中国的FDA旨在通过转向美国临床试验申请流程来加快药物健

StephenW

China's FDA aims to speed drug OKs with shift to U.S.-style clinical trial application process
by Angus Liu | May 15, 2017 10:27am
china
China's FDA is shifting its monitoring of clinical trial sites and processing of clinical trial applications to international standards.

China's FDA is proposing another round of policy changes designed to hasten clinical trial approval and lift restrictions placed on trial sites, with the ultimate goal of allowing drugs to get into the clinic faster.

To foster new trial sites, the agency is backing away from its certification system, which requires any facility that wants to conduct clinical trials to go through a laborious certification process.

And to speed up trial approval—and probably improve the country's position in international clinical studies—the agency is proposing a “no response means approval” mechanism. Akin to the U.S. FDA's trial approach, the new policy would cut the waiting time for researchers starting new studies.  
Clinical trial approval vs. 60 working day response

As part of a series of changes posted online on May 11, the CFDA proposes (Chinese) to change its clinical trial approval system to one similar to the U.S. FDA’s Investigative New Drug (IND) process.

Under current rules, a drug company must wait for the CFDA’s official go-ahead before beginning a clinical trial. The new proposal, however, would give the agency 60 working days to either reject or question a trial application. Otherwise, the application would automatically be considered a go.

Although the time frame is still longer than the U.S. FDA’s 30-day response window, it is a big step forward compared with the previously estimated average of 195 days, according to Helen Chen, managing director and head of life sciences with L.E.K. Consulting’s China branch.

This also marks a conversion toward common guidelines under the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), which are widely followed by developed markets. The change is important given that the agency, just a few weeks ago, proposed a policy change that would allow foreign drugs to be tested in phase 1 in China.

“The key here is that the system now assumes that the applications can go ahead unless rejected, which is different than the requirement for formal approval before,” Chen said in an interview with FierceBiotech.

However, the question is whether the CFDA fully prepared for such a huge speedup. The CFDA pilot-tested a 60-day notification for oncology clinical trial applications, and “presumably the results are sufficiently good to give the agency the comfort to open it up to all,” Chen said.

The staff resources are growing as well. CFDA’s Center for Drug Evaluation (CDE), which is responsible for processing INDs and new drug applications (NDAs), has been on something of a recruiting spree in recent years. For 2016 and 2017 combined, the center has planned more than 400 new hires, the majority of whom are drug evaluation specialists.

Compared with the Center for Drug Evaluation and Research (CDER) in the U.S. and its 5,000-plus reviewers, the Chinese center is quite understaffed with merely 600 drug evaluation specialists, CFDA commissioner Bi Jingquan said in March during the country’s congressional sessions. In 2016, the Chinese center completed processing of applications on 961 new clinical trials, 690 novel drugs and 3,655 new generics.
Clinical trial sites—from certification to registration

Once IND evaluations are accelerated, more drug candidates could enter clinical testing more quickly than before. That means more demand for trial sites, which have been scarce for years. “The number of clinical trial sites has been a bottleneck in China for both innovative and generic drugs,” Chen said.

In a move that seemingly aims to solve that problem, the CFDA also proposes to change its monitoring of clinical trial sites from a certification system to a registration mechanism.

Currently, if an institution in China wants to conduct clinical trials, it needs to be certified by health authorities. Only 822 such organizations, mainly public hospitals, have that certificate. To Chen, that approach has limited the number of trial sites available in China, because the certification process could deter many hospitals that are capable of handling trials—and would very much like to do so.

Under the new proposal, however, new sites would only need to register with the agency. Regulators themselves would shift focus to inspections rather than up-front evaluations. “[This] opens up the system to all qualified facilities and thus is a step in the right direction,” Chen said.

The agency is also encouraging companies and hospitals— both public and private— to establish dedicated trial sites, rather than relying on healthcare treatment facilities at public hospitals. At the same time, foreign companies and research institutes will also be allowed to conduct phase 1 trials in China.

The new rules are likely to boost the supply of phase 1 facilities, Chen said.

The CFDA is also requiring all generic drugs to undergo quality consistency evaluation by the end of 2018, and in another proposal (Chinese) also posted on May 11, it is requiring injectables to go through similar re-evaluations, slated to complete in five to 10 years. Chen said the new facilities could also support those trials.

"While clinical and technical resources are tight, this new field will undoubtedly attract new investments, which will attract resources,” she said.

However, it also remains to be seen whether the Chinese agency, on both the national and local levels, has the manpower to ensure the quality of trial sites and the data they yield. Perhaps the market will help the government out by improving quality up front; after all, bad data or clinical practice, if uncovered by the agency, would only lead to marketing delays and extra costs—not to mention the Chinese government's recent crackdown on faking clinical trial data.
Admission of foreign study data

The CFDA also plans to admit foreign clinical data to support registration of drugs and medical devices in China. “Allowing foreign patient data means that fewer patient samples are needed in China,” said Chen.

Unless otherwise negotiated, CFDA now requires phase 3 trials of at least 200 patients for chemical drugs and 300 patients for biologics. Chen's interpretation is that the new policy would allow data from other countries, generated in international multicenter trials, to be counted toward those CFDA requirements.

