From proof of concept to clinical investigation, when is regulatory approval required?

by Jazmin McCalla-Bedward | 24 Oct 2025

Reading time: 7 minutes

Academic studies span from fundamental to translational research. Understanding the associated regulatory pathway is key for academic innovators developing medical devices. Whether you require ethics approval or a national regulator's authorisation to perform your research, both are designed to ensure the safety, rights, and well-being of participants. This article discusses the different types of research and when regulatory approval is required.

What is a clinical investigation?

A clinical investigation is defined by the Medical Device Regulation (MDR) as any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device. Its purpose is to generate the clinical evidence required for regulatory approval, CE marking under MDR or UKCA marking under UK MDR. It definitively evaluates safety and performance in the intended patient population according to a pre-specified, established protocol.

Your study is a clinical investigation if it involves one or more human subjects and if the device is used for a medical purpose and the objective of the study is to determine one or more of the following: clinical performance, effectiveness, safety of the device.

• diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease
• diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability
• investigation, replacement or modification of the anatomy or of a physiological or pathological process or state
• providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations
• control of conception

If the product you are going to test is being used for one or more of the above purposes, or its mechanism of action achieves one of the above purposes, it means that it now has a medical purpose and the study would be considered a clinical investigation.This means that you need approval from the MHRA in UK or the regulators in your country to perform your study.

When national regulatory approval is NOT required.

Some studies do not need any approval from the regulators, but be mindful that if humans are involved, ethical approval is always needed from your research institution. Let's discuss different types of studies and why they do not require regulatory approval.

If a study does not involve human subjects it does not need MHRA approval.

When you are testing a device to evaluate whether the device concept can be technically realised, focusing on things like engineering challenges, material properties, manufacturing processes, and basic functional requirements. You are only testing whether the device is technically feasible, without testing it in humans.

This does not require an approval from the MHRA, or your local regulators, as there is no medical purpose and this type of testing does not involve human subjects.

An example is when you are creating a basic version of the device to see if it can physically and technically perform its core functions using current technology, such as the correct materials for fluid filled devices.

Another example is when you are testing a new temperature sensor you have developed in the lab, you test its functionality using a waterbath and environments with different temperatures and compare that with an established temperature measurement device.

Studies involving humans: when is regulatory approval mandatory?

General purpose vs a medical device

When testing a device in humans you will have to keep in mind when a study is a clinical investigation: it has to involve one or more human subjects and the device has to be used for a medical purpose and the objective of the study is to determine clinical performance, effectiveness, safety of the device. Therefore if the device does not have a medical purpose as stated above, the study will not qualify as a clinical investigation and no approval is needed from the regulator, but ethics from your research institution will be required.

For example, if you are testing a new bike you have developed. The intended purpose is to maintain a healthy lifestyle for the general healthy population. This bike does not have a medical purpose and is therefore qualified as a wellness device or a general product. Because this bike falls outside the remit of a medical device, it does not require approval from the regulator before testing this bike in humans, as this will not be seen as a clinical investigation.

Whereas, if you are testing a bike that is intended to be used for rehabilitation, on people who require muscle strength due to muscle injury or replacement surgery. This bike now has a medical purpose and a patient population, meaning that it comes within the scope of a medical device. Before performing this study you will need approval from the regulators as this study is now a clinical investigation.

The key distinction between general purpose device and medical device, is the manufacturer's intended purpose, how you describe your device and what the mode of action is, as it determines qualification between medical device and wellness device, as well as the applicability of a clinical investigation.

Research Tools/Studies

If the device is used on humans but not being used for a medical purpose within your study, then it could be categorised as a research tool. The application of the regulation is dependent on the aims and objectives of the study.

If the aims and objectives of the study are to produce generalisable knowledge, the study is likely to be qualified as a research tool. For example, studies using a device which aim to produce a better understanding about a particular aspect of the human body.

Once it has been determined that the device / study is a research tool, it is important that there are no claims or references to a medical purpose in the study documentation. For example, the study information should not imply that a participant’s pathological diagnosis will be updated, or that their disease state will be improved, by participation in the study. Research studies and tools do not require approval from MHRA

However, if these studies explicitly or implicitly make the claims that a participant's pathological diagnosis will be updated, or that their disease state will be improved then this study and device is being used for a medical purpose and is a clinical investigation which requires approval from MHRA.

