The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the virus SARS-CoV-2 or the “novel coronavirus” resulted in new issues the healthcare industry has faced. The demand for certain medical devices actively used in the context of the pandemic increased dramatically, so the regulating authorities responsible for medical devices had to develop and implement special temporary, and extraordinary measures intended to ensure the availability of vitally important devices from the one side, and safety of any and all devices placed on the market from another. In particular, the issues regulating authorities had to find solutions for included, inter alia, the following ones:
- Ensuring timely access to the market of novel medical devices based on innovative technologies,
- Withstanding potential shortages caused by increasing demand, supply issues, or changes to the regulations,
- Encouraging medical device manufacturers working on improvement of medical devices, as well as creating modifications expanding the scope of the intended use of existing devices to other medical purposes,
- Reducing the time necessary to place a new medical device on the market, and also regulatory burden associated thereto,
- Amending the regulatory requirements for certain medical devices to ensure their effectiveness,
- Monitoring safety-related issues associated with novel medical devices placed on the market under simplified frameworks.
In order to achieve these goals, most of the national regulating authorities have developed and introduced special regulatory pathways intended to facilitate the review of applications for marketing authorization for medical devices used in the context of the COVID-19 outbreak and ensure they will become available for healthcare professionals and patients within the shortest period of time reasonably necessary to evaluate their effectiveness and safety-related aspects. Most of these frameworks are temporary in their nature – they are not substituting the ordinary pathways and will remain effective only during the pandemic. However, certain improvements have been introduced to the regulations themselves as well. The increase in clinical evaluation data allowed to create a solid basis for improvement of medical device regulations in general.
Depending on the purpose, all special frameworks and procedures described hereabove could be divided into the following categories:
- Simplified pathways for novel COVID-related medical devices manufactured or imported during the pandemic,
- Special guidelines for medical device manufacturers and other parties involved describing in detail the regulatory requirements the products should meet in terms of safety and effectiveness,
- Allowances for modifications implemented to expand the scope of application of medical devices, under which the manufacturers are allowed to introduce modifications to their devices already placed on the market without additional review or approval, provided that such modifications do not affect the safety and effectiveness.
- Additional regulations on reporting medical device shortages intended to ensure all the parties involved in operations with medical devices, including regulating authority and healthcare facilities, will be timely informed about potential shortages in order to be able to take necessary measures.
- Amended procedure guidelines describing the way certain regulatory procedures, such as on-site inspections should be carried out in the context of COVID-related travel restrictions and quarantine measures.
The particular mechanisms used to achieve the aforementioned goals are quite similar for all the countries. Usually, such measures are implemented by device of special regulations taking effect immediately and remaining in force during the whole period of the pandemic. The limited validity period is based on the idea that the implementation of temporary simplified rules slightly increases the risks for patients, and such an increase is justified only during the COVID-19 outbreak.
FDA Notice on Regulatory Flexibilities and Exemptions
The US Food and Drug Administration (FDA), the country’s agency responsible for medical device regulations, has introduced certain regulatory flexibilities for the products intended to be used for withstanding the COVID-19 outbreak. According to the official notice published by the authority, certain medical devices are exempted from general premarket notification requirements. The exemption for Class I medical devices has been introduced immediately. The FDA states that the clinical benefits associated with the expanded availability of vitally important medical devices actually outweigh the appropriate risks associated thereto. Initially, the authority has also suggested additional exemptions for Class II medical devices. The appropriate question has been brought before the public for consultations, but for some Class II medical devices, this proposal has been declined.
The authority also reminds about the Manufacturer and User Facility Device Experience database (MAUDE) – a solution intended to strengthen and improve the effectiveness of post-market monitoring activities. The database contains information submitted by the responsible entities with regard to medical devices already placed on the market. However, the authority mentions that the information available therein could be “incomplete, inaccurate, or biased”.
Apart from flexibilities described hereabove, the FDA actively applies the Emergency Use Authorization (EUA) – a special framework intended to simplify the process of placing vitally important medical devices on the market during the pandemic. In particular, EUAs are widely used for ventilators and other medical devices facing a significant increase in demand during the pandemic. An EUA granted by the FDA allows the manufacturer to place its product on the market under the expedited procedure within a relatively short period of time.
EC Guidance on Medical Devices in the COVID-19 Context
The European Commission (EC) has also issued guidance describing special regulatory measures for COVID-related medical devices intended to be marketed and used in the European Union. The scope of the document covers general, in vitro diagnostic, and active implantable medical devices.
The general European framework for medical devices is still mostly based on existing Directives since certain elements of the infrastructure necessary to ensure the operability of all the provisions of the new Regulations are still to be created, so the actual implementation of the new Regulations has been postponed in order to avoid additional complications for placing new products on the market due to the changes in applicable regulations, and also to provide all the parties involved with the additional time they may need to achieve compliance with the new requirements.
