In the production of pharmaceuticals, eliminating cross-contamination of active ingredients, eliminating foreign matter, insoluble particulates, reducing or eliminating the contamination of injectables by microorganisms and pyrogens is essential for ensuring the quality and safety of products; The cleaning method of the material system can be divided into three modes: manual, semi-automatic and fully automatic.
1. Manual cleaning mode: such as manual disassembly of filters, filter cartridges, hoses, etc., must be removed and washed to ensure the cleaning effect; it is an unstable treatment method, reproducibility and effectiveness can not be guaranteed, the quality risk level - "high".
2. Semi-automatic cleaning mode: Ultrasonic technology is used to clean the filter and other accessories; it is a relatively stable processing method, and the reproducibility and effectiveness can be basically guaranteed. The quality risk level is “ä¸ä¸â€.
3, fully automatic cleaning mode: the use of human-machine interface, information exchange and functional contact or mutual influence, to achieve a fixed process or procedures to complete the batching equipment or system operation; using CIP / SIP technology, basically have the following conditions : The name of the lotion and the concentration, temperature, flow rate and time of the lotion are used for cleaning purposes; it is a stable treatment method, and the reproducibility and effectiveness can be guaranteed. The quality risk level is “lowâ€.
development trend:
With the continuous improvement of drug quality risk control, the risk control of the batching system has reached the necessary execution level. The manual manual cleaning mode and the semi-automatic cleaning mode must be eliminated to reduce the harm of human error to the product, so the production system of the sterile preparation is used. In addition, the reliable online CIP/SIP function will be added to reduce or remove the substances remaining in the production equipment from the previous batch to the extent that it will not affect the quality and safety of the next batch of products, and can effectively remove the organic matter required for microbial reproduction. The microbial contamination is controlled at a certain level and can achieve the reproducibility and effectiveness required for verification.
First, the program operating system control program
The use of human-machine interface (HMI) is an important central link in human-machine systems: it refers to the areas where people and equipment contact or interact with each other in information exchange and function, information exchange, functional contact or mutual influence, referring to people and machines. Hard contact and soft contact, this joint surface not only includes direct contact of the dotted surface, but also includes the space for information transmission and control at a long distance, and has multi-level password protection and automatic alarm function; PLC control system for batching system through program control Perform predetermined process mode operations to achieve a stable operation mode to improve product quality and safety and reduce risks during the batching process.
Material system operation and cleaning schemes are different according to product or production process requirements. The production process and CIP/SIP process flow are required to refer to the production process; on the basis of ensuring the reproducibility and effectiveness of the operation and verification process, Fixed operating mode via HCI input:
1, production operation mode:
2, CIP rough wash mode:
3, CIP cycle cleaning mode:
4, CIP fine wash mode:
5, SIP sterilization mode:
6, data storage mode:
7, security alarm mode:
8, password protection mode:
The above various operation modes include production operation, cleaning processing, sterilization process, real-time monitoring, recording, alarm, password protection, etc., and online monitoring devices are provided at different control points of the material system to monitor and record the running status in real time. To ensure the effectiveness and safety of its operation.
Second, CIP characteristics and cleaning agent selection
1. Characteristics of conventional cleaning agents:
The Residual Solvent Guide classifies solvents into three levels with clear requirements for their use and residue limits. The cleaning agent should have the advantages of not corroding the equipment, dissolving the residue, and easily removing itself; the chemical cleaning agent can be selected according to the nature, amount, water quality, mechanical material, cleaning method and cost of the dirt.
Generally has the following characteristics:
(1) It is easily soluble in water, is not easy to produce foam, and the reaction with salt in water is as low as possible.
(2) Strong wetting ability and no corrosion equipment.
(3) The cleaning effect on pollutants is good, and the environmental pollution is small.
(4) Low water consumption, low cost, and no safety hazard to the human body.
2. Selection of conventional cleaning agents:
Cleaning agents for pharmaceutical production such as: water, purified water, water for injection, acid, alkali, bactericide, etc. It is very important to select the correct cleaning agent in combination with the product process conditions. Briefly introduce several conventional cleaning agents and their application range. :
(1) Water is a conventional cleaning agent, and water can dissolve inorganic substances and organic substances that are highly polar.
