审查，将形式审查意见、境内
研制现场核查报告、境内临床研究核查报
告、复核检验结果及申报资料进行汇总初
审，并将初审意见和相关资料送交一致性
评价办公室。
由核查中心开展的国内仿制药品的境内
抽查、进口仿制药品的境外检查和境外核
查的结果，及时转交一致性评价办公室。
八、技术评审
一致性评价办公室组织药学、医学及
其他技术人员，对初审意见、药品研制现
场核查报告、药品生产现场检查报告、境
内临床研究核查报告、已转交的境外检查
和核查报告、药品复核检验结果和申报资
料进行技术评审，必要时可要求申请人补
充资料，并说明理由。一致性评价办公室
形成的综合意见和补充申请审评意见，均
提交专家委员会审议。审议通过的品种，
报国家食品药品监督管理总局发布。
九、结果公告与争议处理
国家食品药品监督管理总局对通过一
致性评价的结果信息，及时向社会公告。
申请人对国家食品药品监督管理总局公告
结果有异议的，可以参照《药品注册管理
办法》复审的有关要求，提出复审申请，
并说明理由，由一致性评价办公室组织复
审，必要时可公开论证。
selectively reviewed by CFDI; the domestic clinical study data of imported generic drugs submitted by the applicants shall be reviewed by CFDI; and the overseas clinical study data of imported generic drugs submitted by the applicants shall be selectively reviewed by CFDI. In light of the problems found in the process of technical review of conformance evaluation, the Conformance Evaluation Office shall inform CFDI to carry out causality inspection.
VI. Drug review & test
Testing agencies undertaking verification and inspection of conformance evaluation and supplementary applications shall perform verification and inspection upon receipt of application dossiers and three batches of samples; for domestic generic drugs, submit the verification and inspection results to the provincial food and drug administration departments concerned, and for the imported generic drugs, submit the verification and inspection results to the Acceptance Center.
VII. Collection of the application dossiers
The provincial food and drug administration departments shall collect and perform preliminary review of the formal inspection comments, verification reports of R&D site, inspection reports of production sites, verification report of domestic clinical study, verification and inspection results, and the application dossiers; and submit the preliminary inspection opinions and relevant information to the Conformance Evaluation Office.
The Acceptance Center shall perform formal inspection of the application dossiers for imported generic drugs, summarize and perform preliminary review of the formal inspection comments, verification reports of domestic R&D sites, inspection reports
of domestic production sites, verification report of domestic clinical study, verification and inspection results, and the application dossiers; and submit the preliminary inspection opinions and relevant information to the Conformance Evaluation Office.
CFDI shall perform random inspection of domestic generic drugs; and overseas inspection and verification of imported generic drugs, and timely submit the results to the Conformance Evaluation Office.
VIII. Technical review
The Conformance Evaluation Office shall organize pharmaceutical, medical and other technical personnel, to perform technical review of preliminary inspection opinions, verification reports of pharmaceutical R&D site, inspection reports of pharmaceutical production sites, verification reports of domestic clinical study, referred overseas inspection and verification reports, drug verification test results, and application dossiers; and shall request the applicants, when necessary, to provide supplementary in format ion wi th jus t i f i ca t ion . The comprehensive opinions and review comments on supplementary applications shall be submitted to the Committee of Experts for review. Only those considered and approved can be reported to CFDA for release.
