Tag Archives: Clinicaltrials

Three Things You Should Know about Medical Device Regulations in Russia and the Eurasian Union – February 2022

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  1. Mandatory notification on all imported medical devices since March 1st, 2022

 March 1st, 2022, is the date of enforcement of regulation #11020 (link in Russian) establishing mandatory requirements to notify authorities for every unit of any medical device imported into Russia, as well as manufactured within the country.

According to the regulation, this notification has to be performed for the purpose of safety monitoring by the regulatory agencies. It should be done by the manufacturer, its authorised representative or the importer of a medical device. Information regarding the name of the medical device and its modification, its serial number, its manufacturing and expiration date and the number and date of registration should be submitted using the Roszdravnadzor electronic system within fifteen days of importation or manufacturing release of a product.

2. New guidance on quality management system requirements for the registration of medical devices

On February 9th, 2022, the Russian government released regulation #135 (link in Russian) and established rules for the inspection of quality management systems for medical device manufacturers. The document introduces mandatory requirements to submit QMS inspection reports using national procedures for any amendment to registration certificates from June 1st, 2023, and provides detailed guidance on the organisation of the QMS audit.

In addition, on February 18th, 2022, the Russian Ministry of Health released regulation #91N (link in Russian) on methods for determining the amount of payment for the provision of services related to the inspection of the production of medical devices. The document provides tools to calculate required human resources and costs for the inspection of quality management systems for the registration of medical devices.

According to the document, the maximum cost for an inspection is limited to 1.274 million rubles including VAT for Russian manufacturers (approximately 13,000 USD) and 2.729 million rubles for foreign manufacturers (approximately 28,000 USD).

3. New guidelines for pre-clinical and clinical testing for medical devices in Russia


March 1st, 2022, is also a date of enforcement of regulation # 885N (link in Russian) with a new revision of the guidelines for technical assessments, toxicology testing and clinical trials as part of the national registration procedure of medical devices. The regulation will replace regulation #2N (link in Russian) that was effective since 2014.
It should be recalled that the possibility of reopening submissions according to national registration rules for another year has been debated since the end of December 2021. However, as of the end of February 2022, this remained impossible.

Three Things You Should Know about Medical Device Regulations in Russia: July 2019

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Dear Colleagues,

This is my usual selection of highlights and recent changes in medical device regulations in Russia:

  1. Some Updates in Medical Device Registration and Clinical Trial Requirements in Russia

On 4 July 2019 the Russian Ministry of Health enforced order no. 239N (link in Russian). This updated certain requirements for pre-registration clinical trials (update of order no. 2N), requirements for the content of the technical file and instruction for registration of a medical device (update of order no. 11N). The main updates implemented in the published document are:

  • The clarification of and uniform requirements for documents confirming the quality of the pharmaceutical component of drug-containing medical devices.
    The first amendments of registration rules (regulation no. 1416) to simplify the registration of drug-containing medical devices in Russia were made in June 2018; later in 2018 Roszdravnadzor clarified requirements for confirming the quality of the pharmaceutical component. However, until July 2019 these registration rules were not harmonised with other Russian medical device regulations (order no. 2N and order no. 11Nr). The order no. 239 seems to finally resolve these discrepancies.
  • Henceforth, it is permitted to conduct clinical trials for registration in Russia where a certain type of capital medical equipment is on-site in other countries in ‘organizations where a medical device is located/installed and is approved for use/application’. The possibility of on-site clinical trials is not new, however, previous revisions of order no. 2N permitted clinical trials to be performed ‘during inspection on the place of the manufacturing of a medical device’.
  1. Russia Launches the List of Medical Devices Containing Ethyl Alcohol

On 2 July 2019 the Russian government enforced resolution no. 774 (link in Russian), which approved the rules for the formation of the list of alcohol-containing medical devices. Medical products included in this list are excluded from general alcohol regulations in Russia i.e the Federal law 171 “On state regulation of the production and circulation of ethyl alcohol, alcoholic and alcohol-containing products and on limiting the consumption (drinking) of alcoholic beverages”. The released resolution provides the criteria for inclusion on the list (based on a product’s intended use, the form of the container or package and the product retail price) along with a list of documents  for application for inclusion. Russian healthcare regulator Roszdravnadzor is responsible for the list’s inclusion procedure and has clarified the rules for applications — which should be received <annually> by the regulator between 1 January – 30 June.

