ZUSAMMENFASSUNG DER WESENTLICHEN PUNKTE DURCH EMERGO by UL:

• Die MHRA wird für den britischen Markt zuständig sein;
• Die CE-Kennzeichnung bleibt im Vereinigten Königreich weiterhin gültig und bisher sind keine Kennzeichnungsänderungen vorgesehen;
• Die MDR und IVDR werden im Vereinigten Königreich zur gleichen Zeit wie in der EU inkraft treten
• Hersteller außerhalb des VK, die ihre Produkte im Vereinigten Königreich auf den Markt bringen möchten, müssen eine verantwortliche Person für das VK ernennen. Diese übernimmt eine ähnliche Rolle wie ein EU-Bevollmächtigter.
• Diese im VK ansässige verantwortliche Person oder der im VK ansässige Hersteller müssen das Produkt im VK registrieren.

Die MHRA veröffentlichte am 3. Januar 2019 Richtlinien für den Fall eines No-Deal-Brexits. Falls keine Einigung erzielt wird, kann das Vereinigte Königreich beschließen, die EU ohne eine Abmachung zu verlassen. Es wird dann aus Sicht der EU ein Drittstaat. Importe aus Drittstaaten unterliegen den EU-Regeln, allerdings existieren solche Regeln für den Warenaustausch zwischen der EU und dem VK derzeit noch nicht. Dies gilt auch für Hersteller außerhalb der EU, die ihre Produkte im VK verkaufen möchten. Die Richtlinien der MHRA finden Anklang, wenn auch die Vorbereitungszeit kurz ist.

Dieses Dokument enthält eine Erklärung der Rechtslage, ist aber selbst nicht rechtsverbindlich. Die Folgerungen daraus sollten daher mit Vorsicht umgesetzt werden. Bei Unklarheiten ist die MHRA der beste Ansprechpartner. Fragen können dazu führen, dass möglicherweise weitere Richtlinien veröffentlicht werden.

Einführung von Produkten auf dem Markt im VK

Damit sie Produkte auf dem Markt im VK zulassen kann, wird die MHRA für die Medizinprodukteaufsicht im VK zuständig sein. Für die Produkte wird weiterhin eine CE-Kennzeichnung erforderlich sein und die MDR und IVDR werden im VK genau wie in der EU umgesetzt werden. Die Aktivitäten zur Marktüberwachung werden von der MRHA durchgeführt, sie gehören aber nicht mehr zum EU-System der Marktüberwachung und folgen auch nicht automatisch Entscheidungen des Europäischen Gerichtshof. Zwischen den Märkten im VK und in der EU wird es daher möglicherweise einige Abweichungen geben.

Ein weiterer Unterschied ergibt sich aus den Benannten Stellen im VK. Ab dem Tag des Brexits werden diese Benannten Stellen in den EU-27 nicht mehr anerkannt und damit werden auch ihre Zertifikate ungültig. Die MHRA wird diese Zertifikate allerdings bis auf Weiteres anerkennen. Hersteller, die von einer Benannten Stelle im VK zu einer Benannten Stelle in den EU-27 wechseln, können ihre Produkte außerdem weiterhin im VK verkaufen, da ihre CE-Kennzeichnung in der EU weiterhin Gültigkeit hat.

Fristen für die Registrierung bei der MHRA

Hersteller außerhalb des VK (EU oder nicht EU) müssen eine verantwortliche Person im VK (UK REP) ernennen, die im VK ansässig ist. Die Rolle und die Aufgaben des UK REP sind ähnlich denen des EU-Bevollmächtigten. Bis auf Weiteres muss auf der Produktkennzeichnung keine verantwortliche Person im VK angegeben sein. Hersteller im VK oder deren verantwortliche Person im VK müssen die Produkte bei der MHRA registrieren. Bei der Registrierung gelten diese Fristen:

• innerhalb von vier Monaten nach dem Brexit für Produkte der Klasse III, implantierbare Produkte der Klasse IIb sowie aktive implantierbare Produkte und IVD auf der Liste A;
• innerhalb von acht Monaten nach dem Brexit für nicht implantierbare Produkte der Klasse IIB, Produkte der Klasse IIA, IVD auf der Liste B und IVD für Selbsttests;
• innerhalb von zwölf Monaten nach dem Brexit für alle übrigen Produkte (Klasse I und selbst zertifizierte IVD).

Die anfängliche Registrierung kann mit dem Code der globalen Nomenklatur für Medizinprodukte (Global Medical Device Nomenclature, GMDN) erfolgen. Damit ist es möglich, Produktgruppen auf einmal zu registrieren (Produkte der Klasse III ausgenommen). Derzeit gelten die MDR und IVDR. Die MHRA wird außerdem EUDAMED übernehmen und verlangen, dass Hersteller sich in dieser Datenbank eintragen. Es ist noch nicht klar, ob diese Anforderung mit dem Inkrafttreten der EUDAMED auch im VK vollständig übernommen wird.

Vorbereitungen auf den Brexit

Das letzte Wort ist zwar noch nicht gesprochen, aber es wird immer wahrscheinlicher, dass das Vereinigte Königreich ohne eine Vereinbarung über die zukünftigen Beziehungen aus der EU austreten wird. Auf dieses Szenario sollten sich alle Beteiligten vorbereiten. Außerdem muss die Kontinuität der medizinischen Versorgung gewährleistet werden. Emergo by UL wird die Entwicklungen nah verfolgen und Stakeholder aus der Medizinproduktebranche auf dem Laufenden halten.

