JB 20001-2003 Large volume injection, small volume injection sterilizer
Some standard content:
Pharmaceutical Machinery Industry Standard of the People's Republic of China JB20001-2003
Sterilizer of large capacity infusion and small capacity infusion
Promulgated on 2003-02-12
Implementation on 2003-06-01
Announcement issued by the State Economic and Trade Commission of the People's Republic of China
No. 13 of 2003
Announcement of the Industry Standard of Sterilizer of Large Capacity Infusion and Small Capacity Infusion
The State Economic and Trade Commission approved the Industry Standard of Sterilizer of Large Capacity Infusion and Small Capacity Infusion, with the standard number: JB20001-2003, which is hereby promulgated and will be implemented on June 1, 2003.
State Economic and Trade Commission of the People's Republic of China February 12, 2003
Scope·
2 Normative references
3 Terms and definitions
4 Classification and marking
5 Requirements
6 Test methods
7 Inspection rules
8 Marking, instructions for use, packaging and storage...Appendix A (Informative Appendix)
Appendix B (Informative Appendix)
Appendix C (Informative Appendix) Appendix A (Informative Appendix)
Appendix D (Informative Appendix)
Design Confirmation Test Record
Installation Confirmation Test Record
Operation Confirmation Test Record
Performance Confirmation Test Record
JB20001—2003
JB20001—2003
In order to make this standard more widely applicable and operable, this standard does not specify the series parameters, cavity structure shape, and heating medium of the sterilizer.
Appendix A, Appendix B, Appendix C, and Appendix D of this standard are all informative appendices. This standard is proposed by the China Pharmaceutical Equipment Industry Association. This standard is under the jurisdiction of the China Pharmaceutical Equipment Industry Association. The drafting unit of this standard: Chongqing Pharmaceutical Machinery Factory. The main drafters of this standard: Sun Jinlian and Zhou Jie. 1 Scope
Autoclave for large-volume injection and small-volume injection JB20001—2003
This standard specifies the classification, marking, requirements, test methods, inspection rules, signs, instructions for use, packaging and storage of sterilizers for large-volume injection and small-volume injection
This standard applies to sterilizers for large-volume injection and small-volume injection (hereinafter referred to as sterilizers). 2 Normative references
The clauses in the following documents become the clauses of this standard through reference in this standard. For any dated referenced document, all subsequent amendments (excluding errata) or revisions are not applicable to this standard. However, the parties who reach an agreement based on this standard are encouraged to study whether the latest versions of these documents can be used. For any undated referenced document, the latest version shall apply to this standard. GB150 Steel pressure vessel
GB191—2000 Pictorial mark for packaging, storage and transportation
GB2639-1990 Glass infusion bottle
GB/T5226.11996 Industrial machinery and electrical equipment - Part - Technical conditions for use GB/T6388-1986 Transport packaging, receiving and shipping marks CB7231-1987 Basic identification colors and identification symbols for industrial pipelines GB9969.1-1998 General provisions for instructions for use of industrial products CB/T10111—1988
GB/T 13306—1991
GB/T13384—1992
GB/T16769—1997
JB25361980
Random sampling method using random number age plate
General technical conditions for packaging of electromechanical products
Determination of sound pressure level of noise of metal cutting machine toolsPainting, packaging and transportation of pressure vessels
JB/T4709Welding code for steel pressure vesselsJB4730Nondestructive testing of pressure vessels
YBB00012002 Low-density polyethylene infusion bottle (trial implementation) Polypropylene infusion bottle (trial implementation)
YBB00022002
YY/T0216—1995 Pharmaceutical machinery model reduction method Pharmacopoeia of the People's Republic of China (2000 edition) State Drug Administration Safety Technical Supervision Regulations for Pressure Vessels (1999 edition) Former State Administration of Quality and Technical Supervision Good Manufacturing Practice for Pharmaceuticals (CMP) (Revised in 1998) State Drug Administration 3 Terms and definitions
F. value
F. value is the standard sterilization time, which is the equivalent sterilization time given to the sterilized items at 121°C by the sterilization process, that is, F, value when T=121°C and ZJB20001—2003
10°C. 121°C is the standard state, F. value is the standard sterilization time, expressed in minutes (minutes). F. The value calculation formula is:
r-12uo)ds
Where T is the temperature of the sterilized object measured every △t. t is time. 4 Classification and marking
4.1 Type
The types of sterilizers are static and rotary. The static type is not marked, and the rotary type is marked with H. The types of sterilizers are large-volume injection sterilizers and small-volume injection sterilizers. Large-volume injections are marked with S, and small-volume injections are marked with A. 4.2 Model
4.2.1 The model of the sterilizer shall comply with the provisions of YY/T0216-1995. 4.2.2 Model marking
4.2.3 Marking example
MS(MA)RS(RSH)3000(1.5)
MS(MA)RQ(RQH)3000(1.5)
5 Requirements
5.1 General
Improvement design sequence number
Main parameters (output: bottle/time or chamber effective volume m) Product model and characteristic code
Product function code
First improvement design||t t||Production (500mL, 3000 bottles/time) or chamber volume (1.5m) Water spray heating (rotary water spray latent heating) Large-capacity injection sterilizer (small-capacity injection sterilizer) First improved design
Production (500mL, 3000 bottles/time) or chamber volume (1.5m) Steam heating (rotary steam heating)
Large-capacity injection sterilizer (small-capacity injection sterilizer) The sterilizer shall comply with the requirements of this standard and be manufactured according to the drawings and technical documents approved by the prescribed procedures. 2
5.2 Material requirements
5.2.1 The pressure-bearing parts of the sterilizer shall comply with the material requirements of CB150. JB20001—2003
5.2.2 All metal materials in contact with water and air shall be austenitic stainless steel, and other materials shall be corrosion-resistant, high-temperature-resistant, and rust-proof. A material certificate shall be attached.
