The Medicines & Healthcare products Regulatory Agency (MHRA), the UK regulating authority in the sphere of medical devices, has published detailed guidance dedicated to the off-label use of medical devices. The scope of the guidance covers only the medical devices intended to be marketed and used in Great Britain, including England, Wales, and Scotland.
Regulatory Background
Under the general rule, any medical device should be used strictly in accordance with the instructions for use initially provided by the manufacturer. In case if a medical device is being used for a purpose another then specified by the manufacturer, such use would be considered as “off-label”. The healthcare professional using the device would be solely responsible for such use any consequences thereof unless such use is explicitly approved by the medical device manufacturer. The healthcare professional using a medical device in such a way should consider the risks and potential impact on the safety and performance.
According to the MHRA guidance, the risks associated with off-label use of medical devices may include:
- Adverse reactions,
- Inadequate sterilization,
- Insufficient mechanical strength and/or structural integrity,
- Insufficient durability,
- Misuse due to lack of adequate training for the device.
A medical device that complies with the applicable requirements shall bear a UKCA mark indicating that the device is compliant with the requirements related to safety, quality, and performance. At the same time, the UKCA / CE marking is not required for custom made medical devices – the ones created to meet the needs of the particular patient. Such devices are initially manufactured in accordance with the request submitted by a healthcare professional. Since these devices are not intended to be placed on the market, special marking is not required. The same approach should be applied in the case of medical devices used in clinical trials – they do not require a CE mark as well, since they are not intended to be made available to the patients apart from the clinical trial process.
The MHRA additionally states that under certain conditions it may approve exceptional use of a non-compliant medical device, providing that such use is justified to meet the corresponding needs. In such cases, the requirements on mandatory marking could be waived too.
Another important aspect to be considered relates to modifications to the medical device. For some medical devices, modifications are initially allowed by the manufacturer. In such a case, the manufacturer shall provide detailed instructions in the documentation supplied with the device. These instructions should include the description of the ways the medical device could be modified, for example, to fit the needs of the particular patient. Another type of modification takes place in case if the medical device manufacturer (developer) releases software updates or makes certain changes to the hardware. Such modifications could be made in order to improve the performance of the device, or in the course of corrective and preventive actions intended to improve the safety of the device and address the related matters. In case of hardware changes, the medical device manufacturer may also provide detailed instructions describing the way such changes should be implemented by healthcare professionals or customers already using the device.
The MHRA additionally mentions that under the general rule, single-use medical devices are intended to be used only once. Should the entity take the actions necessary to decontaminate them in order to make possible future use, such entity would be deemed as a medical device manufacturer and, consequently, would have to comply with the appropriate requirements and regulations. Moreover, if a medical device is not properly labeled for such use, the further use of a device would be construed as off-label, and the entity conducting such actions would be solely responsible for any consequences thereof.
Off-label Use in Detail
The MHRA guidance clarifies the cases when off-label use of a medical device would be reasonable and justified. For instance, this could be considered in case if there is no medical device meeting the particular purpose among those duly registered and marked for such a way of use. The options to be considered in such a situation include:
- The off-label use of existing medical device initially intended for other purposes,
- Making changes to an existing medical device in order to be able to use it for the new purpose, or
- Use a different product that is not regulated as a medical device under the applicable legislation and is not marked with CE / UKCA marking.
When considering the options, one shall assess the benefit/risk balance of such use, and also pay attention to the following aspects:
- Proper risk assessment, confirmed by the appropriate documents,
- Evaluation of both ethical and legal consequences,
- Taking all the measures necessary to reduce the risk, associated with the off-label use, to the lowest extent possible,
- Periodical review of the risk assessment,
- Obtaining special approval from the regulating authority regarding the exceptional use of the non-complying medical devices.
The MHRA additionally emphasizes that it is necessary to notify the patient that off-label use of a medical device would take place. The appropriate notice should be also made in the patient’s records.
Additional Rules and Specific Cases
According to the present MHRA guidance on the off-label use of medical devices, it is also important to consider the risks associated with the compatibility issues arising when using third party accessories. Under the general rule, a medical device should be used only with accessories it is initially intended to be used with. However, sometimes necessary accessories could be unavailable. In some cases, different accessories could be used in order to expand the functionality of a medical device or improve its performance. As the result, a medical device could be used for purposes, other than specified by the medical device manufacturer in the appropriate documentation supplied with the device. Such use would be also considered off-label. Thus, an additional risk assessment would be required to evaluate the new risks associated with such a way of use.
The guidance also provides some examples of issues that could take place when using medical devices for purposes other than initially intended by the manufacturer. Such information is provided in a form of a table containing the description of alleged off-label use of the particular medical device and potential consequences thereof. For instance, should a user make attempts to change the configuration of Bain`s breathing system, the system could fail to work properly due to the wrong size oxygen connector.
Summarizing the information provided here above, the present MHRA guidance describes the concept of off-label use in general, outlines the main points to be considered by the party intended to use a medical device in such a way, and also highlights the main risks arising when the medical device is being used for a purpose other than specified by the medical device manufacturer. The document also emphasizes the measures and precautions to be taken before and during the off-label use in order to mitigate the risks associated thereto.
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