(2) The acidic cleaning agent is mainly composed of nitric acid, phosphoric acid, citric acid, etc., and the acidic cleaning agent can remove the stubborn scale which cannot be removed by the alkaline washing agent, such as inorganic acid, calcium salt and the like.
(3) The alkaline cleaning agent is mainly composed of sodium hydroxide and sodium hydrogencarbonate. The alkaline cleaning agent has a good dissolving effect on organic substances and has good emulsifying properties at high temperatures.
(4) The fungicide is mainly composed of high temperature hot water, hydrogen peroxide, peracetic acid, etc., and the fungicide has a killing effect on microorganisms and bacteria.
3, cleaning method design:
Based on the premise of production process, design process modes such as rough washing, circulation and fine washing, define cleaning program control, monitor system cleaning effect parameters in real time, meet process requirements, and prevent pollution to other systems during cleaning.
Third, the important factors affecting the cleaning effect CIP cleaning is the use of water dissolution and scouring turbulence, heat exchange, cleaning agents and sterilant chemical action to remove pollutants on tanks, equipment, pipelines.
There are several main factors that affect the cleaning effect:
(1) Adsorption of dirt.
(2) Surface roughness of the material system.
(3) Kinds and concentrations of cleaning agents.
(4) Cleaning time.
(5) Cleaning temperature.
(6) Washing fluid flow rate.
(7) Washing fluid pressure.
Fourth, SIP concept and sterilization mode
SIP refers to the system or equipment based on the original installation location, without any steam sterilization under disassembly or movement conditions.
According to the sterilization method included in the Chinese Pharmacopoeia, the moist heat sterilization method is heat sterilization, and is also a widely effective method for using various methods in the sterilization method, and is also an effective method for sterilizing the material system.
The following points should be emphasized for the moist heat sterilization method:
1, SIP sterilization requirements:
The permeability of saturated steam is much stronger than that of superheated steam. The relationship between saturated steam temperature and pressure is stable. The potential released during condensation is transferred to the sterilized product, which is heated and sterilized. The microorganisms in the product are hydrated, which accelerates the death of microorganisms; then the sterilization system must meet the following points:
(1) The material system is a container that is subjected to internal steam pressure and must be secured.
(2) The material system has a steam jacket and a heat insulation layer; temperature control is possible.
(3) The material system should be equipped with a suitable steam trap at the specified position to ensure that all condensed water in the pipeline is smoothly discharged.
(4) The material system should set the temperature control point and pressure control point at the specified position.
(5) The material system has periodic time timing and pressure stabilization devices.
(6) The material system should adopt a segmented sterilization design according to user requirements.
2. The key factors of steam sterilization:
In the steam sterilization design, the discharge of “cold air mass†is an important issue; since these cold air forces the temperature of the sterilized part to decrease and prevents the vapor from penetrating to the surface of all sterilized objects, the steam is extinguished. The heat exchange efficiency of the fungus article is lowered.
In order to meet the conditions, gravity replacement, pre-vacuum process, pulse process or discharge method often discharges the cold air inside the system during the sterilization cycle; the design of the steam sterilization cycle is related to the volume, structure and layout of the destroyed material system, and directly affects The effect of cold air discharge, so it is necessary to choose whether to use the emptying, intermittent pulsation or circulation method to meet the requirements, as well as the temperature and F0 value setting range.
V. Material system sterilization verification and control design 1. Material system sterilization verification:
In the "Guidelines for GMP Inspection of Drugs", SIP believes that there should be appropriate air and condensate drains in the system, and the need to set temperature monitoring probes at the possible cold spots of online sterilization should be considered in the design. This shows that the key factor of the SIP-enabled material system is to pass the verification; therefore, when using segmented sterilization, an effective temperature monitoring point should be set in each segment to meet the sterilization verification requirements.
The steam sterilization verification mainly includes the following points:
(1) Sterilization method.