5.2.3 Purchased parts or auxiliary equipment shall comply with the requirements of this standard and be accompanied by product certificates and instructions for use. 5.3 Structural requirements
5.3.1 Main machine requirements
5.3.1.1 The design pressure of the sterilizer shall comply with the requirements of the drug sterilization process and the provisions of CB150. 5.3.1.2
The welding of pressure-bearing parts shall comply with the provisions of JB/T4709. The sterilizer shall be designed with double-profile doors and special interfaces for heat distribution testing. The chamber shall have a lifting ring or hook for safe lifting. 5.3.1.33
5.3.1.4 The chamber volume of the sterilizer shall comply with the design output requirements. 5.3.1.5 The trolley in and out conveyor installed in the sterilizer chamber shall convey smoothly and accurately. The rotating body in the rotary sterilizer shall rotate flexibly and rotate smoothly after loading. 5.3.1.6
5.3.1.7 The sterilizer should be equipped with a pressure gauge and a safety valve. The pressure gauge and safety valve should comply with the provisions of Chapter 7 "Safety Annex" of the "Regulations on Safety Technical Supervision of Pressure Vessels".
5.3.2 Requirements for circulation system
5.3.2.1 A steam trap should be installed in the heat exchange circulation system. 5.3.2.2 A filter with a pore size of 60 mesh should be installed at the inlet of steam, circulating water and cooling water. A filter with a pore size of 0.4um should be installed at the inlet of compressed air for instruments.
5.3.3 Sealing requirements
5.3.3.1 The door seal should be safe and reliable. The automatic quick-opening door should have a safety protection device. 5.3.3.2 The pipe connections of the heat exchange circulation system should be well sealed, and there should be no leakage in the water and air circulation systems during operation. 5.3.3.3 The rotating shaft entering the chamber should be well sealed with the cabinet. 5.3.4 Requirements for control devices
5.3.4.1 Control devices should be set up separately for easy operation. 5.3.4.2 The control system should have F. value monitoring device and multi-point temperature recorder. The accuracy of the test sensor should be Class A, the sensor error should be less than or equal to 0.06℃, and the system temperature error should be less than or equal to 0.2℃. 5.3.4.3 The control system should have display and printing functions. 5.3.5 Appearance requirements
5.3.5.1 There should be a good insulation layer outside the chamber, and the surface of the insulation layer should be flat and smooth, without any particles falling off. 5.3.5.2 The stainless steel surface of the sterilizer should be smooth and free of scratches. 5.3.5.3 The connecting pipes of the sterilizer should be arranged neatly and in a reasonable direction. The supporting equipment is compact and beautiful in appearance. The name and flow direction of the materials in the water and gas pipelines should be marked according to the provisions of 2.7 in CB72311987, and the signs should be fixed in the pipeline positions specified in the standard. 5.4 Functional requirements
5.4.1 Monitoring function
5.4.1.1 When the circulating water reaches the preset amount, the water supply pump shall stop working. 5.4.1.2 The control device shall automatically control the process according to the set sterilization process. 5.4.1.3 Temperature monitoring: The insulation temperature fluctuation of the temperature measuring point shall be ensured to be between 0℃ and 1℃. 5.4.1.4 The rotating body in the chamber shall be controlled to stop in place. 5.4.2 Door safety interlock
5.4.2.1 If the door operation process is blocked, it stops moving forward and returns to its original position. 5.4.2.2 If a circuit fault occurs during the sterilization process, the double doors shall still maintain the sealing pressure. 3
JB20001—2003
5.4.2.3 The opening and closing of the front and rear doors shall be interlocked.
5.4.2.4 A safety interlock device shall be installed on the door, and the door seal shall not be released in the following situations: a) The pressure in the chamber exceeds ±0.027MPa; b) The temperature in the chamber is higher than 60℃;
c) The water level in the chamber is higher than the water collection.
5.4.2.5 The sterilizer shall be equipped with a safety switch. When the operator or maintenance personnel enter the chamber to work, the safety switch shall lock the heat exchange medium and prevent it from working.
