Some standard content:
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The biological properties of this standard refer to the relevant provisions in GB/T16886.1-2001 "Biological Evaluation of Medical Devices Part 1: Evaluation and Testing", the chemical properties refer to the relevant provisions of GB8368-1998 "Disposable Infusion Sets", and the mechanical properties and leakage performance test methods refer to the relevant provisions of ISO8637:1989 "Hemodialyzers, Hemofilters and Hemoconcentrators". Appendix A and Appendix B of this standard are normative appendices. This standard was proposed by the State Food and Drug Administration. This standard is under the jurisdiction of the National Technical Committee for Standardization of Medical Extracorporeal Circulation Equipment. This standard was drafted by Tianjin Urology Research Institute and Tianjin TEDA Biomedical Engineering Co., Ltd. The main drafters of this standard are Gu Hanqing, Lu Mozhu, Zhu Ximing, and Gao Zengli. 1 Scope
Disposable Hemoperfusion Device
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This standard specifies the terms and definitions, requirements, test methods, inspection rules, marking, packaging, transportation and storage of disposable hemoperfusion devices.
This standard applies to disposable hemoperfusion devices (hereinafter referred to as perfusion devices) using activated carbon porous adsorption resin as adsorbent. This product is used in conjunction with hemoperfusion devices (or hemodialysis devices) for plaque perfusion (or combined with hemodialysis) to remove endogenous and exogenous excess drugs, toxins and metabolites in patients. 2 Normative References
The clauses in the following documents become the clauses of this standard through reference in this standard. For dated referenced documents, all subsequent amendments (excluding the contents of the review) or revised versions are not applicable to this standard. However, the parties to the agreement based on this standard are encouraged to study whether the latest versions of these documents can be used. For undated referenced documents, the latest versions shall apply to this standard. GB/T191 Pictorial marking for packaging, storage and transportation
GB/T2828 Batch inspection counting sampling procedures and sampling tables (applicable to continuous inspection) GB/T2829 Periodic inspection counting sampling procedures and sampling tables (applicable to inspection of stable production process) GB8368-1998
Three-time use infusion sets
GB/T13074-1991 Terminology of blood purification, liquid addition dialysis and blood filtration GB/T14233.1998 Inspection methods for medical infusion, infusion III and injection equipment Methods for testing medical infusion, transfusion and injection equipment Part 1: Chemical analysis methods GB/T14233.2-1993 Test methods for medical infusion, transfusion and injection equipment Part 2: Biological test methods GB/T16886.12001 Biological evaluation of medical devices Part 1: Evaluation and testing GB18278-2000 Requirements for sterilization confirmation and routine control of medical care products Moist heat sterilization GB18280-2000 Requirements for sterilization confirmation and routine control of medical care products Radiation sterilization 3 Terms and definitions
The following terms and definitions apply to this standard. 3.1
hemoperfution
Hemoperfusion
A treatment method that removes exogenous and endogenous excess drugs, toxins and metabolites in the blood from the patient's body based on the principles of adsorption and affinity chromatography.
Hemoperfusion device
A therapeutic device filled with adsorbents to remove exogenous and endogenous excess drugs, poisons and metabolites in the blood using the principles of adsorption and affinity chromatography.
Blood flow rate
The amount of blood flowing through the perfusion device per unit time, expressed in mL/min. 3.4
Absorbent volume
The volume (or mass) occupied by the adsorbent in the hemoperfusion device, expressed in mL (or g). YY0464-2003
Absorption characteristicThe mass of endogenous and exogenous poisons adsorbed by unit mass of adsorbent, expressed in mg/g. 3.6
Particle shedding amountThe number of solid particles peeled off from the surface of the adsorbent, expressed in pieces. 4 Classification and naming
4.1 Classification
The perfusion group can be divided into two types: activated carbon type and resin type. 4.2 Basic parameters of the perfusion device
4.2.1 Blood chamber volume of the perfusion device
The blood chamber volume of the perfusion device is specified in Table 1.
