【奥译言】特殊510(k)：对于CDRH提出的扩大试点计划提案，各方反应不一

2018-12-06 10:37 阅读数：3503 标签：

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业界警告称，特殊510(k)计划扩大化提案可能会产生与其预期目标相反的结果，并可能会进一步限制需要进行特殊510(k)审查的变更的资格。

包括赛默飞世尔科技公司（Thermo Fisher Scientific）、库克集团（Cook Group）和费森尤斯卡比（美国）公司（Fresenius Kabi USA）在内的几家医疗器械公司主要担心的是，审查前，机构工作人员为确定提交的特殊510(k)是否将转换为传统510(k)所实施的程序不够明确。

上周五，在美国食品药品监督管理局（FDA）医疗器械和辐射健康中心（CDRH）的特殊510(k)新指南草案的评论中就提到了以上公司所担心的这类问题。CDRH中心于9月发布了指南草案，旨在对特殊510(k)计划进行修改。自2018年10月1日起，向CDRH提交的所有特殊510(k)申请都已在该中心随后为实施扩大提案而启动的试点计划下进行了评估。

针对特殊510(k)，如何确定变更资格的总体政策修改涉及：重点关注变更评估的方式是否完善，能否以汇总方式对数据进行审查。新指南草案还包含一些获得业内支持的政策调整，例如涵盖适应症以及提供转换特殊510(k)的理由。

评论者支持CDRH更新1998年所公布的各项政策的举措，因为与传统510(k)申请相比，特殊510(k)申请可以节省时间和成本。但他们认为，CDRH目前起草的计划扩大框架可能会阻碍更多的项目参与。他们指出，起草的框架和CDRH内部流程缺乏一致性、清晰度和透明度。

所关注的问题

“在一些领域，拟议的提案可能会导致意想不到的后果，并且会对变更某些器械类型加以不必要的限制，使其无法进行特殊510(k)审查，尽管有多种包含明确指标的成熟做法可用于验证变更后的器械与先前获得批准的器械实质等同。“美国先进医疗技术协会（AdvaMed）技术和法规事务副主席Ruey Dempsey表示。评论者建议对CDRH拟议的框架草案进行适当修改，并对相关政策进一步说明，而该行业贸易协会正是众多评论者中的一员。

大多数评论者关注的另一个问题是，需要明确范围内的器械变更，帮助行业和CDRH确定是否适合进行特殊510(k)审查。明确符合条件的器械类型和变更需要向申请人提供更明确的信息, 从而可能会减少转换为传统510(k)的特殊510(k)申请的数量。

据评论者称，在扩大化框架下，对几种常见器械变更的评估方式无从知晓。这类变更包括增加新的适应症、与制造协议偏离以及需要提供生物相容性数据的材料变更。AdvaMed和Deloitte表示，软件和网络相关变更的范围也尚不清楚。

建议

其他问题涉及动物数据、完整试验报告和先前获得FDA认可的修订版自愿共识标准的使用情况。不过，评论者也提出了一些建议，帮助该机构实现扩大计划的预期目的。

Fresenius和Cook呼吁CDRH在特殊510(k)指南草案中对其缩略510(k)计划加以说明。他们指出，CDRH今年早些时候发布的指南草案建议扩大其缩略510(k)计划。该指南草案还引发了行业团体的一些质疑, 即为申请510(k)上市前审查许可的制造商提供更大灵活性的预期好处。

此外，评论者建议在扩大的特殊510(k)计划下实施新的政策和程序，以提高透明度。这些政策包括：如果特殊510(k)转换的理由“有问题”，申请人可以使用一种新的程序，从CDRH获得反馈的“明确机制”，以及与机构工作人员进行“早期咨询的机会”。

成功与否的衡量标准

与此同时，CDRH官员在上个月FDA研讨会上就正在进行的特殊510(k)试点计划透露了部分详细信息。这些官员概述了决定试点计划是否成功的衡量标准。

试点计划能否成功将取决于收到的特殊510(k)的总数和转换为传统510(k)的特殊510(k)的总数。试点计划还将跟踪特殊510(k)被搁置的日期、做出最终决定的原因和做出决定的日期，以及做出决定之前的总时间。

该试点工作可以帮助CDRH确定拟议的新增器械资格是否有助于达到编写510(k)申请资料和进行510(k)审查的预期效率。据CDRH工作人员Angela DeMarco透露, 该试点工作将会一直进行下去，直到有足够的信息来评估其成功与否。

针对特殊510(k)、缩略510(k)和现在的传统510(k)所作出的不懈努力，正是对CDRH在其今年早些时候的三年路线图中所制定的成功与否衡量标准的最好说明，即让50％以上的新型技术制造商率先进入美国，或在进入其他市场的同时进入美国。近期，美国FDA对《医疗器械安全性行动计划》进行了更新，增加了一个关于全球影响力的新目标，进一步说明了这一点。

英文原文

Special 510(k)s: CDRH’s Proposed Program Expansion Draws Mixed Reactions

Industry cautioned the special 510(k) program expansion proposal could yield the opposite of its intended goal and further limit eligibility of changes that undergo special 510(k) reviews.