(2) Sterilization process parameters and operating standards.
(3) Monitoring method of sterilization procedure.
(4) The range of variation allowed by the key parameters.
(5) Automatic and manual control operation steps.
(6) The sterilization system must meet reproducibility and effectiveness.
2, material system SIP control design SIP science control should consider the following aspects:
(1) The application of microcomputer control in electrical control can dynamically reflect the sterilization work and process. There are also recorders and smart printers. Digital instruments and F0 monitors are displayed for sterilization parameters such as temperature, pressure and F0.
(2) Three control modes in the sterilization process: temperature time control, F0 value control, temperature time control and F0 value control dual control, generally between F0≥8~F0≥12.
(3) When the temperature and F0 value are double controlled, ensure that each time F0 ≥ 8, and the sterilization temperature, time, F0 value and pressure are displayed on the screen and can be automatically recorded at any time, and can also be saved.
(4) The batch number, operation number, date, etc. can be input in the control; the sterilization temperature can be automatically controlled or set freely, for example: the control range is 80-127 ° C, the control precision is ≤ ± 0.5 ° C; at the same time, the temperature rise and temperature can be controlled. And constant temperature, and can record curves and various parameters.
(5) Each temperature control point and the temperature transmitter are relatively independent.
(6) The system has a measuring port for collecting internal pressure and temperature. The temperature control point and the temperature measuring point can be set to different locations according to requirements; and a verification interface is preset.
(7) Automatic control of emptying Because the sterilization cycle is different, the control emptying is also different. Considering the pressure control, etc., positive pressure emptying or negative pressure pulse emptying can be adopted.
Different sterilization requirements are designed for different user requirements (URS). If the SIP system does not support DQ and PQ files according to the URS, the meaning of SIP will be lost; the importance of DQ emphasized in cGMP, DQ It is also important to verify the F0 value, so don't ignore it.
Sixth, all intelligent material system hardware design principles
For example, designing an injection intelligent material system requires that the concentrated system and the diluted system can be operated independently or in conjunction; the interlayer has a heating function, and a baffle function is provided to ensure uniform heating or cooling, and the equipment, accessories and tubes involved therein are included. Roads and instruments must comply with the relevant National Pressure Regulations and the current New GMP Standards for aseptic production requirements and certification standards.
Brief description of hardware design principles:
1. It has precise intelligent control process, which can realize independent CIP cleaning and SIP sterilization. Each batching system unit is not affected and restricted by the working environment; it is displayed on the touch screen and has an animation status display.
2. The corresponding metering control system must meet the requirements of the production process, and the error should comply with the new GMP control standard.
3, the inner wall of the tank is required to be made of sanitary grade material, the surface roughness should meet the requirements of the process, the thermal insulation material is added outside the middle interlayer, and the outer surface is a decorative board.
4. The surface temperature of the outer surface of the tank should have a limit.
5. The upper head, side and lower head of the tank are equipped with equipment or various process interfaces.
6. The infusion line, control valve and monitoring device in contact with the liquid are hygienic materials to minimize the amount of residual liquid.
7. The material system uses ultrafiltration or decarbonization filters, pre-filters, sterilization filters, sampling valves and integrity detection interfaces.
8. Set monitoring point devices in key equipment or cold spots.
9. The sanitary hose is used for the soft connecting pipe serving the material system.
10. The pipeline should have an appropriate inclination to ensure that the drainage medium is in use despite the drainage medium; the seal is made of sanitary seals.
11. Regulator valves and filter devices should be installed in steam/cooling water pipelines to avoid damage to valves or accidents.
12. The material system pipeline should reduce the connection point as much as possible, and reserve the joint (Asimim standard) at the appropriate position for easy maintenance, disassembly or cleaning.