Erfahren Sie mehr über die regulatorischen Anforderungen für Medizinprodukte in der EU und im VK:

• Strategie und Beratung zur europäischen CE-Kennzeichnung für Medizinprodukte
• Inlandsvertretung und Beratung für den Brexit-Übergang
• Inlandsvertretungals EU-Bevollmächtigter
• Lückenanalyse und Übergangsstrategie zur EU-Verordnung MDR 2017/745 für Hersteller von Medizinprodukten

EMERGO BY UL 핵심 요약:

• 영국 의약품 및 보건의료제품 규제청(MHRA)이 영국 시장을 담당할 예정입니다
• CE 마킹은 영국 내에서 여전히 유효하며, 현재 라벨 변화는 예고된 바 없습니다
• MDR 및 IVDR이 EU와 영국에서 나란히 시행될 예정입니다
• 영국 의료기기 시장에 진출한 영국 외 제조사는 영국 책임자를 임명해야 하며, 이는 유럽 공인 대리인의 역할과 비슷합니다
• 영국 기반 제조사 또는 영국 책임자는 기기를 영국에서 등록해야 합니다.

영국 의약품 및 보건의료제품 규제청(MHRA)은 2019년 1월 3일 노딜 브렉시트에 대한 지침을 발간했습니다. 합의에 이르지 못하면, 영국은 아무런 협정 없이 EU에서 탈퇴할 가능성이 있습니다. 이로 인해 영국은 EU의 관점에서 볼 때 “제삼국”이 될 수 있습니다. 제삼국에서 수입되는 물품은 EU 규정의 제재를 받지만, EU에서 영국으로 움직이는 물품에는 이러한 규정이 존재하지 않습니다. 영국 시장에 진출하고자 하는 EU 바깥의 제조사에게도 마찬가지가 적용됩니다. 따라서, 짧은 준비 기간에도 불구하고, 이러한 MHRA 지침은 높게 평가됩니다.

이 문서에는 법적 상황에 대한 설명이 포함되어 있지만, 이 문서 자체로서 법적 구속력은 없습니다. 따라서, 이를 시행하는 데 있어 주의를 기울여야 합니다. 분명하지 못한 부분이 있다면 MHRA에 문의해야 합니다. 이러한 문의로 인해 추가 지침이 발행될 수 있습니다.

영국 의료기기 시장 진출

영국 시장에서의 의료기기를 판매를 위해, MHRA가 영국 내 기기 감독을 담당할 예정입니다. 시장에서 판매되는 기기는 여전히 CE 마킹을 획득해야 하며, MDR 및 IVDR이 EU에서와 마찬가지로 영국에서도 시행될 예정입니다. MRHA가 시장 감시를 시행할 예정이지만, MRHA는 EU 시장 감시 시스템에서 벗어날 예정이며, 유럽 사법 재판소(Court of Justice of the EU)의 결정을 자동적으로 따르지도 않을 것입니다. 따라서, 영국과 EU 시장 사이에 차이가 발생할 수 있습니다.

영국 기반 인증 기관(Notified Body, NB)에 또 다른 변화가 생깁니다. 브렉시트 당일부터, 이러한 인증 기관(NB)은 EU27에서 더이상 인정되지 않을 예정이며, 해당 기관으로부터 발행된 인증은 무효화될 것입니다. 그러나, MHRA는 이러한 인증을 당분간은 인정할 예정입니다. 영국 기반 NB에서 EU27 기반 NB로 변경하는 제조사는 영국 시장에서 기기를 계속 판매할 수 있습니다. CE 마킹이 EU에서도 유효하기 때문입니다.

MHRA 등록 일정

영국 바깥에 위치한 제조사는 EU 기반 여부와 상관없이 영국에 위치한 영국 책임자(UK Responsible Person, UK REP)를 임명해야 합니다. 영국 책임자(UK REP)의 역할 및 임무는 유럽 공인 대리인(EU REP)의 역할 및 임무와 유사합니다. 기기 라벨에 UK REP 표기가 의무화됩니다. 영국 기반 제조사 또는 UK REP은 기기를 MHRA에 등록해야 합니다. 등록 일정은 다음과 같습니다.

• 브렉시트 후 4개월이내: 3등급 기기, 2b등급 이식형 기기, 능동 이식형 기기 및 IVD A목록 기기
• 브렉시트 후 8개월이내: 2b등급 비이식형 기기, 2a등급 기기, IVD B목록 기기 및 자가 진단용 IVD
• 브렉시트 후 12개월이내: 기타 모든 기기(1등급 및 자체 인증 IVD).

최초 등록은 국제 의료기기 명명 체계(GMDN) 코드 수준에 따라 시행할 수 있으며, 이로 인해 여러 그룹의 상품을 한 번에 등록할 수 있습니다(3등급 기기 제외). MDR 및 IVDR이 적용되는 순간, MHRA는 Eudamed를 반영하여 제조사가 이 데이터베이스에 등록할 것을 요구하게 됩니다. Eudamed 시행과 완전히 일치할지는 밝혀지지 않았습니다.

브렉시트 준비

영국이 아무런 협정 없이 EU에서 탈퇴할지는 확실하지 않지만, 그럴 가능성이 커지고 있습니다. 모든 관련 당사자는 해당 경우에 대비하여야 하며, 치료 지속성에 지장을 주지 않도록 해야 합니다. Emergo by UL은 이러한 사건을 긴밀히 뒤따르며 의료기기 산업 이해 당사자에게 정보를 제공할 것입니다.

