The Medicines and Healthcare products Regulating Agency (MHRA), the UK agency responsible for medical devices regulations, has published guidance describing the way the study sponsors should notify the authority about a clinical investigation for a medical device. The initial version of the guidance has been published by the authority earlier in December 2014.
According to the general rule, a sponsor (an interested party) of a clinical investigation shall duly notify the regulating authority in advance, but no later than 60 days prior to the commencement date. At the same time, the requirement shall not be applied in the case of medical devices that already have a CE mark.
First of all, the MHRA recommends the sponsor of a clinical investigation to submit the appropriate advance notice via email. The notice shall contain the following information:
- Main details about the medical device subject to the investigation,
- Intended population to be covered by the investigation,
- Type of study,
- Estimated application date.
The authority additionally emphasizes that such an advance notice could not be used instead of the clinical investigation notification. However, advance notice would be useful for the regulating authority.
The MHRA also states that all the information and documents should be prepared by the sponsor in advance before informing the authority about the planned clinical investigation. In particular, in the present guidance, the regulating authority refers to the appropriate guidance on compiling a submission and guidance for manufacturers.
Notification About a Clinical Investigation: Associated Fees
The MHRA guidance on notifying about a clinical investigation also covers the aspects related to the applicable fees. According to the document, the fees payable by the sponsor are prescribed by the Medical Devices (Fees Amendment) Regulations 2017. Under the aforementioned document, the new fees have been implemented for amendments to clinical investigations.
According to the guidance, the sponsor is not obliged to pay the applicable fees in advance – the MHRA states that the appropriate invoice would be issued only after the application filed by the sponsor would be validated by the regulating authority. Actually, this is the most important amendment to the fees payment procedure introduced.
As it was already mentioned before, the sponsor shall duly notify the regulating authority about the amendments made for a clinical investigation, and there are also the fees associated with such notification. In accordance with the guidance, each time planning amendments, the sponsor shall notify the regulating authority in advance and wait for the response – any changes should be agreed with and approved by the MHRA. In particular, the amendment notification rules covers the changes to:
- The medical device subject to review,
- Any documentation related to the investigation (e.g. the clinical investigation plan),
- The investigators or the institution performing the investigation,
- Any changes requested by an ethics committee.
The notification on amendments shall consist of such elements as:
- Cover letter (containing the MHRA reference number, brief information on proposed changes together with the justification),
- Copies of all the documents subject to changes (both clean versions and ones with changes highlighted),
- A statement regarding the potential impact of the changes, indicating that the changes to be made would not increase the risks associated with the device, signed by the manufacturer or on its behalf,
- Company details to be used by the MHRA to issue the invoices (including the company name, its address, and also Tax/VAT numbers).
The notification on amendments could be also submitted to the regulating authority via email.
The authority also emphasizes that the fees prescribed by the aforementioned regulation should be calculated for each medical device subject to review separately, providing that there is no connection between these medical devices.
Application Review by MHRA
The document also describes the processes associated with the review of the notice by the MHRA. In accordance with the information provided, the regulating authority would explicitly confirm the receipt of the documents submitted not later than 5 business days after the receipt by the MHRA. Starting from the date of submission the calculation of a 60-days assessment shall commence. However, the regulating authority is also entitled to get back to the manufacturer with additional requests. In such cases, the calculation of the aforementioned period should commence only after the sponsor will provide all necessary information to the regulating authority. It is also important to mention that for the purpose of the calculation described hereabove, the first day should be the first business day following the day the complete notification has been received by the regulating authority.
Within the whole prior notice period, the MHRA experts may assess the aspects related to the safety and performance of a medical device subject to review. Hence, the regulating authority has a right to request additional information or clarifications needs to assess the case. In this regard, the regulating authority recommends the sponsors to get back with the response within the shortest possible period of time to ensure all important aspects would be closed before the assessment period would expire.
Upon completion of the aforementioned assessment, the MHRA would provide the sponsor with a letter indicating the decision taken by the authority regarding the clinical investigation the sponsor intends to carry out. Such a letter could be provided even before the expiration of the 60-days assessment period, in case if the MHRA would make its decision earlier.
Clinical Investigations for IVDs
The MHRA guidance on notifying about a clinical investigation also addresses the matters associated with the In Vitro Diagnostic Medical Devices (IVDs). According to the general rule, all IVDs should have a properly placed CE mark in order to be allowed for marketing and use, except the cases when an exemption rule could be applied. The scope of this requirement also covers in vitro diagnostic medical devices used in the context of clinical investigations. In case if an IVD is not only used in a clinical trial (initially covering the medicines, for example) but is subject to review itself, the appropriate study should be subject to registration with the MHRA.
The authority also mentions that the concept of self-certified IVDs should be applied. For specific questions, the MHRA refers to the appropriate guidance on in vitro diagnostic investigations for medical devices issued previously by the regulating authority.
According to the present MHRA guidance, there are certain cases when the sponsor of a clinical investigation is not required to notify the regulating authority – for instance, in the case of in-house IVDs manufactured by healthcare institutions and intended to be used solely for internal purposes. At the same time, a notification about clinical trials is required in the case is the IVDs in question are intended to be used by another entity.
Summarizing the information provided here above, the MHRA guidance on notifications about clinical investigations for medical devices describes the way the sponsor of a clinical investigation shall notify the regulating authority about the planned study and also outlines the scope of information and documents to be provided. The document also covers such aspects as applicable fees payable by the sponsor notifying the authority about the amendments to the clinical investigation, as well as certain specific aspects associated with the in vitro diagnostic medical devices.
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