The Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) represent transformative regulatory frameworks for medical devices and in vitro diagnostics within the European Union (EU). These regulations aim to enhance patient safety, streamline market access, and ensure the effectiveness of medical devices and in vitro diagnostics in the context of rapid technological advancements, the increasing complexity of devices, and the need for greater scrutiny of these devices' performance and safety. The MDR focuses on a risk-based approach, mandating stricter clinical evidence requirements, rigorous post-market surveillance, and comprehensive documentation for medical devices. The IVDR similarly emphasizes increased scrutiny for in vitro diagnostics, necessitating greater clinical evidence and traceability throughout the device lifecycle.

Article 5(5) of the MDR and the IVDR specifically deals with in-house devices, which are manufactured and used on a non-industrial scale within healthcare institutions (hospitals, laboratories, public health institutes) to address the specific needs of target patient groups that cannot be met or cannot be met at the appropriate level of performance by an equivalent CE-marked device available on the market. Such devices are not intended for commercial distribution but are used for the exclusive purpose of providing healthcare services to the institution's patients. To this end, the manufacturing process should not produce more than the estimated number of devices to meet the patient group’s needs. With article 5(5), the MDR and IVDR recognize the unique nature of in-house devices and provide a more lenient regulatory pathway for them compared to commercially distributed devices.

This blog post explores the key provisions, requirements, and implications of Article 5(5) of the MDR and IVDR taken into account the information provided in the MDCG 2023-1 guidance.

Exemption from conformity assessment

One of the primary implications of Article 5(5) is that in-house devices are exempted from the rigorous conformity assessment procedures required for commercial devices. This exemption is justified by the low risk posed by these devices since they are used on a limited scale and within a controlled environment.

Compliance with general safety and performance requirements

Although in-house devices are exempt from conformity assessment, Article 5(5) mandates that these devices must still comply with the general safety and performance requirements specified in Annex I of the respective regulation. The healthcare institutions are responsible for ensuring that their devices meet these requirements, maintain comprehensive documentation to demonstrate compliance, and make the records available to competent authorities upon request.

Furthermore, for medical devices under the MDR and for class D IVDs, the regulations specifically state that the health institution is required to draw up documentation that makes it possible to have an understanding of the manufacturing facility, the manufacturing process, the design and performance data of the devices, including the intended purpose, and that this documentation is sufficiently detailed to enable the competent authority to ascertain that the general safety and performance requirements set out in Annex I of the respective regulation are met. Member States may choose to apply these provisions also to class A, B or C devices under the IVDR.

Other important aspects of compliance with Annex I of the MDR and IVDR include:

-       a risk-management system and the regular update of the benefit-risk ratio assessment for the device (Chapter I of Annex I)

-       information regarding design, manufacture, and performance, which is also needed to establish a proof of non-equivalency of available CE-marked devices (Chapter II of Annex I)

-       information to be supplied with the device, which although not as extensive as for commercially-available devices, shall include at least operating instructions/ protocols, information on dangerous substances or mixtures, expiry or production dates, storage and handling conditions, lot/serial number or an equivalent means of identification for traceability purposes

While not explicitly required by Article 5(5), healthcare institutions may choose to designate a person responsible for regulatory compliance, ensuring adherence to the MDR’s and IVDR's requirements for their in-house devices.

Prohibition of transferring the devices to another legal entity

The regulations stipulate that in-house devices shall not be transferred to another legal entity. While the concept of a legal entity can differ on a national level and should be clarified with the national competent authority, the manufacturer shall ensure that devices are both manufactured and used within the respective institution for the care or diagnosis of patients. If, during the lifecycle of the device, it is used outside the health institution’s legal entity, then the device cannot be considered an in-house device. Examples of devices that would, in this context, not fall under Article 5(5) would be orthopedic braces that can be adapted by patients themselves outside the health institution, self-tests, or medical device applications that can be used by patients outside the institution.

In contrast, it has to be noted that, while delivery of the results (reading of the results from the device) should occur in the health institution that manufactured the device, sharing of the results between health institutions and with the patients is possible.

Manufacturing and usage of the devices under an appropriate QMS

Article 5(5) requires that the manufacture and use of in-house devices shall occur under an appropriate quality management system (QMS).

For the manufacturing of devices, as a guideline, health institutions could use Article 10(9) under the MDR and/or Article 10(8) under the IVDR that list minimal quality management system (QMS) requirements for manufacturing CE-marked devices (note that these articles are not a requirement applicable to in-house devices but can be used as a guideline). The QMS aspects covered by these articles include responsibility of the management; risk management; manufacturing; traceability; monitoring, analysis and continuous improvement; and communication with competent authorities. If applicable, ISO-standards such as ISO 13485 (the aspects relating to manufacturing, monitoring, analysis, and continuous improvement) and ISO 14971 (risk management) can be used.

For the use of the devices, the relevant aspects of standards ISO 15189 (medical laboratories) and ISO 15224 (health care institutions) could be incorporated in the institution’s QMS for IVDs and medical devices, respectively. The QMS can cover the whole health institution or only the parts of the institution involved in the manufacturing, modification, and use of the in-house device.

