Several Suggestions on Quality Standards for In vitro Diagnostic Reagents

With the continuous development of modern biological technology, the technical content of diagnostic reagents is constantly improving, the variety is increasing, and the application scope is becoming wider, which has far exceeded the role of simply being an auxiliary tool for clinical diagnosis. In the fields of disease prevention, efficacy determination, drug monitoring, health status evaluation, and genetic disease prediction, diagnostic reagents are playing an increasingly important role. In the standard work of in vitro diagnostic reagents, some problems are encountered, and the following suggestions are proposed.

Increase the precision testing of batches for in vitro reagents

Precision is divided into within-batch precision and between-batch precision, which is an indicator of evaluating the random error of sample detection of reagents. Generally, this indicator is evaluated by repeatedly detecting a specific sample and analyzing the consistency of its values, and expressed in the standard as percentage of coefficient of variation. Different reagents have different requirements for the coefficient of variation, and usually require that the within-batch and between-batch coefficient of variation of reagents should not exceed 15%, and that some special reagents should not exceed 20%.

The standards of in vitro diagnostic reagents generally have the within-batch precision testing project, which is usually to detect the same sample 10 times and calculate the coefficient of variation. However, different concentration samples have different kinetic characteristics for the reagent reaction, and their detection errors are also different. Therefore, in order to better evaluate the precision within the detection range of the ivd diagnostic reagent, samples containing high, medium and low concentrations should be selected for precision testing, and the high and low concentrations should respectively be the upper and lower limits of the detection range of the reagent.

Maintain the stability of the reference materials for in vitro reagents

Almost all reference materials for diagnostic reagents for blood screening are from individuals infected with pathogenic microorganisms. Therefore, the amount of plasma collected each time is limited, and due to the batch-by-batch management of blood screening diagnostic reagents by the country, a large amount of reference materials are used, so the reference materials generally need to be re-prepared every 1-2 years. Each time the replacement is updated, the production unit may adjust the process parameters or formula to meet the requirements of the reference materials, achieve the purpose of passing the inspection standards, and even change the main ivd raw materials of the reagent production, i.e. biological active materials. On the one hand, this may result in violations by the reagent production unit, on the other hand, it may affect the detection specificity of in vitro diagnostic reagents. This problem cannot be reflected at the time of replacement, and when the problem is exposed, the reference material will start a new round of replacement, forming a vicious cycle. Therefore, it is recommended to improve the stability between batches of reference materials, extend the validity period of the reference materials, and minimize the impact of the replacement of reference materials on the quality of the reagents.

Improving the product quality of in vitro reagents can revise the project of sterilization inspection

Currently, in vitro diagnostic reagents are required to undergo sterilization inspection for semifinished products according to the general national standards. The purpose of conducting sterilization inspection for diagnostic reagents used for in vitro diagnosis is different from that of general drugs. It mainly aims to avoid the impact of the growth of bacteria on the quality evaluation indicators such as sensitivity and specificity of reagents. However, in reality, due to the addition of a large amount of preservatives in semi-finished products, most diagnostic reagents can be guaranteed not to breed bacteria during the validity period according to the existing production processes and conditions. Moreover, the indicators for assessing the quality of the reagents need to be tested in both the semifinished and finished product stages, so the significance of this inspection is limited. Most companies have not strictly carried out this standard inspection. It is recommended to revise the sterilization inspection project to allow production units to independently choose based on their own product characteristics and production process conditions without affecting the quality of diagnostic reagents.