IX. Announcement of results and dispute settlement
CFDA shall make public the results of conformance evaluation in a timely manner. Should any disagreement arise against the results in CFDA Announcement, the applicant can refer to the relevant requirements for re-review in the Provisions for Drug Registration, to apply for re-review and provide the justification; the Conformance Evaluation Office shall organize the re-review and perform, if
4 CHINA FOOD AND DRUG NEWSLETTER
CFDA Issued Announcement on Implementing the Opinions of the State Council General Office on Carrying out Conformance Evaluation of the Quality and Efficacy of Generic Drugs
国家食品药品监督管理总局发布《关于落实〈国务院办公厅关于开展仿制药质量和疗效一致性评价的意见〉有关事项的公告》
为贯彻落实《国务院办公厅关于开
展仿制药质量和疗效一致性评价的意见》
（国办发〔2016〕8号），提高仿制药质
量, 2016年5月25日，国家食品药品监督管
理总局发布《关于落实〈国务院办公厅关
于开展仿制药质量和疗效一致性评价的
意见〉有关事项的公告》（2016年第106号），就有关事项公告如下:
一、评价对象和实施阶段
（一）化学药品新注册分类实施前批
准上市的仿制药，包括国产仿制药、进口
仿制药和原研药品地产化品种，均须开展
一致性评价。
（二）凡2007年10月1日前批准上市的
列入国家基本药物目录（2012年版）中的
化学药品仿制药口服固体制剂（附件），
原则上应在2018年底前完成一致性评价。
（三）上述第（二）款以外的化学药
品仿制药口服固体制剂，企业可以自行组
织一致性评价；自第一家品种通过一致性
评价后，三年后不再受理其他药品生产企
业相同品种的一致性评价申请。
To implement the Opinions of the State Council General Office on Carrying out Conformance Evaluation of the Quality and Efficacy of Generic Drugs (State Council General Office [2016] No. 8), so as to improve the quality of generic drugs, on May 25, 2016, CFDA issued the Announcement on Implementing the Opinions of the State Council General Office on Carrying out Conformance Evaluation of the Quality and Efficacy of Generic Drugs (2016, No. 106), the relevant issues are announced as follows:
1 . Ta r g e t f o r e v a l u a t i o n a n d implementation phases
(1) A l l g e n e r i c d r u g s a p p r o v e d f o r marketing before the implementation of new classification of chemicals, including domestic and imported generic drugs, and domestic originators, shall be all subject to conformance evaluation.
(2) The conformance evaluation for all chemical generic drugs of oral solid
dosage forms (see annex) approved for marketing before October 1, 2007 and included in the National Essential Drugs List (2012) shall be, in principle, completed by the end of 2018.
(3) For chemical generic drugs of oral solid dosage forms other than those stated above (paragraph 2), the enterprise can organize conformance evaluation on their own; since the first variety passed the conformance evaluation, the applications for conformance evaluation of the same variety produced by other drug manufacturers shall no longer be accepted within three years.
2. The selection and determination of reference formulations
(4) Pharmaceutical manufacturers shall select the reference formulations for varieties to be evaluated in accordance with the Technical Guidelines for S e l e c t i o n a n d D e t e r m i n a t i o n o f
necessary, public argumentation.
X. Guidance and counseling
The Conformance Evaluation Office shall establish a platform for guidance and counseling regarding to policies and procedures related to conformance eva lua t ion ; CFDA Cente r fo r Drug Evaluation shall be responsible for the counseling of technical requirements for bioequivalence studies and clinical efficacy trials etc.; CFDI shall be responsible for the counseling of technical requirements for inspections of production and R&D sites and review of clinical study; the National Institute for Food and Drug Control and testing agencies responsible for verification and inspection shall be responsible for the counseling of verification and inspection of all varieties.
XI. Information disclosure
CFDA shall make public in a timely manner the information of reference formulation record filing, receipt and acceptance information, verification and inspection results, verification and inspection results; review results; expert deliberation and other information, to ensure the consistency and transparency of conformance evaluation.
(May 26, 2016)
十、咨询指导
一致性评价办公室建立咨询指导平
台，负责对一致性评价有关政策和工作程
序等内容提供咨询指导；国家食品药品监
督管理总局药品审评中心负责对生物等效
性试验和临床有效性试验等工作的技术要
求进行咨询指导；核查中心负责对生产现
场检查、研制现场核查和临床研究核查等
工作的技术要求进行咨询指导；中国食品
药品检定研究院和各承担复核检验工作的
药品检验机构负责对各品种复核检验等工
作的技术要求进行咨询指导。
十一、信息公开
对一致性评价工作中参比制剂备案信
息、接收与受理信息、核查和检查结果、
复核检验结果、评审结果和专家审议信息
等内容，由国家食品药品监督管理总局及
时向社会公布，确保一致性评价工作的公
开和透明。 （2016-05-26）
Volume VII 2016 5
Reference Formulation for Ordinary Oral Dosage Forms (CFDA Announcement No. 61 of 2016).