Table 1 Blood chamber volume
4.2.2 Blood flow rate of the perfusion device
The blood flow rate of the perfusion device should be greater than 200mL/min. 4.2.3 Connection between the blood inlet and outlet of the perfusion device and the pipeline The blood inlet and outlet of the perfusion device should be firmly matched with the pipeline without falling off. 4.2.4 Length-to-diameter ratio of the blood chamber of the perfusion device
The length-to-diameter ratio of the chamber of the perfusion device should be greater than 2.5:1. 4.2.5 Perfusion device filling adsorbent dosage
Blood chamber volume/mL
120-~300
The amount of adsorbent filled in the perfusion device should not be less than one-third of the volume, nor should it be greater than 19/20 of the volume. 4.3 Model naming
Specification code
Series code
5 Requirements
5.1 Appearance
The outer shell of the perfusion device should be transparent (or translucent), the inner and outer shell surfaces should be smooth, and there should be no impurities visible to the naked eye in the liquid channel. 5.2 Perfusion device blood chamber capacity
The blood chamber capacity of the perfusion device should comply with the provisions of 4.2.1. 5.3 Particle shedding
The increase of 15um-~25um particles in 100mlL eluent of the perfusion device shall not exceed 200, and the increase of particles larger than 25μm shall not exceed 100.
5.4 Chemical properties of perfusion devices
5.4.1 Reducing substances (fluoride-prone substances)
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The difference in volume of potassium permanganate solution Lc (KMnO) = 0.002mol/LJ consumed by the test solution and the blank solution shall not exceed 2.0mL. 5.4.2 Metal ions
5.4.2.1 Atomic absorption spectrophotometry (AAS) As the arbitration method, the total content of chromium, copper, lead and tin in the test solution shall not exceed 1 μg/mL, and the content of tin shall not exceed 0.1 ug/mL. 5.4.2.2 Colorimetric analysis method: The color of the test solution should not exceed the mass concentration 0 (Pb2+) = 1ug/ml. Standard control solution. 5.4.3 pH
The difference in pH between the test solution and the blank solution should not exceed 1.5. 5.4.4 Evaporation residue
The total amount of evaporation residue should not exceed 2mg.
5.4.5 Ultraviolet absorbance
The absorbance of the test solution should not be greater than 0.1.
5.5 Biological performance of the perfusion device
5.5.1 Biological evaluation
The perfusion device should be subjected to biological evaluation in accordance with the provisions of GB/T16886.1--2001. 5.5.2 Sterility
The perfusion device should be sterile.
5.5.3 Pyrogen-free
The perfusion device should be pyrogen-free.
5.6 Sealing performance of the perfusion device
The blood chamber of the perfusion device should be able to withstand a positive pressure of 100kPa. 5. 7 Adsorption performance of the perfusion device
5.7.1 Adsorption performance of pentobarbital
The adsorption material adsorbs for 2 hours under the specified conditions, and the decrease rate of pentobarbital (representing small molecular substances) is not less than 80%. 5.7.2 Adsorption performance of creatinine
The adsorption material adsorbs for 2 hours under the specified conditions, and the decrease rate of creatinine (representing metabolites in the body) is not less than 80%. 5.7.3 Adsorption performance of Bt2
The adsorption material adsorbs for 2 hours under the specified conditions, and the decrease rate of B12 (representing medium molecular weight substances) is not less than 60%. 5.8 Temperature resistance of the perfusion device
The perfusion device should not be deformed or cracked within the temperature range of 0℃50℃. 6 Test methods
6.1 Appearance
Visual inspection, should meet the requirements of 5.1.
6.2 Blood chamber volume test
Fill the blood chamber with degassed filling liquid without bubbles, leave it for 60 minutes, use pressurized air (about 50kPa) to drain the water from the blood chamber and measure, should meet the requirements of 5.2.
6.3 Particles
Perform according to Appendix A, should meet the requirements of 5.3.
