A method for discharging waste from a product

Abstract

The present invention relates to a method for discharging waste from product packaging, comprising the following steps: (1) during the discharging process, bottle numbers are marked on some products in the order of discharging; (2) samples are taken from the products with the marked bottle numbers, and the product potency is detected, and the detection result is A; (3) among the products packaged after the products with the marked bottle numbers, the subsequent products are divided into front section, middle section and back section, and the middle section product is taken to detect the potency of human coagulation factor VIII, and the detection result is B; (4) the waste discharge amount is calculated according to the difference C between B and A. After the waste is discharged by the method provided by the present invention, the potency of the product can be improved, so that the potency difference of the final product at each stage of discharging is small, which has the advantages of improving product uniformity, improving internal quality, yield and economic benefits, etc., and is simple to operate and has strong promotion, and can be widely used in actual production.

Description

Technical Field

[0001] The invention belongs to the field of biopharmaceuticals, and in particular relates to a method for packaging and discharging waste of a product. Background Art

[0002] Hemophilia is an X-linked recessive genetic disease caused by mutations in genes encoding coagulation factors. It is a common hereditary disease characterized by permanent bleeding. Currently, there is no cure for hemophilia. Replacement therapy has a history of more than 100 years, but it is still the main treatment for hemophilia. With the deepening of understanding of hemophilia and the continuous development of science and technology, both in the research of new drugs for replacement therapy and in the development of new therapy such as gene therapy, the treatment of hemophilia has made gratifying progress. In the past seventy years, the life expectancy and quality of life of hemophilia patients have improved significantly, and are gradually approaching that of healthy people.

[0003] Human coagulation factor VIII (FVIII) is one of the products and one of the most commonly used coagulation factor products in clinical practice. It is mainly used for coagulation dysfunction caused by FVIII deficiency, prevention and treatment of bleeding symptoms caused by hemophilia A and acquired FVIII deficiency, and surgical bleeding treatment of such patients. The content of FVIII in human plasma is low, with a concentration of 50-100 ng / mL. Traditional methods for preparing FVIII include low-temperature ethanol method, glycine precipitation method, PEG segmented precipitation method, PEG-glycine segmented precipitation method, acid precipitation method, etc. With the increasing maturity of chromatography technology, the current production methods for FVIII also include gel filtration purification method, ion exchange chromatography method, hydrophobic chromatography method, monoclonal antibody affinity chromatography method, etc. Compared with other methods, the new process of combining A-50 gel and FFactogelF EMD TMAE (M) is used, and the production process is gradually optimized through continuous exploration in small-scale and pilot production. A relatively stable production process has been formed to ensure product quality.

[0004] After the semi-finished product of human coagulation factor VIII solution is prepared, it needs to go through the steps of sterilization, packaging, freeze-drying and virus inactivation to obtain the finished product. The packaging pipeline and filter element will be cleaned with injection water before packaging, and then sterilized before use. After such treatment, there will be residual liquid in the filter element and pipeline. The multi-fold fan-shaped hot-pressed filter membrane effectively increases the filtration area and improves the filtration volume, but it also makes the liquid easy to remain. The residual liquid will dilute the drug solution, resulting in a decrease in the potency of the product, and there will be differences in the potency of each stage of packaging. Therefore, some products in the front stage of packaging need to be discharged for waste treatment.

[0005] How to choose the appropriate waste discharge volume is related to product yield, quality and economic benefits, and is crucial. Excessive waste discharge will lead to problems such as reduced yield and reduced economic benefits, especially when the batch size of the product (for example, human coagulation factor VIII) is small, the impact of excessive waste discharge on product yield is more significant and affects subsequent research. If the waste discharge volume is too small, it will lead to problems such as reduced potency of the drug solution and large potency differences. Summary of the invention

[0006] In view of the problems existing in the prior art, the present invention provides a method for packaging and discharging waste of a product, which improves the intrinsic quality and yield of the product and reduces the potency difference of the final product at each packaging stage.

[0007] The technical solution of the present invention to solve the above technical problems is as follows:

[0008] A method for discharging waste from a product comprises the following steps:

[0009] (1) During the packaging process, some products are marked with bottle numbers in the order of packaging;

[0010] (2) Take a sample from the product with the marked bottle number and test the potency of the product. The test result is A, in IU / mL;

[0011] (3) Among the products packaged after the product with the bottle number, the subsequent products are divided into the front section, the middle section and the back section, and the middle section product is taken for potency testing. The test result is B, and the unit is IU / mL;

[0012] (4) Calculate the waste discharge based on the difference C between B and A.

