Standards and guidelines for IVD studies
When planning performance studies for IVDs, there are several standards and guidelines that provide useful advice for study design concepts. However, some even define essential requirements for the acceptability of the obtained data to ensure accuracy, reliability, and safety of the diagnostic tests. Compliance with standards and guidelines is often necessary for obtaining regulatory approval for IVD tests. Examples of common standards, principles and guidelines are:
- GCP
The principles of Good Clinical Practice (GCP) provide guidance and standards for ethical conduct, study design, data collection, and reporting of clinical trials, including those involving IVDs.
- GCLP (Link: EMA Reflection paper)
Good Clinical Laboratory Practice (GCLP) ensures quality in clinical research labs, integrating Good Laboratory Practice (GLP) and Good Clinical Practice (GCP) for reliable data generation in clinical trials.
- ISO 13485
This standard specifies requirements for the quality management system for medical devices, including IVDs. Compliance with ISO 13485 is often a regulatory requirement for the approval of an IVD test within the EU. The FDA pendant to the ISO 13485 is 21 CFR part 820 (Quality System Regulation, QSR). According to the most recent development, the FDA plans to adopt most requirements from the ISO 13485 resulting in the Quality Management System Regulation (QMSR) issued in the final rule on 02-Feb-2024.
- ISO 14971 (in conjunction with ISO 24971)
This standard defines the application of risk management to medical devices, including IVDs. It provides a framework for identifying, evaluating, and mitigating risks associated with the use of IVDs throughout their lifecycle.
- ISO 20916
ISO 20916 outlines principles for good study practice (GSP) for medical devices, including IVD tests. This standard is intended to ensuring robustness and reliability in study design, execution, and reporting.
- ISO 14155
ISO 14155 offers guidelines for performance studies of medical devices, ensuring ethical and scientific integrity. It helps safeguard participant rights and ensures data reliability for regulatory compliance.
Please note that this standard is only applicable for medical devices but not for IVD tests.
- ISO 15189
Specifically for medical laboratories, ISO 15189 defines requirements for quality and competence. This standard is intended to set the requirements for developing a quality management system.
- CLSI
The Clinical and Laboratory Standards Institute (CLSI) develops standards and guidelines for clinical laboratory testing, including IVD studies. These documents provide vast guidance during study design development and study conduction. Especially the FDA relies on the CLSIs but these documents are also well accepted by stakeholders within the EU. The CLSI has published hundreds of different guidance documents covering various aspects for analytical and clinical performance studies, sample handling and laboratory testing.
- FDA Guidance documents
The U.S. Food and Drug Administration (FDA) provides guidance documents for conducting studies and obtaining regulatory approval for IVDs. One example for IVDs is the FDA guidance document “In Vitro Diagnostic (IVD) Device Studies – Frequently Asked Questions”. This document provide answers to common questions regarding the design and performance of clinical studies for IVD tests.
- Common specifications
Common specifications (CS) are detailed practical rules as well as essential requirements setting out how particular types of devices should comply with certain requirements of the IVDR. In the context of in vitro diagnostic devices (IVDs), common specifications serve as a set of predefined parameters or benchmarks that must be met by manufacturers to ensure the safety, performance, and reliability of their products. These specifications typically cover aspects such as analytical performance, clinical performance, usability, and safety.
One prominent example of CS during the last years was the “Commission Implementing Regulation (EU) 2022/1107 focusing on certain class D devices, including SARS-CoV-2 tests.
- MDCG documents
MDCG (Medical Device Coordination Group) documents provide guidance and interpretation of regulations for medical devices in the European Union. They ensure consistency and clarity for manufacturers, notified bodies, and regulatory authorities.
- IVDR
The In Vitro Diagnostic Regulation (IVDR, 2017/746) is an EU regulation governing the safety, performance, and regulatory oversight of in vitro diagnostic medical devices, aiming to enhance patient safety and ensure product effectiveness.
- MDR
The Medical Device Regulation (MDR, 2017/745) is an EU regulation governing the safety and performance of medical devices. It enhances patient safety, ensures transparency, and harmonizes regulations across member states.
