SFDA Review/Approval Process Chen Xiaoyuan, CDE, SFDA, 2008 * SFDA/CDE Workload Dong Lu and Wenlong Huang, Overview of drug evaluation system in China, 2010 * New Drug Application: FDA vs. SFDA * Dale Chenoweth , DDT. Volume 10, Number 17, September 2005 SFDA Progress: Review Timeline Application Type Timeline (Day) New Drug Clinical Trial 90 New Drug Manufacture 150 Change of Formulation 160 Generic Drug 160 Supplement 40 Import Re-registration 80 * 美国FDA 与中国药监局US FDA History: 100 year Budget: $3.2 billion (2010) Employees: as of Oct. 1, 2009 CBER 946 CDER 2,889 Total 11,516 Application approvals: 	IND: 2577 (2009) 		investigational, treatment, 	exploratory 	NDA: 131 		505(b)(1); 505(b)(2) 	ANDA: 599 		505(j) Chinese SFDA History: 8 years (SDA) Budget: RMB 707M (2010) Employees: as of Dec. 31, 2009 	CDE 120 	Total 47,472 Application approvals: 	New Drugs: 		CTA: 298; NDA: 164 	Generic Drug: 		CTA: 196; ANDA: 1623 	Import Drug: 		CTA: 320; NDA: 489 	Supplement: 		SFDA: 2492; PFDA: 8537 * 相关指导原则US FDA Advertising 3 (6 draft) Chemistry 31 (draft 12) Clinical Medical 47 (draft 29) Clinical Pharmacology 8 (draft 4) Combination Products 1 (drat 2) Current GMP/Compliance 29 (draft 12) Drug Safety 2 (draft 2) Electronic Submissions 7 (draft 7) Generic Drug 17 (draft 3) Good Review Practices 3 Pharmacology/Toxicology 14 (draft 6) ICH –Efficacy 22 (6) ICH - Joint Safety/Efficacy 10 (2) ICH - Quality 33 (9) ICH - Safety 15 (3) Chinese SFDA Chemical drugs: 32 TCM/Natural drugs: 14 Biologics: 26 Scientific review writing: 6 Review principles 6 Technical standards 13 US FDA Guidance Translation: CMC: 12 clinical pharmacology: 15 Clinical: 64 GRP: 2 Procedure: 3 * 阳性药选择FDA 对于仿制药所使用的参比制剂都有着硬性的规定。FDA 在其处方药及非处方药的目录中都规定了参比的药品产品。以此来避免由于参比制剂使用的不同而可能导致的各仿制品之间发生显著的差异。SFDA 申请注册分类6 的药品，应根据品种的工艺、处方进行全面的质量研究，按国家标准与已上市产品进行质量对比研究。无法按照国家标准与已上市产品进行质量对比研究的，应按照新药的要求进行质量研究，必要时对国家药品标准项目进行增订和/ 或修订。* BIOSIMILARS Patient Protection and Affordable Care Act (PPACA) of 2010 created a pathway for regulation and approval of: –Biosimilar biological products –Interchangeable biological products Have chartered internal committees to collaborate on policy issues and address product specific review and science Part 15 Hearing on November 1st & 2nd Many challenges: Definition of protein, Transition provisions, Standards For interchangeability, Standards for naming, “Publicly‐Available Information”化药与生物药各国医疗改革, 鼓励仿制药发展今后几年有数百亿美元的专利药专利将到期熟悉美国现行仿制药管理的法律法规以及申报的程序应用质量源于设计药物研发理念，改进生产和分析技术，提高质量准备高质量的申报材料，申报并争取获得FDA 的批准。中国仿制药的机会* Regulatory Authorities FDA SFDA EMEA …Industries Pfizer Sanofi-Aventis GSK Merck …Win –Win –Win Public Bring safe and effective drugs to patients quickly and cheaply Questions? Visit us at www.joinnlaboratories.com or contact me at john.gong@joinnlaboratories.com * 日程安排表1 月15 日（星期六）08:30-11:30 	 仿制药研发趋势及中美仿制药申报注册要求对比1 月15 日（星期六）14:00-17:00 	 新药制剂与仿制药物研发药理毒理研究的技术要求与问题1 月16 日（星期日）08:30-11:30 	 《药品注册管理办法》对仿制药和改剂型品种的技术评价要求1 月16 日（星期日）14:00-17:00 	 仿制药品质量研究及稳定性研究的技术要求1 月17 日（星期一）08:30-11:30 	 1 、生物等效性实验设计2 、药物杂质研究基本思路及控制方法1 月17 日（星期一）14:00-17:00 	 药品制剂专利保护与仿制药开发中规避专利侵权* * Much of FDA’s review of generic drugs and brand-name drugs is the same. There are 8 major parts to the FDA’s review of a generic drug company’s application to sell a generic drug. We will go over each of these 8 parts now. * ·The generic must have the same active ingredients and the same labeled strength as the drug of which it is a copy, also called the “referenced drug.”In the United States, trademark laws do not allow a generic drug to look exactly like the brand-name drug. The shape or color may be different, and colorings, flavors, and certain other inactive ingredients may be different. ·The generic drug must have the same dosage form. Tablets, capsules, patches and liquids are examples of different dosage forms. ·The generic drug must be administered the same way, for example, swallowed as a pill, or injected as a shot, rubbed on the skin, as the drug it copies. (also could be said “to the drug to which it is referenced.”