IVDR Performance Studies and the ISO 20916:2024 Revision
ISO 20916:2024—Clinical performance studies using specimens from human subjects: Good study practice—was first introduced in 2019. In March 2024, it was published as EN ISO 20916:2024, marking a major step in ISO 20916 2024 IVDR harmonization IVD studiesacross Europe. This update aligns clinical performance study requirements directly with the IVDR.
In today’s rapidly evolving IVD landscape, safety and performance remain top priorities. ISO 20916 provides a solid framework to ensure clinical performance studies are planned, executed, recorded, and reported with scientific rigor. Its goal is simple: ensure IVD studies are ethical, reliable, and aligned with regulatory expectations.
This standard supports robust study design, promotes high‑quality data generation, and strengthens compliance for IVD manufacturers navigating the IVDR.
MDx hosted a live webinar on «Preparing for IVDR Clinical Performance Studies under ISO20916 and the new annex ZA» on the 30th April 2024.
The importance of Annex ZA of ISO 20916:2024 in IVDR performance studies
The March 2024 revision introduced a key milestone: Annex ZA, which formally harmonizes ISO 20916 with the IVDR. While the IVDR already referenced ISO 20916, the addition of Annex ZA creates a unified regulatory pathway for clinical performance studies.
Annex ZA bridges the remaining gaps between the standard and the regulation. As a result, manufacturers benefit from clearer expectations and a more predictable approval process.
EN ISO 20916:2024 was approved by CEN without modification, reinforcing its relevance for EU regulatory compliance. However, at the time of writing, official recognition of ISO 20916:2024 as an IVDR harmonized standard in the EU Official Journal is still pending.
Note: As of the date this article was written, the official recognition of ISO 20916:2024 as an IVDR harmonized standard for clinical performance studies in theEuropean Union’s Official Journal was awaiting confirmation.
Success in IVD Clinical Performance Studies with MDx CRO
At MDx CRO, we navigate the complexities of IVDR and the latest ISO 20916 revision for in vitro diagnostic (IVD) studies with unmatched expertise. Our commitment to rigorous clinical operations ensures that every clinical performance study meets all regulatory standards, incorporating strategic risk management and adaptability for maximum compliance and integrity.
Partnering with us offers manufacturers a significant advantage, rigorously evaluating IVDs to ensure adequate performance and safety, a critical component of regulatory approvals.
Choose MDx CRO for excellence in IVD clinical performance studies, driving success and enhancing patient outcomes. Contact us for a discussion today!
Highlights from Annex ZA include
1. Presumption of Conformity
Compliance with the ISO 20916 clauses listed in Table ZA.1 gives manufacturers a presumption of conformity with IVDR GSPRs. This presumption simplifies regulatory alignment across IVD clinical performance studies.
2. Definition Alignment
When definitions differ between ISO 20916 and the IVDR, Annex ZA prioritizes IVDR terminology. This ensures consistency across regulatory submissions.
3. Risk‑Management Updates
Annex ZA strengthens risk‑management expectations. It requires alignment with IVDR principles such as “reducing risks as far as possible.” It also notes that ISO 20916 does not include foreseeable misuse, while the IVDR does—requiring sponsors to bridge this gap.
4. Acceptable Risk Policies
Manufacturers must align acceptable risk decisions with specific GSPRs. Annex ZA also clarifies that while ISO 20916 excludes training as a risk‑reduction measure, the IVDR allows it.
Synergies between ISO 20916 and IVDR:
- Despite some differences, the ISO and IVDR frameworks remain closely aligned in key areas:
- Clinical performance parameters: Nearly identical, except ISO 20916 omits expected values for normal and affected populations.
- Ethical considerations: ISO 20916 provides more detail, defining responsibilities for sponsors and investigators.
- Bias mitigation: ISO 20916 offers explicit direction on preventing population, protocol, and reference‑method bias.
- Site qualification: More detailed under ISO 20916, specifying resources, equipment validation, and QMS expectations.
