The landscape of clinical investigations for medical devices continues to evolve under the Medical Device Regulation (MDR) and the updated ISO 14155:2026 standard. For Contract Research Organisations (CROs) supporting sponsors in clinical operations, the revision provides not only a regulatory framework but a practical guideline for ensuring that every clinical activity — from first subject enrolment to post-market follow-up — meets the highest standards of quality, ethics, and scientific integrity.

Protection of patients and scientific credibility

At the core of ISO 14155 remains the dual foundation of Good Clinical Practice (GCP): the protection of human subjects and the reliability of scientific data. The updated standard reinforces these principles through a stronger emphasis on:

  • safeguarding participant rights, safety, and well-being,
  • ensuring the scientific validity of study design,
  • maintaining credibility and reproducibility of clinical outcomes.

These align directly with MDR Annex XV and the General Safety and Performance Requirements (GSPR), forming the baseline for conformity assessment. In practical terms, this means that every CRO must ensure that site monitoring, data verification, and investigator training are executed in a way that traceably supports regulatory compliance and ethical oversight.

Clarified roles and responsibilities

One of the most valuable aspects of the revision is its clarification of roles and obligations across stakeholders. The standard clearly distinguishes the responsibilities of:

  • sponsors, who retain ultimate accountability for the study’s scientific and operational quality,
  • investigators, responsible for clinical conduct and subject management,
  • ethics committees and competent authorities, ensuring independent oversight.

For multi-centre and geographically distributed studies, this level of clarity is crucial. CROs are increasingly asked to manage complex study governance, requiring documented role definitions, communication pathways, and quality agreements that align with ISO 14155 expectations.

Post-Market Clinical Follow-up

Under MDR, clinical evidence is no longer static — it must be continuously updated throughout the device lifecycle. ISO 14155 now explicitly references post-market clinical follow-up (PMCF) investigations, confirming that GCP principles remain relevant beyond pre-market studies.

For CROs like us, this reflects a shift toward lifecycle data strategies: integrating PMCF studies, registries, and real-world evidence generation under one unified quality framework. Manufacturers are encouraged to embed GCP principles early, ensuring that post-market activities remain scientifically robust and auditable.

New considerations for Software as a Medical Device (SaMD)

The revision sensibly addresses the increasing role of digital health technologies. For Software as a Medical Device, ISO 14155 highlights the need to substantiate three distinct layers of evidence:

  • analytical validity of software algorithms and outputs,
  • scientific validity with respect to clinical conditions,
  • clinical performance aligned with intended use.

At the same time, the standard recognises that traditional elements, like direct patient exposure, may not apply, allowing for tailored GCP implementation. For CROs managing digital device studies, this introduces a need for hybrid models of clinical evaluation that combine human factors validation, usability testing, and performance verification under a GCP-aligned structure.

Scope and relation to IVDR

While ISO 14155 does not directly apply to in vitro diagnostic (IVD) devices, its ethical and operational principles often serve as a reference for performance studies under IVDR. CROs operating across both frameworks must therefore maintain procedural harmonisation while respecting regulatory distinctions.

Summary

In practice, compliance with ISO 14155:2026 requires sponsors to reassess their clinical governance systems. Key actions include:

  • updating Clinical Investigation Plans (CIP) and Standard Operating Procedures (SOPs),
  • aligning templates and documentation with MDR Annex XV,
  • integrating ISO 14155 principles into PMCF strategies,
  • ensuring readiness for hybrid device–software studies through cross-functional teams.

For CROs like Pure Clinical, the revision underscores the need for strong clinical quality management, capable of supporting manufacturers through both regulatory alignment and operational execution.

ISO 14155:2024 reinforces a future where clinical evidence is holistic, transparent, and sustained throughout the product lifecycle. For manufacturers and CROs alike, early alignment with the updated GCP framework will not only facilitate smoother conformity assessments but also strengthen the scientific and ethical foundation of medical device research in the EU market.