* Rather than repeating very costly research, the generic drug companies instead must show the FDA that their drug is “bioequivalent”to the brand-name drug. When a drug is “bioequivalent”to another, it means that its active ingredient works in the same way and in the same amount of time as the brand-name drug. (The generic version must deliver the same amount of active ingredient into a patient’s bloodstream in the same amount of time as the brand-name drug.) Scientists measure a generic drug’s “bioavailability,”or the amount of the generic drug in the bloodstream and how long it takes to get there. Then they compare that measurement to the brand-name drug. When drug companies develop a new drug, they submit full “new drug applications”or NDAs. Generic drug companies submit what are known as “abbreviated new drug applications”or ANDAs. * The generic drug’s labeling must be basically the same as that of the The generic drug’s labeling must be basically the same as that of the approved brand-name drug. * The drug company must: ·fully document the generic drug’s chemistry, manufacturing steps, and quality control measures ·detail each step of the process for FDA review * The drug company must ensure FDA that the raw materials for the generic drug and the finished generic drug meet USP specifications, if these have been set. The USP, or U.S. Pharmacopeia, is a non-profit, scientific organization, chartered by Congress, to set standards for drug purity in this country. * The drug company must show that its generic drug will remain potent (strong, stable) and unchanged until the expiration date on the label before it can be sold. Once the generic drug is on the market and being sold, the drug company must continue to monitor the drug’s stability. * Drug companies that manufacture generic or brand name drugs must comply with federal regulations for good manufacturing practices and provide the FDA a full description of facilities they use to manufacture, process, test, package, label, and control the drug. * Before FDA approves a generic drug, it usually conducts an inspection at the proposed manufacturing site to make sure the firm is capable of meeting its application commitments and to ensure the firm can manufacture the product consistently. Generic Drug Review The generic drug’s labeling must be basically the same as that of the approved brand-name drug. Generic Drug Review 4.	The drug company must: fully document the generic drug’s chemistry, manufacturing steps, and quality control measures detail each step of the process Generic Drug Review 5.	The raw materials and the finished 	product must meet USP specifications, 	if these have been set. 	USP-United States Pharmacopeia Generic Drug Review The drug company must: show that its generic drug maintains stability as labeled before it can be sold continue to monitor drug’s stability Generic Drug Review The drug company must: comply with federal regulations for current good manufacturing practices give a full description of the facilities it uses to manufacture, process, test, package, label, and control the drug Generic Drug Review 8.	Inspection at the proposed manufacturing site ensures that the firm: is capable of meeting commitments of the application can manufacture the product consistently * 问卷式评审- FDA 仿制药评审模式问卷式评审模式（Question-based-Review ，QbR ）1) 在于帮助仿制药评审部门有效地评估制剂的关键属性，有效控制配方，生产工艺及参数，并建立与临床疗效相关的产品质量标准，准备完整统一的评审报告。2) 帮助制药企业了解仿制药评审部门的评审标准和程序。3) 指导制药企业把药品质