6.4 Chemical property test method
6.4.1 Preparation of test solution
Take a sterilized product and connect it to a glass flask to form a circulation system. First, use physiological saline to irrigate the perfusion device from bottom to top. After the bubbles are cleared, keep it at 37℃±1℃. Use an end-acting pump to act on a medical silicone rubber tube as short as possible to circulate water at a flow rate of 1L/h for 2h. Take 50mL of the circulating liquid and dilute it to 1000mL for standby use. 6.4.2 The test for reducing substances (oxidizing substances) shall be carried out in accordance with the provisions of 5.2.2 Method 2 of GB/T14233.1-1998 and shall meet the requirements of 5.4.1. 6.4.3 Gold black ion test
6.4.3.1 The absorbance of the test solution shall not be greater than 0.1 and shall meet the requirements of 5.4.2.1. 6.4.3.2 Colorimetry: Conduct according to the method specified in 5.5.1 of GB/T14233.1-1998, and shall meet the requirements of 5.4.2.2. 6.4.4 pH
Conduct according to the method specified in 5.4.1 of GB/T14233.1-1998, and shall meet the requirements of 5.4.3. 6.4.5 Evaporation residual flow
Perform according to the provisions of (GB/T14233.1-1998 and shall meet the requirements of 5.4.4. 6.4.6 Ultraviolet absorbance
Perform according to the provisions of GB/T14233.1-1998 within the wavelength range of 250nm~320nm and shall meet the requirements of 5.4.5. 6.5 Biological performance test method
6.5.1 Biological evaluation
Enterprise product registration shall be in accordance with the provisions of GB/T16886.1-2001 Conduct biological performance evaluation. If tests are required, the following should be conducted:
6.5.1.1 Cytotoxicity: According to the provisions of Chapter 7 of GB/T14233.2-1993, it should be ≤ Grade 1. 6.5.1.2 Intradermal irritation: According to the provisions of Chapter 8 of GB/T14233.2-1993, it should have no irritation. 6.5.1.3 Sensitization test: According to the provisions of Chapter 9 of GB/T14233.2-1993, it should have no sensitizer. 6.5.1.4 Acute toxicity test: According to the provisions of GB/T14233.2-1993, it should have no sensitizer. 233.2-1993, Chapter 5, and there should be no acute systemic toxicity. 6.5.1.5 Blood compatibility, hemolysis test shall be carried out in accordance with the provisions of Chapter 6 of GB/T14233.2-1993, and the hemolysis rate shall be ≤5%. 6.5.1.6 Animal experiment for hemocytopenia shall be carried out in accordance with Appendix B, with thrombocytopenia ≤25%, leukopenia ≤15%, and erythropenia ≤10%.
6.5.2 Sterility test
Perfusion device shall be carried out in accordance with GB/T18278-2000 or GB/T1828 0-2000 confirmed sterilization process to make it sterile. After that, the sterilization process of each production batch must be monitored.
6.5.3 Non-pyrogen test
The non-pyrogen process should be confirmed before the perfusion device is sold. After that, the production must be regularly tested for pyrogen to ensure that the components are non-pyrogen. 6.6 Sealing performance test
Seal the perfusion device end and apply air pressure of 100kPa to the other end. Record the pressure for 10 minutes and visually inspect the device. When the pressure drops by more than 1%, the structural material shows leakage. 6.7 Adsorption performance test
6.7.1 Adsorption performance test of pentobarbital Prepare a pentobarbital solution with a concentration of 250 mg/mL, take 25 ml and place it in a 50 mL stoppered conical bottle. Weigh 1.0 g of adsorbent and put it into the bottle. Place it in a constant temperature water bath oscillator at 37°C ± 1°C and oscillate at a rate of not less than 10 times/min for 2 hours. Use ultraviolet spectrophotometry to measure and calculate the pentobarbital solution before and after adsorption at 240 nm. Calculate the decline rate according to formula (1): cr(%) = C8=ct × 100%
Where:
cr-pentobarbital decline rate,
co-pentobarbital solution concentration before adsorption, unit is milligram per liter (mmL) c-pentobarbital solution concentration after 2 hours of adsorption, unit is milligram per liter (mg/mL). 4
**( 1)
The decrease rate shall meet the requirements of 5.7.1.
