Spotlight on ISO 15189 and In-House IVDR requirements
Your next steps as a medical laboratory
ISO 15189 specifically focuses on the unique requirements of medical laboratories and the significance should not be underestimated, especially in the field of public health. ISO 15189 was fundamentally revised at the end of 2022. It sets out more detailed requirements and emphasizes the importance of risk management even more strongly. Furthermore Vitro Diagnostic Medical Devices regulation (IVDR) now makes concrete demands on laboratories. A lot of medical laboratories are not fully aware of the existing and the new requirements. Lets review some of the main points:
In-house IVD: What are they? An IVD is “a laboratory developed test (LDT) that is designed, manufactured and used within a single laboratory or within health institutions established in the Union”. This includes any device used to examine or monitor humans, including “software or systems” connected to in vitro activity.
A medical laboratory can also create CE Marked devices to an LDT by:
- combining products or processes that are not intended for the combination, or
- uses a CE-IVD device outside its intended purpose, e.g., when they:
- misuse the device (off-label use) or
- modify commercial devices (including if they deviate from the instructions for use of conventional IVD devices).
What are Legal requirements for IVDR?
Laboratories must develop, manufacture and surveil their own Laboratory Developed Tests (largely) in conformity with the requirements of the IVDR depending on a product’s risk classification. There are four categories (A to D) with A representing the lowest risk and D the highest.
The use of commercially available IVD devices is preferred and laboratories can only offer their own LDTs if the devices on the market do not meet the required performance.
Your next steps as a medical laboratory?
- You first need to identify and determine your product/assay's risk classification.
- Comply with the additional requirements of Article 5 (5) of the IVDR. This in main requires a clinical validation.
- Expand your quality management system to include regulations of laboratory developed tests.
Focus on In-house tests
Conditions to consider
When the manufacturer's validation isn't enough
A manufacturer's performance data may not fully apply when your laboratory changes how an IVD is used.
For example, you may be:
- Using a different specimen type
- Modifying sample preparation
- Changing an extraction process
- Using different instrumentation
- Altering analytical parameters
- Combining reagents or platforms
- Using an assay outside its intended purpose
- Developing your own laboratory method
- Using an RUO reagent within a clinical workflow
- Applying an established assay to a new clinical indication
In these situations, your laboratory needs to consider what evidence is required for your specific intended use.
Learn More
ISOCHECKS supports the transition from manufacturer assay to routine clinical laboratory service, with documentation designed around laboratory quality and accreditation requirements.
Focus on IQC for ISO 15189
IQC ISO15189 2022 Standard 7.3.7.2
IQC ISO15189 2022 Standard 7.3.7.2
IQC ISO15189 2022 Standard 7.3.7.2
The structure and content of ISO 15189:2022 have been revised.
For IQC Standards 7.3.7.2 focus is on specifications based on the intended clinical application of the examination.
Routine QC Is Essential. Decision-Level QC Adds Clinical Relevance.
Don't assess assay performance only where results are comfortably within the expected range.
Challenge your assay where the clinical decision matters most.
Key Change
IQC ISO15189 2022 Standard 7.3.7.2
IQC ISO15189 2022 Standard 7.3.7.2
The IQC section has been expanded from three subclauses to seven (a-g) where ‘a’ is defined as:
a1) The intended clinical application of the examination should be considered, as the performance specifications for the same measurand can differ in different clinical settings.
For assays such as ADAMTS13 activity, where results around the 10% threshold can have major diagnostic significance in suspected thrombotic thrombocytopenic purpura (TTP), control materials with appropriately characterised activity levels can provide valuable evidence of performance near this critical threshold.
IQC Design Requirements
IQC ISO15189 2022 Standard 7.3.7.2
How to select IQC materials? To be fit for purpose!
When designing an appropriate QC strategy several risk factors need to be taken into consideration:
- High-risk tests with a large impact on the wrong result
- Tests used to support the clinician’s decision in isolation
- Tests acted upon immediately
How to select IQC materials? To be fit for purpose!
How to select IQC materials? To be fit for purpose!
How to select IQC materials? To be fit for purpose!
- Stability concerning properties of interest.
- Matrix as close as possible to the examination method & as close as possible to the patient sample.
- Concentration levels at/near the clinical decision limits and, when possible, covering the measurement range.
Third-party quality control materials
How to select IQC materials? To be fit for purpose!
Third-party quality control materials
Manufactured based on the intended clinical application specifications of the examination to monitor.
They are designed to deliver an unbiased and independent assessment of performance with any instrument or method, enabling laboratories to gain accreditation and ensure optimum performance and accuracy in clinical laboratory.
Become Compliant
How to select IQC materials? To be fit for purpose!
Third-party quality control materials
Embed Third party controls in clinical testing to cover critical decision points to avoid testing accreditation noncompliance.
Remember, IQC is not just about compliance; it is about managing quality effectively. Implementing correct levels of IQC in a medical laboratory is essential to ensure accurate and reliable test results.
Support ISO 15189 compliance — demonstrate that quality control arrangements are appropriate for the intended use of the examination and the clinical decisions informed by results.
UKAS & ISO 15189 Validation Evidence Requirements
Many laboratories perform validation activities but fail to retain sufficient objective evidence to satisfy UKAS assessors and demonstrate compliance with ISO 15189. When introducing an LDT, modifying a manufacturer's method, or implementing a new analyser, laboratories should be able to demonstrate the following:
Method Verification or Validation Plan
- Defined scope and intended use
- Acceptance criteria
- Validation protocol and study design
- Risk assessment and justification
Precision Studies
- Within-run (repeatability) data
- Between-run and between-day reproducibility
- Statistical analysis and conclusions
Accuracy & Method Comparison
- Comparison against an established method
- Bias calculations
- Clinical impact assessment of observed differences
Reference Interval Verification
- Evidence supporting manufacturer reference intervals or locally derived ranges
- Population selection criteria
- Statistical analysis and approval
Analytical Measurement Range (AMR)
- Linearity studies
- Measuring range verification
- Dilution and recovery studies where applicable
Cut-Off Verification
- Clinical decision limits
- Diagnostic thresholds
- Supporting patient data and rationale
Interference & Sample Stability
- Haemolysis, lipaemia, and icterus assessments
- Freeze-thaw stability
- Specimen transport and storage studies
Quality Assurance
- IQC data and performance monitoring
- External Quality Assessment (EQA) participation
- Trend analysis and corrective actions
Staff Competency
- Training records
- Competency assessments
- Authorisation records
Documentation Required by UKAS
- Validation report with conclusions
- Risk assessments
- Standard Operating Procedures (SOPs)
- Change control records
- Verification of intended use
- Evidence of management approval before implementation