5.4.2.6 The door shall be self-locking. When the sterilizer chamber door is opened, the heat exchange medium shall be locked and prevented from working. 5.4.3 Display function
5.4.3.1 The display shall display the temperature, pressure, F value and their curve graphs of the sterilization process in real time. 5.4.3.2 The display shall be able to display the fault and location of the temperature sensor and pressure transmitter. 5.4.3.3 The pressure gauge on the sterilizer shall display the pressure in the chamber and the door seal pressure in real time. 5.4.4 Printing function
After the sterilization process is completed, the printing device shall automatically print the following information: Drug name:
Sterilization date:
Insulation time:
Drug out-of-cabinet temperature:
F. value, pressure, temperature curve graph:
Drug batch number:
Sterilization start time:
Cooling time:
Cabinet number:
Packaging specification:
Heating time:
End time:
Operator:
5.4.5 Large-volume injection sterilizers shall be applicable to the sterilization of glass bottles, plastic bottles and plastic bags for infusion. 5.4.6 Small-volume injection sterilizers shall have a leak detection function. 5.5 Sterilizer working conditions
5.5.1 The circulating water, cooling water, steam, compressed air and power supply provided shall meet the following requirements: Circulating water: Purified water [Comply with the requirements of the Pharmacopoeia of the People's Republic of China (2000 Edition)] Cooling water pressure: 0.15MPa~0.5MPa
Saturated steam pressure: 0.3MPa~0.6MPa
Compressed air pressure: 0.4MPa~0.8MPa
Power supply: AC three-phase 380(1±10%)V, single-phase 220(1±10%)V5.5.2 Glass infusion bottles shall comply with the provisions of CB2639-1990. Plastic bottles (bags) shall comply with the provisions of YBB00012002 and YBB00022002.
5.5.3 The determination of the sterilization temperature, time and F. value of the sterilized items shall comply with the sterilization process requirements. 5.6 Sterilizer performance requirements
5.6.1 Temperature distribution and control.
5.6.1.1 No-load heat distribution test, the difference between the cold spot temperature and the average chamber temperature is required to be less than or equal to ±1°C. 5.6.1.2 Full-load heat distribution test, the difference between the cold spot temperature and the average chamber temperature is required to be less than or equal to ±1°C. 5.6.1.3 Heat penetration test, the F. of each measuring point is required to be >8, and the difference between the cold spot F. and the average chamber F. is less than or equal to 2min. 5.6.1.4 Microbiological target test results, the probability of microbial survival is less than or equal to 10-°. 5.6.2 The outer surface temperature of the sterilizer is not higher than the ambient temperature by 15°C. 5.6.3 There is no abnormal noise when the sterilizer is working, and the noise level does not exceed 75dB(A). 5.6.4 Electrical system quality requirements.
5.6.4.1 The continuity of the protective grounding circuit of the electrical system shall comply with the provisions of 20.2 of CB/T5226.1-1996. 5.6.4.2 The insulation resistance of the electrical system shall comply with the provisions of 20.3 of CB/T5226.1-1996. 4
5.6.4.3 The withstand voltage of the electrical system shall comply with the provisions of 20.4 of CB/T5226.11996. JB20001—2003
5.6.4.4 The color, marking and circuit layout of wires and electrical components shall comply with the provisions of GB/T5226.1-1996. 6 Test methods
6.1 Design confirmation
For the test record form of design confirmation, please refer to Appendix A. During each test, the main inspector shall fill in the test record form, and the project leader shall review and sign after the test, and the chief technical person in charge shall approve it. 6.1.1 Welding test
The weld appearance quality inspection shall be carried out in accordance with CB150 and "Regulations on Safety Technical Supervision of Pressure Vessels" (1999 Edition), and the non-destructive testing shall be carried out in accordance with JB4730 standard, and level III shall be qualified. The test results shall comply with the provisions of 5.3.1.2. 6.1.2 Pressure test
The pressure test shall be carried out in accordance with the provisions of GB150 standard, and the test results shall comply with the provisions of 5.3.1.1. 6.1.3 Egg laying test
Put the designed number of bottles (bags) in the sterilization cart, push them into the sterilizer chamber according to the designed number of carts, and the double doors can be opened and closed freely. The test results meet the requirements of 5.3.1.4.
6.1.4 Daily test to check whether 5.3.1.3, 5.3.1.7, 5.3.3.1, 5.3.3.2, 5.3.4.1, 5.3.5.1, 5.3.5.3, 5.3.5.2, 5.6.4.4 meet the requirements of this standard.
6.1.5 Function test
Before the equipment leaves the factory, confirm the control program. Convert the temperature and pressure into electrical signals for program simulation The test results shall meet the requirements of 5.4.1.2.
6.1.6 Idle running test
6.1.6.1 The transmission system and circulating water system are started and run for 30 minutes. The operation results shall meet the requirements of 5.3.4.2 and 5.3.4.3. 6.1.6.2 Trolley conveyor device test. Start the trolley conveyor device in the chamber, push the load trolley into the chamber, and observe whether the conveyor device meets the requirements of 5.3.1.5.
6.1.6.3 Rotary device operation test. Start the load rotary body movement alone, and visually check whether it stops in place and runs smoothly. The test results shall meet the requirements of 5.3.1.6.5.4.1. 4 requirements.
