IVD Newbie: Here are 7 reagent basics!
In my country, most in vitro diagnostic reagents are managed as medical devices, and some are managed as drugs. The main items subject to drug management are in vitro diagnostic reagents used for blood source screening and in vitro diagnostic reagents labeled with radionuclides.
1. Classification
All in vitro diagnostic reagents on the market must be registered or filed with the drug regulatory department and obtain the relevant medical device registration certificate or filing certificate. Classification of in vitro diagnostic reagents. According to the degree of product risk from low to high, in vitro diagnostic reagents are divided into Category I, Category II and Category III products.
The first category of in vitro diagnostic reagent products mainly includes:
(1) Microbial culture medium (not used for microbial identification and drug susceptibility testing);
(2) Products for sample processing, such as hemolysis reagents, diluents, staining solutions, etc.
The second category of in vitro diagnostic reagent products mainly includes:
(1) Reagents for protein detection;
(2) Reagents for sugar detection;
(3) Reagents for hormone detection;
(4) Reagents for enzyme detection;
(5) Reagents for ester detection;
(6) Reagents for vitamin testing;
(7) Reagents for inorganic ion detection;
(8) Reagents for detection of drugs and drug metabolites;
(9) Reagents for autoantibody detection;
(10) Reagents used for microbial identification or drug susceptibility testing;
(11) Reagents used for the detection of other physiological, biochemical or immune function indicators.
The third category of in vitro diagnostic reagent products mainly includes:
(1) Reagents related to detection of pathogenic pathogen antigens, antibodies, nucleic acids, etc.;
(2) Reagents related to blood type and tissue matching;
(3) Reagents related to human genetic testing;
(4) Reagents related to genetic diseases;
(5) Reagents related to the detection of narcotic drugs, psychotropic drugs, and medical toxic drugs;
(6) Reagents related to detection of therapeutic drug action targets;
(7) Reagents related to tumor marker detection;
(8) Reagents related to allergic reactions (allergens).
2. Expression forms of in vitro diagnostic reagents
In vitro diagnostic reagents are not all liquids, but also come in other forms such as test strips.
In vitro diagnostic reagents are mainly used for in vitro testing of human samples, including reagents, kits, calibrators, quality control products and other products.
3. The life of in vitro diagnostic reagent products
The naming of in vitro diagnostic reagents should follow the following principles:
Product names can generally consist of three parts. Part 1: Name of the substance to be tested; Part 2: Usage, such as diagnostic serum, measurement kits, quality control materials, etc.; Part 3: Method or principle, such as enzyme-linked immunosorbent assay, colloidal gold method, etc., this part should be listed in parentheses.
If the substance to be tested has many components or there are other special circumstances, the indication name related to the product or other alternative names can be used.
Category 1 products, calibrators, and quality control products are named according to their intended use.
4. Do in vitro diagnostic reagents need to be registered and tested before they are put on the market?
When applying for registration of Class II or Class III in vitro diagnostic reagents, registration testing must be carried out. The production of samples for registration inspection should comply with the relevant requirements of the medical device quality management system. Only those who pass the registration inspection can conduct clinical trials or apply for registration.
When filing for Class I in vitro diagnostic reagents, a product self-inspection report must be submitted.
5. Are clinical trials required before in vitro diagnostic reagents are approved for marketing?
When filing for Class I in vitro diagnostic reagents, clinical trials are not required.
To apply for registration of Class II and Class III in vitro diagnostic reagents, clinical trials must be conducted.
Under any of the following circumstances, clinical trials may be exempted:
(1) The reaction principle is clear, the design is finalized, and the production process is mature. The same type of in vitro diagnostic reagent that has been on the market has been used clinically for many years without serious adverse event records. The regular use will not change. The applicant can provide equivalence evaluation data with the already marketed products. of;
(2) The safety and effectiveness of the in vitro diagnostic reagent can be proven through evaluation of clinical samples covering the intended use and interference factors.
6. Intended uses of in vitro diagnostic reagent products
The intended use of in vitro diagnostic reagent products is generally approved by the drug regulatory department and has its scientific and legal nature, such as "auxiliary diagnosis" and "diagnosis", "early diagnosis", "screening", "treatment monitoring", "Individualized medication" (companion diagnosis), etc. At the same time, the instructions should indicate whether it is a quantitative test or a qualitative test, what are the requirements for sample types, etc. The intended use of the product must be consistent with the corresponding content in the product registration or filing certification document.