(5) Pharmaceutical manufacturers shall, in accordance with Procedures for Filing and Recommendation of Reference F o r m u l a t i o n s f o r C o n f o r m a n c e Evaluation of the Quality and Efficacy of Generic Drugs (CFDA Announcement No. 99, 2016), submit the selected reference formulation to CFDA Office of Quality Conformance Evaluation of Generic Drugs (hereinafter referred to as the Conformance Evaluation Office) for record filing. Industry associations can recommend reference formulations to the Conformance Evaluation Office; manufacturers of or iginators and internationally recognized similar drugs may apply for reference formulations to the Conformance Evaluation Office. The latter shall voluntarily make public the record filing, recommendation and application information of the reference formulations. CFDA shall timely disclose the information of recommended and determined reference formulations; and pharmaceutical manufacturers should, in principle, select the published reference formulations to carry out conformance evaluation.
(6) Where the enterprise cannot find and determine the reference formulation, the drug manufacturers should conduct clinical efficacy trials.
3. Research contents of conformance evaluation
(7) While carrying out the conformance evaluation, the drug manufacturer shall take the reference formulation as a control to carry out in-depth comparative study, encompassing the comparison of prescriptions, quality standards, crystal form, particle size, impurities and other primary pharmaceutical indicators; as well as the comparative study of the dissolution profile of a solid formulation, in order to improve the success rate of in vivo bioequivalence study, and
provide the basis for the inclusion of the dissolution profile in appropriate quality standards. Varieties meeting the Guidelines on Exemption of Biological Equivalence Trials in Human Subjects (CFDA Announcement No. 87, 2016) shall be applied by drug manufacturers and released by the Conformance Evaluation Office after review, allowing the manufacturers to take in vitro dissolution test method for conformance evaluation.
(8) Bioequivalence study should be subject to record filing as per the requirements of the Announcement on Implementing Record Management for Bioequivalence Studies of Chemical Drugs (CFDA Announcement No. 257, 2015), and be conducted in accordance with the Technical Guidelines for Bioequivalence Study of Chemical Generic Drugs in Human Subjects Taking Pharmacokinetic Parameters as Endpoin t s (CFDA Announcement No. 61 of 2016) and other relevant requirements.
(9) Clinical efficacy trials of varieties without reference formulations are classified into: (1) if the prescription and production process have not changed, the trials shall be recorded as per the requirements of Conformance Evaluation Office, and performed in accordance with the corresponding requirements and guidelines of drug clinical trials; (2) if the prescription and production process have not changed, the trials shall be performed according to the requirements for supplementary application in the Provisions for Drug Registration.
二、参比制剂的选择和确定
（四）药品生产企业对拟进行一致性评
价的品种，参照《普通口服固体制剂参比
制剂选择和确定指导原则》（食品药品监
管总局公告2016年第61号）要求选择参比
制剂。
（五）药品生产企业按照《仿制药质量
和疗效一致性评价参比制剂备案与推荐程
序》（食品药品监管总局公告2016年第99号），将选择的参比制剂向食品药品监管
总局仿制药质量一致性评价办公室（以下
简称一致性评价办公室）备案。行业协会
可向一致性评价办公室推荐参比制剂，原
研药品生产企业、国际公认的同种药物生
产企业可向一致性评价办公室申报参比制
剂。一致性评价办公室主动对参比制剂的
备案、推荐和申报信息向社会公开。食品
药品监管总局及时公布推荐和确定的参比
制剂信息，药品生产企业原则上应选择公
布的参比制剂开展一致性评价。
（六）企业找不到且无法确定参比制
剂的，由药品生产企业开展临床有效性试
验。
三、一致性评价的研究内容
（七）在开展一致性评价过程中，药品
生产企业须以参比制剂为对照，全面深入
地开展比对研究。包括处方、质量标准、
晶型、粒度和杂质等主要药学指标比较研
究，以及固体制剂溶出曲线的比较研究，
以提高体内生物等效性试验的成功率，并
为将药品特征溶出曲线列入相应的质量标
准提供依据。对符合《人体生物等效性试
验豁免指导原则》（食品药品监管总局通