[0013] The beneficial effects of the present invention include: the method can obtain a suitable waste discharge amount. After the waste discharge, the potency of the product can be improved, so that the potency difference of the final product in each stage of packaging is small, which has the advantages of improving product uniformity, improving internal quality, yield and economic benefits, etc., and is simple to operate, has strong promotion, and can be widely used in actual production.

[0014] Based on the above technical solution, the present invention can also be improved as follows.

[0015] Furthermore, in step (4), if the batch of the product is 1, calculating the waste discharge volume includes the following steps: when the difference C ≤ 3 IU / mL, selecting the minimum bottle number, and calculating the waste discharge volume based on the minimum bottle number and the amount in each bottle.

[0016] The beneficial effects of adopting the above further scheme include: the present invention has found through preliminary experiments that when the difference is selected to be ≤3IU / mL, the potency difference of the final product in each packaging stage can be small, which has the advantages of improving product uniformity, improving the intrinsic quality, yield and economic benefits of the product.

[0017] Furthermore, in step (4), if the sample batches are multiple (i.e., the sample batches are ≥ 2), calculating the waste discharge volume includes the following steps:

[0018] (i) Select the minimum bottle number of each batch, and the selection standard is: select the minimum bottle number of the batch of samples under the condition that the difference C ≤ 3 IU / mL;

[0019] (ii) comparing the minimum bottle numbers among multiple batches of samples and selecting the minimum bottle number with the largest value among different batches;

[0020] (iii) Calculate the waste discharge amount based on the smallest bottle number with the largest value obtained in step (ii) and the amount of each bottle.

[0021] The beneficial effects of adopting the above further scheme include: since different batches of products have different waste discharge amounts, the uniformity of the products can be ensured by calculating the highest waste discharge amount.

[0022] Furthermore, the product is human coagulation factor VIII; in step (2) and step (3), the method for detecting the titer of human coagulation factor VIII comprises the following steps:

[0023] (a) preparing human coagulation factor VIII national standard solution;

[0024] (b) Prepare quality control solution;

[0025] (c) preparing test sample solutions;

[0026] (d) using a fully automatic coagulation analyzer for testing;

[0027] (e) Select and run the factor VIII quality control procedure and calibration procedure. After the quality control and calibration are passed, the test sample can be tested; the potency of the test sample human coagulation factor VIII is calculated based on the conversion value measured by the fully automatic coagulation analyzer and the dilution multiple of the test sample.

[0028] The beneficial effects of adopting the above further scheme include: the above method can accurately determine the titer of human coagulation factor VIII.

[0029] Furthermore, step (a) of preparing the national standard solution of human coagulation factor VIII includes the following steps: taking human coagulation factor VIII as the standard, adding sterile water for injection to reconstitute it, and then diluting the standard with human coagulation factor VIII-deficient plasma or 0.85%-0.90% sodium chloride solution to form a solution containing 1 IU of coagulation factor VIII per 1 mL.

[0030] Furthermore, step (b) of preparing the control solution includes the following steps: re-dissolving the system coagulation control product and the coagulation control product with water for injection respectively, and placing them at room temperature for 30 minutes for use.

[0031] Furthermore, step (c) of preparing the test solution comprises the following steps: diluting the test sample with a 0.85%-0.90% sodium chloride solution and a diluent.

[0032] Further, in step (d), the fully automatic coagulation analyzer is turned on and reagents are loaded; the diluent for coagulation analysis is placed at position 8# in the sample compartment, and the calcium chloride solution, APTT reagent, coagulation quality control product, system coagulation quality control product, and 1IU / mL coagulation factor VIII national standard solution are placed at positions of the same size in the reagent compartment.

[0033] Further, in step (e), the quality control program and calibration program of factor VIII are selected and run. After the quality control and calibration are passed, the test sample is tested; the prepared test sample solution is placed in the sample compartment, the name and batch number of the test sample are added, the test items are selected, and the program is run; the conversion value measured by the fully automatic coagulation analyzer is multiplied by the dilution factor of the test sample to obtain the potency of the test sample human coagulation factor VIII.

[0034] Furthermore, in step (1), during the packaging process, the first 300 bottles of the product are marked, and the bottle numbers are recorded from 1 to 300 in the order of packaging.

[0035] The beneficial effects of adopting the above further scheme include: according to the preliminary experimental results, the top 300 are selected, which have the advantages of small potency difference and good uniformity.