유럽 및 영국 의료기기 인허가 요구사항에 대해 더 알아보기:

• 의료기기를 위한 유럽 CE 마킹 전략 및 컨설팅
• 브렉시트 전환 컨설팅 및 각국 내 대리인 서비스
• 유럽 공인 대리인 각국 내 대리인 서비스
• 의료기기 제조 업체를 위한 유럽 MDR 2017/745 격차 평가와 전환 전략

EMERGO BY UL关键点摘要：

• MHRA将负责英国市场的监管；
• CE标志在英国仍然有效，目前预计不会有变化；
• 英国将与欧盟同步实施MDR和IVDR
• 在英国销售器械的非英国制造商需要任命一位角色类似于欧盟授权代表的英国负责人
• 英国制造商或英国负责人必须在英国注册器械。

2019年1月3日，MHRA公布了应对无协议脱欧的指南。 如果无法达成协议，英国可能决定无协议脱欧。 那么从欧盟的角度来说，英国将变成“第三国”。 来自第三国的进口货物适用于欧盟规则，但对于从欧盟进入英国的货物，目前还没有适用的规则。 想要进入英国市场的非欧盟制造商也面临无规则可循的情况。 因此，MHRA的这些 指南受到热烈欢迎，尽管留给制造商的准备时间很短。

此文件含有法律情形的解释，但其本身并不具有法律约束力。 因此，制造商在遵照此文件行事时应当谨慎。 如有不明之处，制造商应当询问MHRA。 提出的问题可能促使MHRA发布补充指南。

进入英国市场销售器械

为了允许医疗器械进入英国市场，MHRA将负责英国市场的器械监管。 进入英国市场的器械将会仍然需要CE标志，并且MDR和 IVDR将同步在英国和欧盟实施。 市场监管活动将由MRHA进行，但他们将不再是欧盟市场监管体系的一部分，而且他们也将不会再遵循欧盟法院的判决。 因此，我们可能会在英国和欧盟市场之间看到一些分歧。

另外一个变化与英国的公告机构（NB）有关。 从英国脱欧之日起，欧盟27国不再认可这些公告机构，他们的证书也将因此无效。 然而，MHRA将会暂时认可这些证书。 弃用英国的公告机构、转而使用欧盟27国的公告机构的制造商可以继续在英国市场销售他们的器械，这是因为他们的CE标志仍然有效。

MHRA注册时间表

非英国制造商，无论是欧盟还是非欧盟制造商，必须指定一名必须位于英国的英国负责人（UK REP）。 英国负责人的角色和任务与欧盟授权代表（EU REP)的角色和任务相似。 目前尚不要求在器械标签上注明英国负责人的信息。 英国的制造商或他们的英国负责人必须向MHRA注册他们的器械。 注册时间表如下：

• 脱欧之后的4个月内——适用于III类器械、IIB类可植入器械、有源可植入器械和IVD List A器械；
• 脱欧之后的8个月内——适用于IIB类不可植入器械、IIA类器械、IVD List B器械和自我检测IVD；
• 脱欧之后的12个月内——适用于所有其他器械（I类器械和自我认证的IVD）。

注册可以先在全球医疗器械命名（GMDN）代码的层面进行，允许成组的产品注册在一条记录之中（III类器械除外）。 当MDR和IVDR适用时，MHRA将会制作欧洲医疗器械数据库（Eudamed）镜像，并要求制造商也在此数据库中注册。 目前尚不清楚这是否与欧洲医疗器械数据库（Eudamed）的实施完全同步。

英国脱欧准备工作

虽然不确定英国是否会无协议脱欧，但这种可能性正在增加。 所有相关方都应当为这种情况做好准备，并确保服务的连续性不会中断。 Emergo by UL将会密切关注英国脱欧进展，并及时将有关情况告知医疗器械行业的利益相关者。

进一步了解欧盟和英国的医疗器械监管要求：

• 欧盟医疗器械CE认证策略和咨询
• 英国脱欧过渡咨询和当地代表服务
• 欧盟授权代表 当地代表服务
• 针对医疗器械公司的欧洲MDR 2017/745差距评估和过渡战略

With Brexit Day now just a month away, medical device companies active in UK and European markets should be mapping out the impact of a no-deal Brexit on their operations.

Following Emergo by UL’s recent webinar on a no-deal Brexit’s impact on the medical device industry, we discuss some key questions many manufacturers are facing.

How would a no-deal Brexit affect REACH in the UK?

The Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation is part of the EU requirements for placing products on the EU Single market. If the UK leaves, those rules do not automatically apply. However, British authorities have indicated they will make EU laws into UK laws. That means that legislation such as the REACH and ROHS will also apply in the UK. They will be supervised by UK authorities and interpreted by UK judges.

Are you aware of plans for any kind of triage system for trucks moving in or out of the UK, so that certain shipments such as medical products can be prioritized?

In a way this can be expected as the UK is trying to organize special ferry services for emergency goods. However, I don’t how they think they can organize that. Those trucks need to be singled out from the lines of waiting trucks. That means that someone with a certain authority of checking the contents of a truck needs to be available for checking trucks in those pile-ups, and then these trucks somehow need to be able to move to a specific point so they can get on board. I don’t expect this will work.

What would be the impact on vigilance reporting and FSCAs of a no-deal Brexit? This is for cases that potentially cross the hard border.

This is a rather complex question to answer. Let’s look as some scenarios for incidents happing after Brexit Day:

1. An incident happens in Europe with a device from a European manufacturer or a non-EU manufacturer using an EU-based Authorized Representative. Parties determine that a Field Safety Corrective Action (FSCA) is required. This FSCA is also carried out in the UK. The manufacturer reports the incident to the national Competent Authority (CA) of the Member State where the incident happened, and also informs them about the FSCA. All Member States involved in the FSCA will be informed. This manufacturer should also inform the UK CA, MHRA. However, MHRA will be cut off from European networks and databases in which these cases are handled, so the agency will not know about it until notified directly by the manufacturer. EU data on this FSCA will also not be shared with MHRA. The manufacturer will have to report this case to the MHRA as if it were a EU case. MHRA will then draw its own conclusions, but will not be able to communicate that with the EU authorities.

