A method for simultaneously controlling heat and moisture balance and wind balance in a sterile drug filling room

Abstract

The present invention relates to the technical field of clean rooms, and in particular to a method for simultaneously controlling the heat and moisture balance and wind balance of a sterile drug filling room, comprising a clean room and a main air conditioning air supply system, an exhaust system, a variable air volume valve, a PID controller and an auxiliary air conditioning air supply system connected to the clean room. A temperature sensor and a humidity sensor are also provided in the clean room, the temperature sensor and the humidity sensor communicate with the control system of the auxiliary air conditioning air supply system, the pressure detection end of the PID controller is provided in the clean room, the signal output end of the PID controller is connected to the control end of the variable air volume valve, and the implementation steps of the pressure and heat and moisture balance control in the clean room can ensure the stability of the pressure and heat and moisture balance in the clean room and reduce energy consumption.

Description

Technical Field

[0001] The invention relates to the technical field of clean rooms, and in particular to a method for simultaneously controlling the heat and moisture balance and the wind balance in a sterile drug filling room. Background Art

[0002] The washing, drying, filling and sealing rooms in the aseptic production lines of the pharmaceutical industry generate heat and have a large exhaust volume due to the operation of process filling equipment. This can easily lead to an imbalance in the coupled control of thermal and moisture balance and wind balance, causing temperature and humidity imbalance and pressure out of control, as well as room cleanliness imbalance, and the quality of drug production cannot be guaranteed.

[0003] In order to prevent pollution and cross-contamination and maintain indoor cleanliness, clean rooms need to maintain stable pressure to ensure that pressure fluctuations are within the allowable range. The method of clean room pressure control is usually: by adjusting the air inlet and outlet of the clean room, using the difference in air volume in and out, to obtain positive or negative pressure results. It is very important to use valves that accurately control the air volume. At present, the most common mainstream fixed and variable air volume control valves in China are butterfly valves and Venturi valves. Butterfly valves usually adopt a closed-loop control method of "measurement-comparison-execution", with an average response time of no more than 3s and an accuracy of 5%; Venturi valves adopt a feedforward control method, with the fastest response time within 1s and an accuracy of 3%. These valves have achieved good results in clean room applications. However, even under the condition that the valves achieve such accuracy, in some special clean rooms, due to improper selection, when the air volume changes greatly, they still cannot meet the pressure control requirements.

[0004] Due to the large exhaust volume of the filling equipment, the room air volume change range may exceed the control range of the variable air volume valve, resulting in room pressure imbalance; when the variable air volume butterfly valve is responsible for large air volume regulation, due to the limitations of accuracy and response time, the movement stroke and adjustment time are long. It takes a long time for the clean room to gradually stabilize after the pressure fluctuations, so during this adjustment process, the room pressure deviates; the disadvantage of the Venturi valve is that it has weak anti-interference ability. Once there is a disturbance factor, and the pre-set air volume cannot meet the pressure requirements, the lack of a correction mechanism will cause a deviation in the clean room pressure. Both types of air valves have the characteristics of large deviations between the final state and the set value when regulating the air volume over a large range.

[0005] To ensure that the room's environmental parameters such as temperature are stable within the design range, it is necessary to maintain indoor heat and humidity balance. When the process filling equipment is put into operation, the indoor heat dissipation changes. The traditional method is to use two treatment methods at the end while keeping the air conditioning partition treatment unchanged.

[0006] One is to add a surface cooler at the end, and bear the heat and humidity load of the indoor equipment by cooling the centrally processed air supply at the end. This method brings the following disadvantages: a) Adding a surface cooler at the end will increase the chilled water piping, and the surface cooler will generate condensed water, which will pose a safety hazard to the clean room and is unacceptable in high-level clean rooms; b) When the process filling equipment is not running, although the surface cooler is not working, the air still has to pass through, which increases the pressure loss of the pipeline and does not save energy; c) There is serious waste of heat and cold offset, which is particularly prominent in winter.

[0007] The second is to increase the air supply in summer to bear the heat dissipation of indoor equipment by increasing the air volume; in winter, due to the cleanliness requirements, the air supply volume cannot be lower than the air supply volume standard that meets the cleanliness level requirements, and the indoor heat source will cause the room temperature to be high and unable to meet the indoor temperature and humidity requirements. Summary of the invention

[0008] In view of the deficiencies in the prior art, the object of the present invention is to provide a method for simultaneously controlling the heat and moisture balance and the wind balance in a sterile drug filling room.