6. 7.2 Test on adsorption performance of creatinine
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Prepare 150mg/L creatinine solution, take 25mL and place it in a 50mL stoppered conical bottle, weigh 1.0g adsorbent and put it into the bottle, place it in a constant temperature water bath oscillator at 37℃±1℃ at a rate of not less than 10 times/min for 2h, measure and calculate the creatinine solution before and after adsorption by ultraviolet spectrophotometry at 232nm, and calculate the creatinine decrease rate according to formula (2): cr(%) = = × 100%
Where:
Cratinine decrease rate;
Co——Concentration of creatinine solution before adsorption, in milligrams per liter (mg/L); ct——Concentration of creatinine solution after 2h adsorption, in milligrams per liter (mg/L). The decline rate shall meet the requirements of 5.7.2.
6.7.3 Test on the adsorption performance of B12
(2)
Prepare a B12 solution with a concentration of 100 mg/L, take 25 mL and place it in a 50 mL stoppered conical bottle, weigh 1.0 g of adsorbent and put it into the bottle, place it in a constant temperature water bath oscillator at 37℃±1℃ at a rate of not less than 10 times/min for 2 hours, measure it at 361nm by ultraviolet spectrophotometry, calculate the B12 solution before and after adsorption, and calculate the Bi2 decline rate according to formula (3): cr(%) = co= × 100%
Where:
-B2 decline rate;
B12 solution concentration before adsorption, unit is milligram per liter (mg/L); -Bi2 solution concentration after adsorption for 2 hours, unit is milligram per liter (mg/L). The decline rate shall meet the requirements of 5.7.3.
6.8 Temperature resistance test of perfusion device
(3)
Put the perfusion device in the refrigerator at 0℃ for 30min, then put it in the constant temperature box at 50℃ for 3h, take it out and restore it to room temperature for observation. And do pressure test, which should meet the requirements of Article 5.8. 7 Inspection rules
7.1 Factory inspection
7.1.1 Factory inspection is batch inspection.
7.1.2 Batch inspection takes each production batch as an inspection batch. 7.1.3 Batch inspection should meet the relevant provisions of GB/T2828. The inspection adopts a one-time sampling plan, and its inspection classification, inspection items, acceptable quality level (AQL) and inspection level are specified in Table 27.1.4
.
Table 2 Sampling plan for batch inspection
Inspection classification
Inspection items
Inspection level
7.2 Periodic inspection
All qualified
Periodic inspection shall be carried out in one of the following cases: a) When the product is registered;bzxZ.net
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When there is a major change in the process, formula or material, at least once a year in normal production;
When production is resumed after a suspension of more than half a year;
When the national quality supervision department makes a request. Periodic inspection shall be in accordance with the provisions of GB/T2829.
Periodic inspection adopts a single sampling plan, and its inspection classification, unqualified quality level (RQL) and discrimination level shall be in accordance with the provisions of Table 3. Table 3 Periodic inspection sampling plan table
Inspection classification
Classification group
Inspection items
Discrimination level
Inspection cycle
30(A=0 R 1)
Once a year
40(A.-0 R.=1)
Once every six months
60(A.=1 R.=2)
Once every six months
7.2.4 Periodic inspection should be carried out after each batch is inspected and qualified. The treatment of unqualified periodic inspection shall be carried out in accordance with GB/T2829. 7.2.5 Re-evaluate the biological performance in accordance with the requirements of 3.7 of GB/T16886.1-2001. 8 Markings
8.1 Each perfusion device shall have the following markings on a conspicuous position on the outer shell: a)
Manufacturer name, address and trademark;
Product name and model;
Production batch number and date;
Sterilization method and expiration date;
Specifications and adsorbent capacity;
Maximum operating pressure;
One-time use;
h) Product registration number.
8.2 The certificate shall have the following markings:
a) Manufacturer name;
b) Product name and model;
c) Inspector code;
d) Inspection date;
8.3 The following marks should be on the outer package:
Manufacturer name and address;
b) Product name and model;
c) Quantity;
Gross weight;
Volume (length × width × height);
Production batch number and sterilization date;
Product certificate and validity period;
Product registration number
Product standard number,
Word of single use,
k) Words or marks such as "Handle with care", "Do not press heavily", "Afraid of moisture", etc. should comply with the provisions of GB/T191. Packaging, transportation and storage
9.1 Packaging
9.1.1 Single packaging of perfusion device
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Each perfusion device shall be packaged in a composite film bag, sealed and then packed in a packaging box, which shall contain a copy of the instruction manual and a copy of the inspection certificate.