6.1.6.4 Water level gauge function test. Add baffles to the door frames at both ends of the chamber, start the water supply pump, and when the water level of the circulating water in the chamber reaches the set value, the water supply pump stops supplying water. The test results should meet the requirements of 5.4.1.1. 6.2 Sterilizer document and working condition inspection, that is, installation confirmation. See Appendix B for the confirmation test record form. During each test, the main inspector should fill in the test record form, which will be reviewed and signed by the project leader after the test is completed and approved by the chief technical officer. 6.2.1 Document inspection
Visually inspect the sterilizer material certificate, instruction manual and certificate of conformity (including supporting equipment), pressure gauge, safety valve, and temperature sensor. Calibration certificate, etc. The test results shall meet the requirements of 8.3.2. 6.2.2 Working condition test
After the equipment is installed properly, use a pressure gauge to test the steam, cooling water and compressed air pressures; use a voltmeter to test the power supply and control power supply; and test the quality of purified water in accordance with the provisions of the Pharmacopoeia of the People's Republic of China (2000 edition). The test results meet the requirements of 5.5.1. 6.2.3 Packaging material confirmation
Glass infusion bottles shall be tested in accordance with CB26391990. Plastic bottles (bags) shall be tested in accordance with YBB00012002 and YBB00022002. The test results meet the requirements of 5.5.2.
6.3 Function confirmation
is operation confirmation. For the confirmation test record form, please refer to Appendix C. During each test, the main inspector shall fill in the test record form, and after the test, the project leader shall review and sign, and the chief technical person in charge shall approve it. 5
JB20001—2003
6.3.1 Automatic control process test
The test shall be carried out according to the operating procedures of the sterilizer, and the test results shall meet the requirements of 5.4.1.2, 5.4.3.1, 5.4.3.3, and 5.4.4. 6.3.2 Safety failure simulation test
6.3.2.1 During the door closing process, set up obstacles, and the door will stop moving forward and return to its original position when it hits the obstacle. It meets the requirements of 5.4.2.1. 6.3.2.2 Cut off the power supply and observe that the double doors are still in a normal sealing state, which meets the requirements of 5.4.2.2. 6.3.2.3 The front door is open, and the rear door opening button is pressed, but the door does not open. Similarly, the rear door is open, and the front door opening button is pressed, but the door does not open. The test meets the requirements of 5.4.2.3. 6.3.2.4 Sterilizer door opening protection test. Use electrical signal conversion to perform simulation tests, the chamber pressure exceeds ±0.027MPa; the chamber temperature is greater than 60℃; the chamber water level is higher than the sump. Press the door opening button respectively, and the door cannot be opened. The test results meet the requirements of 5.4.2.4. 6.3.2.5 Fault display test. Use the damaged pressure transmitter or temperature sensor at the test site, and the sensor position and fault display should be observed on the display screen. Meet the requirements of 5.4.3.2. 6.3.2.6 Press the safety switch and start the control program again, and the sterilizer will not enter the working state. Meet the requirements of 5.4.2.5. 6.3.2.7 Open the sterilizer chamber door, start the control program, and the sterilizer will not enter the working state. Meet the requirements of 5.4.2.6. 6.4 Sterilizer performance test
is performance confirmation, and the test record form is shown in Appendix D. During each test, the main inspector shall fill in the test record form, and after the test is completed, the project leader shall review and sign it, and the chief technical investor shall approve it. 6.4.1 Heat distribution test
6.4.1.1 Test verification equipment (see Table 6.4.1-1) Table 6.4.1-1 Test verification equipment list
Equipment name
Temperature sensor
Verifier
≤0.1℃
Note: It is allowed to use sensors and instruments with the same accuracy level in the table. 6.4.1.2 No-load heat distribution test
Calibration instruments
Low-temperature, oil-based, second-class mercury standard thermometer standard resistance box
10 temperature sensors are placed: 1 is placed at the heating medium inlet at the top of the chamber, 1 is placed at the circulating water or cold water outlet at the bottom of the chamber, two are placed next to the temperature control and recording temperature sensor at the bottom of the chamber, and the rest are distributed throughout the chamber. The temperature sensors are all suspended and do not contact the metal surface.
Run 3 times according to the 115℃, 30min sterilization procedure or the sterilization process parameters proposed by the pharmaceutical factory. The test results should comply with the provisions of 5.6.1.1. 6.4.1.3 Full-load heat distribution test
The temperature sensors are placed according to the no-load heat distribution test, and the sensors are placed in the air and do not contact the sterilized items. Run 3 times according to the 115℃, 30min sterilization procedure or the sterilization process parameters proposed by the pharmaceutical factory. The test results should comply with the provisions of 5.6.1.2. 6.4.1.4 Heat penetration test
The temperature sensor placement for the heat penetration test is shown in Figure 6.4.1 and Table 6.4.1-2. After the temperature sensor is fixed, run the sterilization procedure at 115℃, 30min or the sterilization process parameters proposed by the pharmaceutical manufacturer for 3 times. The test results all meet the requirements of 5.6.1.3.