告2016年第87号）的品种，由药品生产企
业申报，一致性评价办公室组织审核后公
布，允许该药品生产企业采取体外溶出试
验的方法进行一致性评价。
（八）开展生物等效性试验的品种，应
根据《关于化学药生物等效性试验实行备
案管理的公告》（食品药品监管总局公告
2015年第257号）规定的程序备案，并按照
《以药动学参数为终点评价指标的化学药
物仿制药人体生物等效性研究技术指导原
则》（食品药品监管总局通告2016年第61号）等的有关要求进行试验研究。
（九）对无参比制剂需开展临床有效性
试验的品种，区分两种情况处理：（1）如
属于未改变处方、工艺的，应按一致性评
价办公室的要求进行备案，并按照有关药
品临床试验指导原则的相应要求开展试验
研究；（2）如属于改变已批准处方、工艺
6 CHINA FOOD AND DRUG NEWSLETTER
的，按照《药品注册管理办法》补充申请
有关要求开展试验研究。
四、一致性评价的程序
（十）药品生产企业完成一致性评价
研究后，按照《仿制药质量和疗效一致性
评价工作程序》（食品药品监管总局公告
2016年第105号）进行申报：（1）国产仿
制药由省级食品药品监督管理部门负责本
行政区域内一致性评价资料的接收和相关
补充申请资料的受理，组织研制现场核查
和生产现场检查，现场抽取连续生产的三
批样品送指定的药品检验机构进行复核检
验。完成上述工作后，由省级食品药品监
督管理部门汇总报送一致性评价办公室。
（2）进口仿制药由食品药品监管总局行政
服务受理和投诉举报中心（以下简称受理
和举报中心）受理，对申报资料进行形式
审查，并通知企业送三批样品至指定的药
品检验机构进行复核检验。完成上述工作
后，由受理和举报中心汇总报送一致性评
价办公室。
（十一）在中国境内用同一条生产线生
产上市并在欧盟、美国或日本获准上市的
药品，由受理和举报中心负责申报资料受
理；一致性评价办公室通知食品药品监管
总局药品审评中心（以下简称药审中心）
对原境内、外上市申报资料进行审核，通
知食品药品监管总局食品药品审核查验中
心（以下简称核查中心）对生产现场进行
检查。经一致性评价办公室审核批准视同
通过一致性评价。
（十二）国内药品生产企业已在欧盟、
美国或日本获准上市的仿制药，按照《关
于发布化学药品注册分类改革工作方案的
公告》（食品药品监管总局公告2016年第
51号）的有关要求申报仿制药注册申请，
由药审中心审评，批准上市后视为通过一
致性评价。
五、复核检验与核查
（十三）一致性评价样品的复核检验不
适用属地原则。同一品种的复核检验，原
则上由食品药品监管总局指定的同一药品
检验机构进行（名单另行公布）；补充申
请样品的复核检验，按照上述原则执行。
对未分配复核检验药品检验机构的品种，
企业在提交申报资料前，向一致性评价办
公室提出相关申请，由一致性评价办公室
提出复核检验药品检验机构名单，报食品
药品监管总局批准后执行。
（十四）对生物等效性试验和临床有效
4. Procedures for conformance evaluation
(10) After drug manufacturers completed conformance evaluation study, the application shall be made according to the Work Procedures for Conformance E v a l u a t i o n o f t h e Q u a l i t y a n d Efficacy of Generic Drugs (CFDA Announcement No. 105, 2016) : (1) The provincial food and drug administration departments shall be responsible for the receipt and acceptance of conformance e v a l u a t i o n a n d s u p p l e m e n t a r y application dossiers, and organizing the inspection of the R&D and production site, and performing on-site sampling of three consecutive batches of product, which are to be submitted to designated testing agencies for testing. After the completion of the above work, the provincial food and drug administration departments shall submit a summary to the Conformance Eva lua t ion Office. (2) CFDA Acceptance Center for Administrat ive Services and Complaints & Reports (hereinafter referred to as the Acceptance Center) shall accept the conformance evaluation application of import generic drugs, perform formal inspection of the application dossiers, and notify the enterprise to submit three batches of samples to designated testing agencies for testing. After the completion of the above work, the Acceptance Center shall submit the summary report to the Conformance Evaluation Office.
(11) The Acceptance Center shal l be responsible for the acceptance of application dossiers of drugs produced in China with the same production l ine and approved for marketing
in EU, Japan or the United States; the Conformance Evaluation Office shall notify CFDA Center for Drug Evaluation (hereinafter referred to as CDE) to verify the original application dossiers for domestic and offshore marketing, and notify the CFDA Center for Food and Drug Inspection (hereinafter referred to as CFDI) to perform production site inspection, the results of which, after review and approval by the Conformance Evaluation Office, can be deemed as passing the conformance evaluation.
(12) According to the relevant requirements of the Announcement on Releasing t h e Wo r k P r o g r a m f o r R e f o r m of Registration Classification of Chemicals (CFDA Announcement No. 51, 2016), CDE shall review the registration application of domestic generic drugs that have been approved for marketing in EU, the United States or Japan, the approval for marketing c a n b e d e e m e d a s p a s s i n g t h e conformance evaluation.