For medical devices already approved abroad—unless they're life-supporting products categorized as Type 3, the agency's highest safety level—the CFDA would also allow data supporting foreign approval to be used for the device's Chinese application. “The in-China clinical trial requirement has been contentious for the international med techs, who will clearly benefit from this change,” Chen said.

StephenW

中国的FDA旨在通过转向美国临床试验申请流程来加快药物健康
作者Angus Liu | 2017年5月15日上午10:27
中国
中国FDA正在将临床试验点的监测和临床试验应用的处理转变为国际标准。

中国FDA正在提出另一轮政策变更，旨在加速临床试验审批，提高对试点的限制，最终目标是让药物更快进入诊所。

为了培育新的试验场所，该机构正在退出其认证体系，该体系需要任何想要进行临床试验的设施进行艰苦的认证过程。

并加快审批程序，并可能提高国家在国际临床研究中的地位 - 该机构正在提出“无响应意见审批”机制。类似于美国FDA的试用方法，新政策将减少研究人员开始新研究的等待时间。
临床试验批准与60个工作日的反应

作为在5月11日在线发布的一系列变化的一部分，CFDA建议（中文）将其临床试验审批制度改为类似于美国FDA的调查新药（IND）流程。

根据目前的规定，一家药物公司必须在开始进行临床试验之前等待CFDA官方的预约。然而，新的建议将给予该机构60个工作日拒绝或质疑审判申请。否则，应用程序将被自动考虑。

根据L.E.K.的总经理兼生命科学主管陈海伦表示，虽然时间比美国食品药物管理局30天响应窗口更长，但与之前估计的平均195天相比，这是一大进步。咨询中国分公司。

这也标志着国际医药卫生技术协调理事会（ICH）的共同指导原则得到了转变，这是由发达市场广泛遵循的。这个变化很重要，因为该机构在几个星期前提出了一项政策改变，允许外国毒品在中国的第一阶段进行测试。

“这里的关键是，系统现在假设应用程序可以继续进行，除非被拒绝，这与正式批准的要求不同，”Chen在接受FierceBiotech采访时说。

不过，问题是CFDA是否充分准备了如此巨大的加速。 CFDA试点测试了60天的肿瘤临床试验申请通知书，“据推测，结果足够好，给予该机构一切安慰，”陈说。

员工资源也在增长。 CFDA负责处理IND和新药申请的药物评估中心（CDE）近年来一直在招聘。在2016和2017年合并后，该中心计划了400多名新员工，其中大多数是药物评估专家。

与美国药物评估和研究中心（CDER）及其5,000多名审评人员相比，中国中心的人员不足，只有600名药物评估专家，CFDA专员Bi Jingquan在3月份在国会期间表示。 2016年，中国中心完成了961项新临床试验，690种新药和3,655种新型仿制药的应用处理。
临床试验网站 - 从认证到注册

一旦IND评估加速，更多的候选药物可以比以前更快地进入临床检测。这意味着更多的需求多年来一直很少的试验场。 “临床试验场的数量一直是中国创新型和仿制药的瓶颈，”陈说。

此外，CFDA也提出将临床试验点的监测从认证制度改为注册机制。

目前，如果中国的一个机构想进行临床试验，需要得到卫生部门的认证。只有822个这样的组织，主要是公立医院，有这样的证书。对于陈，这种方法限制了在中国的试点数量，因为认证过程可能会阻止许多能够处理审判的医院，而且非常希望这样做。

但是，根据新提案，新的网站只需要向该机构注册。监管机构本身将重点转移到检查，而不是前期评估。 “这将为所有合格的设施开放系统，是朝正确方向迈出的一步。

该机构还鼓励公共和私人公司和医院建立专门的试验场，而不是依靠公立医院的医疗保健设施。同时，外国公司和研究机构也将被允许在中国进行第一阶段的审判。

陈水扁说，新规定有可能推动第一阶段的供应。

CFDA还要求所有仿制药在2018年底之前进行质量一致性评估，另外在5月11日发布的另一项提案（中文）中，要求注射剂进行类似的重新评估，预计将在五个月内完成10年。陈仪说，这些新设施也可以支持这些试验。

“临床技术资源紧张，这个新领域无疑将吸引新的投资，吸引资源，”她说。

不过，中国国家和地方一级机构是否有人力资源来确保试点的质量和数据。也许市场会通过提高质量来帮助政府;毕竟，不良数据或临床实践，如果机构发现，只会导致营销延误和额外的成本 - 更不要说中国政府最近打击伪造临床试验数据。
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CFDA还计划接受国外临床资料，支持在中国注册药品和医疗器械。 “允许外国患者数据意味着中国需要的病人样本较少，”陈说。

除非另有谈判，CFDA现在需要至少200名化学药物患者和300名生物制剂患者进行III期试验。陈先生的解释是，新政策将允许国际多中心试验中产生的其他国家的数据计入这些CFDA要求。

对于已经在国外批准的医疗器械，除非是生命支持的产品，分类为第3类，该机构的最高安全级别 - CFDA还将允许支持外国批准的数据用于该设备的中文应用。陈先生说：“中国的临床试验要求对国际医药技术人员来说是有争议的，他们将从这一变化中获益。”

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