Seven, the material system process requirements
1. Design the material system control system design drawing, program control chart and operation instructions, design and install the system layout according to the design plan, and determine the effective operation mode. (Design plan - slightly)
2. The control system is the control mode of the HMI of the human-machine interface, which can automatically control the completion of various processes and parameter settings (program design - slightly)
3. Material system production operation, CIP, SIP mode, using full intelligent control mode, using the set program to complete the process flow set by the material system. (process flow - slightly)
4. When cleaning the material system, the flushed sewage should be removed as soon as possible. (Exclusion method - slightly)
5. Appropriate cleaning methods and sterilization methods should be designed to achieve the reproducibility and effectiveness of all CIP/SIP processes. (CIP/SIP--slightly)
6. When SIP is sterilized, appropriate process control measures should be taken to avoid damage to the filter membrane, and the filter membrane must be safely sterilized. (System Sterilization Method - Slightly)
Eight, public works and pipeline requirements
1. Power distribution: It can meet the requirements of the material system for the power distribution box, and must meet the requirements of the corresponding regulations for China's electricity use.
2. The process water should comply with the “new GMP standard†and should indicate the process water consumption and temperature requirements in the designed system.
3. The steam should be designed and connected to the batching tank according to the production process requirements. The steam consumption and parameters in the designed system should be stated.
4. The pressure range used by compressed air or nitrogen should indicate the gas consumption and parameters used in the designed system.
5. The pressure range used for cooling water should indicate the gas consumption and parameters used in the designed system.
6. Set the condensate point and discharge point access location.
Nine, stress testing technology
After the construction of the material system is completed, the pressure test should be carried out and the record should be retained. The pressure test application should be higher than the working pressure for a reasonable period of time and the pressure test data should be recorded and archived.
10. Pickling passivation technology (1), the installed material system, are applied for cyclic cleaning or direct cleaning to remove insoluble particles.
(2) The welded outer surface of all stainless steel pipes after installation shall be passivated and rinsed with cold water.
(3) After the installation, the material system must be sterilized by passivation and kept positive pressure.
(4) After the installation of the material system, all construction plans, parameters, records, and inspection reports shall be kept and archived.
XI. Technical requirements and acceptance criteria of the automatic control system 1. Each batching tank is an independent control system. The PLC and MCC cabinets are placed between the same type of tanks. The control cabinet is made of stainless steel control cabinet with protection class IP54.
2. The process interface of all automatic instruments complies with the “new GMP standardâ€; the signal cable of the instrument uses shielded cable, the signal cable should be ≤10m length; the power cable of the inverter to the motor uses the shielded power cable.
3. The stainless steel cable tray with cover and stainless steel threaded pipe will be used in the clean room; the control voltage of all control cabinets is DC 12V~24V, the control circuit of the motor starter is 220V AC, and all the threading pipes are directly sealed.
4. The stainless steel pipe with the head will be threaded in the clean room. The wiring is neat and beautiful, there is no sanitary corner, and the shielded cable must be grounded reliably.
5. The signal cable of the instrument uses shielded cable; the power cable uses a power cable with a shield.
6. All cables must be marked with a cable label consistent with the drawing; each core must be marked with a line number consistent with the drawing.
7. The grounding will be limited to the control platform, tank, and control cabinet; the equipment control system in the same category or in the same area is installed in a control cabinet for easy management.
8, should comply with the "China's corresponding regulations for electricity use" and "China's new GMP standards."
XII. Project Management and Quality Control
1. The on-site equipment supplier shall send qualified projects to carry out quality control and progress control, and attach the original qualification certificate at the time of bidding.
2. There are detailed construction plans and quality control plans, systems and measures; detailed time schedules and measures to ensure that they are carried out on schedule.
3. On-site civilized construction to ensure safe construction. All equipment safety is caused by the equipment supplier due to the safety precautions caused by the equipment supplier's safety precautions and management defects.
4. Verification of field instruments, including: verification of temperature, pressure, conductance, weighing module, liquid level and other parameter instruments.
5. Confirmation and verification of DQ, IQ, OQ, PQ.
6. All sensors and instruments have verification reports from qualified domestic units.
7. Imported goods should provide proof of customs declaration, certificate of conformity and certificate of origin.
8. The supplier shall provide all the certification documents conforming to the new edition of China and assist in installation, commissioning and certification.