2. An incident happens in the EU with a device from a UK-based manufacturer, or non-EU manufacturer using a UK-based AR, that has been placed on the market before Brexit. After investigating the incident, the manufacturer decides to issue an FSCA. In this case the device is not represented by an E- based legal person. The incident should be reported to the CA in the Member State where the incident happened. This CA will take the lead in the FSCA. They will reach out to the UK-based manufacturer. If this is not successful, this may indicate the device is not sufficiently represented on the EU market. EU authorities cannot formally reach out to MHRA to require action. They may decide the device must be recalled from the EU market (current article 8 procedure). For cases in which a device placed on the market by an EU-based manufacturer/AR with an incident in the UK, the situation is similar: the EU cannot formally be approached, and may not act.

3. An incident happens with a device placed on the EU market after Brexit by a UK-based manufacturer, using an EU-based AR, where the incident results in an FSCA. From an EU perspective this is fully covered, because this would be treated the same way as for a  device placed on the EU market by any non-EU manufacturer. UK citizens may be kept exposed to a device with an issue, because MHRA is no longer part of the EU vigilance system.

In case of a no-deal Brexit, would the MDR still be implemented in the UK?

We will see the current directives becoming UK law and it is highly likely this will also happen with the Regulations. Of course there will be some differences regarding CE Marking, the functioning of Notified Bodies and the roles of the European Commission, MDCG and European Court of Justice. So far Emergo by UL has not seen any information on how that will be organized in the UK.

For UK-based manufacturers with UK Notified Bodies, how likely will it be that European authorities block imports from the UK on Day One of a no-deal Brexit? And what about devices made in the UK that are currently marketed in Europe?

This is a very difficult question to answer. On the one hand, these are devices that are no longer in compliance with the requirements and they should be kept off the market. On the other hand, currently they are in compliance and they can be used safely. Immediately after Brexit Day there is only an administrative difference, and therefore it will be very difficult to explain to European citizens what the difference is. Apart from that, there are some practical issues. There will probably not be enough time for doing these border checks, and if this would happen and be effective, this might disrupt the continuity of care. Such disruption could be blamed on Brussels’ bureaucracy and it is likely the authorities would rather not want to see that.

The short answer to this question is: nobody knows.

Are there any solid timelines as to when manufacturers can start appointing UK REPs?

There is not a starting date mentioned, but it is necessary to have one designated after Brexit. Emergo by UL therefore thinks it is best to start this now. We have a “delayed start” option for this service that implies that all will be prepared and this agreement kicks into force at the moment it is needed. Until then the manufacturer is still operating under current EU rules.

Will current self-declarations under the IVDD enable IVD products to stay on the market during the MHRA’s transition period?

It is highly likely MHRA will use the same transition period as the EU for these products. That would imply self-certified IVDs can remain being placed on the market in parallel with the current IVDD.

Does MHRA plan to publish any new registration requirements to obtain import approval into the UK? How will any new requirements affect supplies and access to medical devices in the UK?

For now we have to do with these guidelines. But Emergo by UL expects that in case of a no-deal Brexit more will be published in the months to follow. For now we know that devices need to be registered by the UK-based manufacturer or the UK REP, but the details of how to do this and what is exactly required are not yet clear.

After the withdrawal date, will there be a transition period in the EU for companies to make required changes to labeling?

At this moment no transition period is mentioned. However, it can be expected that for practical reasons there will be some sort of transitional period. It is not clear how that will work out in practice.

Learn more about Brexit and European medical device regulatory issues:

• Brexit transition consulting and in-country representation support
• European Authorized Representation in-country representation
• European MDR gap assessment and CE Mark transition strategy
• Whitepaper: Preparing for a no-deal Brexit
• Webinar: Impact of a no-deal Brexit for medical device companies

EMERGO by UL このニュースのポイント

• BSI UKは、NANDOに指定されています。
• この機関は、BSI NLをサポートしていません。
• 他の公認機関はまもなく従う予定です。

新しい医療機​​器規制（EU）2017/745は、現行の医療機器指令93/42 / EEC（MDD）および能動埋込み型医療機器指令90/382 / EEC（AIMDD）を更新したものではありません。すべての機器は再度認証されることが求められています。

クラスIの自己認定機器を除いて、すべての機器は公認機関（NB）による新しい認定を必要とします。 NBは、指定されている場合にのみMDRを認証できます。 指定プロセスは正式には2017年11月26日に始まっており、それはMDRの権威開始日の6か月後でした。 この日に、潜在的なNBは、医療機器とIVDのための1つ以上のスコープコードに対して指定されることへの関心を表明することができました。 これらのスコープコードは、新たに設置された医療機器調整グループ（MDCG）によって採択された後、前日に欧州委員会によって公開されていました。 NBが関心を表明した後、共同評価チームによる監査、是正措置、およびNB指定のための国内管轄当局による正式な指定で構成される指定プロセスが開始される可能性があります。 これは複雑で時間のかかるプロセスで、開始から約14か月後に最初のNBがMDRに対して指定されました。

BSI-UK

欧州公認機関データベース、NANDOに見られるように、英国の公認機関BSI-UKがその境界を越えた最初の機関です。 NANDOによると、IVDに指定されたNBはまだないとのことですが、この当機関がまもなく指定されるかもしれません。 指定はすべてのNBOGコードを網羅し、これらすべてのコードについてBSIは附属書IX（I）（品質管理システム）、附属書IX（II）（技術文書の評価）および附属書XI（A）（製造品質保証）に対して指定されています。

