美国FDA新药审批速度和数量均超加拿大和欧洲

耶鲁大学的Nicholas Downing及其同事开展的一项调查研究显示，2001~2010年期间，与加拿大和欧洲的药监机构相比，美国食品药物管理局(FDA)审查新药申请的速度更快、数量更大。这篇报告发表在5月16日出版的《新英格兰医学杂志》上(N. Engl. J. Med. 2012 May 16 [doi:10.1056/NEJMsa1200223])。
Downing及其同事利用FDA、欧洲药品管理局(EMA)和加拿大卫生部(HC)公布的2001~2010年数据，对新处方药和生物制剂的审查速度进行了比较。研究者排除了新配方药物和复方药物。在本次研究之前，几乎没有关于FDA审查新药申请所需时间、以及与其他国家药监机构比较的客观数据。
结果显示，在这10年期间，共有510次新药申请获得批准，其中FDA批准了225次，而EMA和HC分别批准了186次和99次申请。其中共涉及289种独特的新治疗药物，包括72种在上述3家药监机构均获得批准的新药。3家机构在审查的治疗药物种类上和是否采取优先审查方面没有明显差异，唯一的例外是：EMA批准的孤儿药所占比例明显高于FDA(28% vs. 17%)。在这289种新药中，190种在美国和欧洲均获得批准。其中，121种(64%)首先被FDA批准。在154种美国和加拿大均批准的新药中，132种(86%)首先在美国获准。
多数新药在1个审查周期内即获准，但这一比例在EMA最高(96%)，而FDA和HC分别为62%和 69%。完成首次审查的中位时间(从提交申请到药监机构通知申请者其决定的间隔天数)，FDA为303天，EMA为366天，HC为352天，3家机构之间均有统计学差异。在72种3家机构均批准的新药中，FDA完成首次审查的中位时间比另2家机构缩短约100天：FDA为254天，EMA为356天，HC为346天。
作者称，上述调查结果带来了一个问题：在新的《处方药使用者费用法》(PDUFA)中进一步加快审批流程是否合理？1992年PDUFA获得通过使得FDA拥有了向提出新药申请的公司收费的权利；这笔费用被用来加速审查流程，包括雇用额外的员工。这部法案每5年重新授权1次，今年将再次重新授权(PDUFA V)。今年，FDA已与制药行业共同商议如何使新药和生物制剂审查流程变得更加高效，以及如何增加单个审查周期中批准的药物种数。研究者认为，这可被视为FDA对“以牺牲及时审批的代价换取安全性”批评的回应。但该研究结果却与上述批评相矛盾，因为FDA的新药审查速度和数量仍然超过欧洲和加拿大的同行。
这项研究获得了Pew慈善信托基金的支持。作者报告称无相关利益冲突。


BY ELIZABETH MECHCATIE
Elsevier Global Medical News
Breaking News
The U.S. Food and Drug Administration reviewed new drug applications significantly faster, and approved more new drugs first, than did its European and Canadian counterparts between 2001 and 2010.
These and other findings of practices at the three agencies raise question about whether speeding the review process further in the renewal of the Prescription Drug User Fee Act (PDUFA) is justified, according to Nicholas Downing, of Yale University, New Haven, Connecticut, and his associates. The findings were published May 16 in the New England Journal of Medicine.
Passed in 1992, PDUFA authorizes the FDA to collect fees from companies for each new drug application filed; the fees are used to speed of the review process, which includes hiring extra staff members. The law is reauthorized every 5 years, including this year (PDUFA V).
Previous renewals have identified areas of specific emphasis, such as drug safety and postmarketing surveillance (in 2007). This year, the FDA has worked with the pharmaceutical industry on how to make the new drug and biologic approval process more effective and efficient, and how to increase the number of agents approved in a single review cycle. The emphasis reflects “a response to criticism that the FDA has focused on safety at the expense of timely reviews,” the researchers noted.
But their findings “contradict recent criticisms of the speed of review by the FDA and lead to question about whether the speed of the review process is justified as an emphasis for PDUFA V, particularly since the FDA continues to outpace its European and Canadian peers.”
Mr. Downing and his colleagues used publicly available information from the FDA, the European Medicines Agency (EMA) and Health Canada for 2001-2010 to compare the speed of review of new prescription drugs and biologics; they excluded reformulated drugs and combination drugs (N. Engl. J. Med. 2012 May 16 [doi:10.1056/NEJMsa1200223]).
Until their review, little objective information has been available regarding the time it takes the FDA to review applications for new therapeutic agents, and how that review time compares with those of agencies in other countries, they noted.
Of the 510 applications for new drugs that were approved during this time, 225 were approved by the FDA, 186 by the EMA, and 99 by Health Canada. Of these drugs, 289 were considered unique new therapeutic agents, including 72 that were approved by all three agencies.
There were no significant differences in the therapeutic drug class reviewed or whether a priority review was used between the three agencies, with one exception: the proportion of orphan products approved by the EMA was significantly higher than that of the FDA (28% vs. almost 17%).
Of the 289 new agents, 190 were approved in the United States and in Europe. Of these, 121 64%) were approved in the United States first. Of the 154 that were approved in the United States and in Canada, 132 (86%) were first approved in the United States.
Most of the new agents were approved within a single cycle, but the rate was highest at the EMA (96%) compared with 62% at the FDA and 69% at Health Canada.
The median time to complete the first review (the number of days from the time the application was submitted to the date the agency notified the applicant of its decision) was 303 days for FDA-approved applications, 366 days for the EMA, and 352 days for Health Canada – a statistically significant difference across the agencies.
For the 72 new agents approved by all three agencies, the median time of the first review was about 100 days faster at the FDA: 254 days, compared with a median of 356 days at the EMA and 346 days at Health Canada.
The study was supported by the Pew Charitable Trusts. The authors disclosed no relevant conflicts of interest.