9. The quality guarantee period of the whole project is one year, and the starting time is based on the time of completion of the completion acceptance report signed by both parties.
1. Manual cleaning mode: such as manual disassembly of filters, filter cartridges, hoses, etc., must be removed and washed to ensure the cleaning effect; it is an unstable treatment method, reproducibility and effectiveness can not be guaranteed, the quality risk level - "high".
2. Semi-automatic cleaning mode: Ultrasonic technology is used to clean the filter and other accessories; it is a relatively stable processing method, and the reproducibility and effectiveness can be basically guaranteed. The quality risk level is “ä¸ä¸â€.
3, fully automatic cleaning mode: the use of human-machine interface, information exchange and functional contact or mutual influence, to achieve a fixed process or procedures to complete the batching equipment or system operation; using CIP / SIP technology, basically have the following conditions : The name of the lotion and the concentration, temperature, flow rate and time of the lotion are used for cleaning purposes; it is a stable treatment method, and the reproducibility and effectiveness can be guaranteed. The quality risk level is “lowâ€.
development trend:
With the continuous improvement of drug quality risk control, the risk control of the batching system has reached the necessary execution level. The manual manual cleaning mode and the semi-automatic cleaning mode must be eliminated to reduce the harm of human error to the product, so the production system of the sterile preparation is used. In addition, the reliable online CIP/SIP function will be added to reduce or remove the substances remaining in the production equipment from the previous batch to the extent that it will not affect the quality and safety of the next batch of products, and can effectively remove the organic matter required for microbial reproduction. The microbial contamination is controlled at a certain level and can achieve the reproducibility and effectiveness required for verification.
First, the program operating system control program
The use of human-machine interface (HMI) is an important central link in human-machine systems: it refers to the areas where people and equipment contact or interact with each other in information exchange and function, information exchange, functional contact or mutual influence, referring to people and machines. Hard contact and soft contact, this joint surface not only includes direct contact of the dotted surface, but also includes the space for information transmission and control at a long distance, and has multi-level password protection and automatic alarm function; PLC control system for batching system through program control Perform predetermined process mode operations to achieve a stable operation mode to improve product quality and safety and reduce risks during the batching process.
Material system operation and cleaning schemes are different according to product or production process requirements. The production process and CIP/SIP process flow are required to refer to the production process; on the basis of ensuring the reproducibility and effectiveness of the operation and verification process, Fixed operating mode via HCI input:
1, production operation mode:
2, CIP rough wash mode:
3, CIP cycle cleaning mode:
4, CIP fine wash mode:
5, SIP sterilization mode:
6, data storage mode:
7, security alarm mode:
8, password protection mode:
The above various operation modes include production operation, cleaning processing, sterilization process, real-time monitoring, recording, alarm, password protection, etc., and online monitoring devices are provided at different control points of the material system to monitor and record the running status in real time. To ensure the effectiveness and safety of its operation.
Second, CIP characteristics and cleaning agent selection
1. Characteristics of conventional cleaning agents:
The Residual Solvent Guide classifies solvents into three levels with clear requirements for their use and residue limits. The cleaning agent should have the advantages of not corroding the equipment, dissolving the residue, and easily removing itself; the chemical cleaning agent can be selected according to the nature, amount, water quality, mechanical material, cleaning method and cost of the dirt.
Generally has the following characteristics:
(1) It is easily soluble in water, is not easy to produce foam, and the reaction with salt in water is as low as possible.
(2) Strong wetting ability and no corrosion equipment.
(3) The cleaning effect on pollutants is good, and the environmental pollution is small.
(4) Low water consumption, low cost, and no safety hazard to the human body.
2. Selection of conventional cleaning agents:
Cleaning agents for pharmaceutical production such as: water, purified water, water for injection, acid, alkali, bactericide, etc. It is very important to select the correct cleaning agent in combination with the product process conditions. Briefly introduce several conventional cleaning agents and their application range. :
(1) Water is a conventional cleaning agent, and water can dissolve inorganic substances and organic substances that are highly polar.