BSIは、コードMDA 0305（刺激または抑制のための能動的非埋込み型装置）、MDN 1210（避妊または性感染症の感染予防に使用される非能動的かつ埋込み型の機器）、MDN 1214（医療で使用される一般的な非能動的非埋込み型機器およびその他の非能動的非埋込み型機器 - 手袋に限る）に対する、附属書X（タイプ検査）および附属書XI（B）（製品検証）にのみ指定されます。 より一般的に言えば、BSIは品質システムを監査し、技術文書を審査することができますが、それらの試験能力は限られています。

BSIと英EU離脱

2019年3月29日に英国が取引なしでEUを離脱する可能性があるため、この指定は、自社の機器を英国市場だけに提供する製造業者にのみ該当する可能性があります。 取引無しの英EU離脱の場合、英国を拠点とするすべてのNBは3月29日以降に指定解除され、その証明書は直ちに無効になります。 BSIはオランダに事務所を開設し、独自のNB番号で運営しています。 したがって、BSI-NLはBSI-UKと同じNBではないため、証明書を自動的に交換することはできません。 ただし、オランダ管轄当局は、これら2つの組織間での証明書の転送は、管理上の負担をできるだけ少なくする形で、非常にスムーズに行えることに同意しています。

その他のNB

Emergo by ULは、他のNBもまもなくMDRに指定されることを想定しています。 NBが指定されると、MDRの見積もり、監査、審査、および認証を開始できます。 認証を必要とするすべての機器に対して、近いうちに十分なキャパシティがあることを願います。 現在指定されているBSIは、MDRの実施における新たな段階を示しています。

Emergo by ULからの欧州MDRおよび医療機器規制関連リソース：

• 医療機器向けの欧州CEマーキング戦略
• IVD機器向けの欧州CEマーキングサポート
• EU MDRギャップ評価と移行コンサルティング
• ウェビナー：公認機関を選択または変更する方法
• ホワイトペーパー： 欧州MDRについて
• ホワイトペーパー： 欧州体外診断用医療機器規則（IVDR）について

EMERGO BY UL キーポイントのまとめ：

• オーストラリアの TGA による欧州のMDR 規則に基づいた脊椎インプラント機器の区分格上げの提案。
• 提案されたルールでは対象となる機器はクラス II からクラス III へと移行。
• TGA は2019年3月31日まで提案されたルールについてのコメントを受け付けています。

オーストラリアの医療機器規制当局は、これらの機器のリスクプロフィールをより良く反映するために欧州医療機器規則（MDR）に従って脊椎インプラント機器の一部を再分類するかもしれません。

オーストラリアの薬品・医薬品行政局（Therapeutic Goods Administration： TGA）は新たな コンサルテーションを発行しました。それは脊椎移植可能な機器に適用する新たな分類ルールを提案しています。そのような機器は、オーストラリアではクラス II からクラス III に格上げ分類されることになるでしょう。

TGA のルールは、EU MDR のルール8 と一致するでしょう。 TGA は、MDR のルールがより徹底的にそして明白に、これらの機器の技術設計、製造、侵襲性、その他の関連する特質がもたらすリスクに対処すると断定しています。 TGA の提案はこのルールを採択し、新たな要件がより適切にオーストラリアの規制環境、市場環境に適合するように必要な調整を行うでしょう。

TGA は、提案中のルール変更に関するコメントを2019年3月31日まで受付中です。これまでのところ TGAは脊椎インプラント可能な機器のみについて分類変更を提案してきましたが、規制当局は、技術上の発達やリスクの増大によりこれらの提案された変更はやがてもっと多くの種類の機器に適用されるかもしれないことをコンサルテーションにおいて注記しています。

影響を受ける可能性のある脊椎インプラント機器の種類

TGA の提案する分類格上げによって影響を受ける機器には、脊柱固定用ケージおよび脊椎円盤置換インプラント、ならびに脊柱に接触する機器が含まれています：

• 解剖面置換システム（Anatomic facet replacement systems：AFRS）
• 椎骨充填剤
• 整形セメント
• 骨移植
• 骨ねじ体内脊柱固定システム
• 頸部小関節面関節ディストラクター

移行期間

提案中のルール変更が実施された後にオーストラリア薬品登録制度（Australian Register of Therapeutic Goods：ARTG）に含まれる影響を受けた脊椎インプラント機器には、新たなクラス III の分類要件が2020年8月に開始するでしょう。

提案されたルール変更実施の前にARTGの登録のためにTGAに提出されて影響を受けたデバイスは、新たな規制に移行するまでに4年間の猶予があります。

オーストラリアの医療機器規制について詳細を知るには：

• オーストラリアTGA医療機器登録コンサルティング
• オーストラリア TGA スポンサー 国内窓口
• 医療機器分類 コンサルティング
• プロセスチャート: 医療機器に対するオーストラリア TGA規制当局の承認
• ホワイトペーパー: オーストラリアとニュージーランドにおける医療機器の登録

EMERGO BY UL 핵심 요약:

• 호주 식약청(TGA)이 유럽 MDR 규칙에 기반한 척추 삽입형 기기 등급 상승안을 발표했습니다.
• 발표된 규정에 따르면 대상 의료기기는 2등급에서 3등급으로 상승하게 됩니다.
• TGA는 2019년 3월 31일까지 해당 규정에 대한 의견을 수용할 방침입니다.

호주 의료기기 규제 기관이 유럽 의료기기 규정(MDR)에 따라 일부 척추 삽입형 기기의 등급을 재분류할 가능성이 있습니다. 의료기기의 위험 특성을 더 잘 반영하기 위함입니다.

호주 식약청(TGA)이 새로운 협의안을 통해 척추 삽입형 기기를 포함하는 새로운 등급 분류 규정을 발표했습니다. 해당 의료기기는 호주 내에서 2b등급에서 3등급으로 상승할 예정입니다.

