SO 13485: 2016的三年过渡期于上周四（2月28日）正式结束。自3月1日起，所有的ISO 13485: 2003证书均已无效，无论其原有效期是什么时候。修订后的ISO 13485: 2016标准在全球旨在实现国际协调的重大监管举措中发挥着重要作用。

由国际标准化组织（ISO）制定的这份全球共识标准的两个版本（即2003版和2016版）直到上周四之前一直处于共存状态。

负责ISO 13485修订的技术委员会秘书Wil Vargas在接受Focus的采访时指出，这是13年来首次需要通过修订版来纳入大多数医疗器械制造商已经开始实施的工作。Vargas认为过渡期非常重要，尤其是对国际器械公司而言，因为并不是所有器械都属于这一类。

Vargas表示，"目前针对ISO 13485有很多事情要做。"他指出，好几个国家有了新的监管要求，及其在不断完善的审核程序中所扮演的角色。

2016修订版的ISO 13485更关注整个供应链中的质量管理体系（QMS），旨在阐述医疗器械的产品全生命周期，当然，这只是相比2003版所存在的变化之一。关于对制造商有哪些影响，则会因其医疗器械经营和销售的司法管辖区而异。

▍澳大利亚、加拿大、欧盟、美国

澳大利亚药品管理局（TGA）于上周五（3月1日）发布通知，解释说明了需要通过ISO 13485符合性来证明其符合澳大利亚符合性评定程序的质量管理体系要求的制造商所面临的新情况。从1月初到3月1日，所有针对2016版的TGA审核都已开始进行，并提交可以证明制造商已经实施了符合ISO 13485: 2016规定的质量管理体系的相关证据，以便为符合性评定申请提供支持。

同样，加拿大卫生部（Health Canada）也在3月1日前完成了向修订版13485标准的过渡，成为所有II类、III类和IV类医疗器械制造商必须符合的强制性要求。自去年12月以来，加拿大卫生部已不再认可加拿大医疗器械符合性评定体系（CMDCAS）证书。

在此之前，加拿大市场的医疗器械制造商一度面临时间紧迫的压力，因为当时加拿大卫生部要求他们向医疗器械单一审核程序（MDSAP）过渡，并在1月1日之前向该监管机构提交有效的MDSAP证书。

来自NSF International的Kim Trautman告诉Focus：“鉴于加拿大卫生部先前要求其在2019年1月1日前过渡到MDSAP（有一些延期规定），向ISO 13485: 2016过渡的过程相对来说比较平稳”。她指出，2016年加拿大卫生部关于要求向MDSAP过渡的决定也提及了关于要求向13485过渡的事宜。她说：“加拿大卫生部的这个决定目的性很强，允许制造商将两种过渡结合起来实施，并适当制定战略。”

自2017年以来，欧盟一直在进行监管改革。根据MDR和IVDR的相关要求，本月开始实施修订版ISO 13485: 2016，但MDR和IVDR直到2020年和2022年才会完全施行。“因此，ISO 13485: 2016的过渡期也是至关重要的，因为“并非所有国家都有三年的时间来做尽可能多的工作，毕竟审核机构和公告机构都有一大堆工作要做，包括继续实施欧盟医疗器械指令，并为MDR做好准备，”Trautman说。她认为，由于与其他过渡（如MDSAP和MDR/IVDR）相一致，向ISO 13485的过渡进展颇为顺利。

美国FDA并未要求在美国经营和销售的医疗器械制造商遵守ISO 13485: 2016的规定。但是那些还没有考虑新版ISO 13485的医疗器械制造商不得不考虑一点：那就是国际协调的趋势是如何在最近几年“逐渐升温”的。MDSAP正好体现了这一发展势头，因为越来越多的企业通过单一审核程序来满足多个监管管辖区域的要求，达到减轻负担的目的。

▍国际协调

与此同时，FDA一直致力于将现行的质量体系法规（美国21 CFR Part 820）与ISO 13485：2016相结合。此外，FDA去年就这些计划进行了讨论，并确定其行动日期为2019年4月。FDA打算采用MDSAP程序。

FDA表示：“这些修订旨在通过协调国内和国际要求，减轻医疗器械制造商的合规性和记录保存负担。”这与FDA通过采纳国际医疗器械监管机构论坛（IMDRF）的MDSAP等程序，加强全球协调，从而减少监管方面的负担所采取的一系列措施正好相吻合。美国FDA、加拿大卫生部、澳大利亚TGA以及欧盟委员会都是IMDRF管理委员会的成员，除此之外，IMDRF还包含其他六个全球监管机构。

FDA尚未具体说明其打算如何对该法规展开审查，尽管FDA已通过与美国医疗仪器促进协会（AAMI）合作，共同制定了AAMI技术信息报告（TIR）。那些已经完成向ISO 13485: 2016过渡的医疗器械制造商将会更好地适应FDA的举措。