  1. Russia: New Administrative Provision on Medical Device Registration

On 26 July 2019 the Russian Ministry of Health published order no. 3371 (link in Russian) – with a new version of the administrative provision of Russian medical device regulator Roszdravnadzor – on the procedure for the registration of medical devices in Russia. Simultaneously, the previous version of the same document (the Ministry of Health order no. 737) was annulled.

Administrative provision on the procedure for the registration of medical devices is a regulation that establishes the following: the terms and sequence of administrative procedures of the regulator during the approval process, the procedure for interaction between its structural divisions and the interaction between applicants/manufacturers and other government bodies. The new version of administrative provision does not contain critical changes but it is aligned with the last changes of the registration rules and other medical device regulations.

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Three Things You Should Know about Medical Device Regulations in Russia, May 2018

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Dear Colleagues, 

Here is my usual monthly selection of highlights about what happened in the Russian medical device regulations landscape in May 2018:

  1. Simplification Requirements for Substance-based Medical Devices (draft)On 30 May 2018, the Russian Ministry of Health published a draft regulation suggesting the simplification of requirements for registration and pre-registration testing of substance-based medical devices in Russia.
    According to regulation #11N, enforced in March 2017, one of the requirements for registration of medical devices with ancillary pharmaceutical substances is mandatory registration of the pharmaceutical component of the product in the Russian register of medicinal products prior to registration of the device. This became one of the most pressing regulatory problems in Russia and increased the number of registration rejections in 2017.
    The amendments proposed in the published draft suggest replacing the requirement above with submitting ‘…documents on quality of pharmaceutical substance <…> taking into account the intended use of a medical device <…> and issued according to the regulation of the country of origin of this pharmaceutical component’. The published draft is now passing through the procedure of public discussions by the end of June 2018.
  1. Mandatory Multi-Central Clinical Trials for IIB and III class devices (draft) 

    Another suggestion of the published draft regulation is the expansion of the list of cases when clinical trials involving human subjects are required for medical device approval in Russia.
    Currently, according to resolution 2N, registration of most medical devices in Russia is mainly based on evaluation of clinical data, and clinical trials involving human subjects must be conducted in accredited clinics after the approval of the ethics council in a limited number of cases: for new types of medical device; for new complex or unique or special methods of prevention, diagnosis or treatment; and in cases where the effectiveness or safety of the medical device are not confirmed in the evaluation of clinical data.
    The published draft document tightens these rules and introduces a requirement for all medical devices of IIB and III classes to undergo mandatory clinical trials involving human subjects, to be conducted in at least two medical organisations under a single clinical trials protocol.
    The same draft document also suggests the innovative new possibility of conducting on-site clinical trials in limited cases.
    It should be also noted that the amendments suggested in the draft document would make Russian and Eurasian clinical trial requirements more similar. Proposed amendments are now passing through the procedure of public discussions by the end of June 2018.

  2. Clarification on application of a reduced tax rate for medical devices in RussiaAt the end of May 2018, the Ministry of Finance of Russia published a letter On the application of the VAT rate of 10 per cent for imported and sold medical products in Russia (link in Russian). In this letter, the regulator clarifies that the list of medical devices taxed at a rate of 10% is approved by Decree of the Government of the Russian Federation N 688 (link in Russian to the latest version, updated on January 23, 2018). This should be guided by the codes of medical products, determined in accordance with the nomenclature of Eurasian customs commodity code EAEU TNVED and Russian product classification code OKPD 2.