TGA의 새로운 규정은 EU MDR 규정 8조와 궤를 같이합니다. TGA는 MDR 규정이 이러한 의료기기의 기술 설계, 생산, 침습성 및 관련 특징으로 인한 위험을 보다 더 철저하고 명확하게 명시한다는 점을 상정하고 있습니다. TGA는 이 규정을 채택하여 새로운 요구 사항이 호주 규제 기관 및 시장 환경에 더 적절하게 적용될 수 있도록 수정을 거칠 것입니다.

TGA는 2019년 3월 31일까지 해당 규정 변경에 대한 의견을 수용할 예정입니다. TGA가 등급 분류 변화를 예고한 것은 오직 척추 삽입형 기기뿐이지만, 규제 기관에 따르면 기술 발전과 위험 발생으로 인해 결국 더 많은 유형의 의료기기에 변화가 적용될 수 있습니다.

영향을 받을 가능성이 있는 척추 삽입형 기기 유형

TGA의 등급 상승 규정에 영향을 받는 의료기기에는 추간 케이지, 인공 추간판 치환 삽입물, 그리고 척추에 접촉하는 의료기기가 포함될 전망입니다.

• 관절면 치환 시스템(Anatomic facet replacement systems, AFRS)
• 척추 필러
• 정형외과용 시멘트
• 골이식재
• 골나사 척추 내고정 시스템
• 경추 후관절 분산기

전환 기간

호주 치료제 등록부(ARTG)에 등록된 의료기기 중 규정 변경안 발효에 영향을 받는 척추 삽입형 기기를 위한 새로운 3등급 분류 요구사항이 2020년 8월에 시작될 예정입니다.

규정 변경안 시행 전에 TGA에 ARTG 등록을 제출한 의료기기 중 해당 변경안의 영향을 받는 기기는 새로운 규정에 대한 4년의 전환기를 부여받게 됩니다.

호주 의료기기 규제 기관 이슈에 대해 더 알아보기:

• 호주 TGA 의료기기 등록 컨설팅
• 호주 TGA 스폰서 국가 내 대리인 서비스
• 의료기기 등급 분류 컨설팅
• 절차 차트: 호주 TGA 의료기기 규제 승인
• 백서: 호주 및 뉴질랜드에서의 의료기기 등록

EMERGO BY UL关键点摘要：

• 澳大利亚药品管理局（TGA）提议根据欧盟医疗器械法规对脊柱植入器械进行分类升级；
• 根据拟议的规则，目标器械将从II类转为III类；
• 澳大利亚药品管理局将在2019年3月31日前听取业界对拟议规则的意见。

澳大利亚医疗器械监管机构可能根据欧盟医疗器械法规对部分脊柱植入器械进行重新分类，以更好地反映这些器械的风险状况。

澳大利亚药品管理局（TGA）发布了一份新的咨询文件，这份文件提出了新的脊柱植入器械分类规则；在澳大利亚，这些器械将从IIb类升为III类。

TGA的规则将与欧盟医疗器械法规（MDR）的第8条规则保持一致。 TGA认为MDR规则更彻底、更明确地应对这些器械的技术设计、生产、侵入性和相关特性所带来的风险。 TGA的提议将会采用这一规则，并进行必要的修改，以使新的要求更适合澳大利亚的监管和市场环境。

TGA将在2019年3月31日前听取业界对拟议的规则变更的意见。虽然目前为此TGA仅针对脊柱植入器械提出了分类规则变更，但它在咨询文件中指出，随着技术和风险的发展，这些拟议的变更最终可能应用于更多类别的器械。

各种类型的脊柱植入器械可能受到影响

受到TGA拟议的分类升级规则影响的器械包括脊柱融合器和椎间盘替代植入物，以及接触脊柱的器械：

• 解剖小关节替代系统（AFRS）
• 椎骨填充物
• 骨水泥
• 骨移植物
• 骨螺钉内脊柱固定系统
• 颈椎小关节牵引器

过渡期

拟议的规则变更生效之后，对于被列入澳大利亚医疗用品登记表（ARTG）的受到影响的脊柱植入器械，新的III类分类要求将于2020年8月开始执行。

在拟议的规则变更实施之前，为了列入ARTG而提交给TGA的受影响器械将获得四年的过渡期以适应新的法规。

进一步了解澳大利亚医疗器械监管问题：

• 澳大利亚TGA医疗器械注册登记咨询服务
• 澳大利亚TGA代理人本国代理服务
• 医疗器械分类咨询
• 流程图： 澳大利亚TGA医疗器械监管审批
• 白皮书：澳大利亚和新西兰的医疗器械注册登记

EMERGO BY UL SUMMARY OF KEY POINTS:

• The European Medical Device Coordination Group (MDCG) plans to use Italy’s CND codes as the basis for the Eudamed device database nomenclature.
• CND codes will be mapped to Global Medical Device Nomenclature (GMDN) for ease of use.
• Using CND nomenclature provides public access to medical device codes within Eudamed.

Authorities overseeing implementation of the European Database for Medical Devices (Eudamed) have decided to adapt medical device codes used by the Italian Ministry of Health for use as nomenclature for the database.

The Medical Device Coordination Group’s (MDCG) decision stems from requirements in the European Medical Devices Regulation (MDR) and In-Vitro Diagnostic Medical Devices Regulation (IVDR) that free nomenclature for devices be made available in Eudamed. Global Medical Device Nomenclature (GMDN), currently used worldwide as a nomenclature tool, requires membership fees for access.

To meet MDR and IVDR requirements, MDCG will map Italian CND (Classificazione Nazionale dei Dispositivi medici) codes to GMDN codes for ease of use by manufacturers and other entities utilizing Eudamed. The Italian coding system has been in use since 2007 to support that country’s device database; the CND system is up-to-date and used on a daily basis.