According to the document, any and all medical devices intended to be placed on the European market, as well as the manufacturer itself and the processes it employs should meet the regulatory requirements set forth under the appropriate Directive. Under the risk-based approach, the procedures to be performed in order for the medical device to be allowed for marketing and use, including conformity assessment, should depend on the risks associated with the medical device in question. In particular, the following approach applies:
- If the risks associated with the medical device subject to review are relatively low, such a device could be placed on the market under the simplified procedure on the basis of a declaration of conformity to be issued by the manufacturer in order to demonstrate that the device complies with the applicable regulatory requirements set forth by the current legislation.
- In the case of medium and high-risk devices, the involvement of a notified body is required. According to the EU framework, a notified body is a conformity assessment body entitled to assess medical devices within the scope of its designation in order to evaluate their safety and effectiveness. It is important to mention that the lack of notified bodies duly designated to perform conformity assessment under the new Regulations could potentially result in issues related to the availability of medical devices.
The regulatory approach employed in the EU also prescribes the wide use of international standards the medical device manufacturers are allowed to refer to for the purpose of demonstrating conformity with the applicable requirements. The authority states that the standards related to COVID-19 are available for free.
The same as the FDA, the European Commission also announces additional regulatory flexibilities for COVID-related medical devices. According to the document, the national regulating authorities of the EU Member States are allowed to permit the use and marketing of medical devices without the usual conformity assessment. The appropriate measures are intended to expand the possibilities for the regulating authority in terms of ensuring the availability of vitally important medical devices during the pandemic. Each national regulating authority is entitled to make such decisions at its sole discretion while considering the following aspects:
- The availability of the substituting products,
- The importance of the particular type of devices under current circumstances,
- The presence of the technical documentation confirming compliance with the requirements set forth by the appropriate Directive,
- Evaluation of tests reports provided by the conformity assessment bodies,
- Data collection in the course of post-marketing surveillance.
However, such additional flexibilities could be implemented on a temporary basis. Actually, permission to market medical devices without passing the appropriate conformity assessment should be granted only for the period of time reasonably necessary to pass such conformity assessment and demonstrate compliance with the applicable regulatory requirements. Under the simplified procedure, the manufacturer shall notify the national regulating authority about placing a new medical device on the market and provide additional details including information about the device in question and the manufacturer. In the case of the products manufactured by a foreign manufacturer, an authorized representative should be duly appointed. The manufacturer shall also clearly indicate the intended purpose of a medical device in documentation accompanying it, including its labeling and instructions for use. However, the European Commission acknowledges that in certain cases the use behind the initial intended purpose (the “off-label use”) is justified and could be permitted in order to deal with the absence of duly registered medical devices intended to perform the same functions. Due to the increased risk associated with off-label use, a rigorous risk assessment should be performed in order to evaluate all the risks and benefits associated thereto. The scope of such assessment shall cover:
- The assessment of risks associated with the use of the device,
- The analysis of legal implications,
- The description of special measures taken to mitigate the potential risk,
- Additional review of the risk assessment from time to time,
- Applying to the national regulating authorities for approval.
In summary, the regulatory measures applicable in the EU include the postponement of the implementation of new Regulations, and a special pathway entitling the national regulating authorities to allow the marketing and use of certain medical devices before they will pass the appropriate conformity assessment.
MHRA Regulatory Flexibilities and COVID-19 Response
The UK Medicines and Healthcare products Regulatory Agency (MHRA), the country’s regulating authority in the sphere of medical devices and healthcare products in general, has also implemented certain regulatory measures intended to expand and ensure the uninterrupted availability of medical devices used in the context of the pandemic.
The MHRA acknowledges the increasing demand for respiratory devices, such as ventilators and their accessories, which are widely using to withstand the outbreak of the COVID-19, and respiratory illnesses resulting from complications associated thereto. The measures announced by the MHRA are entering into force immediately and intended to be applied for a limited period of time – the same as similar measures implemented in the US. In particular, the authority announces the following:
- Medical device manufacturers and researchers focused on seeking the treatment for the novel coronavirus could benefit from the expedited scientific advice and accelerated review of the applications for clinical trials.
- The requirement to notify the regulating authority on the temporary suspension of clinical trials and also of its renewal could be waived in case of COVID-related trials.
- The consent of the participants could be obtained in a verbal form.
- It is allowed to use remote monitoring systems and technologies providing remote access to records (provided that the appropriate security measures are duly taken to mitigate identified risks associated with remote connections).
- It is allowed to reduce the number of monitoring visions without making significant changes to the clinical trial`s plan.
- The authority acknowledges that sometimes safety report submissions could be delayed.
