The impact of Article 5(5) on clinical trials overview – Article 5(5) of the In Vitro Diagnostic Medical Devices Regulation (IVDR) provides an exemption for in-house developed tests used within healthcare institutions. With most of its requirements coming into force on the 26^th of May 2024 failing to meet the compliance deadline may have significant consequences for healthcare institutions and organizations involved in diagnostic testing.

Possible impacts of Article 5(5) include:

Operational Disruption

• Impact on Patient Care: One of the most immediate consequences of non-compliance with Article 5(5) is the potential disruption to patient care. Healthcare institutions may be required to stop using non-compliant in-house tests, leading to delays in diagnosis and treatment that could negatively impact patient outcomes.
• Effect on Laboratory Operations: Laboratories may also face workflow disruptions and potential backlogs as they try and transition to compliant alternatives, reducing the efficiency of diagnostic services.
• Allocation of Resources: To manage and address the new requirements, there will be a need to reallocate resources potentially shifting focus away from other crucial areas within the organization.

Impact on Clinical Trials

• Delays in Research: Clinical trials relying on in-house diagnostics may experience delays that could affect the timelines for crucial research and development activities. These delays could slow down the progress of new treatments and innovations.
• Necessity for Study Redesign: Clinical trials might need to be restructured to incorporate compliant diagnostic tests. This process can be time-consuming and resource-intensive, and potentially delay the introduction of new diagnostic and therapeutic options to the market.

Regulatory Consequences

• Enhanced Regulatory Oversight: Organizations that fail to comply with Article 5(5) may find themselves under increased scrutiny from regulatory authorities. This could result in an increased administrative workload and disruptions to day-to-day operations.
• Legal Challenges: Non-compliance with Article 5(5) may also result in legal issues and litigation, which may cause further financial and operational challenges.

Financial Ramifications

• Escalating Compliance Expenses: The costs associated with addressing compliance issues after the deadline has passed can be higher than those of taking proactive compliance measures.
• Fines: Regulatory authorities may impose financial penalties on institutions that fail to comply with Article 5(5), further straining budgets.
• Investment in New Technologies: To replace non-compliant in-house diagnostics, healthcare facilities may need to invest in recent technologies or external diagnostic tests, leading to added financial pressure.
• Revenue Decline and Patient Attrition: Disruptions in diagnostic services can result in direct revenue loss, particularly if patients decide to choose alternative providers for their diagnostic requirements. This can have an impact on long-term revenue.

Harm to Reputation

• Deterioration of Confidence: Failure to comply with Article 5(5) can significantly damage the trust and confidence that patients, partners, and regulatory bodies have in an institution and affect its reputation.
• Impact on Partnerships: Trust plays a vital role in collaborations with other healthcare providers, researchers, and suppliers. Non-compliance can put these relationships at risk, potentially limiting future opportunities.
• Concerns from the Public and Stakeholders: Inquiries about the reliability and safety of in-house diagnostics may raise concerns among the public and stakeholders, potentially harming the institution’s reputation and credibility.
• Negative Media Attention: If non-compliance issues become public, media coverage could further damage the institution’s reputation, impacting public trust and confidence.

In conclusion, non-compliance with IVDR Article 5(5) requirements may have significant and varied consequences, such as operational disruptions, regulatory penalties, financial repercussions, and harm to reputation. Healthcare Institutions should prioritize compliance to avoid these serious outcomes and ensure the continued delivery of high-quality diagnostic services. Proactive planning, investment in compliance measures, and effective management of regulatory requirements are crucial for effectively addressing the challenges posed by the IVDR and lowering the impact of Article5(5) non-compliance.

Clinical trial sponsors also need to be aware of  the impact of Article 5(5) and its requirements when using local testing during trials.

 Tips for Clinical Trial Sponsors to Ensure Compliance with Article 5(5) include:

Educate your teams and make them aware of the risks: Ensure that all the members of the clinical trial teams receive thorough training on the specific requirements of Article 5(5). This training should include how to identify the specific risks, difficulties, and challenges for the trial. Awareness is key to mitigating potential issues.

Identify and Document All In-House Tests required to be listed on the CTA Cover Letter: (i.e. required by the protocol to achieve the objectives of the clinical trial). Include the name of the health institution responsible for manufacturing and using these tests, along with a link to their IVDR Article 5(5) declaration. This ensures transparency and demonstrates compliance to regulatory authorities.

Conduct Due Diligence on Laboratories: assess whether the laboratories involved in local testing within your clinical trial can meet the requirements of Article 5(5). This includes checking that they have an appropriate Quality Management System (QMS) in place, as well as the technical capacity to perform the necessary tests. Note that this may apply to more than just tests used for inclusion and/or exclusion.

Consider Alternatives: Explore central testing options and alternatives where possible and be mindful of the additional requirements for IVD performance studies under the IVDR.

To learn more about how to prepare for the changes and guidance on how to meet the Article 5(5) requirements, contact ARC experts. or watch our webinar “Article 5(5) Are you ready for the inhouse exemption”

Article 5(5) Summary of Requirements