Small-volume injections can be exempted from the heat penetration test. Note: The ampoule has a thin wall and a small volume. The temperature inside and outside the ampoule is basically the same during the heat exchange process. Therefore, the heat penetration test can be exempted. 6.4.1.5 Microbial target test
The microbial target test can be carried out together with the heat penetration test or separately. Repeat three times. Test procedure: Use 20 bottles of NCTCI0007 (or NCIMB8157, ATCC7953) thermophilic Bacillus liquid as test bottles and number them. Place them near the temperature measurement points. The position numbers of the test bottles should be marked, and then sterilize them according to the sterilization process procedure for Bacillus. After sterilization, take out the test bottle and perform sterilization test according to Appendix XI "H Sterility Test Method" of Part II of the Pharmacopoeia of the People's Republic of China (2000 Edition). The inspection result should meet the requirements of 5.6.1.4.
1) A, B, C, D indicate that the sterilization chamber is divided into four equal parts horizontally; 2) I-V indicates that the sterilization chamber is divided into five equal parts in height; 3) 1-5 indicates that the sterilization chamber is divided into five equal parts vertically. B
Schematic diagram of sterilizer chamber section
Table 6.4.1-2 Temperature sensor loading position table Sensor number
Sensor position
Sensor number
Sensor position
II-3-B
Sensor number
JB2 0001—2003
Sensor location
Ⅲ-4-B
Ⅲ-2-C
Note 1: Temperature sensor location description: No. 1 temperature sensor is placed at the circulating water inlet, and No. 2 temperature sensor is placed at the circulating water outlet. No. 3 to 6 temperature sensors are placed at the bottom four corners of A and D, and No. 7 to 10 temperature sensors are placed at the center of B and C. Among them, No. 3 to 10 temperature sensors are all inserted into the liquid medicine bottles at their locations.
Note 2: Temperature sensor quantity description: As the volume of the sterilizer chamber increases, the number of temperature sensors increases accordingly, up to a maximum of 20. 6.4.2 Seedling sterilizer surface temperature measurement
When the sterilization temperature is reached in the sterilization chamber, Use an industrial thermometer to measure the center of the doors at both ends of the shell for 5 minutes. The larger value should meet the requirements of 5.6.2.
6.4.3 Leak detection function test of small-volume injection sterilizer Arrange the finished small-volume injection bottles neatly in the sterilization box, leaving no space for sliding or tipping over the bottles, and cover them tightly with a stainless steel cover with a water diversion hole. Invert the sterilization box 180° and place it in the sterilization cart, and push it into the sterilizer chamber. After sterilization is completed, start the vacuum program and the vacuum degree reaches -0.086MPa. Maintain the pressure for 5 minutes, slowly start the air intake, and when the pressure gauge pointer in the control chamber points to zero, inject deionized water into the chamber to spray the bottle wall for 5 minutes, and then drain the remaining water in the chamber. Open the door, push out the sterilization cart, open the sterilization box lid, Detect empty bottles or half bottles. Note: Leak detection principle: Invert the finished small-volume injection bottles 180° and arrange them neatly in the sterilization box, and the sterilization and drainage are completed. During the process of vacuuming the sterilizer chamber, the pressure decreases, the boiling point of the drug solution decreases, an evaporation process occurs, and it is emitted from the cracks at the bottom of the bottle. After vacuuming, the sum of gravity and the pressure inside the bottle is greater than the pressure outside the bottle, forming a pressure difference of 4. Under the action of the pressure difference, the liquid in the bottle is squeezed out of the bottle. When the pressure in the sterilizer chamber returns to normal pressure, due to the existence of inverted gravity, the liquid outside the bottle will not automatically penetrate into the bottle. The purpose of leak detection is achieved. 6.4.4 Noise detection
When the sterilizer is working, test the machine noise in accordance with CB/T16769-1997. The results should meet the requirements of 5.6.3. 74 Sterilizer performance test
is performance confirmation, and the test record form is shown in Appendix D. During each test, the main inspector shall fill in the test record form, and after the test is completed, the project leader shall review and sign it, and the chief technical investor shall approve it. 6.4.1 Heat distribution test
6.4.1.1 Test verification equipment (see Table 6.4.1-1) Table 6.4.1-1 List of test verification equipment
Equipment name
Temperature sensor
Verifier
≤0.1℃
Note: It is allowed to use sensors and instruments with the same accuracy level in the table. 6.4.1.2 No-load heat distribution test
Calibration instruments
Low-temperature, oil-based, second-class mercury standard thermometer standard resistance box
10 temperature sensors are placed: 1 is placed at the heating medium inlet at the top of the chamber, 1 is placed at the circulating water or cold water outlet at the bottom of the chamber, two are placed next to the temperature control and recording temperature sensor at the bottom of the chamber, and the rest are distributed throughout the chamber. The temperature sensors are all suspended and do not contact the metal surface.
Run 3 times according to the 115℃, 30min sterilization procedure or the sterilization process parameters proposed by the pharmaceutical factory. The test results should comply with the provisions of 5.6.1.1. 6.4.1.3 Full-load heat distribution test
The temperature sensors are placed according to the no-load heat distribution test, and the sensors are placed in the air and do not contact the sterilized items. Run 3 times according to the 115℃, 30min sterilization procedure or the sterilization process parameters proposed by the pharmaceutical factory. The test results should comply with the provisions of 5.6.1.2. 6.4.1.4 Heat penetration test
The temperature sensor placement for the heat penetration test is shown in Figure 6.4.1 and Table 6.4.1-2. After the temperature sensor is fixed, run the sterilization procedure at 115℃, 30min or the sterilization process parameters proposed by the pharmaceutical manufacturer for 3 times. The test results all meet the requirements of 5.6.1.3.