(2) The acidic cleaning agent is mainly composed of nitric acid, phosphoric acid, citric acid, etc., and the acidic cleaning agent can remove the stubborn scale which cannot be removed by the alkaline washing agent, such as inorganic acid, calcium salt and the like.
(3) The alkaline cleaning agent is mainly composed of sodium hydroxide and sodium hydrogencarbonate. The alkaline cleaning agent has a good dissolving effect on organic substances and has good emulsifying properties at high temperatures.
(4) The fungicide is mainly composed of high temperature hot water, hydrogen peroxide, peracetic acid, etc., and the fungicide has a killing effect on microorganisms and bacteria.
3, cleaning method design:
Based on the premise of production process, design process modes such as rough washing, circulation and fine washing, define cleaning program control, monitor system cleaning effect parameters in real time, meet process requirements, and prevent pollution to other systems during cleaning.
Third, the important factors affecting the cleaning effect CIP cleaning is the use of water dissolution and scouring turbulence, heat exchange, cleaning agents and sterilant chemical action to remove pollutants on tanks, equipment, pipelines.
There are several main factors that affect the cleaning effect:
(1) Adsorption of dirt.
(2) Surface roughness of the material system.
(3) Kinds and concentrations of cleaning agents.
(4) Cleaning time.
(5) Cleaning temperature.
(6) Washing fluid flow rate.
(7) Washing fluid pressure.
Fourth, SIP concept and sterilization mode
SIP refers to the system or equipment based on the original installation location, without any steam sterilization under disassembly or movement conditions.
According to the sterilization method included in the Chinese Pharmacopoeia, the moist heat sterilization method is heat sterilization, and is also a widely effective method for using various methods in the sterilization method, and is also an effective method for sterilizing the material system.
The following points should be emphasized for the moist heat sterilization method:
1, SIP sterilization requirements:
The permeability of saturated steam is much stronger than that of superheated steam. The relationship between saturated steam temperature and pressure is stable. The potential released during condensation is transferred to the sterilized product, which is heated and sterilized. The microorganisms in the product are hydrated, which accelerates the death of microorganisms; then the sterilization system must meet the following points:
(1) The material system is a container that is subjected to internal steam pressure and must be secured.
(2) The material system has a steam jacket and a heat insulation layer; temperature control is possible.
(3) The material system should be equipped with a suitable steam trap at the specified position to ensure that all condensed water in the pipeline is smoothly discharged.
(4) The material system should set the temperature control point and pressure control point at the specified position.
(5) The material system has periodic time timing and pressure stabilization devices.
(6) The material system should adopt a segmented sterilization design according to user requirements.
2. The key factors of steam sterilization:
In the steam sterilization design, the discharge of “cold air mass†is an important issue; since these cold air forces the temperature of the sterilized part to decrease and prevents the vapor from penetrating to the surface of all sterilized objects, the steam is extinguished. The heat exchange efficiency of the fungus article is lowered.
In order to meet the conditions, gravity replacement, pre-vacuum process, pulse process or discharge method often discharges the cold air inside the system during the sterilization cycle; the design of the steam sterilization cycle is related to the volume, structure and layout of the destroyed material system, and directly affects The effect of cold air discharge, so it is necessary to choose whether to use the emptying, intermittent pulsation or circulation method to meet the requirements, as well as the temperature and F0 value setting range.
V. Material system sterilization verification and control design 1. Material system sterilization verification:
In the "Guidelines for GMP Inspection of Drugs", SIP believes that there should be appropriate air and condensate drains in the system, and the need to set temperature monitoring probes at the possible cold spots of online sterilization should be considered in the design. This shows that the key factor of the SIP-enabled material system is to pass the verification; therefore, when using segmented sterilization, an effective temperature monitoring point should be set in each segment to meet the sterilization verification requirements.
The steam sterilization verification mainly includes the following points:
(1) Sterilization method.
(2) Sterilization process parameters and operating standards.
(3) Monitoring method of sterilization procedure.
(4) The range of variation allowed by the key parameters.
(5) Automatic and manual control operation steps.