7. Basic performance of in vitro diagnostic reagent products
Indicator 1 - Reagent blank
The reagent blank can be understood as the value detected when the content of the substance to be measured is the theoretical zero value. The general practice is to use water as a sample for measurement, and theoretically this value should be zero. But the actual situation is not like this. Even if the sample added is water, it will show a certain degree of reactivity. A constant blank reactivity does not affect the performance of the reagent. However, if the blank reactivity fluctuates greatly, it may lead to inaccurate clinical results. The main reason is that It is caused by the instability of the reaction system of the reagent, such as the instability of the preservative system, buffer system, enzymatic reaction system, etc., which will lead to changes in the blank reaction degree.
Indicator 2 - Analytical sensitivity
Analytical sensitivity refers to the slope of the calibration curve (or analytical curve), which can reflect the sensitivity of the diagnostic reagent to changes in the content of the substance to be tested. If the sensitivity is higher, corresponding to the same amount of change in the content of the substance to be detected, the greater the change in the detected experimental value will be. In this way, even small changes in the content of the substance to be detected will be easily detected.
Indicator three--Linear range
If within a numerical interval, the physical content of the substance to be tested forms a good one-to-one correspondence with the analytical detection value, then we can call this numerical interval the linear range of the diagnostic reagent. The wider the numerical interval covered by the linear range, the wider the coverage of clinical samples. Two diagnostic reagents that detect the same substance to be tested, reagent A has a linear range from 0 to 100, and reagent B has a linear range from 10 to 90; then reagent A will be more popular because it takes care of the samples from 0 to 10 and 90 to 100 , there is no need to think of ways to re-test alone, saving time and energy.
Indicator 4 - Precision
Precision simply means the repeatability of test results. Two shooters shoot 5 bullets each. Player A's 5 bullets all hit a fixed point in the 6 rings. Player B's 2 bullets hit the 7 ring, 2 bullets hit the 5 ring, and 1 bullet hit the 6 ring. The bullets were scattered on the target; the average score was 6 ring. Now if you are asked to choose a player to shoot birdie, who would you choose? Don't hesitate to choose player A, because his performance is more stable. As long as player A's aiming system is slightly improved, it is very likely that the gun will hit the target. Player B, on the other hand, has to rely on uncertain factors such as mood, luck, character, Mercury retrograde, etc. In short, it is unreliable.
Indicator 5 - Accuracy
Accuracy reflects the consistency between the detection value of the substance to be tested and the actual value. Let's use target shooting as an example again. Two shooters each fired 5 bullets. Player A's 5 bullets were all near the 9th ring, and player B's 5 bullets were all near the 8th ring. Naturally, player A's level is higher, because the result Both are closer to the bull's-eye 10 rings.
Here is a little logic: high accuracy means high precision; high precision does not mean high accuracy, but there are some ways to improve accuracy.
Indicator Six - Analysis Specificity
Analytical specificity refers to the ability of the test result to be free from interference from other components. In other words, the test results of diagnostic reagents will be affected by the presence of some substances, leading to deviations from the actual situation. Common interfering factors include hemolysis, blood lipids, bilirubin and VC.
If the test results are not affected at all, unless these substances are not present in the human body, they will interfere with the diagnostic test, but they are components that maintain human body functions, so there is no problem. In this case, the diagnostic reagent itself can only overcome the difficulties. How to overcome it? Improve your own anti-interference ability. If the diagnostic reagent can control the deviation between the test result and the actual value within an acceptable range in an environment where a large number of interfering substances exist, then the reagent's anti-interference ability will pass.
Indicator 7 - Stability
Stability can be understood as the shelf life of diagnostic reagents, which ensures that the test results of the reagents are stable and reliable within a certain period of time.
Stability can be divided into long-term stability and bottle opening stability. Let’s take cans as an example. If a can manufacturer states that the can is safe to eat for three years as long as the can is unopened, then that three-year period represents long-term stability. If a can is opened, the manufacturer says: Dear, in order to ensure the best flavor, please finish the contents of the can within a week after the can is opened. The one-week period represents the stability of the can. The manufacturer is not responsible for expired consumption.