Small-volume injections can be exempted from the heat penetration test. Note: The ampoule has a thin wall and a small volume. The temperature inside and outside the ampoule is basically the same during the heat exchange process. Therefore, the heat penetration test can be exempted. 6.4.1.5 Microbial target test
The microbial target test can be carried out together with the heat penetration test or separately. Repeat three times. Test procedure: Use 20 bottles of NCTCI0007 (or NCIMB8157, ATCC7953) thermophilic Bacillus liquid as test bottles and number them. Place them near the temperature measurement points. The position numbers of the test bottles should be marked, and then sterilize them according to the sterilization process procedure for Bacillus. After sterilization, take out the test bottle and perform sterilization test according to Appendix XI "H Sterility Test Method" of Part II of the Pharmacopoeia of the People's Republic of China (2000 Edition). The inspection result should meet the requirements of 5.6.1.4.
1) A, B, C, D indicate that the sterilization chamber is divided into four equal parts horizontally; 2) I-V indicates that the sterilization chamber is divided into five equal parts in height; 3) 1-5 indicates that the sterilization chamber is divided into five equal parts vertically. B
Schematic diagram of sterilizer chamber section
Table 6.4.1-2 Temperature sensor loading position table Sensor number
Sensor position
Sensor number
Sensor position
II-3-B
Sensor number
JB2 0001—2003
Sensor location
Ⅲ-4-B
Ⅲ-2-C
Note 1: Temperature sensor location description: No. 1 temperature sensor is placed at the circulating water inlet, and No. 2 temperature sensor is placed at the circulating water outlet. No. 3 to 6 temperature sensors are placed at the bottom four corners of A and D, and No. 7 to 10 temperature sensors are placed at the center of B and C. Among them, No. 3 to 10 temperature sensors are all inserted into the liquid medicine bottles at their locations.
Note 2: Temperature sensor quantity description: As the volume of the sterilizer chamber increases, the number of temperature sensors increases accordingly, up to a maximum of 20. 6.4.2 Seedling sterilizer surface temperature measurement
When the sterilization temperature is reached in the sterilization chamber, Use an industrial thermometer to measure the center of the doors at both ends of the shell for 5 minutes. The larger value should meet the requirements of 5.6.2.
6.4.3 Leak detection function test of small-volume injection sterilizer Arrange the finished small-volume injection bottles neatly in the sterilization box, leaving no space for sliding or tipping over the bottles, and cover them tightly with a stainless steel cover with a water diversion hole. Invert the sterilization box 180° and place it in the sterilization cart, and push it into the sterilizer chamber. After sterilization is completed, start the vacuum program and the vacuum degree reaches -0.086MPa. Maintain the pressure for 5 minutes, slowly start the air intake, and when the pressure gauge pointer in the control chamber points to zero, inject deionized water into the chamber to spray the bottle wall for 5 minutes, and then drain the remaining water in the chamber. Open the door, push out the sterilization cart, open the sterilization box lid, Detect empty bottles or half bottles. Note: Leak detection principle: Invert the finished small-volume injection bottles 180° and arrange them neatly in the sterilization box, and the sterilization and drainage are completed. During the process of vacuuming the sterilizer chamber, the pressure decreases, the boiling point of the drug solution decreases, an evaporation process occurs, and it is emitted from the cracks at the bottom of the bottle. After vacuuming, the sum of gravity and the pressure inside the bottle is greater than the pressure outside the bottle, forming a pressure difference of 4. Under the action of the pressure difference, the liquid in the bottle is squeezed out of the bottle. When the pressure in the sterilizer chamber returns to normal pressure, due to the existence of inverted gravity, the liquid outside the bottle will not automatically penetrate into the bottle. The purpose of leak detection is achieved. 6.4.4 Noise detection
When the sterilizer is working, test the machine noise in accordance with CB/T16769-1997. The results should meet the requirements of 5.6.3. 74 Sterilizer performance test
is performance confirmation, and the test record form is shown in Appendix D. During each test, the main inspector shall fill in the test record form, and after the test is completed, the project leader shall review and sign it, and the chief technical investor shall approve it. 6.4.1 Heat distribution test
6.4.1.1 Test verification equipment (see Table 6.4.1-1) Table 6.4.1-1 Test verification equipment list
Equipment name
Temperature sensor
Verifier
≤0.1℃
Note: It is allowed to use sensors and instruments with the same accuracy level in the table. 6.4.1.2 No-load heat distribution test
Calibration instruments
Low-temperature, oil-based, second-class mercury standard thermometer standard resistance box
10 temperature sensors are placed: 1 is placed at the heating medium inlet at the top of the chamber, 1 is placed at the circulating water or cold water outlet at the bottom of the chamber, two are placed next to the temperature control and recording temperature sensor at the bottom of the chamber, and the rest are distributed throughout the chamber. The temperature sensors are all suspended and do not contact the metal surface.
