FDA新藥審批流程簡述(中英文)

1、FDA新藥審批流程 美國的新藥審批可以說是世界上最嚴格和規(guī)范的，作為一個公司通常需要花費5億美元資金，用 12到15年的時間才能將一個新藥從試驗室走入市場。在5000個臨床前化合物中大約只有5個化合物可以進入臨床試驗（Clinical Trials），而這5個化合物中只有一個才能被批準用于臨床治療病人，成為真正的藥物。 從一個實驗室發(fā)現(xiàn)的新化合物發(fā)展成為一個治療疾病的藥物，需要經(jīng)過如下開發(fā)階段：一、 臨床前試驗將一個新發(fā)現(xiàn)的化合物經(jīng)過實驗室和動物試驗，證明該化合物針對特定目標疾病具有生物活性，并且要評估該化合物的安全性。二、 新藥臨床研究申請當一個化合物通過了臨床前試驗后，需要向FDA提交新藥

2、臨床研究申請，以便可以將該化合物應(yīng)用于人體試驗。如果在提交申請后30天內(nèi)FDA沒有駁回申請，那么該新藥臨床研究申請即被視為有效，可以進行人體試驗。新藥臨床研究申請需要提供先前試驗的材料；以及計劃將在什么地方，由誰以及如何進行臨床試驗的說明；新化合物的結(jié)構(gòu)；投藥方式；動物試驗中發(fā)現(xiàn)的所有毒性情況；該化合物的制造生產(chǎn)情況。所有臨床方案必須經(jīng)過機構(gòu)審評委員會（Institutional Revuew Board，IRB）的審查和通過。每年必須向FDA和IRB 匯報一次臨床試驗的進程和結(jié)果。三、 一期臨床試驗這一階段的臨床試驗一般需要征集20100名正常和健康的志愿者進行試驗研究。試驗的主要目的是提供

3、該藥物的安全性資料，包括該藥物的安全劑量范圍。同時也要通過這一階段的臨床試驗獲得其吸收、分布、代謝和排泄以及藥效持續(xù)時間的數(shù)據(jù)和資料。 四、二期臨床試驗 這一期的臨床試驗通常需要征集100500名相關(guān)病人進行試驗。其主要目的是獲得藥物治療有效性資料。五、三期臨床試驗 這一期的臨床試驗通常需 10005000名臨床和住院病人，多在多個醫(yī)學中心進行，在醫(yī)生的嚴格監(jiān)控下，進一步獲得該藥物的有效性資料和鑒定副作用，以及與其他藥物的相互作用關(guān)系。該階段試驗一般采取多中心，安慰劑（或/和有效對照劑）對照和雙盲法試驗。第三期臨床試驗是整個臨床試驗中最主要的一步。 六、新藥申請在完成所有三個階段的臨床試驗并分

4、析所有資料及數(shù)據(jù)，如證明該藥物的安全性和有效性，則可以向 FDA提交新藥申請。新藥申請需要提供所有收集到的科學資料。通常一份新藥申請材料可多達 頁，甚至更多！按照法規(guī)，F(xiàn)DA應(yīng)在6個月內(nèi)審評完新藥申請。但是由于大部分申請材料過多，而且有許多不規(guī)范，因此往往不能在這么短的時間內(nèi)完成。 1999年對于單個化學分子藥的審評時間平均為 12.6個月。 七、批準上市 一旦FDA批準新藥申請后，該藥物即可正式上市銷售，供醫(yī)生和病人選擇。但是還必須定期向FDA呈交有關(guān)資料，包括該藥物的副作用情況和質(zhì)量管理記錄。對于有些藥物FDA還會要求做第四期臨床試驗，以觀測其長期副作用情況。（中國醫(yī)藥市場信息2002第2

5、期16頁） The Food and Drug Administration (FDA) regulates the development of novel drugs. Both prescription and over-the-counter drugs are regulated by the Center for Drug Evaluation and Research (CDER). CDER has been established to ensure that drug products are safe and effective. All new drug product

6、s must undergo a rigorous process of pre-clinical and clinical evaluation. According to a 1999 report from PhRMA, it takes 15 years and $500 million for an experimental drug to travel from the lab bench to the patient. For every 5000 compounds that enter pre-clinical testing, only five will continue

7、 on to clinical trials in humans and only one will be approved for marketing in the United States. After each stage of development, the sponsor of the new product meets with the FDA to determine next steps and establish end points for future trials. Similar processes are required in other countries.

8、 Preclinical Testing. A pharmaceutical or biotechnology company conducts laboratory and animal studies to demonstrate biological activity of the compound against the targeted disease, and the compound is evaluated for safety. Investigational New Drug Application (IND). After completing preclinical t

9、esting, the company files an IND with the FDA to begin to test the drug in humans. The IND becomes effective if the FDA does not disapprove it within 30 days. The IND shows results of previous experiments and studies; how, where and by whom the new studies will be conducted; the chemical structure o

10、f the compound; how it is thought to work in the body; any toxic effects found in the animal studies; and how the compound is manufactured. The IND must be reviewed and approved by the Institutional Review Board (IRB) where the studies will be conducted, and progress reports on clinical trials must

11、be submitted to the FDA at least once annually. Phase I Human Clinical Trials. These tests involve approximately 20 to 80 normal, healthy volunteers. These tests study a drugs safety profile , including the safe dosage range. The studies also analyse how a drug is absorbed, distributed, metabolised

12、and excreted, and the duration of its action. Phase II Human Clinical Trials. Controlled studies of approximately 100 to 300 volunteer patients (people with disease being treated) to assess the drugs effectiveness and further analyse safety. Dose ranges may also be analysed during Phase II studies.

13、More than one Phase II study may be conducted. Phase III Clinical Trials. Approximately 1,000 to 3,000 patients in clinics and hospitals. This phase is used to determine whether the drugs effectiveness is statistically significant. Patients are continuously monitored for safety or adverse reactions.

14、 Typically, more than one Phase III study is conducted. New Drug Application (NDA). Following successful completion of all three phases of human clinical trials, the company analyses all of the data and files an NDA with the FDA if the data successfully demonstrate safety and effectiveness. The NDA

15、must contain all of the scientific information that the company has gathered on the compound. NDAs can exceed 100,000 pages or more. By legislation, the FDA is allowed six months to review an NDA filing. In 2000, the average review time for approved products was 16 months. FDA Panel Review. Once CDE

16、R has reviewed the NDA, the products sponsor presents the data to a panel of experts. The members of the panel may ask for clarification of specific data points, request explanations for certain outcomes or events observed in the trial or pose questions on potential issues that may occur if the product is approved for marketing. The members of the panel then vote in favour of or against recommending marketing