[0036] Furthermore, after calculating the waste discharge amount, the product is subjected to waste discharge treatment.

[0037] The beneficial effects of adopting the above further scheme include: through waste discharge treatment, the potency of the product can be improved, so that the potency difference of the final product in each packaging stage is small, which has the advantages of improving product uniformity, improving the intrinsic quality, yield and economic benefits of the product, etc., and is simple to operate, has strong scalability, and can be widely used in actual production. DETAILED DESCRIPTION

[0038] The principles and features of the present invention are described below. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0039] A method for packaging and discharging freeze-dried human coagulation factor VIII comprises the following steps:

[0040] (1) During the packaging process, the first 300 bottles of human coagulation factor VIII were marked and numbered from 1 to 300 in the order of packaging;

[0041] (2) From No. 1 to No. 300, take samples at appropriate intervals and test the human coagulation factor VIII titer of the samples. The test result is A (unit IU / mL);

[0042] (3) After 300 bottles were dispensed, the subsequent dispensed liquid was divided into three sections: front, middle, and back. The middle section sample was taken to test the potency of human coagulation factor VIII. The test result was B (unit IU / mL).

[0043] The method for detecting the potency of human coagulation factor VIII in the middle section sample is the same as the detection method in step (2).

[0044] (4) Calculate the difference between the test results of step (3) and step (2), denoted as C (in IU / mL), using the calculation formula C=BA.

[0045] If the sample batch is single (i.e., batch 1), use the following steps to calculate the waste volume: When the difference C ≤ 3 IU / mL, select the smallest bottle number, and use the value of the smallest bottle number multiplied by the amount in each bottle as the waste volume.

[0046] If there are multiple batches of samples (i.e. batches ≥ 2), use the following steps to calculate the waste volume:

[0047] (i) Select the minimum bottle number of each batch, and the selection standard is: select the minimum bottle number of the batch of samples under the condition that the difference C ≤ 3 IU / mL;

[0048] (ii) comparing the minimum bottle numbers among multiple batches and selecting the minimum bottle number with the largest value among different batches;

[0049] (iii) The waste discharge amount is obtained by multiplying the value of the smallest bottle number with the largest value obtained in step (ii) by the amount filled in each bottle.

[0050] Subsequently, the sample (drug solution) is discharged for waste treatment according to the obtained waste discharge amount, and then enters the subsequent process (for example, freeze-drying, virus inactivation, etc.).

[0051] In the above method, the method for detecting the potency of human coagulation factor VIII may include the following steps:

[0052] (a) Preparation of human factor VIII national standard solution: human factor VIII is used as the standard, and after reconstitution with sterile water for injection according to the labeled amount, the standard is diluted with human factor VIII-deficient plasma or 0.85%-0.90% sodium chloride solution to a solution containing 1 IU of factor VIII per 1 mL.

[0053] (b) Preparation of quality control solution: According to the quality control product label requirements, reconstitute the system coagulation quality control product and the coagulation quality control product with water for injection, and leave them at room temperature for 30 minutes for use.

[0054] (c) Prepare the test sample solution: dilute the test sample with 0.85%-0.90% sodium chloride solution and diluent.

[0055] (d) Prepare the reagents required for the experiment, such as 1IU / mL coagulation factor VIII national standard solution, coagulation quality control products, system coagulation quality control products, and coagulation analysis diluent according to the experimental requirements, turn on the fully automatic coagulation analyzer, and load the prepared reagents. The coagulation analysis diluent is placed in the 8# position in the sample compartment, and the calcium chloride solution, APTT reagent, coagulation quality control products, system coagulation quality control products, and 1IU / mL coagulation factor VIII national standard solution are placed in the same size position in the reagent compartment.

[0056] (e) Select to run the quality control program and calibration program for factor VIII. After the quality control and calibration are passed, the test sample can be tested. Place the prepared test sample solution into the sample compartment, add the test sample name and batch number, double-click the selected test item, and confirm to return to the main interface. The test program will automatically run. Multiply the conversion value measured by the instrument by the dilution factor of the test sample to obtain the potency (IU / mL) of the test sample human coagulation factor VIII.

[0057] The final product obtained by the present invention has a small difference in potency at each stage of subpackaging, which ensures the uniformity of the liquid medicine during the subpackaging process, and can further purify human coagulation factor VIII to improve its intrinsic quality. The method of the present invention is simple, and the product quality is stable. After the industrialization of human coagulation factor VIII, the output can be increased, the utilization rate of plasma resources can be improved, the market supply can be increased, and the tense situation of human coagulation factor VIII medication in the domestic market can be alleviated.