5. Inspection and verification
(13) The principle of territoriality does not apply to the testing of samples for conformance evaluation. The testing of the same varieties shall be, in principle, conducted by the same testing agencies (the list of which will be published separately) designated by CFDA; the above principle applies to the testing of samples in supplementary application. For varieties without designated test ing agencies, the enterprises shall raise relevant application to the Conformance Evaluation Office before submission of application dossiers, the latter shall provide a list of testing agencies for testing, which are to be submitted to CFDA for approval and implementation.
(14) CFDI shall be responsible for the overall organization and coordination of the verification of the authenticity, compliance and integr i ty of the
Volume VII 2016 7
性试验等临床研究数据的真实性、规范性
和完整性的核查，由核查中心负责总体组
织协调。其中，对申请人提交的国内仿制
药的临床研究数据，由省级食品药品监督
管理部门进行核查，核查中心进行抽查；
对申请人提交的进口仿制药的国内临床研
究数据，由核查中心进行核查；对申请人
提交的进口仿制药的国外临床研究数据，
由核查中心进行抽查。一致性评价办公室
可根据一致性评价技术评审过程中发现的
问题，通知核查中心开展有因核查。
六、保障措施
（十五）食品药品监管总局一致性评价
办公室负责一致性评价工作。组织专家审
核确定参比制剂；对企业提交的一致性评
价资料进行评价；对有关政策和工作程序
等内容进行咨询指导。并负责组织药审中
心对生物等效性试验和临床有效性试验等
工作的技术要求进行咨询指导；负责组织
核查中心对生产现场检查、研制现场核查
和临床核查等工作的技术要求进行咨询指
导；负责组织中国食品药品检定研究院和
各承担复核检验工作的药品检验机构对各
品种复核检验等工作的技术要求进行咨询
指导。
（十六）一致性评价办公室组织设立
专家委员会，专业范围覆盖药学、临床医
学、药物经济学、统计学、法学等。专家
委员会负责对一致性评价办公室的评价品
种选择、参比制剂审核、品种评价等工作
提出咨询意见；负责审议参比制剂选择结
果和品种评价结果；负责对一致性评价工
作总体部署、重大政策和关键技术问题提
供决策咨询意见。
（十七）食品药品监管总局和中国食品
药品检定研究院在门户网站开设“仿制药
一致性评价”信息专栏，及时发布一致性
评价工作进展，公开参比制剂备案、品种
申报、受理等动态信息，全面引导和规范
企业开展一致性评价工作。一致性评价办
公室加快建立专门的信息工作平台，对工
作流程进行信息化管理，确保一致性评价
工作的公开和透明。
（十八）各省级食品药品监督管理部
门要按照本公告要求，做好对行政区域内
药品生产企业一致性评价工作的督导，同
时要落实好资料受理、现场核查和抽样检
验、资料汇总和报送工作。
附件：2018年底前须完成仿制药一致
性评价品种目录（略） （2016-05-26）
Bioequivalence Studies and clinical efficacy trials and other clinical study data. Wherein the clinical study data of domestic generic drugs submitted by the applicants shall be verified by the provincial food and drug administration departments, and selectively reviewed by CFDI; the domes t ic c l in ica l study data of imported generic drugs submitted by the applicants shall be verified by CFDI; and the overseas clinical study data of imported generic drugs submitted by the applicants shall be selectively reviewed by CFDI. In light of the problems found in the technical review of conformance e v a l u a t i o n , t h e C o n f o r m a n c e Evaluation Office shall inform CFDI to carry out causality inspection.
and inspection of all varieties.
(16) T h e C o n f o r m a n c e E v a l u a t i o n Office shall organize and establish a Committee of Experts covering p h a r m a c y, c l i n i c a l m e d i c i n e , pharmacoeconomics, statistics, law and other professions. The Committee shall be responsible for providing counseling to Conformance Evaluation Office on the selection of varieties to be evaluated, the review of reference formulations and varieties etc.; and providing decision-making advice to the overall deployment of conformance evaluation, the major policies and key technical issues.