“就现行版本的21 CFR Part 820 (QSR 820)而言，其大约90％的条款已经与2016版的ISO 13485保持一致，所以过度将不是什么大问题，”同时还担任AMMI标准主任的Vargas说。Trautman也认同这一点，她在加入NSF之前曾担任FDA官员，编写了现行版本的QSR 820。

Trautman告诉Focus，在她编写当前版本的QSR 820或任何其他国际行业特定标准时，还没有可以用来参考的ISO 13485。她说，ISO 13485标准自上世纪90年代建立以来，每一个版本都使得监管趋同越来越明显。Trautman补充道，这种趋同不仅蔓延至FDA和ISO 13485，还蔓延至巴西、日本、欧洲以及其他几个国家。

她认为制造商不应该担心FDA的举措。Trautman还说:“FDA将会继续采取适当措施，并朝着这一趋同迈进，其意图无疑是正确的。事实上，FDA通过纳入ISO 13485的一些内容，使QSR 820更加完善。”风险管理以及将纠正措施与预防措施彼此分开就是其中的一些例子。

Vargas说，AAMI目前正致力于编制技术信息报告，以在FDA的21 CFR Part 820和2016修订版ISO 13485标准之间建立连接。Vargas表示，这项工作涉及将ISO 13485与现行法规进行比较，反之亦然，技术信息报告将作为一份过渡文件，帮助业界完成这一过渡。AAMI计划在未来几个月公布该技术信息报告。

▍ISO高级结构（HLS）修订

据Focus报道，将对ISO 13485: 2016进行修订，以符合ISO高级结构（HLS）。此次修订旨在反映HLS术语和定义，包括风险术语和定义。Vargas指出，TC 210 WG 1（负责ISO 13485的工作小组）即将就HLS修订方向做出决定。

针对HLS对ISO 13485进行修订预计会产生连锁反应。Vargas认为，最显著的问题可能涉及对FDA举措的影响，因为更改ISO 13485: 2016中定义的核心原则（如风险方面）可能会对ISO 13485: 2016标准文件的布局和理解方式产生巨大影响。

然而，该举措得到了广泛支持，包括AAMI的支持。“如果FDA决定完全按照ISO 13485: 2016执行，将会是全球协调方面史无前例的一步，”Vargas说。从某种意义上来说，这将在今年夏天引起巨大的轰动。

另一个连锁反应与ISO 13485: 2016标准在MDSAP中所起到的基础作用有关。自2017年初对MDSAP审核模式以及修订版ISO 13485: 2016的审核模式相关文件完成修订以来，MDSAP程序采用了ISO 13485。

Trautman指出：“MDSAP审核涉及很多工作内容，不仅是ISO 13485方面，事实上也不仅仅是质量管理体系方面。”但很明显，这是一项基础性工作。因此，从ISO 13485到加拿大卫生部（关于要求向MDSAP过渡）决定的过渡似乎再自然不过了。”

英文原文

Transition to ISO 13485:2016 Comes to an End

Published: Mar 01, 2019

The three-year transition period for ISO 13485:2016 officially ended Thursday and as of Friday all ISO 13485:2003 certificates are now null and void, regardless of their original expiration date. The role of the revised standard plays into major regulatory initiatives worldwide aimed at international harmonization.

Both the 2003 and the 2016 version of the global consensus standard—developed by the International Organization for Standardization (ISO—co-existed until Thursday.

Wil Vargas, secretary of the technical committee responsible for the 13485 revision, noted in an interview with Focus that the revision was needed for the first time in 13 years to incorporate work that most medical device manufacturers were already implementing. Vargas argued the transition period was important, particularly for international device companies, as not all fell into this category.

“There is a lot going on with 13485 these days,” Vargas said, noting the new regulatory requirements in several different countries and its role in a growing audit program.

The 2016 revision for 13485 placed more emphasis on quality management systems (QMS) across the entire supply chain and is intended to address the total product lifecycle of medical devices, among other changes to the previous edition. Implications for manufacturers differ depending on the jurisdiction in which they seek to operate and market medical devices.

▍Australia, Canada, EU, US

Australia’s Therapeutic Goods Administration (TGA) posted a notice on Friday to explain the new situation facing manufacturers that rely on 13485 compliance to demonstrate conformity with the QMS requirements of Australia’s conformity assessment procedures. All TGA audits began being conducted against the 2016 edition at the beginning of January and from Friday, submitting evidence that a 13485:2016-compliant QMS has been implemented is required to support conformity assessment applications.

Similarly, Health Canada set transitioning to the revised standard by 1 March as mandatory for all manufacturers of class II, III and IV medical devices. And it has not accepted Canadian Medical Devices Conformity Assessment System certificates since last December. This came after medical device manufacturers in the Canada market faced an aggressive timeline when Health Canada required them to transition into the Medical Device Single Audit Program (MDSAP) and submit valid MDSAP certificates to the regulator no later than 1 January.