Learn more about European medical device regulations and Eudamed requirements:

• European MDR gap assessment and transition strategy for medical device companies
• On-site European MDR training for manufacturers
• Webinar: Eudamed requirements under the European MDR and IVDR
• Whitepaper: The role of Eudamed under the MDR and IVDR

EMERGO BY UL SUMMARY OF KEY POINTS:

• European MDR clinical data requirements may result in up-classification or recertification of some medical devices.
• Manufacturers with CE Marked devices should be preparing post-market clinical follow-up (PMCF) studies now in order to comply with MDR requirements in 2020.
• Meeting the MDR’s PMCF requirements may impact some manufactures’ budgets in unforeseen ways.

The uncertainties about a “No-Deal Brexit” may distract many manufacturers from preparing adequately for the new requirements associated with the new Medical Device Regulation (MDR), including clinical data rules.

The need to provide clinical data for a significantly increased number of medical devices, whether the data is collected on a predicate device, during pre-CE clinical trials or during Post Market Clinical Follow-up (PMCF) studies, will present a big challenge for most manufactures.

It is safe to say that the number of CE Mark certifications based solely on clinical literature comparisons to equivalent devices will be reduced considerably, as it cannot be expected that manufactures will gain full access to clinical data that their competitors collected on predicate devices. Other devices might be up-classified, potentially requiring clinical data for re-certification.

In any case, when it comes to re-certification manufacturers will need to provide PMCF study data (from completed or ongoing studies), or at least PMCF study outlines for many devices currently on the market, especially in cases where devices whose safety or performance characteristics must be assessed over longer time periods are concerned.

MDR transition period ends soon

The MDR came into force on May 25^th, 2017 and the Regulation’s three-year transition period will end in spring (May 24^th), 2020. We expect that starting towards the end of 2019, an increasing number of devices will not be able to obtain certification or re-certification under the Medical Devices Directive (MDD) anymore. By May 25^th, 2020, all new and re- certifications will be governed by the MDR.

Notified Bodies (NB) will likely enforce the requirements for clinical data, so manufacturers should not wait with the initiation of their PMCF or Pro-Active PMS activities until their NBs request clinical data. Not providing requested clinical data may ultimately result in the loss of CE Mark certification.

How are manufactures addressing increased requirements for clinical data?

Some manufactures are in the process of evaluating their portfolios to identify which devices will be subject to additional clinical data rules. Unfortunately, they may decide to discontinue  their - less-profitable devices  once they realize that costly additional clinical data are needed for re-certification, even if those products have been on the market for decades without problems (“legacy products”).

For their remaining medical devices that may need additional data, these manufacturers are in the process of preparing and implementing PMCF plans, including PMCF studies.

However, many manufacturers may not be prepared to conduct PMCF studies. They do not (yet) plan PMCF studies even though it is foreseeable that they will need additional clinical data for re-certification of their devices. More importantly, these manufacturers may not have included the costs of conducting PMCF studies in their budget planning.

Other manufacturers underestimate the efforts needed to conduct PMCF studies, and do not assign personnel experienced in study planning and conduct. Once started, these studies quite often will need additional support resulting in increased, unbudgeted costs.

Conclusion: Post-market clinical planning should start now

If they have not yet started, manufacturers are advised to start planning their needed post-market activities now. Furthermore, firms should ensure to involve internal and/or external experts who are experienced in the early study planning period. -Proper planning is the first step for a successful post-market clinical study.

Dietmar Falke is Heaf of CRO at Emergo Clinical BV.

Related European medical device clinical regulatory resources from Emergo by UL:

• European CE Marking strategy for medical device companies
• European PMCF study support for medical devices
• EU MDR gap assessment and transition consulting
• Medical device clinical trial management and monitoring support
• Whitepaper: European PMCF studies

EMERGO BY UL SUMMARY OF KEY POINTS:

• European MDR requirements will increase the need for clinical studies;
• Proper investigator and investigation site selection is essential for successful studies;
• PMCF study sponsors and investigators should not underestimate requirements and obligations;
• In-person facility inspections and personnel interviews should be conducted to mitigate risks and determine proper clinical study support.

With the requirement in the new European Medical Devices Regulation (MDR) to provide an increased amount of clinical evidence, more and more surgeons and physicians will need to be involved, not only in studies conducted to obtain the CE Mark (pre-CE  clinical studies), but also in studies conducted after marketing of the medical  device (post-market clinical follow up or PMCF studies). This is expected to lead, especially in some “popular” indications, to a shortage of surgeons and physicians willing or able to participate in clinical studies.

Pre-CE clinical studies

For pre-CE clinical studies, very stringent requirements apply to the investigators and involved study personnel qualifications, such as certified Good Clinical Practice (GCP) training or documented experience in conducting clinical trials, as well as to the composition of the study team and for the facility and facility equipment. Please note that these requirements can vary to some extent from country to country.

Due to these strict standards the number of investigators who qualify to conduct pre-CE clinical studies is limited. For example, obtaining required GCP training is often a hurdle for otherwise qualified  investigators, as it is often difficult to incorporate these trainings into their busy clinical daily routines.

PMCF studies

For PMCF studies the requirements are less stringent, and generally any surgeon or physician with experience in the field of investigation can become an study investigator. However, whenever possible it is advisable to exclusively include investigators, who are experienced in conducting  clinical studies and ideally also trained in GCP (required in many countries).

Unfortunately, when selecting investigators for PMCF studies the duties and tasks related to the conduct of the study are often underestimated by both the sponsor (device manufacturer) and also the involved investigator. This introduces the risk that the investigator may not be able to include the expected number of patients, or that the quality of the data to be collected suffers.