Клинические испытания медицинских изделий. Обзор проекта правил Евразийского Союза

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The English version of this post is comming soon

В августе 2015 года на сайте Евразийского Союза был опубликован проект правил проведения клинических испытаний медицинских изделий. Разрешите представить Вашему вниманию мой небольшой обзор этого документа.

Как известно, на сегодняшний день в России для регулирования обращения медицинских изделий Росздравнадзор оперирует определениями для клинического исследования (испытания), приведенных в Постановлении Правительства № 1416:

клиническое испытание – разработанное и запланированное систематическое исследование, предпринятое, в том числе с участием человека в качестве субъекта для оценки безопасности и эффективности медицинского изделия;

или  ГОСТ Р ИСО 14155-2014:

клиническое испытание-  Системное исследование с участием одного или более человека в качестве субъекта, проводимое для оценки безопасности или функциональных характеристик медицинского изделия.

Согласно действующему приказу Минздрава № 2Н, клинические исследования медицинских изделий проводятся в России в двух формах: оценки клинических данных и клинических испытаний с участием человека.

Обратим внимание, что в проекте новых правил в определении клинического исследования появляется  формулировка «с непосредственным участием человека в качестве субъекта исследования» (см. п. 3), таким образом, существующая форма оценки клинических данных выводится из определения клинического исследования.

Правилами также закреплено определение «клинико-лабораторных испытаний медицинского изделия для диагностики invitro” как систематическое  исследование аналитических характеристик и, где применимо, клинической эффективности, проводимые с целью установления или подтверждения соответсвия медицинского изделия […] назначению, установленному производителем.  Обоснованию клинической эффективности медицинских изделий для диагностики in vitro посвящен отдельный раздел (см. раздел VII).

Принципиальным требованием, закрепленным в проекте новых правил, является необходимость производителя доказать соответствие его медицинского изделия Общим требованиям безопасности и эффективности медицинских изделий.  Если обратиться к п. 4.7 Общих требований…   клиническое обоснование на основе клинических данных должно быть использовано для  доказательства соответствия  общим требованиям, установленным в пунктах 1.1, 1.3, 1.6.

Согласно проекту правил, источником клинических данных признаются (см. п.4):

  • Данные в научной литературе;

  • Опыт клинического применения на территории Евразийского союза;

  • Результаты клинических испытаний;

  • Опыт клинического применения эквивалентных медицинских изделий при условии, что эта эквивалентность доказана (см. пп. 3,7).

Согласно проекту, сам производитель должен определить, какие требования из контрольного перечня могут быть доказаны с помощью различных форм приведенных выше клинических данных (см. п. 3). При этом правилами установлен ряд случаев, при которых клинические данные могут быть получены только путем клинических испытаний:

  • Для имплантируемых медицинских изделий и изделий высокого класса риска  (с некоторыми исключениями);

  • При наличии новых, контактирующих с организмом человека, материалов.

  • При изменении принципа действия или модификации изделия, появление новых свойств или показаний;

  • В случае если принцип действия, показания ли свойства медицинского изделия ранее не исследовались.

Здесь также необходимо отметить, что согласно п. 4.10 Общих требований безопасности и эффективности медицинских изделий  «для медицинских изделий класса риска 3, а также для имплантируемых медицинских изделий, клинические данные должны быть получены при проведении клинических испытаний только заявляемых медицинских изделий».

Интересными являются критерии признания зарубежных клинических данных. Согласно проекту правил, для признания клинические данные должны быть «подтверждены публикациями в профильных международных медицинских журналах или отчетами Всемирной организации здравоохранения…», а результаты клинических испытаний должны соответствовать «международным требованиям» (см. п. 6). Вспомним, что общепринятыми международными требованиями для проведения клинических испытаний являются принципы GCP, которые для медицинских изделий заложены в стандарте ISO 14155:2011, кроме того, Международной Конференцией по Гармонизации (ICH) давно предложены четкие руководства по  международному признанию клинических данных. Идет ли речь в проекте правил о признании именно этих стандартов,  из текста остается не ясным.