The main concern among several device companies, including Thermo Fisher Scientific, Cook Group and Fresenius Kabi USA, relates to a lack of clarity around the process used by agency staff to determine whether a submitted special 510(k) will be converted to a traditional 510(k) prior to being reviewed.

The concerns were raised in comments, posted Friday, on the US Food and Drug Administration’s (FDA) Center for Devices and Radiological Health’s new special 510(k) draft guidance. The center released the draft guidance in September to lay out changes to the special 510(k) program. All special 510(k)s submitted to CDRH after 1 October have been evaluated under a pilot the center subsequently launched to operationalize the proposed expansion.

An overarching policy modification in how change eligibility is determined for the purposes of a special 510(k) involves focusing on whether the method to evaluate a change is well-established and data can be reviewed in summary formats. The new draft guidance also includes industry-supported policy changes such as covering indications for use and providing a justification for converting special 510(k)s.

The commenters supported CDRH’s move to update the 1998 policies as the special 510(k) approach can provide time and cost savings compared to traditional 510(k) submissions. But they argued that CDRH’s expansion framework, as currently drafted, may hinder greater program participation. They cited a lack of consistency, clarity and transparency around the drafted framework and CDRH internal processes.

Concerns

“In a few areas, the proposed text may cause unintended consequences and unnecessarily restrict changes in certain device types from being reviewed through a special 510(k), even though there are well-established methods with clearly defined endpoints available to verify that the modified device will be substantially equivalent to the previously cleared device,” said Ruey Dempsey, VP of technology and regulatory affairs at AdvaMed. The industry trade association was among the commenters that recommended several changes to CDRH’s proposed draft framework and additional policy clarifications.

Another concern among most commenters relates to identifying in-scope device changes to aid industry and CDRH in determining whether special 510(k) reviews are appropriate. The argument for clearly identifying eligible device types and changes specifically involves a potential decrease in the number of special 510(k) submissions converted to traditional 510(k)s by providing greater clarity to applicants.

How several common device changes will be considered under the expanded framework remains unclear, according to commenters. These include the addition of new indications for use, deviations to manufacturing protocols and material changes that require biocompatibility data. The scope of software- and cyber-related modifications remains unclear as well, according to AdvaMed and Deloitte.

Recommendations

Other concerns relate to the use of animal data, complete test reports and revised voluntary consensus standards that previously received FDA recognition. The commenters, however, also offered recommendations to aid the agency in achieving the intended purpose of the expanded program.

Fresenius and Cook called on CDRH to address its abbreviated 510(k) program in the special 510(k) draft guidance. They pointed to draft guidance CDRH issued earlier this year to propose an expansion of its abbreviated 510(k) program. This draft guidance also raised questions among industry groups with regard to the intended benefit of providing greater flexibility to manufacturers seeking 510(k) clearance.

In addition, the commenters suggested implementing new policies and procedures under the expanded special 510(k) program to deliver on transparency. These include a new process that can be used by an applicant if a CDRH rationale for special 510(k) conversion is “questionable,” a “defined mechanism” to obtain feedback from CDRH and an “option to have an early consultation meeting" with agency staff.

Measures of Success

Meanwhile, CDRH officials offered some additional details around the ongoing special 510(k) pilot during an FDA workshop last month. They outlined the measures that will dictate the pilot’s success.

Pilot success will be based on total number of special 510(k)s received and the total number of special 510(k)s converted to traditional 510(k)s. The pilot will also track the day a special 510(k) was placed on hold, the reason for the decision and the day on which it was made, as well as total time to decision.

The pilot will serve CDRH in determining whether the proposed device eligibility expansion can help achieve the efficiencies sought in preparing 510(k) submissions and conducting 510(k) reviews. It will run until there is sufficient information to evaluate its success, according to CDRH’s Angela DeMarco.

The efforts around special 510(k)s, abbreviated 510(ks) and now traditional 510(k)s speak to the measure of success CDRH set in its three-year roadmap earlier this year to have upwards of 50% of novel technology manufacturers come to the US first or in parallel with other markets. This was reinforced with a new goal on global impact added via recent updates to FDA’s medical device safety action plan.

内容来自：RAPS

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