The Medicines & Healthcare products Regulatory Agency (MHRA or the Agency), the UK`s regulating authority in the sphere of medical devices, has published an updated version of its guidance dedicated to clinical investigations. The new version describes regulatory aspects related to Northern Ireland.
First, the authority mentions that the applicable regulatory requirements for clinical investigations of medical devices in Great Britain and Northern Ireland are slightly different. In particular, the latter will apply the new European regulatory framework, including the Medical Device Regulation 2017/745 (MDR) and the In Vitro Diagnostic Medical Device Regulation 2017/746. Consequently, any and all clinical investigations of medical devices carried out in Northern Ireland shall comply with the aforementioned regulations. The appropriate notifications should be submitted to the UK authority accordingly. At the same time, the investigations carried out in Great Britain should comply with the applicable national regulations.
Another important aspect relates to when clinical facilities involved in the investigation are located both in Great Britain and Northern Ireland. Since the regulatory requirements implemented under the EU MDR are similar to those prescribed by the UK legislation, it would be sufficient to comply with the former. Hence, an application to be submitted to the authority should comply with the requirements set forth by the EU MDR.
Like the previous version, the present guidance describes the approach for clinical investigations in general, while the specific aspects related to conducting clinical investigations of medical devices in Northern Ireland are provided in separate sections of the document.
The present MHRA guidance outlines cases when clinical investigations should or should not be conducted. Under the general rule, clinical investigations are mandatory for all implantable and Class III medical devices, except the following cases:
- The product in question constitutes a modification of another product currently marketed by the same responsible entity,
- The modified medical device is equivalent to the one already placed on the market, and
- The clinical evaluation related to an existing device could be applied for the new one and is sufficient to demonstrate compliance with the relevant regulatory requirements.
- If the modified device subject to review is manufactured by a different entity than the one responsible for the existing medical device, the following rules apply:
- There should be an agreement between two entities establishing an efficient exchange of information and documentation for medical devices, and
- The clinical evaluation for the initial medical device already placed on the market should be carried out in accordance with the EU MDR.
According to the guidance, clinical investigations of implantable and Class III medical devices are also not required in the following cases:
- The marketing of a medical device commenced under the Directives 90/385/EEC or 93/42/EEC prior to the EU MDR entered into force, and there is sufficient clinical data in place; or
- The product in question constitutes sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors, and there is sufficient clinical data in place demonstrating compliance of the medical device with the applicable regulations and specifications.
As stated by the MHRA, the primary purposes of clinical investigations is to:
- Establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is suitable for one or more of the specific purposes listed in point (1) of Article 2 [of the regulation], and achieves the performance intended as specified by its manufacturer;
- Establish and verify the clinical benefits of a device as specified by its manufacturer; and
- Establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.
Commencement of a Clinical Investigation
The document further describes specific aspects related to the commencement of clinical investigations of medical devices in Northern Ireland. According to the applicable regulatory requirements, the interested entity (a sponsor or its authorized representative based in the EU) shall submit the appropriate notice to the MHRA 45 days in advance. It will take an additional 45 days for the regulating authority to review the notice and issue the decision. The MHRA explicitly mentions that it is strictly prohibited to commence the clinical investigation of medical devices before a positive response has been received from the regulating authority. The latter is entitled to refuse in giving such permission in the following cases:
- The clinical investigation does not meet the requirements of the regulation,
- The application is incomplete,
- The device or the Clinical Investigation Plan and Investigators Brochure do not correspond to state of scientific knowledge and do not provide evidence for safety, performance or benefit of the device.
According to the guidance, the aforementioned review period could be extended for additional 20 days if the authority will have to engage external experts to assess the request. In such a case, the MHRA will send the appropriate notice to the interested party.
Methodology for Clinical Investigations
In addition to the general questions described above, the present MHRA guidance also highlights certain specific aspects related to clinical investigations of medical devices in Northern Ireland. It is stated that the methodology used in clinical investigations should comply with the regulatory requirements set forth by the EU MDR.
The MHRA emphasizes the importance of ensuring:
- The safety of subjects participating in the clinical investigations,
- Protection of vulnerable subjects,
- Potential risks associated with the clinical investigation are justified by the expected benefits,
- That an informed consent has been provided either by subjects themselves or by their authorized representatives,
- Protection of privacy and data,
- Minimal pain or other discomforts for subjects of the clinical investigations,
- The necessary medical care is provided to the subjects,
- There is no influence caused in any form on the subject of clinical investigations or his/her authorized representatives,
- That any and all investigational medical devices used are compliant with the safety and performance requirements such devices should comply with,
- The subject or his/her authorized representative are allowed to withdraw informed consent and suspend participation in the clinical trial,
- The investigator has the necessary qualification and knowledge,
- The clinical investigation is carried out in a clinical site that is suitable for this purpose and is similar to the one in which the medical device subject to investigation is intended to be used.
In summary, the present MHRA guidance describes certain specific regulatory requirements related to planning and conducting clinical investigations of medical devices in Northern Ireland. In particular, the document highlights the main differences in regulatory frameworks and describes the requirements clinical investigations shall meet.
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