Принципиальным возможным нововведением является требование получения разрешения на проведение клинического испытания и подтверждения его программы экспертной организацией (сегодня разрешение выдает Росздравнадзор на основании первого этапа экспертизы).   Раздел III проекта правил подробно описывает требования к документам и сроки (5+20+5 рабочих дней) для получения этого разрешения. Перед началом испытаний программа клинических испытаний также должна быть рассмотрена и одобрена Этическим комитетом  и согласована с Исследователем (медицинской организацией). Раздел IV проекта правил содержит достаточно подробные требования к рабочим документам: брошюре исследователя, программе и протоколу  клинических испытаний.

Обоснование клинической эффективности и безопасности медицинского изделия, включающее все клинические данные является частью технического файла (см. п. 8) детальное описание структуры которого представлено в приложении 1. Проект правил требует, чтобы клинические данные в техническом файле поддерживались в актуальном состоянии с учетом данных, полученных в ходе постпродажного мониторинга и (или) при появлении новой информации из научных литературных источников.

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Данный обзор является моим профессиональным анализом общедоступного документа и не является позицией какого-либо регуляторного органа или организации.
Буду рад  Вашим дополнениям и комментариям.

Алексей Степанов

Alexey@MedicalDevicesInRussia.com
http://www.MedicalDevicesInRussia.com

Roszdravnadzor Clarifies Requirements for Clinical Data for Registration of Class I Medical Devices.

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clinical trialsOn 8th of September 2015, the Russian medical device regulator (Roszdravnadzor) clarified requirements for submission of clinical data for simplified approval process for Class I medical devices. For the fastest approval of low class devices, Roszdravnadzor previously recommended submitting in the registration dossier “documents confirming clinical efficiency and safety”. Today the agency confirmed that clinical data should mandatory come from the accredited Russian clinical centers listed in the database of Roszdravnadzor.  The Russian regulator highlights, that clinical reports should be designed according the procedure regulated by Decree 2N (link in Russian) and for the simplified registration process does not requires prior application for clinical trial authorization.

Three Things You Should Know about Medical Device Regulations in Russia and CIS, June 2015

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Dear Regulatory Colleagues,

Please find below my monthly update of important news on medical device regulations in Russia and the CIS region:

1.Ukraine: The Transformation of the Medical Device Regulatory System – Will it be Painful for the Industry?

1 July 2015 is the enforcement date for the new medical device approval procedures in Ukraine. After this, new products will only be able to access the Ukrainian market by conforming to assessment procedures similar to those used by the European regulatory model. The Ukrainian Ministry of Health should promptly adopt additional regulations for the transition to the new regulatory system. It should be remembered that the introduction of new regulations has already been postponed three times in the last several years. Industry players consistently express fears about a possible crisis in the medical device sector in the country due to incomplete legislation covering the transitional period. Another concern of local trade associations is the introduction of mandatory inspection for foreign medical device manufacturers as a part of the assessment procedures for certain types of device. This has a high probability of causing extra delays in market approval due to the lack of qualified inspectors.

2. Russia: Revised Standards on Clinical Trials

A new Russian national standard (GOST ISO 14155-2014 “Clinical trials: Good Clinical Practice” – link in Russian) came into force on 1 June 2015 and replaced the previously enacted GOST R ISO 14155-1-2008 and GOST R ISO 14155-2-2008 standards. This standard has been designed to harmonize with the similar international standard ISO 14155: 2011, which addresses planning, documentation and proper representation of the results of clinical trials to ensure the validity of the data, as well as to protect the rights, safety and well-being of human subjects and define the responsibility of sponsors. It should be highlighted that this standard is highly recommended by Roszdravnadzor (Russian medical device regulator) for clinical trials related to the registration of medical devices in Russia, and it is not applicable to in-vitro diagnostic devices.

