1) Evaluation of validity period stability
The validity period stability evaluation is the real-time stability evaluation, which is a test to establish or verify the shelf life of the in vitro diagnostic reagent under the conditions specified by the manufacturer.
Ivd reagents can be inspected according to the specific conditions of the product, and intensive testing should be carried out for the time period when the product performance may change.
The time of registration inspection and clinical trial before submitting the registration application for ivd reagent products can be included in the time limit of product stability research.
2) Accelerated stability evaluation
Accelerated stability evaluation is a study that examines various physical, chemical and biological properties of in vitro diagnostic solutions by setting extreme conditions such as temperature, humidity, light or vibration, so as to infer the validity period of ivd reagents.
Since the main components of most diagnostic reagents are protein substances, in accelerated stability studies, increasing the temperature to examine the stability of reagents has become a common method, usually raise at least 15 °C under the temperature conditions of long-term stability studies.
The accelerated stability research method is: put the three batches of in vitro diagnostic kits into a 37°C constant temperature incubator, take the original unopened reagents on the 0th, 3rd, 6th, and 10th days respectively, and refer to the relevant tests in the product technical requirements. All indexes shall meet the performance index requirements in the proposed technical requirements.
Due to the complex structure of in vitro diagnostic reagents, there may be multiple degradation pathways at the same time, and the degradation, polymerization, denaturation, inactivation, and interactions with IVD raw materials packaging under different conditions are different. Therefore, in general, the accelerated stability study can only be used to study the general performance of in vitro diagnostic reagents, not to deduce the expiration date of products.
3) Evaluation of transportation stability
The transportation stability evaluation is based on the knowledge of the actual transportation conditions of the reagents (such as transportation time, expected temperature and humidity) to simulate the transportation conditions and store the product to evaluate the stability of the product.
The main conditions to be considered in the transportation stability investigation of ivd reagents are: extreme temperature conditions, temperature cycle conditions, shock and vibration, pressure and humidity, etc.
Manufacturers can track and record the logistics and transportation of ivd reagent products on the spot to provide a reference for the determination of simulated transportation modes.
4) Opening stability
That is, bottle opening stability is to investigate the influence of external factors on the performance indicators of in vitro diagnostic reagents under normal conditions of use.
Since the IVD kit, test strips, etc. will come into contact with the air to produce oxidation, degradation and other reactions after opening, the external conditions of some reagents after they are opened and put into the machine are very different from the original storage conditions, and some reagents will have secondary preparation by users. Therefore, various environmental factors should be fully considered when formulating the research method of opening stability.
If the in vitro diagnostic reagent contains alkaline substances and is placed in the biochemical analyzer for a long time after opening the bottle, the carbon dioxide in the air will react with the alkaline components in the reagent, thus affecting the accuracy of the heart marker test results.
Therefore, for the above reagents, the caps should be tightly closed after each use to avoid contact with air. The temperature range of the reagent tray of the biochemical analyzer is generally 5~15℃. Therefore, when the reagent contains temperature-sensitive components, the reagent should be put back in the refrigerator at 2~8℃ immediately after use, and used as soon as possible.
Usually, 7 days after the reagent is opened, it should be re-calibrated before the test to improve the accuracy of the test results.
Stability study is an important part of ivd reagent product quality evaluation, and the results of stability study should conform to the acceptable range of results set in the stability study protocol.
Enterprises should conduct consistency analysis on the research results of different batches of products to verify whether there are batch-to-batch differences in IVD reagents.
At the same time, at the end of the investigation period, the variation analysis of the test results of the same batch of products in different periods should be carried out to investigate the trend of its performance decreasing with time, and finally the storage conditions and validity period of the product should be determined according to the acceptable result range set in the research plan.