[0058] In addition to human coagulation factor VIII, other products can also refer to this waste treatment to improve the yield. Since all human coagulation factor VIII on the market are freeze-dried products, due to their product characteristics, freeze-dried products are easy to store and transport. The following is an introduction using freeze-dried human coagulation factor VIII as an example.

[0059] Human coagulation factor VIII was purchased from China Food and Drug Inspection Institutes as a standard product.

[0060] Systemic coagulation quality control and coagulation quality control were purchased from DIAGNOSTICA STAGO Diagnostics Co., Ltd. The production batch number of systemic coagulation quality control is 257162, and the production batch number of coagulation quality control is 257472.

[0061] Fully automatic coagulation analyzer, manufacturer: DIAGNOSTICA STAGO Diagnostics Co., Ltd., model: STA Compact Max.

[0062] APTT reagent was purchased from DIAGNOSTICA STAGO Diagnostics Co., Ltd., production batch number APTT reagent 257208.

[0063] Samples with production batch numbers FⅧ202107S05, FⅧ202107S06, FⅧ202107S07, FⅧ202204S04, FⅧ202205S05, and FⅧ202205S06, although with different batch numbers, are all prepared by the same preparation method. The preparation method refers to the invention patent that has been applied for: A method for preparing freeze-dried human coagulation factor VIII (application number 202011107419.9; application publication number CN112028988A; application publication date December 4, 2020).

[0064] Unless otherwise specified, the methods used in the examples are all conventional methods in the art. The materials, reagents, and instruments used are all conventional materials, reagents, and instruments in the art, unless otherwise specified, and can be obtained through commercial channels or prepared by conventional methods.

[0065] Example 1

[0066] A method for packaging and discharging freeze-dried human coagulation factor VIII comprises the following steps:

[0067] (1) During the filling process (i.e., the dispensing process), according to the preliminary experimental results, it is confirmed that the waste volume is set to 3000 mL, the dispensing volume of each bottle is 10 mL, and the first 300 bottles are numbered in the order of dispensing, from No. 1 to No. 300;

[0068] (2) sampling at appropriate intervals to detect the titer of human coagulation factor VIII, for example, sampling multiple samples between bottles 90 and 300 according to the marked bottle numbers to detect the titer of human coagulation factor VIII, wherein the method for detecting the titer of human coagulation factor VIII comprises the following steps:

[0069] (2a) Preparation of human factor VIII national standard solution: human factor VIII is used as the standard. After reconstitution with the labeled amount (generally 1 mL) of sterile water for injection, the standard is diluted with human factor VIII-deficient plasma or 0.85%-0.90% sodium chloride solution to a solution containing 1 IU of factor VIII per 1 mL.

[0070] (2b) Preparation of control solution:

[0071] According to the labeling requirements of quality control products (labeling requirements are provided by DIAGNOSTICA STAGO Diagnostics Co., Ltd.), reconstitute the system coagulation quality control product and coagulation quality control product with water for injection, and place them at room temperature for 30 minutes for use.

[0072] (2c) Prepare the test sample solution: dilute the test sample with 0.85%-0.90% sodium chloride solution and diluent.

[0073] (2d) Prepare the reagents required for the experiment, such as 1IU / mL coagulation factor VIII national standard solution, coagulation quality control products, system coagulation quality control products, and diluent for coagulation analysis, according to the experimental requirements of steps 2a to 2c, turn on the fully automatic coagulation analyzer, and load the prepared reagents. The diluent for coagulation analysis is placed at position 8# in the sample compartment (according to the experimental instrument settings, the diluent is fixed at position 8#), and the calcium chloride solution (calcium chloride concentration is 0.025 mol / L), APTT reagent, coagulation quality control products, system coagulation quality control products, and 1IU / mL coagulation factor VIII national standard solution are placed at positions of the same size in the reagent compartment.

[0074] (2e) Set up according to the human coagulation factor VIII assay method in the Pharmacopoeia of the People's Republic of China, select and run the factor VIII quality control program and calibration program. After the quality control and calibration are passed, the test sample can be tested. Put the prepared test sample solution into the sample compartment, add the test sample name and batch number, double-click the selected test item, and confirm to return to the main interface. The test program will run automatically. The conversion value measured by the instrument multiplied by the dilution factor of the test sample is the potency (IU / mL) of the test sample human coagulation factor VIII.