Run 3 times according to the 115℃, 30min sterilization procedure or the sterilization process parameters proposed by the pharmaceutical factory. The test results should comply with the provisions of 5.6.1.1. 6.4.1.3 Full-load heat distribution test
The temperature sensors are placed according to the no-load heat distribution test, and the sensors are placed in the air and do not contact the sterilized items. Run 3 times according to the 115℃, 30min sterilization procedure or the sterilization process parameters proposed by the pharmaceutical factory. The test results should comply with the provisions of 5.6.1.2. 6.4.1.4 Heat penetration test
The temperature sensor placement for the heat penetration test is shown in Figure 6.4.1 and Table 6.4.1-2. After the temperature sensor is fixed, run the sterilization procedure at 115℃, 30min or the sterilization process parameters proposed by the pharmaceutical manufacturer for 3 times. The test results all meet the requirements of 5.6.1.3.
Small-volume injections can be exempted from the heat penetration test. Note: The ampoule has a thin wall and a small volume. The temperature inside and outside the ampoule is basically the same during the heat exchange process. Therefore, the heat penetration test can be exempted. 6.4.1.5 Microbial target test
The microbial target test can be carried out together with the heat penetration test or separately. Repeat three times. Test procedure: Use 20 bottles of NCTCI0007 (or NCIMB8157, ATCC7953) thermophilic Bacillus liquid as test bottles and number them. Place them near the temperature measurement points. The position numbers of the test bottles should be marked, and then sterilize them according to the sterilization process procedure for Bacillus. After sterilization, take out the test bottle and conduct the test according to Appendix XI "H Sterility Test Method" of Part II of the Pharmacopoeia of the People's Republic of China (2000 Edition). The test results should meet the requirements of 5.6.1.4.
1) A, B, C, D indicate that the sterilization chamber is divided into four equal parts horizontally; 2) I-V indicates that the sterilization chamber is divided into five equal parts in height; 3) 1-5 indicates that the sterilization chamber is divided into five equal parts vertically. B
Schematic diagram of sterilizer chamber section
Table 6.4.1-2 Temperature sensor loading position table Sensor number
Sensor position
Sensor number
Sensor position
II-3-B
Sensor number
JB2 0001—2003
Sensor location
Ⅲ-4-B
Ⅲ-2-C
Note 1: Temperature sensor location description: No. 1 temperature sensor is placed at the circulating water inlet, and No. 2 temperature sensor is placed at the circulating water outlet. No. 3 to 6 temperature sensors are placed at the bottom four corners of A and D, and No. 7 to 10 temperature sensors are placed at the center of B and C. Among them, No. 3 to 10 temperature sensors are all inserted into the liquid medicine bottles at their locations.
Note 2: Temperature sensor quantity description: As the volume of the sterilizer chamber increases, the number of temperature sensors increases accordingly, up to a maximum of 20. 6.4.2 Seedling sterilizer surface temperature measurement
When the sterilization temperature is reached in the sterilization chamber, Use an industrial thermometer to measure the center of the doors at both ends of the shell for 5 minutes. The larger value should meet the requirements of 5.6.2.
6.4.3 Leak detection function test of small-volume injection sterilizer Arrange the finished small-volume injection bottles neatly in the sterilization box, leaving no space for sliding or tipping over the bottles, and cover them tightly with a stainless steel cover with a water diversion hole. Invert the sterilization box 180° and place it in the sterilization cart, and push it into the sterilizer chamber. After sterilization is completed, start the vacuum program and the vacuum degree reaches -0.086MPa. Maintain the pressure for 5 minutes, slowly start the air intake, and when the pressure gauge pointer in the control chamber points to zero, inject deionized water into the chamber to spray the bottle wall for 5 minutes, and then drain the remaining water in the chamber. Open the door, push out the sterilization cart, open the sterilization box lid, Detect empty bottles or half bottles. Note: Leak detection principle: Invert the finished small-volume injection bottles 180° and arrange them neatly in the sterilization box, and the sterilization and drainage are completed. During the process of vacuuming the sterilizer chamber, the pressure decreases, the boiling point of the drug solution decreases, an evaporation process occurs, and it is emitted from the cracks at the bottom of the bottle. After vacuuming, the sum of gravity and the pressure inside the bottle is greater than the pressure outside the bottle, forming a pressure difference of 4. Under the action of the pressure difference, the liquid in the bottle is squeezed out of the bottle. When the pressure in the sterilizer chamber returns to normal pressure, due to the existence of inverted gravity, the liquid outside the bottle will not automatically penetrate into the bottle. The purpose of leak detection is achieved. 6.4.4 Noise detection
When the sterilizer is working, test the machine noise in accordance with CB/T16769-1997. The results should meet the requirements of 5.6.3. 71-2 Temperature sensor loading position table Sensor number
Sensor position
Sensor number
Sensor position
II-3-B
Sensor number
JB20001—2003
Sensor position
Ⅲ-4-B
Ⅲ-2-C
Note 1: Temperature sensor position description: No. 1 temperature sensor is placed at the circulating water inlet, and No. 2 temperature sensor is placed at the circulating water outlet. No. 3~6 temperature sensors are placed at the bottom four corners of A and D, and No. 7~10 temperature sensors are placed at the center of B and C. Among them, No. 3~10 temperature sensors are all inserted into the liquid medicine bottles at their locations. www.bzxz.net
Note 2: Temperature sensor quantity description: As the volume of the sterilizer chamber increases, the number of temperature sensors increases accordingly, up to 20. 6.4.2 Surface temperature measurement of sterilizer
When the sterilization temperature is reached in the sterilization chamber, measure the temperature with an industrial thermometer at the center of the doors at both ends of the chamber shell for 5 minutes. The larger value should meet the requirements of 5.6.2.