(6) The sterilization system must meet reproducibility and effectiveness.
2, material system SIP control design SIP science control should consider the following aspects:
(1) The application of microcomputer control in electrical control can dynamically reflect the sterilization work and process. There are also recorders and smart printers. Digital instruments and F0 monitors are displayed for sterilization parameters such as temperature, pressure and F0.
(2) Three control modes in the sterilization process: temperature time control, F0 value control, temperature time control and F0 value control dual control, generally between F0≥8~F0≥12.
(3) When the temperature and F0 value are double controlled, ensure that each time F0 ≥ 8, and the sterilization temperature, time, F0 value and pressure are displayed on the screen and can be automatically recorded at any time, and can also be saved.
(4) The batch number, operation number, date, etc. can be input in the control; the sterilization temperature can be automatically controlled or set freely, for example: the control range is 80-127 ° C, the control precision is ≤ ± 0.5 ° C; at the same time, the temperature rise and temperature can be controlled. And constant temperature, and can record curves and various parameters.
(5) Each temperature control point and the temperature transmitter are relatively independent.
(6) The system has a measuring port for collecting internal pressure and temperature. The temperature control point and the temperature measuring point can be set to different locations according to requirements; and a verification interface is preset.
(7) Automatic control of emptying Because the sterilization cycle is different, the control emptying is also different. Considering the pressure control, etc., positive pressure emptying or negative pressure pulse emptying can be adopted.
Different sterilization requirements are designed for different user requirements (URS). If the SIP system does not support DQ and PQ files according to the URS, the meaning of SIP will be lost; the importance of DQ emphasized in cGMP, DQ It is also important to verify the F0 value, so don't ignore it.
Sixth, all intelligent material system hardware design principles
For example, designing an injection intelligent material system requires that the concentrated system and the diluted system can be operated independently or in conjunction; the interlayer has a heating function, and a baffle function is provided to ensure uniform heating or cooling, and the equipment, accessories and tubes involved therein are included. Roads and instruments must comply with the relevant National Pressure Regulations and the current New GMP Standards for aseptic production requirements and certification standards.
Brief description of hardware design principles:
1. It has precise intelligent control process, which can realize independent CIP cleaning and SIP sterilization. Each batching system unit is not affected and restricted by the working environment; it is displayed on the touch screen and has an animation status display.
2. The corresponding metering control system must meet the requirements of the production process, and the error should comply with the new GMP control standard.
3, the inner wall of the tank is required to be made of sanitary grade material, the surface roughness should meet the requirements of the process, the thermal insulation material is added outside the middle interlayer, and the outer surface is a decorative board.
4. The surface temperature of the outer surface of the tank should have a limit.
5. The upper head, side and lower head of the tank are equipped with equipment or various process interfaces.
6. The infusion line, control valve and monitoring device in contact with the liquid are hygienic materials to minimize the amount of residual liquid.
7. The material system uses ultrafiltration or decarbonization filters, pre-filters, sterilization filters, sampling valves and integrity detection interfaces.
8. Set monitoring point devices in key equipment or cold spots.
9. The sanitary hose is used for the soft connecting pipe serving the material system.
10. The pipeline should have an appropriate inclination to ensure that the drainage medium is in use despite the drainage medium; the seal is made of sanitary seals.
11. Regulator valves and filter devices should be installed in steam/cooling water pipelines to avoid damage to valves or accidents.
12. The material system pipeline should reduce the connection point as much as possible, and reserve the joint (Asimim standard) at the appropriate position for easy maintenance, disassembly or cleaning.