(17) CFDA and the National Institute for Food and Drug Control shall establish a special information column of Generic Drugs Conformance Evaluation in their web portals, to timely release the work progress of conformance evaluation, publicize the record filing of reference formulations, variety application and acceptance, and other updates, to comprehensive guide and regulate the enterprises to carry out conformance e v a l u a t i o n . T h e C o n f o r m a n c e Evaluation Office shall accelerate the establishment of special ized information work platform, to achieve workflow information management, and ensure openness and transparency of conformance evaluation.
(18) A l l p r o v i n c i a l f o o d a n d d r u g administration departments shall, in accordance with the requirements of this Announcement, effectively guide drug manufacturers within their administrative regions to conduct conformance evaluation, and to ensure the acceptance of application dossiers, the on-site inspection and sampling, data aggregation and submission.
ANNEX: Catalog of generic drugs whose conformance evaluations are to be completed by the end of 2018 (Not enclosed).
(May 26, 2016)
6. Safeguard measures
(15) CFDA Conformance Evalua t ion Off ice sha l l be respons ib le fo r overall coordination of conformance evaluation. The Office shall organize experts to review and determine the reference formulation; evaluate the conformance evaluation data submitted by enterprises; provide counseling of the relevant policies and procedures. The Office is also responsible for organizing CDE to provide counseling o f t e c h n i c a l r e q u i r e m e n t s f o r bioequivalence studies and clinical efficacy trials etc.; for organizing CFDI to p rov ide counse l ing o f technical requirements for inspections of production sites, verification of R&D Venue and clinical study; for organizing the National Institute for Food and Drug Control and testing agencies responsible for verification and inspection to provide counseling of technical requirements for verification
8 CHINA FOOD AND DRUG NEWSLETTER
国家食品药品监督管理总局专项治理保健食品等三类食品非法添加非法声称问题
CFDA Launched Special Project to Address Illegal Additives and Promotion Targeting at Three Food Categories Including Health FoodTo protect the legitimate interests and safety of consumers, on May 23, 2016, CFDA issued a Notice requiring the food and drug administration departments at all levels nationwide to carry out special projects to address illegal additives and promotion in three food categories: health food, compound liquor (mainly containing Chinese herbal medicine ingredients), and Maca products.
The Notice stressed that, manufacturers of health food, compound liquor, and Maca products shall organize self-inspection in strict accordance with the requirements of the Announcement on Supervising Food Manufacturers and Distributors to Strictly Implement Their Principal Responsibility for Food Safety and relevant laws and regulations. The Notice also requires all local food and drug administration departments to organize inspections over
the corresponding manufacturers and distributors within their administrative areas.
The Notice pointed out that, manufacturers and distributors found with problems in self-inspections, inspections and sampling inspections shall timely make public the list of defective products that are recalled or withdrawn, inform consumers of the reason for recall and withdrawal, and issue risk alerts. Food and drug administration departments concerned shall supervise the en terpr i ses to implement reca l l and withdrawal of defective products, and shall severely punish and timely inform the public of those enterprises that perfunctorily implement recall and withdrawal measures.
(May 27, 2016)
为保障消费者合法权益和消费安全，
2016年5月23日，国家食品药品监督管理总
局下发通知，要求全国食品药品监管部门
开展保健食品、配制酒（主要是含中药材
成分的配制酒）、玛咖制品等三类食品非
法添加、非法声称问题专项治理工作。
通知强调，保健食品、配制酒、玛咖
制品生产经营企业要按照法律规定和《关
于监督食品生产经营者严格落实食品安全
主体责任的通告》要求，认真组织开展自
查。 通知要求，各地食品药品监管部门要
组织对本行政区域生产经营企业检查。 通知指出，对自查、检查和抽检中发
现问题的生产经营者，应当及时向社会公
布执行产品召回和下架措施的问题产品名
单，并向消费者说明召回和下架原因，并
发布消费风险提示。生产经营企业所在地
食品药品监管部门应监督企业对问题产品
召回、下架措施的执行，对召回、下架不
到位、走过场的，要予以从严惩处并及时
向社会公布。 （2016-05-27）
食品Food
CFDA Released 2015 Annual Report for National Medical Device Adverse Event Monitoring
国家食品药品监督管理总局发布《2015年医疗器械不良事件监测年度报告》
医疗器械Medical Devices
On May 27, 2016, CFDA released the 2015 Annual Report for National Medical Device Adverse Event Monitoring, which includes the overview of medical device adverse event reporting, the statistical analysis of medical device adverse events, and measures against safety risks of three kinds of medical devices including x-ray machine, external defibrillator, and low frequency e lect romagnet ic therapy equipment . The report reflects comprehensively the performance of China’s medical device
adverse event monitoring in 2015.
