For in-vitro diagnostic devices, ISO 23640 plays a key role as it defines the requirements related to the stability of in-vitro diagnostic reagents used within an IVD devices. We have been talking in previous post about IVD devices and specifically about the introduction of new European In-Vtro Diagnostic Regulation 2017/746 ; other topics that have been discussed are related to the classification introduced by the new EU IVDR 2017/746 and the requirements associated to ISO 20916 related to clinical performance study for IVD devices.
In this article we will provide an overview of the main requirements associated to ISO 23640 related to the stability of in-vitro diagnostic reagents used within IVD devices.
Scope of ISO 23640
The scope of ISO 23640 is described within Chapter 1 of the Standard. The overall scope of the standard is related to specify general requirements for stability evaluation; the standard provides specific requirements for stability evaluation in the context of the following activities:
- The definition of an IVD shelf life
- The establishment of the stability of an IVD reagents in use after the opening of the primary packaging
- The monitoring of IVD reagents already placed on the market
- The monitoring and verification of stability specifications after modifications of the IVD reagents that might affect the stability.
General Principles for Stability Evaluation according to ISO 23640
Section 4 of ISO 23640 defines the general principles related to the evaluation of the stability of in vitro diagnostic medical devices, including reagents, calibrators, control materials, diluents, buffers and reagent kits (IVD reagents).
In general, claims related to stability shall be justified by adequate data, taking in consideration the risks associated to the device. Initial expiry date shall be defined considering either stability tests or the experience of the manufacturer gained with the specific IVD reagents.
Evaluation of the stability shall be performed on IVD reagents manufactured under the same conditions of the ones used in the final product and produced under routing manufacturing operations.
Protocol for Stability Evaluation
ISO 23640 defines in details what are the requirements associated to the protocol containing the description of the methodologies used to evaluate the stability of the specific reagents. The contents of the protocol may be summarised here below:
- Responsibilities;
- IVD Reagents Identification;
- Use conditions (worst case environmental condition to be considered);
- Purpose of the evaluation;
- Discussion on the potential influence of critical components;
- Storage conditions recommended for the reagent samples;
- Simulation on transport;
- The number of examination to be performed with an IVD reagent which basically depends on the precision of the test method used;
- The duration of the stability study protocol
- Description of data analysis
- Acceptance criteria to be met
- Interpretation of data.
Stability Report
Stability reports shall be documented in order to provide evidence on the specific stability study. The contents of the stability reports according to ISO 23640 are the following:
- Reference to the protocol which was followed
- The batch(es) involved
- All results obtained
- Analysis of data
- Acceptance criteria
- Overall conclusion about stability
NUmber of batches to be examined
The minimum number of batches are defines in the ISO 23640 and it is dependent on the type of tests to be performed. Specifically:
| Type of test | Number of batches to be tested |
| Evaluation of a new IVD reagent shelf life | 3 batches |
| Extension of an IVD reagent shelf life | 3 batches |
| Transport Simulation | 1 batch |
| In-use stability of the IVD reagent | 1 batch |
| IVD Reagent modification | 1 batch (if the risk assessment for the IVD reagent in question indicates that stability evaluation is needed). |
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