Seven, the material system process requirements
1. Design the material system control system design drawing, program control chart and operation instructions, design and install the system layout according to the design plan, and determine the effective operation mode. (Design plan - slightly)
2. The control system is the control mode of the HMI of the human-machine interface, which can automatically control the completion of various processes and parameter settings (program design - slightly)
3. Material system production operation, CIP, SIP mode, using full intelligent control mode, using the set program to complete the process flow set by the material system. (process flow - slightly)
4. When cleaning the material system, the flushed sewage should be removed as soon as possible. (Exclusion method - slightly)
5. Appropriate cleaning methods and sterilization methods should be designed to achieve the reproducibility and effectiveness of all CIP/SIP processes. (CIP/SIP--slightly)
6. When SIP is sterilized, appropriate process control measures should be taken to avoid damage to the filter membrane, and the filter membrane must be safely sterilized. (System Sterilization Method - Slightly)
Eight, public works and pipeline requirements
1. Power distribution: It can meet the requirements of the material system for the power distribution box, and must meet the requirements of the corresponding regulations for China's electricity use.
2. The process water should comply with the “new GMP standard†and should indicate the process water consumption and temperature requirements in the designed system.
3. The steam should be designed and connected to the batching tank according to the production process requirements. The steam consumption and parameters in the designed system should be stated.
4. The pressure range used by compressed air or nitrogen should indicate the gas consumption and parameters used in the designed system.
5. The pressure range used for cooling water should indicate the gas consumption and parameters used in the designed system.
6. Set the condensate point and discharge point access location.
Nine, stress testing technology
After the construction of the material system is completed, the pressure test should be carried out and the record should be retained. The pressure test application should be higher than the working pressure for a reasonable period of time and the pressure test data should be recorded and archived.
10. Pickling passivation technology (1), the installed material system, are applied for cyclic cleaning or direct cleaning to remove insoluble particles.
(2) The welded outer surface of all stainless steel pipes after installation shall be passivated and rinsed with cold water.
(3) After the installation, the material system must be sterilized by passivation and kept positive pressure.
(4) After the installation of the material system, all construction plans, parameters, records, and inspection reports shall be kept and archived.
XI. Technical requirements and acceptance criteria of the automatic control system 1. Each batching tank is an independent control system. The PLC and MCC cabinets are placed between the same type of tanks. The control cabinet is made of stainless steel control cabinet with protection class IP54.
2. The process interface of all automatic instruments complies with the “new GMP standardâ€; the signal cable of the instrument uses shielded cable, the signal cable should be ≤10m length; the power cable of the inverter to the motor uses the shielded power cable.
3. The stainless steel cable tray with cover and stainless steel threaded pipe will be used in the clean room; the control voltage of all control cabinets is DC 12V~24V, the control circuit of the motor starter is 220V AC, and all the threading pipes are directly sealed.
4. The stainless steel pipe with the head will be threaded in the clean room. The wiring is neat and beautiful, there is no sanitary corner, and the shielded cable must be grounded reliably.
5. The signal cable of the instrument uses shielded cable; the power cable uses a power cable with a shield.
6. All cables must be marked with a cable label consistent with the drawing; each core must be marked with a line number consistent with the drawing.
7. The grounding will be limited to the control platform, tank, and control cabinet; the equipment control system in the same category or in the same area is installed in a control cabinet for easy management.
8, should comply with the "China's corresponding regulations for electricity use" and "China's new GMP standards."
XII. Project Management and Quality Control
1. The on-site equipment supplier shall send qualified projects to carry out quality control and progress control, and attach the original qualification certificate at the time of bidding.
2. There are detailed construction plans and quality control plans, systems and measures; detailed time schedules and measures to ensure that they are carried out on schedule.
3. On-site civilized construction to ensure safe construction. All equipment safety is caused by the equipment supplier due to the safety precautions caused by the equipment supplier's safety precautions and management defects.
4. Verification of field instruments, including: verification of temperature, pressure, conductance, weighing module, liquid level and other parameter instruments.
5. Confirmation and verification of DQ, IQ, OQ, PQ.
6. All sensors and instruments have verification reports from qualified domestic units.
7. Imported goods should provide proof of customs declaration, certificate of conformity and certificate of origin.
8. The supplier shall provide all the certification documents conforming to the new edition of China and assist in installation, commissioning and certification.
9. The quality guarantee period of the whole project is one year, and the starting time is based on the time of completion of the completion acceptance report signed by both parties.
Suzhou Escomedical Equipment Co.,Ltd , https://www.escodental.com