[0075] In the above steps, the diluent is prepared according to the requirements of the human coagulation factor VIII assay in the Pharmacopoeia of the People's Republic of China. The preparation method of the diluent includes the following steps: taking 1 volume of 3.8% sodium citrate and adding 5 volumes of imidazole buffer and mixing.

[0076] The preparation method of 3.8% sodium citrate solution comprises the following steps: weighing 9.5 g of anhydrous sodium citrate, adding purified water to dissolve and dilute to 250 mL.

[0077] The preparation method of imidazole buffer (pH 7.3) is as follows: weigh 0.68 g of imidazole and 1.17 g of sodium chloride, add purified water to dissolve into 100 mL, add 42.2 mL of 0.1 mol / L hydrochloric acid solution, and then add purified water to dilute to 200 mL.

[0078] (3) After 300 bottles have been dispensed, the subsequent dispensed liquid is divided into three sections: front, middle, and back (divided into three sections according to the specific quantity), and a sample from the middle section is taken to test the potency of human coagulation factor VIII.

[0079] The method for detecting the titer of human coagulation factor VIII is the same as step (2).

[0080] (4) The test result of step (2) is recorded as A (in IU / mL), and the test result of step (3) is recorded as B (in IU / mL). The difference between the two is calculated and recorded as C (in IU / mL), C=B A.

[0081] If there is only one batch of samples, when the difference C≤3IU / mL, select the smallest bottle number and use the value of the smallest bottle number multiplied by the volume in each bottle as the waste volume.

[0082] If there are multiple batches, use the following method to calculate the waste volume:

[0083] First, for each batch, when the difference C ≤ 3 IU / mL, select the minimum bottle number of each batch of samples;

[0084] Secondly, compare the minimum bottle numbers among multiple batches and select the minimum bottle number with the largest value;

[0085] Finally, the waste discharge is obtained by multiplying the value of the smallest bottle number with the largest value by the amount in each bottle.

[0086] (5) Three batches of human coagulation factor VIII were subjected to a waste discharge test, the production batch numbers of which were: FVIII202204S04, FVIII202205S05, and FVIII202205S06, and the operation was the same as steps (1) to (4);

[0087] (6) Determine the amount of human coagulation factor VIII waste from the packaging according to the results of step (5).

[0088] The product obtained in the example was tested according to the test method specified in General Rule 3521 "Human Coagulation Factor VIII Potency Assay (Phase I Method)" of the 2020 Edition (Part III) of the Pharmacopoeia of the People's Republic of China, and the test results are shown in Table 1.

[0089] As can be seen from Table 1, the 239th bottle of both batches FⅧ202204S04 and FⅧ202205S05 can meet the requirement that the difference with the middle sample is less than or equal to 3IU / mL, while the difference with the middle sample is less than or equal to 3IU / mL only when the 270th bottle of FⅧ202205S06 is met, indicating that there are differences in the amount of waste discharged from different batches. In order to ensure the uniformity of the drug, the highest waste discharge should be calculated, that is, the waste discharge should be calculated based on 270 bottles, and the volume of each bottle is 10mL. After calculation, the waste discharge amount is 2700mL. After that, the product can be treated with waste discharge, and the waste discharge amount is 2700mL.

[0090] Table 1 Results of human coagulation factor VIII titer test

[0091]

[0092] Comparative Example

[0093] In order to verify the beneficial effects of the present invention, a human coagulation factor VIII product prepared by the same method was treated by a method without waste discharge treatment and a method with waste discharge treatment respectively. The difference between the two methods is whether waste is discharged. Except for whether waste is discharged, other operating steps are the same.

[0094] No waste treatment: production batches FⅧ202107S05, FⅧ202107S06, and FⅧ202107S07 were used as samples. During the filling process, the liquid medicine of each batch was divided into three sections: front, middle, and back (divided into three sections according to the specific quantity), and samples of each section were taken to test the potency of human coagulation factor VIII.

[0095] Waste discharge treatment: Production batches FⅧ202204S04, FⅧ202205S05, and FⅧ202205S06 were used as samples and waste discharge treatment was performed using the method of Example 1. The packaged liquid of each batch was divided into three sections: front, middle, and back (divided into three sections according to specific quantities), and samples of each section were taken to detect the potency of human coagulation factor VIII.

[0096] In the above two methods, the method for detecting the titer of human coagulation factor VIII is the same as the method for detecting the titer of human coagulation factor VIII in Example 1. The test results are shown in Table 2.

