In Vitro Diagnostic Reagent Performance Index: Stability

Ⅰ. Current status of research on stability of ivd reagents

At present, most enterprises have begun to pay attention to the content of stability research in the process of research and development, but there are still many problems in the stability research materials submitted by some enterprises during the product registration process. Such as:

① The company focuses on the research on the stability of validity period and accelerated stability, ignoring the research on the stability of ivd reagents in unsealing and transportation, and the stability of quality control and calibrator contained in reagents ;

② Enterprises have different inspection items for product stability. Some enterprises only inspect whether the final chemical and biological properties of the reagents meet the requirements, while some enterprises increase the inspection of the physical properties of the reagents, such as appearance, loading, migration speed, etc.;

③ In the study of validity period stability, some companies are studying the ivd diagnostic reagent stored under the specified storage conditions until the end of the validity period, and some companies are studying the products that are stored under the specified storage conditions until 1, 2 months or even half a year after the validity period;

④ In the research on the product transportation stability project, the simulated transportation conditions of the same variety in the research projects of different production enterprises are very different;

⑤ In product stability research, some companies only inspected the "accuracy" items of in vitro diagnostic reagent calibrators and quality control products, while ignoring the inspection of "uniformity" and other items;

⑥ When formulating the validity period of products, most enterprises rely on the research data on the stability of the product validity period, and a small number of enterprises rely on the research data on the accelerated stability of the product;

⑦ The stability study of only one batch of products has been carried out, and the stability experiments of three batches of products have not been carried out according to the regulations;

⑧ Some enterprises use the samples from the previous laboratory research and development process instead of the actual production samples to investigate the product stability due to the short time limit for retaining samples during the registration and declaration of the actual IVD reagent manufacturing;

⑨ The description of the experimental results of stability research is too general. For example, the use of sentences such as "CV value less than 10%" and "in compliance with product technical requirements", etc., should provide specific test data according to the actual measurement results;

⑩ Only the research data at the end of the stability investigation period is provided, and the stability research data at different time periods during the stability investigation of ivd reagents are not provided;

Ⅱ. Scheme of the stability study of ivd reagents

1. The purpose of stability research

As an important indicator of ivd reagents to keep products safe and effective, stability has important guiding significance for the production, transportation, storage and use of products.

Ivd reagents are biological reagents themselves, and some active groups have different chemical instability trends, and are prone to hydrolysis, enzymatic hydrolysis and oxidation reactions, which affect the quality and stability of the reagents.

Therefore, the objectives of stability studies include:

① Determine the transportation, storage and preservation conditions of the product after opening;

② Determine the shelf life of the product and the shelf life after opening;

③ When product storage conditions and shelf life are changed, verify the stability of the changed in vitro diagnostic reagents;

④ According to the stability study results, evaluate and adjust the product formulation, process, packaging IVD raw materials, etc.

2. Materials for stability studies

Materials for stability study include test instruments, test reagents (3 batches), calibrators, quality control products, etc. The test instrument in the stability study shall be the applicable model of the product.

In addition to test instruments, in vitro diagnostic reagent stability studies will also use incubators, refrigerators, and humidity chambers and other instruments. The above instruments should be checked regularly to prevent failure of the stability test due to instrument failures.

3. Stability research projects

The items of the stability study should be selected according to the product composition and methodological principles to evaluate the quality and effectiveness of the product.

Generally, the items specified in the product technical requirements are selected, such as the minimum detection limit, accuracy, repeatability, linear range, specificity, negative/positive reference product conformity rate of in vitro diagnostic reagents, etc.

If the results of the stability study do not meet the evaluation indicators determined in the study protocol, the reasons should be further analyzed.

The cause of product instability may be unstable components, damaged packaging materials, or changes in storage and transportation conditions. Enterprises should take improvement measures after determining the cause, and re-study the stability of in vitro diagnostic reagents after improvement.