[0009] To achieve the above object, the present invention provides the following technical solution: a method for simultaneously controlling the heat and moisture balance and wind balance of a sterile drug filling room, comprising a clean room and a main air conditioning air supply system, an exhaust system, a variable air volume valve, a PID controller and an auxiliary air conditioning air supply system connected to the clean room, wherein a temperature sensor and a humidity sensor are also arranged in the clean room, the temperature sensor and the humidity sensor communicate with the control system of the auxiliary air conditioning air supply system, the pressure detection end of the PID controller is arranged in the clean room, the signal output end of the PID controller is connected to the control end of the variable air volume valve, and the implementation steps of the pressure and heat and moisture balance control in the clean room are as follows:

[0010] (1) Determine the air supply volume and air supply status of the auxiliary air conditioning system based on the heat dissipation of process equipment and indoor environmental parameters;

[0011] (2) Tune the parameters of the PID controller and determine the key control parameters;

[0012] (3) The auxiliary air conditioning system is started when the process filling equipment is running;

[0013] (4) Monitor the pressure inside the clean room using an air differential pressure gauge;

[0014] (5) Control the exhaust air volume of the variable air volume valve through the PID controller;

[0015] (6) The auxiliary air conditioning system adjusts the supply air temperature and humidity by receiving detection data from the temperature sensor and humidity sensor.

[0016] Preferably, priority is given to ensuring the cleanliness of the room without reducing the number of room ventilation times, and the air volume and air supply status of the main air conditioning air supply system are kept unchanged regardless of whether the process filling equipment is running or not.

[0017] Preferably, the auxiliary air conditioning supply system is a DC fresh air air conditioning system.

[0018] Preferably, according to step (1), specifically according to the design state points In and Dn of the clean room, a heat-humidity ratio line ε=Q / W=∞ is drawn from the indoor point on the enthalpy-humidity diagram, and the air supply state points Io and Dn are determined given a suitable temperature difference, and the air supply volume G is determined by the heat-humidity balance formula Q=G(Io-In).

[0019] Preferably, the indoor pressure caused by the difference between the air supply volume G and the exhaust volume G1 of the process filling equipment is controlled through steps (2) and (3).

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: the present invention starts with the analysis of the drawbacks of the traditional solution, and proposes to add an auxiliary air-conditioning air-supply system on the basis of the original main air-conditioning air supply system, and sets the auxiliary air-conditioning air supply system to operate in linkage with the process filling equipment, and configures a variable air volume air valve at the same time, so as to ensure that the air volume difference between the air supply of the auxiliary air-conditioning air supply system and the exhaust of the process filling equipment is accurately and quickly released, and well solves the coupling problem of room temperature, humidity and pressure control. The specific process is as follows:

[0021] 1. Priority should be given to ensuring the cleanliness of the room without reducing the number of room ventilation. Here, regardless of whether the process filling equipment is running or not, the air supply volume and air supply status of the main air conditioning air supply system are kept unchanged;

[0022] 2. The auxiliary air conditioning air supply system is linked with the process filling equipment to determine the air supply volume according to the heat dissipation of the process filling equipment, which can ensure that it independently bears the additional cooling load of the room caused by the heat dissipation of the process filling equipment and achieves heat and humidity balance;

[0023] 3. Consider using a variable air volume valve to bear the difference in air volume caused by the auxiliary air conditioning air supply system and the exhaust air volume of the process filling equipment to achieve air balance;

[0024] 4. In order to solve the pressure fluctuation amplitude and stabilization time problems in the process of wind balance adjustment, PID control (Proportion Integration Differentiation, proportional-integral-differential controller, the same below) is introduced to ensure that the room pressure fluctuation is within a controllable range and the pressure is quickly stabilized.

[0025] As a crucial link in the entire pharmaceutical production process, the clean system needs to be continuously innovated and developed based on actual conditions. In a clean room with intermittent operation of heat dissipation, moisture dissipation and large exhaust volume process filling equipment, this paper solves the coupling problem of temperature and humidity control and pressure control while ensuring the cleanliness level of the clean room, avoiding the drawbacks of traditional methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 It is the clean room air treatment flow chart of the present invention;

[0027] Figure 2 For the present invention Figure 1 The legend in the figure explains;

[0028] Figure 3 For the present invention Figure 1 Clean room air handling diagram in summer state;

[0029] Figure 4 For the present invention Figure 1 Clean room air handling diagram in winter condition. DETAILED DESCRIPTION

[0030] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] See also Figures 1 to 4 The present invention provides a technical solution: a method for simultaneously controlling the heat and moisture balance and wind balance of a sterile drug filling room, characterized in that: it comprises a clean room and a main air conditioning air supply system, an exhaust system, a variable air volume valve, a PID controller and an auxiliary air conditioning air supply system connected to the clean room, the clean room is also provided with a temperature sensor and a humidity sensor, the temperature sensor and the humidity sensor communicate with the control system of the auxiliary air conditioning air supply system, the pressure detection end of the PID controller is arranged in the clean room, the signal output end of the PID controller is connected to the control end of the variable air volume valve, and the implementation steps of the pressure and heat and moisture balance control in the clean room are as follows:

[0032] (1) Determine the air supply volume and air supply status of the auxiliary air conditioning system based on the heat dissipation of process equipment and indoor environmental parameters;

[0033] (2) Tune the parameters of the PID controller and determine the key control parameters;

[0034] (3) The auxiliary air conditioning system is started when the process filling equipment is running;

[0035] (4) Monitor the pressure inside the clean room using an air differential pressure gauge;

[0036] (5) Control the exhaust air volume of the variable air volume valve through the PID controller;

[0037] (6) The auxiliary air conditioning system adjusts the supply air temperature and humidity by receiving detection data from the temperature sensor and humidity sensor.