6.4.3 Leakage detection function test of small-volume injection sterilizer Arrange the finished small-volume injection bottles neatly in the sterilization box, without sliding or tipping bottles, and cover them with a stainless steel cover with a water separation hole. The sterilization box is inverted 180° and placed in the sterilization trolley, and pushed into the sterilizer chamber. After sterilization, start the vacuum program, and the vacuum degree reaches -0.086MPa. Maintain the pressure for 5 minutes, slowly start the air intake, and when the pressure gauge pointer in the control chamber points to zero, inject ionized water into the chamber to spray the bottle wall for 5 minutes, and then drain the remaining water in the chamber. Open the door, push out the sterilization trolley, open the sterilization box cover, and detect the empty or half bottle. Note: Leak detection principle: Invert the finished small-volume injection bottles 180° and arrange them neatly in the sterilization box, and the sterilization and drainage are completed. During the process of vacuuming the sterilizer chamber, the boiling point of the drug solution decreases due to the pressure reduction, resulting in an evaporation process, and the drug is emitted from the cracks at the bottom of the bottle. After vacuuming, the sum of gravity and the pressure inside the bottle is greater than the pressure outside the bottle, forming a pressure difference of 4. Under the action of the pressure difference, the liquid in the bottle is squeezed out of the bottle. When the pressure in the sterilizer chamber returns to normal pressure, due to the existence of inverted gravity, the liquid outside the bottle will not automatically penetrate into the bottle. The purpose of leak detection is achieved. 6.4.4 Noise detection
When the sterilizer is working, test the machine noise in accordance with CB/T16769-1997. The results should meet the requirements of 5.6.3. 71-2 Temperature sensor loading position table Sensor number
Sensor position
Sensor number
Sensor position
II-3-B
Sensor number
JB20001—2003
Sensor position
Ⅲ-4-B
Ⅲ-2-C
Note 1: Temperature sensor position description: No. 1 temperature sensor is placed at the circulating water inlet, and No. 2 temperature sensor is placed at the circulating water outlet. No. 3~6 temperature sensors are placed at the bottom four corners of A and D, and No. 7~10 temperature sensors are placed at the center of B and C. Among them, No. 3~10 temperature sensors are all inserted into the liquid medicine bottles at their locations.
Note 2: Temperature sensor quantity description: As the volume of the sterilizer chamber increases, the number of temperature sensors increases accordingly, up to 20. 6.4.2 Surface temperature measurement of sterilizer
When the sterilization temperature is reached in the sterilization chamber, measure the temperature with an industrial thermometer at the center of the doors at both ends of the chamber shell for 5 minutes. The larger value should meet the requirements of 5.6.2.
6.4.3 Leakage detection function test of small-volume injection sterilizer Arrange the finished small-volume injection bottles neatly in the sterilization box, without sliding or tipping bottles, and cover them with a stainless steel cover with a water separation hole. The sterilization box is inverted 180° and placed in the sterilization trolley, and pushed into the sterilizer chamber. After sterilization, start the vacuum program, and the vacuum degree reaches -0.086MPa. Maintain the pressure for 5 minutes, slowly start the air intake, and when the pressure gauge pointer in the control chamber points to zero, inject ionized water into the chamber to spray the bottle wall for 5 minutes, and then drain the remaining water in the chamber. Open the door, push out the sterilization trolley, open the sterilization box cover, and detect the empty or half bottle. Note: Leak detection principle: Invert the finished small-volume injection bottles 180° and arrange them neatly in the sterilization box, and the sterilization and drainage are completed. During the process of vacuuming the sterilizer chamber, the boiling point of the drug solution decreases due to the pressure reduction, resulting in an evaporation process, and the drug is emitted from the cracks at the bottom of the bottle. After vacuuming, the sum of gravity and the pressure inside the bottle is greater than the pressure outside the bottle, forming a pressure difference of 4. Under the action of the pressure difference, the liquid in the bottle is squeezed out of the bottle. When the pressure in the sterilizer chamber returns to normal pressure, due to the existence of inverted gravity, the liquid outside the bottle will not automatically penetrate into the bottle. The purpose of leak detection is achieved. 6.4.4 Noise detection
When the sterilizer is working, test the machine noise in accordance with CB/T16769-1997. The results should meet the requirements of 5.6.3. 7
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