Selecting investigators and investigational sites

When selecting investigators and investigational sites, a personal site visit is highly recommended even if a good relationship with the potential investigator has already been established for quite some time.

During this visit the planned study should be discussed with the investigator and her/ his interest in participation confirmed. This visit should also be used to assess the site’s infrastructure. A tour through the facilities and discussions with site staff who would be involved in the study should make up a central part of  the program. Experienced clinical research personnel (sponsor personnel or personnel of a Clinical Research Organization or CRO) should be able to identify site-related risks (e.g., lack of study team members, scheduled leave of absence, other foreseeables) and hurdles (e.g., missing or inadequate support by hospital administration).

Conclusion

Investigator and investigation site selection are pivotal for the successful conduct of any clinical study. Unless absolutely impossible, a proper site assessment should be conducted and identified risks should be mitigated. This might even mean that the surgeon or physician intended as an investigator cannot be admitted to participate in the study.

Not appropriately addressing identified risks is very dangerous. For example inclusion of investigational sites which might need additional site support such as additional extensive site trainings or provisions for freelance study personnel will most likely have an impact on timelines and potentially also on data quality. Ultimately this will have an impact on the study costs.

Under no circumstance is it acceptable to attempt to convince physicians or surgeons whose interest in conducting your study is limited or whose capacities are exhausted to participate in your study, as this may lead to problems with a site.

Dietmar Falke is Head of CRO at Emergo Clinical BV.

Related medical device clinical resources from Emergo by UL:

• Medical device clinical trial management and monitoring
• GCP and ISO 14155 compliance consulting for medical device companies
• European post-market clinical follow-up (PMCF) study support for medical devices
• Whitepaper: Conducting medical device PMCF studies

Spotlight on MDR impact on drug-device combination products

The European Medicines Agency (EMA), which oversees the European Union’s pharmaceutical market, has begun rolling out guidance and clarifications regarding Medical Devices Regulation (MDR) compliance issues for manufacturers of combination products with drug and medical device components.

According to the EMA website as well as Emergo by UL consultants in Europe, the agency plans to publish draft guidelines in June 2019 covering quality requirements for combination medicinal products that include device components, or drug-device combination products. The guidelines will specifically address Article 117 of the MDR, which will establish new compliance obligations for drug-device combination products.

EMA plans to finalize these guidelines ahead of the May 2020 deadline whereby the MDR becomes fully applicable.

EMA and Notified Body roles under MDR Article 117

Earlier in 2019, EMA published a Q&A guide for manufacturers of drug-device combination products that will have to meet MDR Article 117 regulatory requirements next year. EMA notes that Article 117 of the Regulation requires Notified Body involvement for European market authorization of a medicinal product that incorporates an integral medical device, or drug-device combination product.

“This applies to medicinal products that form an integral product with a medical device, where the action of the medicinal product is principal i.e. those that fall under second subparagraph of Article 1(8) and where a medical device is used to administer a medicinal product, i.e. second subparagraph of Article 1(9) of the medical devices Regulation,” EMA states in the Q&A document.

Some key issues addressed by the EMA Q&A include:

• For qualifying drug-device combination products, marketing authorization dossiers should include conformity assessment results or CE Mark issued by Notified Bodies for device components); for device components lacking CE Marking, manufacturers will have to submit opinions from Notified Bodies regarding conformity of those components to MDR requirements.
• In order to fall under MDR Article 117 requirements, a product’s device and medicinal components must form a “single integral product;” the product must be intended for use only in the drug-device combination; and the product must not be reusable.
• For new marketing authorization applicants, a Declaration of Conformity or CE Mark will be required for the device component of a drug-device combination product, which will help to determine whether the device component meets MDR requirements established in Annex I of the Regulation. Otherwise, applicants must provide opinions from Notified Bodies supporting conformity to MR Annex I rules.
• Drug-device combination products currently authorized for sale in the European Union or those whose applications will be submitted prior to the May 26, 2020 MDR enforcement date will not be impacted by MDR Article 117 requirements, according to the EMA. However, such products may become subject to MDR Article 117 requirements if manufacturers make substantial changes to, replace or add device components to their products.

Emergo by UL will provide additional coverage of EMA’s draft guidelines on drug-device combination products and MDR requirements following their publication.

Learn more about European medical device and combination product regulations:

• EU Medical Devices Regulation (MDR) 2017/745 gap assessment and transition consulting
• Medical device classification consulting for Europe
• European CE Marking strategy for medical devices
• Whitepaper: Understanding the European MDR
• Whitepaper: EU classification of borderline and combination products

TÜV Süd is now the second Notified Body designated to issue CE Mark certifications under the upcoming European Medical Devices Regulation (MDR).

TÜV Süd’s designation covers all Notified Body Operations Group (NBOG) scope codes, but with some minor limitations:

• Scope code MDN 1104 Non-active soft tissue and other implants: Annexes X and XI without breast implants
• Scope code MDT 2013 Devices which have undergone reprocessing: Only for medical devices that are foreseen by the manufacturer to undergo reprocessing

Surprisingly, the designation’s horizontal scope includes MDS 1012 Products without an intended purpose listed in Annex XVI to Regulation (EU) 2017/745, considering that the Common Specifications for Annex XVI of the MDR have not officially been published yet.

TÜV Süd’s designation to the MDR follows that of BSI earlier in 2019.

Related European MDR and Notified Body information from Emergo by UL:

• On-site EU Medical Devices Regulation (MDR) training for manufacturers
• Medical device classification consulting for Europe
• CE Mark training for EU medical device regulations
• Webinar: How to select or change your European Notified Body
• Whitepaper: Understanding Europe’s new MDR