[0097] According to the results in Table 2, compared with the batches without waste discharge treatment (FⅧ202107S05, FⅧ202107S06 and FⅧ202107S07) and the batches with waste discharge treatment (FⅧ202204S04, FⅧ202205S05 and FⅧ202205S06), the potency of human coagulation factor VIII in the batches with waste discharge treatment is significantly higher than that in the batches without waste discharge treatment; at the same time, the potency difference of the final product in each stage of packaging is small. It is thus confirmed that the method provided by the present invention can improve the uniformity of the product, thereby further improving the intrinsic quality and yield of human coagulation factor VIII; and it is simple to operate, has strong promotion, and can be widely used in actual production.

[0098] Table 2 Comparison results of human coagulation factor VIII titer test

[0099]

[0100]

[0101] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for discharging waste from a product, characterized in that: The following steps are involved: (1) During the repackaging process, some products are marked with bottle numbers in the order of repackaging; (2) Take a sample from the product with the marked bottle number and test the potency of the product. The test result is A, in IU / mL; (3) Among the products packaged after the product with the bottle number, the subsequent products are divided into the front section, the middle section and the back section, and the middle section product is taken for potency testing. The test result is B, in IU / mL; (4) Calculate the waste volume based on the difference C between B and A, using the formula C=BA; If the batch of the product is 1, the calculation of the waste volume includes the following steps: when the difference C ≤ 3 IU / mL, select the smallest bottle number, and take the result of multiplying the number value of the smallest bottle number by the volume per bottle as the waste volume; If there are multiple batches of products, the calculation of waste volume includes the following steps: (i) Select the minimum bottle number for each batch. The selection criteria are: select the minimum bottle number of the batch of products under the condition that the difference C ≤ 3 IU / mL; (ii) comparing the minimum bottle numbers among multiple batches of samples and selecting the minimum bottle number with the largest value among different batches; (iii) The waste discharge amount is the product of multiplying the number of the smallest bottle number with the largest value obtained in step (ii) by the amount filled in each bottle.

2. The method according to claim 1, characterized in that: The product is human coagulation factor VIII; in step (2) and step (3), the method for detecting the potency of human coagulation factor VIII comprises the following steps: (a) preparing human coagulation factor VIII national standard solution; (b) Prepare quality control solution; (c) preparing test sample solutions; (d) Detection using a fully automatic coagulation analyzer; (e) Select and run the factor VIII quality control procedure and calibration procedure. After the quality control and calibration are passed, the test sample can be tested; calculate the potency of the test sample human coagulation factor VIII based on the conversion value measured by the fully automatic coagulation analyzer and the dilution multiple of the test sample.

3. The method according to claim 2, characterized in that: Step (a) preparing the human coagulation factor VIII national standard solution comprises the following steps: using human coagulation factor VIII as a standard, adding sterile water for injection to reconstitute the standard, and then diluting the standard with human coagulation factor VIII-deficient plasma or 0.85%-0.90% sodium chloride solution to form a solution containing 1 IU coagulation factor VIII per 1 mL.

4. The method according to claim 2, characterized in that: Step (b) preparing the control solution comprises the following steps: re-dissolving the system coagulation control and the coagulation control with water for injection respectively, placing them at room temperature for 30 minutes for later use; step (c) preparing the test solution comprises the following steps: diluting the test sample with 0.85%-0.90% sodium chloride solution and diluent.

5. The method according to claim 2, characterized in that: In step (d), turn on the fully automatic coagulation analyzer and load the reagents; the diluent for coagulation analysis is placed at position 8# in the sample compartment, and the calcium chloride solution, APTT reagent, coagulation quality control product, system coagulation quality control product, and 1 IU / mL coagulation factor VIII national standard solution are placed at positions of the same size in the reagent compartment.

6. The method according to claim 2, characterized in that: In step (e), select and run the factor VIII quality control program and calibration program. When the quality control and calibration are passed, perform the test sample test; place the prepared test sample solution into the sample compartment, add the test sample name and batch number, select the test items, and run the program; multiply the conversion value measured by the fully automatic coagulation analyzer by the test sample dilution multiple to obtain the potency of the test sample human coagulation factor VIII.

7. The method according to any one of claims 1 to 6, characterized in that: In step (1), during the packaging process, the first 300 bottles of the product are marked, and the bottle numbers are recorded from 1 to 300 in the order of packaging.

8. The method according to any one of claims 1 to 6, characterized in that: After calculating the waste volume, the product is treated for waste.

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