Generally speaking, in 2015, the national medical device adverse event reporting showed a good development momentum, the number of reports continued to grow to exceed 320,000 cases, the average number of reports per million people amounted to 240. Among them, the reports submitted from user units, manufacturers, distributors and individuals amounted to 259,219/5 ,352/56,315/364 cases ,
2016年5月27日，国家食品药品监管总
局发布了《2015年医疗器械不良事件监测
年度报告》，报告包括医疗器械不良事件
报告概况、医疗器械不良事件报告统计分
析、对医用血管造影x射线机、体外除颤器
和低频电磁治疗设备三种医疗器械产品安
全性问题采取的措施等内容。报告比较全
面的反映了2015年我国医疗器械不良事件
监测工作情况。
总体来说，2015年全国医疗器械不良
事件报告工作呈良好发展态势，报告数量
持续增长，已突破32万份，平均百万人口
报告数已达240份。其中，使用单位上报
259,219份，占报告总数的80.6%；生产企业
上报5,352份，占报告总数的1.7%；经营企
业上报56,315份，占报告总数的17.5%；还
有364份报告来自于个人；41.6%的报告涉
Volume VII 2016 9
及Ⅲ类医疗器械， 39.3%的报告涉及Ⅱ类医
疗器械，15.6%的报告涉及Ⅰ类医疗器械。
报告中部分图表如下：
0
50000
100000
150000
200000
250000
300000
350000
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
366 451 1887 6101 1237440940
6030568191
121601
181255
238650265246
321254
05000
100001500020000250003000035000400004500050000
2011 2012 2013 2014 2015
2061023548
34599
41018
47249
图1-1 2002-2015年全国可疑医疗器械不良事件报告数量
Figure 1-1 The number of national suspected medical devices adverse events from 2002 to 2015
图1-3 2011-2015年全国每百万人口平均报告数比较
Figure 1-3 A comparison of the national average number of reports per million from to 2011 to 2015
图1-2 2011-2015年全国死亡及严重伤害可疑不良事件报告数比较
Figure 1-2 A comparison of national numbers of death report and serious suspected adverse events from 2011 to 2015
图1-4 2015年全国医疗器械不良事件监测系统注册基层用户情况
Figure 1-4 The situation of registered users of national medical device adverse event monitoring system at the community level in 2015
0
50
100
150
200
250
2011 2012 2013 2014 2015
82
137
179198
240
96870,48.8%
10344,5.2%
91322,46%
respectively, accounting for 80.6%, 1.7%, 17.5% and 0.2% of the total; 41.6%, 39.3% and 15.6% of the reports are involved with Class III, Class II and Class I medical
devices, respectively.
Some of the Figures in the Report are as follows:
图1-5 2014年和2015年全国注册基层用户分类比较情况
Figure 1-5 Classified comparison of national registered users at the community level in 2014 and 2015
一、全国医疗器械不良事件报告总体情况1. Overview of medical device adverse event reporting
0
20000
40000
60000
80000
100000
120000
User units Distributors Manufacturer
9687091322
10344
90115
75002
9255
20152015 Registration numbers
20142014 Registration numbers
10 CHINA FOOD AND DRUG NEWSLETTER
图2-2 2015年医疗器械不良事件报告事件伤害程度情况
Figure 2-2 Grades of injuries in the medical device adverse event report in 2015
表2-1 2015年医疗器械不良事件报告数量排名前十位的产品类别情况
Table 2-1 2015 Top ten product categories in terms of the number of medical device adverse event reports
排名产品类别
Product Category报告数
Number of reports占总数的百分比
Percentage of total
1 6866医用高分子材料及制品 6866 Medical polymer materials and products 67629 21.05%
2 6851注射穿刺器械 6851 Injection & puncture instruments 41936 13.05%
3 6864医用卫生材料及敷料 6864 Health care materials and dressings 39231 12.21%
4 6826物理治疗设备 6826 Physical therapy equipment 26173 8.15%
5 6846植入材料和人工器官 6846 Implant materials and artificial organs 21307 6.63%
6 6821医用电子仪器设备 6821 Medical electronic equipment and devices 14347 4.47%
7 6820普通诊察器械 6820 Diagnosis & examination equipment 13681 4.26%