“With the Health Canada required transition to MDSAP as of 1 January 2019 (with some provisions for extensions), the transition to ISO 13485:2016 has been a relatively smooth one,” NSF International’s Kim Trautman told Focus. She noted that the decision Health Canada reported in 2016 on the required MDSAP transition also informed of the required 13485 transition. This was a purposeful decision of the regulator to allow manufacturers to combine the transitions and “appropriately strategize,” she said.

The EU has been undertaking a regulatory overhaul since 2017. The medical device regulation (MDR) and in vitro diagnostic regulation (IVDR) began requiring adherence to the revised 13485:2016 this month, though MDR and IVDR will not come into full effect until 2020 and 2022. The transition period for 13485:2016 was thus also critical since “not all had three years to get done as much as possible because auditing organizations and Notified Bodies have a whole bunch on their plate to include the continuation of the EU device directives and getting prepared for MDR,” Trautman said. She argued the 13485 transitions seem to be going well due to alignment with others, such as MDSAP and MDR/IVDR.

Compliance with 13485:2016 is not a US Food and Drug Administration (FDA) requirement for medical device manufacturers to operate and market within the US. But those that have yet to mind the new edition should consider how the trend toward international harmonization has picked up steam in recent years. MDSAP demonstrates the momentum as a growing body of device firms seek relief by meeting requirements across several jurisdictions.

▍Global Harmonization

FDA, meanwhile, has been working on a blend of the current Quality System regulation and 13485:2016. It discussed these plans last year, with a set action date of April 2019. FDA intends to leverage MDSAP.

“The revisions are intended to reduce compliance and recordkeeping burdens on device manufacturers by harmonizing domestic and international requirements,” FDA said. This is in line with FDA efforts around reduced regulatory-related burden via greater global harmonization using programs such as MDSAP—a cornerstone of the International Medical Device Regulators Forum (IMDRF). FDA, Health Canada, TGA and the European Commission all form part of the IMDRF management committee along with six other global regulators.

FDA has yet to specify how it intends to review the regulation, though it tapped the Association for the Advancement of Medical Instrumentation (AAMI) to jointly develop an AAMI technical information report (TIR). Those that transitioned to 13485:2016 will be better positioned with FDA’s initiative.

“If they are already aligned with the 2016 version, they are about 90% there and it's really not a big deal,” said Vargas, who also serves as the AMMI standards director. This was echoed by Trautman, who authored the current version of 21 CFR Part 820 while she served as an FDA official prior to joining NSF.

Trautman told Focus that there was no 13485 when she wrote the current version of 820 or any other international sector-specific standard to rely on. Each version of the standard since its inception in the 1990s has brought greater regulatory convergence, she said. Trautman added that the convergence spread not just with FDA and 13485, but also with Brazil, Japan, Europe, among several other nations.

She argued that manufacturers should not be worried about FDA’s initiative. "FDA has the right intention to continue to strive and move towards that convergence and in fact it makes 820 better by incorporating some of the things that 13485 was able to add in overtime,” Trautman said. Risk management and the separation between corrective action and preventive action are some examples.

AAMI is currently focused on developing the TIR to connect the dots between FDA’s 21 CFR Part 820 and the current 2016 edition of the standard 13485, Vargas said. The work involves comparing 13485 against the existing regulations and vice versa for the TIR to serve as a transitional document to aid industry with the shift, according to Vargas. AAMI intends to publish this TIR in the coming months.

▍HLS Revisions

ISO 13485:2016 is set to undergo revisions to conform with the ISO High Level Structure (HLS), as reported by Focus. This is to reflect HLS terms and definitions, including that of risk. Vargas noted TC 210 WG 1—the working group responsible for 13485—is nearing a decision on the direction of the HLS revisions.

Revising 13485 against HLS is expected to have ripple effects. Vargas argued the most notable issue could potentially involve the impact on FDA’s initiative because changing how core principles, such as risk, are defined in 13485:2016 could have “a real dramatic impact to the way that the document is laid out and understood.”

Yet the initiative has received widespread support, including AAMI’s.

“If FDA decides to go completely with 13485:2016, that will be an unprecedented step for global harmonization,” Vargas argued. “That would be the amazing smash hit of the summer in the sense that it opens the floor for other things to come forward because that paved the way and made it that much easier.”

Another ripple effect relates to the standard’s foundational role n MDSAP. MDSAP programs have used 13485 since the early 2017 revised MDSAP audit model and the audit model companion document for the revised 13485:2016.

“There is a lot more to an MDSAP audit that just 13485 and in fact more than just QMS,” Trautman noted. “But clearly it is a foundational piece. So the transition between 13485 and Health Canada's decision [on the required transition into MDSAP] seemed to be a natural one.”