- CPSR content: ISO 20916 includes additional requirements, especially for interventional studies.
- Comparator devices: The standard requires clear listing with commercial name, manufacturer, and catalog number.
- Investigator’s Brochure: Both the IVDR and ISO 20916 are aligned, though ISO adds more detail on risk‑benefit documentation.
Differences to be aware of:
- Differences in Annex XIV studies (and IVDR article 58): The definitions of an Annex XIV study in IVDR (i.e. interventional and other performance studies involving risks to the subjects) are different from ISO 20916. Although Annex ZA considers both the standard and regulation to cover the same elements and therefore being aligned, the description of what is in essence an Annex XIV study is different when we look at the detail. For example, the IVDR recognizes surgically invasive sample taking as being an Annex XIV study, while ISO 20916 does not use this terminology.
- Adverse events: Although both IVDR and ISO 20916 are considered aligned, there are differences in the categorization of adverse events occurring in clinical performance studies. ISO 20916 provides two main types of events: non-device-related and device-related, and further categorizes this into non-serious and serious, anticipated, and non-anticipated. The IVDR is not as prescriptive in this area.
- Clinical performance study plan (CPSP): ISO 20916 is more prescriptive on the specimen details to be listed in the CPSP, including their storage. In addition, ISO 20916 does not require reference to the current state of the art in diagnosis and/or medicine, whereas this is a requirement from IVDR. Last but not least, ISO 20916 has specific requirements for the CPSP synopsis.
- Monitoring plan: ISO 20916 is a lot more prescriptive on the requirements for the monitoring plan, including qualification and training of monitors. According to ISO 20916 sponsors can also develop a rationale for remote monitoring. In addition, whereas IVDR requires that sponsors appoint a monitor independent of the investigation site, this point is not mandated by ISO 20916.
- Informed Consent: A lot more detail is provided in ISO 20916 when compared to IVDR. The standard offers a detailed framework for obtaining informed consent.
Who Benefits from EN ISO 20916:2024?
- Manufacturers of in vitro diagnostic medical devices
- In vitro diagnostic clinics and laboratories
- Test centres for in vitro diagnostic medical devices
- Regulatory authorities
- IVDR Notified Bodies
- IVD Clinical research organizations (CROs)
- Investigators and sponsors
Advantages of Adopting EN ISO 20916 for IVD Performance studies
- Robust Results: It ensures high-quality, accurate, and reliable data generation, pivotal for safe healthcare decisions.
- Ethical Standards: It upholds the rights, safety, dignity, and well-being of study subjects.
- Study Planning and Conduct: It facilitates the meticulous planning and execution of IVD performance studies, ensuring regulatory and ethical compliance alongside scientific validity.
- Compliance and Clarity: It provides a framework for compliance with IVDR, clarifying roles and responsibilities of all parties involved.
- Risk Management: It emphasizes subject safety, especially regarding specimen collection risks, and ensures data integrity.
Implications for IVD Performance Studies and CRO Services
The integration of ISO 20916 with the IVDR, highlighted by the inclusion of Annex ZA, significantly transforms IVD clinical performance studies and CRO operations. This crucial alignment demands a comprehensive revision in study design, execution, and reporting methodologies, highlighting the importance of compliance with the unified ISO 20916 and IVDR standards. It emphasizes the need for robust quality and risk management systems and ethically responsible study development.
This evolution signifies more than standard adherence; it represents a commitment to elevating IVD performance and efficacy in line with the highest EU regulatory standards. It requires IVD stakeholders, including CROs, sponsors and manufacturers, to deeply understand and agilely apply these standards, not only for compliance but to set new quality and safety benchmarks in diagnostics.
This commitment is fundamental to advancing patient care and public health, marking a significant step forward in regulatory compliance and industry excellence.
Since its foundation, MDx CRO has consistently used ISO 20916 as the benchmark for all our IVD clinical performance studies. The release of Annex ZA and its harmonization with IVDR reinforces our status as the leading CRO for IVD clinical performance studies.