3.Eurasian Union: Draft of Harmonized Technical Testing Rules

As is commonly known, the requirements of the technical testing (a form of conformity assessment) for medical devices, as well as requirements for laboratory accreditation, currently differ between Russia, Belarus and Kazakhstan. This means that the results of tests conducted in any one of these countries are not recognized or accepted in the others. On 22 June 2015 the Eurasian commission published a draft of harmonized rules (link in Russian) for technical testing of medical devices, establishing common requirements for technical test procedures across the Eurasian Economic Union (EEU). This document is a second-level guideline which (together with other second level regulations) complement the agreement on the common principles of the circulation of medical devices (link in Russian), which are expected to come into force on 1 January 2016 and thenceforth govern a common market for medical devices in the EEU.

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As usual, I would also like to remind you that the objective of this blog is to make Russian and Eurasian medical device regulations clearer. I therefore encourage you to post your comments and questions either here or on the Russian medical device regulations LinkedIn group.

Ten Questions about Clinical Trials of Medical Devices in Russia

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On the 2nd of October 2014 Russian medical device regulator Roszdravnadzor organised a one-day seminar fully devoted to different aspects of clinical trials for registration of medical and in-vitro devices. More than 100 questions on this topic were put to officials by representatives of international medical device manufacturers and local clinics. Below I would like to post ten the most interesting of them answered:

1. Regulations permit two forms of clinical trials: evaluation of clinical data without patient involvement and full-scale clinical trials with patients. Who decides the form in which clinical trials will be required for registration in my particular case? According to regulations, full-scale clinical trials with involvement of patients are required for registration of new types of devices and new treatments or diagnostic methods as well as in cases when safety of medical devices has not been proved with evaluation of clinical data. In the near future Roszdravnadzor expects that all implantable 2b and 3 class medical devices will pass through full-scale clinical trials with patients. Currently, a clinic or trial centre decides if full-scale or reduced trials are required for every particular case.

2. Are clinical trials programmes (plans) and clinical data mandatory in the registration dossier? Yes. Roszdravnadzor confirmed that clinical trials plans and clinical data must be submitted in the first step of the registration (before expertise).

3. Who draws up the plan/programme of clinical trials? Local clinics or trial centres are responsible for composing the plan of the trials together with applicant for registration of the medical device in question. The clinic should be accredited by Roszdravnadzor. ISO 14155 is recommended for trial plans.

4. At what point are clinical trials officially started? Current regulations do not clarify this. The start of clinical trials could be considered as the point of signature of a contract with a clinic or an initial clinical visit or signature of informed consent from the first patient. Applicants must inform Roszdravnadzor about the start of clinical trials for their device within five business days.

5. Is an ethical committee mandatory for clinical trials? Roszdravnadzor confirmed that an ethical committee has worked within the Ministry of Health since July 2014. All clinical trials on patients must be approved by the ethical committee. The procedure of assessment of clinical data should be agreed by the ethical committee only if this data contains personal information of patients.

6. Is the ISO 14155 standard mandatory for clinical trials? National standards are not mandatory in Russia. Meanwhile it should be noted that this standard is considered a minimal requirement. In cases when companies or clinics do not have their own standards or procedures, ISO 14155 is highly recommended

7. What documents are needed to start full-scale clinical trials? Two documents are mandatory for any clinical trial on patients: authorisation from Roszdravnadzor and approval from the ethical committee.

8. Can clinical trials for registration in Russia be performed abroad? Yes. Clinical trials can be performed out of Russia if samples of the device cannot be shipped in the country because of technical reasons (e.g. equipment requires complex installation). In such cases trials must be performed by Russian experts from clinics accredited by Roszdravnadzor during inspection visits. Places where trials have been performed should be noted in the clinical report.

9. How many samples do we need for trials? Samples of medical devices must be provided to the clinic in cases of full-scale clinical trials and clinical data assessment. The quantity of samples required is defined by clinics for every particular case. Samples must be imported according to special procedures with permission issued by regulator.

10. Is it allowed by law to pay patients for participation in clinical trials? Yes, but any payment to a patient must be agreed by the ethical committee of the Ministry of Health.