2 External packaging of perfusion device
The external packaging shall be in a corrugated packaging box.
The transportation method shall be in accordance with the provisions of the order contract. During transportation, heavy pressure, collision and rain and snow shall be avoided. Storage
The packaged perfusion device shall be stored in a cool, dry, well-ventilated and clean environment with a relative humidity not exceeding 80% and without corrosive gases. The sterilization validity period of perfusion device is 2 years under the conditions that meet the storage regulations. YY 0464--2003
A.1 Principle
Appendix A
(Normative Appendix)
Method for Determination of Particle Content in Hemoperfusion Device
This method evaluates contamination by flushing the surface of the inner liquid channel, collecting particles in the eluate on the channel surface, and counting them. A.2 Test Instruments
The instruments and devices are shown in Figure A.1
Air filter;
An air inlet needle;
3-Sodium chloride injection;
Filter device;
"Three-way switch,
Polyvinyl chloride hose;
7The perfusion device under test;
Particle counter;
Sampling cup.
Particle content determination device
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A.2.1 Resistance particle counter; with stirring system, one sampling volume of 100mL, can count particles of 15um～25μm and larger than 25μm at the same time.
A.2.2 Filter device: microporous filter membrane with internal diameter of 50mm and pore size of 0.45um. A.2.3 Flushing liquid: sodium chloride injection.
A.2.4 Polyvinyl chloride hose, hose length 1m, outer diameter 3.5mm~4mm. A.2.5 Three-way conversion
A.3 Steps
The filter device is connected to the infusion bottle containing sodium chloride injection through the bottle stopper piercer. The lower end of the filter device is connected to a three-way switch, and the lower end is connected to a hose to the particle counter sampling cup. A.3.2 Rinse the filter, three-way switch and hose with 100mL of flushing liquid. Note: The flushing liquid for the initial test should be no less than 2L. A.3.3 Under a static pressure head of about 1m, allow 200mL of flushing liquid to pass through the hose. The outflowing liquid flows into the sampling cup of the counter to obtain the background solution. Determine 100 The number of particles in mL of background solution.
Note: Environmental pollution should be paid attention to during the test.
A.3.4 Repeat the steps in A.3.3, and the average of the two counts is the particle content in 100mL of background solution. A.3.5 Prepare the test solution using aseptic operation, and first irrigate and soak from bottom to top with 500mL of normal saline. A.3.6 Under a static pressure head of 1m, irrigate the perfusion device from top to bottom with 2500mL of normal saline at a flow rate of 200mL/min for 12 minutes, collect the last 100mL of eluate, and measure the number of particles in 100mL of eluate. A.4 Result expression
The difference between the particle readings of the eluate and the background solution is the particle content in the eluate. 9
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Appendix B
(Normative Appendix)
Animal Experiment on Hemocytopenia
Healthy mongrel dogs (weight greater than 15kg) were selected for the experiment. According to the conventional method, the blood was perfused for 2 hours using a blood perfusion device. The blood of the animals was taken before and after the perfusion for testing. The number of platelets, red blood cells and white blood cells was determined. The hemocytopenia rate was calculated according to formula (B.1): N— Nt
+×100%
Nr(%) =
Where:
N. —The number of blood cells (platelets, red blood cells and white blood cells) in the blood before perfusion, N. —The number of blood cells (platelets, red blood cells and white blood cells) in the blood after perfusion. 10
..........( B. 1 )1) Calculate the blood cell reduction rate: N— Nt
+×100%
Nr(%) =
Wherein:
N. —The number of blood cells (platelets, red blood cells, and white blood cells) in the blood before perfusion, N. —The number of blood cells (platelets, red blood cells, and white blood cells) in the blood after perfusion. 10
..........( B. 1 )1) Calculate the blood cell reduction rate: N— Nt
+×100%
Nr(%) =
Wherein:
N. —The number of blood cells (platelets, red blood cells, and white blood cells) in the blood before perfusion, N. —The number of blood cells (platelets, red blood cells, and white blood cells) in the blood after perfusion. 10
..........( B. 1 )
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