The MHRA also announces wider application of desk-based (remote) inspections intended to replace actual on-site inspections during the COVID-related quarantine and travel restrictions, as well as a slight reduction of the testing burden. Additionally, all inquiries related to the medical devices intended to be used in the COVID context will be treated by the authority as the highest priority. All changes to the ongoing clinical investigation resulting from the impact of the pandemic will be subject to expedited review, as well as all new applications for clinical investigations related to the COVID-19. Moreover, it is allowed to waive the requirements to notify the authority about deviations to the protocol of trials, provided that such deviations will be duly recorded and reported later under the general procedure.
Apart from this, the MHRA has already developed minimal requirements for ventilators intended to be used in the context of the pandemic. The authority also outlines certain elements and functions of ventilators that could be treated as supplementary.
In summary, the MHRA implements the measures intended to reduce the regulatory burden for the medical device manufacturers in terms of clinical trials and reporting. The authority also assures it will facilitate and accelerate to the maximum extent possible the review of all requests associated with COVID-related medical devices.
Peru Guidelines on COVID-related Medical Devices Validation
The Ministry of Healthcare of Peru has developed special guidelines describing the validation of COVID-related medical devices. According to the document, the authority intends to create a favorable framework for importing medical devices since now only 2% of medical devices are manufactured in the country, while all others are imported. However, the domestic medical device manufacturers and developers will benefit from the new rules as well.
The new regulation introduced in Peru prescribes the rules related to the validation of the safety, quality, and performance of in vitro diagnostic medical devices to be performed in the course of marketing approval. In particular, the authority clarifies the technical requirement such devices should meet in order to be allowed for marketing and use in the country. Actually, the document outlines the main principles to be considered by all the parties involved. The new rules are binding for all industry representatives intended to place their products on the local market. However, these rules will remain in effect only during the pandemic – as in the case with similar rules implemented in other countries, the ones introduced in Peru are also temporary in nature and are not intended to substitute existing general procedures and requirements.
The new rules pay the most attention to the aspects related to the development stage. During this step, the manufacturer shall consider:
- The purpose of the test,
- Methods, principles, effectiveness criteria, and limitations of the methods used,
- The type of infection agent to be identified,
- Clinical disease,
- Biological sample,
- Calculations and interpretation of the results,
- Accuracy of the test in various temperatures and time,
- Identification threshold,
- Consistency of the results,
- The form of use,
- Useful life,
- Shelf life,
- Storing conditions,
- Warnings and safety measures,
- National or international standards to be applied.
In the course of validation, the manufacturer shall provide sufficient evidence demonstrating that the medical device subject to review complies with the applicable requirements in terms of the accuracy and consistency of the results. All important information related to safety, quality, and performance should be reflected in technical specifications. Additionally, the manufacturer shall provide a protocol of investigation containing, inter alia, the details about the theoretical basis, methodology used, and applicability of the results. The authority additionally emphasizes that the requirements for technical documentation in terms of accuracy of the information provided are applicable to the instructions for use and user manuals as well.
The entity responsible for a medical device placed on the market is also obliged to ensure that all information kept in the registers and databases is accurate and up-to-date. In this regard, the responsible entity shall duly notify the authority about any changes or modifications made to the device itself, or documentation accompanying it. The authority reserves the right to collect the samples of medical devices placed on the market in order to perform an additional assessment aimed at and evaluation of compliance with the applicable regulatory requirements.
In summary, the new regulation issued in Peru moves focus to the core principles rather than the particular requirements a device should meet. This approach provides medical device manufacturers with additional flexibility in complying with the regulatory requirements.
Health Canada Framework for COVID-related Medical Devices
Health Canada, a country’s authority responsible for medical device regulations, has introduced a special framework for the importation and marketing of COVID-related medical devices. The appropriate measures have been introduced by the device of the Interim Order, a specific type of regulations used by the Canadian authority to implement additional rules. In contrast to similar measures introduced in other countries, certain measures implemented in Canada are permanent and will become a part of existing legislation on medical devices.
In particular, Health Canada announces the following:
- New rules are intended to streamline and simplify the process of placing new COVID-related medical devices on the market in order to ensure their uninterrupted availability,
- Special transitional regime to be introduced before the new framework will take effect,
- The particular rules to be applied would depend on the class of a medical device in question under the risk-based classification,
- For importing and distributing medical devices associated with the lowest risk, a medical device establishment license would be sufficient, while the medical device license for the particular product is not required,
- For importing and distributing higher risk medical devices a transitional medical device license is required, while later it should be replaced with an ordinary one,
- The transitional period is limited to 2 years.
Thus, during the transitional period, any and all medical device manufacturers shall achieve compliance with the new requirements in order to be allowed to market their products in Canada thereafter.
Health Canada announces simplified rules for Class I medical devices – during the transitional period, such devices could be imported and marketed under the respective transitional license. However, the requirements for medical devices assigned to Classes II, III, and IV are more strict and detailed.
Summarizing the information provided hereabove, special frameworks for COVID-related medical devices introduced in different countries have the same intended purpose, but the way they are actually implemented depends on the specific aspects of the respective legislation.
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