8 6854手术室、急救室、诊疗室设备及器具 6854 Equipment and apparatus for operating rooms, emergency rooms and clinics rooms 13003 4.05%
9 6822医用光学器具、仪器及内窥镜设备 6822 Medical optical equipment, instruments and endoscopic equipment 12797 3.98%
10 6840临床检验分析仪器 6840 Clinical laboratory analytical instruments 7440 2.32%
图2-3 2015年医疗器械不良事件报告涉及产品管理类别情况
Figure 2-3 Product category involved in medical device adverse event reporting in 2015
Death, 184Serious injury, 47065
Others, 274005
50213,15.6%
126284,39.3%133548,41.6%
11209,3.5%
Class I Class II Class III Not specified
图2-4 2015年医疗器械不良事件报告涉及实际使用场所情况 Figure 2-4 Actual using places involved in medical device adverse event reporting in 2015
二、2015年医疗器械不良事件报告统计分析2. The statistical analysis of medical device adverse events in 2015
图2-1 2015年医疗器械不良事件报告来源情况
Figure 2-1 Sources of Medical Device Adverse Event Reporting in 2015
Manufacturer5352
Distributors56315
User units259219
Individuals364
Not specified4
232641,72.4%
39632,12.3%
8438,2.6%
40543,12.6% Medical institutionsHomeOthers
Not specified
Volume VII 2016 11
表2-2 报告数量排名前十位的无源医疗器械 Table 2-2 Top ten passive medical devices in terms of number of reports
排名产品名称
Product name报告数
Number of reports占总数的百分比
Percentage of total
1 一次性使用输液器 Disposable infusion sets 36902 11.49%
2 一次性使用无菌注射器 Disposable sterile syringes 20854 6.49%
3 宫内节育器 IUD 15834 4.93%
4 静脉留置针 Indwelling venous needles 11298 3.52%
5 角膜接触镜 Contact lens 9045 2.82%
6 玻璃体温计 Glass thermometer 5676 1.77%
7 导尿包 Urethral catheterization kits 5508 1.71%
8 医用胶带 Medical tape 4341 1.35%
9 普通血压计 Sphygmomanometer 3919 1.22%
10 导尿管 Catheter 3721 1.16%
合计 total 117093 36.45%
表2-3 报告数量排名前十位的有源医疗器械 Table 2-3 Top ten active medical devices in terms of number of reports
排名产品名称
Product name报告数
Number of reports占总数的百分比
Percentage of total
1 病人监护仪 Patient monitor 6827 2.13%
2 输液泵和注射泵 Infusion pumps and syringe pumps 5442 1.69%
3 电子血压计 Electronic sphygmomanometer 2341 0.73%
4 血液透析机 Hemodialysis machine 2125 0.66%
5 心电图机 ECG 1641 0.51%
6 血糖仪 Blood glucose meter 1634 0.51%
7 呼吸机 Ventilator 1234 0.38%
8 电子体温计 Digital thermometer 751 0.23%
9 婴儿培养箱 Infant Incubator 614 0.19%
10 微波治疗机 Microwave therapy unit 609 0.19%
合计 total 23218 7.23%
(May 27, 2016) （2016-05-27）
12 CHINA FOOD AND DRUG NEWSLETTER
China Center for Food and Drug International Exchange (CCFDIE)中国食品药品国际交流中心
Address: Room 1106, 11th Floor, Office Building B, Maples International Center, No. 32, Xizhimen North Street, Haidian District, Beijing, 100082, P.R.C.
中国北京市海淀区西直门北大街32号枫蓝国际中心B座写字楼11层1106室邮编：100082
Tel: 010-8221 2866 Fax: 010-8221 2857Email: [email protected]: www.ccfdie.org
Servier (Tianjin) Pharmaceutical Co., Ltd.施维雅（天津）制药有限公司
Address: 6 Floor, West Building, World Financial Center, No.1, East 3rd Ring Middle Road, Chaoyang District, 100020 Beijing, China
北京市朝阳区东三环中路1号环球金融中心西楼6层 邮政编码：100020
Tel: 010-6561 0341Fax: 010-6561 0348Website: www.servier.com.cn
Notes: • All Chinese information in the Newsletter is extracted from newspapers and the Internet. All English articles are translations from the Chinese version.
• For electronic version of the Newsletter please visit http://www.ccfdie.org 备 注： • Newsletter中所有中文信息摘自报刊及网络。英文均系中文翻译。
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