In the context of Article 5(5), there is a need to collect and analyze supporting data to justify that the target patient group’s specific needs cannot be met or cannot be met at the appropriate level of performance in another way or by a commercially available device. A process for the collection, maintenance, and analysis of this data, including the collection of information about equivalent CE-marked devices that become available on the market, should be part of the institution’s QMS.

Compliance with ISO 15189

An additional requirement of the IVDR is that the laboratory of the health institution is compliant with ISO 15189 or, where applicable, national provisions, including national provisions regarding accreditation.

It has to be noted that, as the manufacturing process of the device and compliance to the requirements of Annex I of the respective regulations is not within the scope of ISO 15189, compliance with this standard alone does not constitute an appropriate QMS for manufacturing of in-house IVDs. Rather, the QMS shall incorporate the relevant aspects for both manufacturing (ISO 13485 or equivalent) and use of devices (ISO 15189) as described above.

Post-market surveillance

Healthcare institutions are expected to conduct reviews of the experience gained from clinical use of the devices and take all necessary corrective actions for their in-house devices. The institutions shall gather data regarding the performance of the device during routine use, including incidents or complaints, and document all corrective actions undertaken. This approach ensures that any adverse events or performance issues are promptly identified and addressed.

National legislations should be consulted about possible requirements regarding the reporting of incidents and corrective actions.

Justification of non-equivalence

The health institution is required to justify in its documentation that the target patient group's specific needs cannot be met, or cannot be met at the appropriate level of performance by an equivalent device available on the market.

In this context, a target patient group is understood to have in common the same disease, condition, or characteristics and could benefit from a specific device or a certain level of performance of a device.

While discussing the justification of non-equivalence, the MDCG 2023-1 guidance cites Annex XIV 3. of the MDR and divides device characteristics that should be considered for a demonstration of (non-)equivalence into technical, biological, and clinical. Based on this, the guidance concludes that the equivalence characteristics mentioned in the MDR should be taken as a guidance and a justification of non-equivalence based on technical, biological, and clinical aspects of the device should be documented.

From our standpoint, the justification of non-equivalence is primarily concerned with the clinical performance of the device in the target patient group and the demonstration that the clinical benefits for the patients cannot be achieved at the same level of performance by any device that exists on the market. We find that considering the technical and biological properties of devices in the justification of non-equivalence should be secondary to the documentation of the clinical performance of the in-house device in the target patient group. For example, there might be devices on the market with equivalent technical and biological properties, but reduced clinical performance for the intended use and in the target patient population of the in-house device.

As mentioned, the health institution should have in place a process to continuously examine the market for the presence and availability of equivalent CE-marked devices and should review its justification of non-equivalence on a regular basis in view of these findings.

If, while an in-house device is in use, a CE-marked device that is at least equivalent to it and meets the patient group’s requirements at the needed level of performance is placed on the market, the health institution should commence a transition process to the usage of the CE-marked device.

Other Requirements/ Interaction with competent authorities

The legislations require that the health institution that manufactures and uses an in-house device shall:

-       provide information upon request on the use of such devices to the competent authority, which shall include a justification of their manufacturing, modification and use

-       draw up a declaration which it shall make publicly available according to the specifications in the respective regulations and national provisions

The information required by the competent authorities might include, but not be limited to, data on the device type, intended purpose, target patient group, design, safety and performance, potential benefit of the device, the justification of non-equivalence, a description of the manufacturing process and the modifications performed, or information regarding the use of the device. Once the device has been used routinely, competent authorities might require information about the number of batches manufactured in a certain time period and a justification of the production numbers, as well as post-market surveillance data as described above.

Both the MDR and the IVDR outline the content of the declaration to be drawn up by manufacturers of in-house devices, but health institutions are advised to also consult the national legislations for specific content and publication requirements for such a declaration. Once the declaration is public, it should be reviewed regularly and updated if necessary.

Timelines

Article 5(5) of the MDR has been fully applicable since 26 May 2021.

In what the IVDR is concerned, from May 26, 2022, all lab-developed tests in the EU must meet the general safety and performance requirements set out in Annex I of the IVDR, including the performance evaluation, and may not be provided to another legally independent facility. The deadline for the implementation of subsections (b) QMS and (c) ISO 15189, and (e) through (i) of Article 5(5) of the IVDR is May 26, 2024.

For subsection (d) justification of non-equivalence of Article 5(5) of the IVDR, the implementation deadline is May 26, 2028.

Conclusion

The incorporation of in-house devices within the MDR and the IVDR offers a stronger, more transparent, and enduring regulatory structure with international recognition, enhancing clinical safety in the context in which such devices play a crucial role in diagnosis and treatment, particularly of patients with rare medical conditions.

While exempt from formal conformity assessment, healthcare institutions are still obliged to comply with general safety and performance requirements and maintain appropriate documentation. This approach strikes a balance between ensuring patient safety and reducing the burden on healthcare institutions that use in-house medical devices or IVDs for the benefit of their patients.

If you need support with the preparation of the conformity documentation or the regulatory strategy for your in-house device, please contact us at: info@quaregia.com. Our expertise draws on 35-plus years of experience with medical devices, medical device software, in vitro diagnostic devices, and combination products.

Last updated 2023-08-24