Regulatory requirements by research type

Proof of concept

If you are testing a device’s functionality, without a medical purpose or intent, this is usually completed through prototyping and laboratory testing to determine whether a device or component works. If you will be testing on human subjects, first determine if the device has a medical purpose and if the study is to determine clinical performance, effectiveness, safety of the device.

When no human is involved, a regulatory approval is not required. For example, testing if a device can perform its core function. If you are testing whether a pump is able to deliver a specific volume of a solution at a certain rate. You will do this test in the lab without any humans involved. The study is to test the functionality of the pump itself and at this stage does not have a medical purpose. The reason is because the pump is not yet part of a medical device, it is just the component for a product.

However, if you are testing the same pump, but now you will test if this pump can deliver a solution to a person, e.g an insulin pump, this would need to be tested on human subjects. This study will test the functionality of the pump being able to carry the solution to a person or patient.

This study will require a notification to the MHRA, as there is a clear medical purpose, you are testing the safety and performance of a medical device and this type of testing involves human subjects. In general, proof of concept clinical investigations are designed to enrol a limited number of subjects to assess a device early in its development phase with respect to the initial clinical safety and/or performance (e.g. device functionality). The results of this kind of clinical investigation may guide further device design modifications or provide further information for the design of a subsequent clinical investigation (MDCG 2021-6 Rev. 1).

Comparison study

When conducting studies involving the comparison of a new device against existing products, predicate devices, current standard of care, or competitor products. This type of testing establishes competitive positioning and identifies advantages/disadvantages relative to established alternatives.

If human subjects are not used for this type of study, then regulatory approval is not required. For example: Pushing the device beyond its normal operating capacity to identify potential failure points and determine its behaviour under extreme conditions against products that are already on the market, this test would not involve human subjects to test this product.

Or when measuring the tensile strength and compression of a wearable medical device to determine the material’s resistance to being pulled apart or squeezed against, using a machine to perform the test.

For some comparison studies, human subjects are required such as: a study comparing a new continuous glucose monitor against the current standard device in 200 adults with Type 2 diabetes, measuring accuracy of glucose readings and patient satisfaction over 14 days with participants randomly assigned 1:1 to either device, with glycaemic control outcomes assessed.

In this study the device is considered to have a medical purpose. The question would then be whether the device is being used to determine the clinical performance, effectiveness and safety of the device. If the answer is yes, this could be considered a clinical investigation and does require a notification to the MHRA.

If the answer is no and the study is investigating the usability of a device, not the clinical performance, safety or effectiveness then this does not require a notification to the MHRA.

Conclusion

The journey from a proof of concept to a clinical investigation is marked by a critical transition: the introduction of a medical purpose and the involvement of human subjects. For academic innovators developing medical devices, understanding when and what kind of regulatory approval is needed isn't just a compliance hurdle, it's a foundational element of responsible research, safeguarding participant safety and rights.

In summary:

• No human subjects, no regulatory approval: Studies focused on technical feasibility, engineering challenges, or basic component functionality without human subjects (for example: lab testing, bench comparisons) generally do not require authorisation from a national regulator like the MHRA.
• Medical purpose: A study becomes a clinical investigation, requiring national regulatory approval, when it involves human subjects and the device is used for a medical purpose (diagnosis, treatment, monitoring, etc.), with the objective of determining its clinical performance, effectiveness, or safety.
• General purpose vs. Medical device: The intended purpose is the key differentiator. A wellness or general purpose device tested in humans (for example: a non-rehabilitation bike) typically does not require regulatory approval for the study, as it lacks a medical purpose.
• Ethics approval is always essential: Regardless of the need for national regulatory authorisation, any study involving human participants, from a general purpose device test to a full clinical investigation, always requires ethical approval from your research institution or an independent ethics committee.

Academic researchers must diligently assess the aims and objectives of their study and the intended purpose of their device. This careful evaluation ensures that fundamental research can progress efficiently, while translational research is conducted within the necessary, strict regulatory framework designed to ensure safe and credible clinical evidence.

References: Flow Chart for Clinical Investigations - MHRA, Microsoft Word - GB Flow Chart Accompanying Guidance_v2, Clinical investigations for medical devices - GOV.UK