[0038] Priority should be given to ensuring the cleanliness of the room without reducing the number of room ventilation. Regardless of whether the process filling equipment is running or not, the air supply volume and air supply status of the main air conditioning system should be kept unchanged;

[0039] The auxiliary air conditioning system is a DC fresh air air conditioning system, which is interlocked with the process filling equipment. The air supply volume is determined according to the heat dissipation and moisture dissipation of the process filling equipment to ensure that it independently bears the additional cold load and moisture load of the room caused by the process filling equipment to achieve heat and moisture balance;

[0040] The difference in air volume caused by the difference in exhaust air volume between the auxiliary air conditioning system and the process filling equipment is considered to be borne by a variable air volume damper to achieve air balance;

[0041] In order to solve the problems of pressure fluctuation amplitude and stabilization time in the process of wind balance adjustment, PID control (Proportion Integration Differentiation, proportional-integral-differential controller, the same below) is introduced to ensure that the room pressure fluctuation is within a controllable range and the pressure is quickly stabilized.

[0042] In this technical solution, the pressure of the clean room is a key parameter. Pressure out of control will lead to the risk of contamination and cross-contamination, which will lead to serious consequences such as microbial contamination of sterile drugs. However, it is difficult to obtain stable pressure at all times and under all working conditions. The main reason is that the start and stop of the process filling equipment causes a large range of changes in the air volume in and out of the clean room, resulting in pressure changes and pressure difference deviations.

[0043] The scenario set in this application is a Class C clean room, i.e., a washing, drying, filling and sealing room. The intermittently operated process filling equipment not only dissipates heat but also exhausts air. Its exhaust air is affected by the load of the production line and varies greatly, about 40-50%. In view of the operating conditions of the process filling equipment, it is necessary to comprehensively consider the environmental control of the room, to meet both the heat and humidity balance and the wind balance, and to consider the pressure fluctuation range and pressure stabilization time of the room when the supply and exhaust air volume changes.

[0044] The air supply volume of the auxiliary air conditioning system is determined by the heat and humidity balance of the room, which is mainly determined by the heat dissipation of the process filling equipment. There is a numerical difference with the exhaust volume of the process filling equipment. When the process filling equipment is running, the original wind balance of the room is destroyed. The difference in the air volume between the supply and exhaust of the room is considered to be released by setting a variable air volume valve VVA (variable air volume butterfly valve, the same below) on the exhaust duct leading to the outside. Since the maintenance effect and accuracy of the room wind balance are determined by the control of VVA, how to control VVA has become the focus, and PID control is introduced here. Because what is considered here is the difference between the exhaust volume of the process filling equipment and the supply volume of the auxiliary air conditioning system, compared with the exhaust volume of the process filling equipment that needs to be considered in the traditional method, when the process filling equipment is intermittently running, the adjustment range of the air volume undertaken by VVA when the room air volume is balanced again is smaller, and it is easier to quickly achieve the purpose of room pressure control.

[0045] The characteristic of PID control is to use the proportion, integration and differentiation to calculate the control quantity according to the system error or the rate of change of the system error. The adjustment goal is to make the system response reach the best state of fast (fast), accurate (accurate) and stable (stable). The main work of PID adjustment is how to achieve this goal.

[0046] Increasing the proportional P term will speed up the system response, which is to amplify the error amplitude, and it can quickly affect the control output value of the system. However, the system cannot be well stabilized at an ideal value by the proportional coefficient alone. As a result, although it can effectively overcome the influence of disturbances, steady-state errors will appear. Too large a proportional coefficient will also cause the system to have a large overshoot and oscillation, making the stability worse.

[0047] The function of the integral I term is to eliminate the steady-state error. It can perform error trimming on the system with accumulated error after stabilization and reduce the steady-state error. In integral control, the output of the controller is proportional to the integral of the input error signal. For an automatic control system, if there is a steady-state error after entering the steady state, the control system is called a differential system. In order to eliminate the steady-state error, an integral term must be introduced in the controller. The effect of the integral term on the error depends on the integral of time. As time increases, the integral term will increase. In this way, even if the error is very small, the integral term will increase with time, and it will push the output of the controller to change in the direction of reducing the steady-state error until the steady-state error is equal to zero.

[0048] The differential D term has a leading effect. For control systems with hysteresis, the introduction of differential control has a significant effect on improving the dynamic performance indicators of the system when the differential term is properly set. It can reduce the overshoot of the system, increase stability, and reduce dynamic errors. In differential control, the output of the controller is proportional to the differential of the input error signal (i.e., the rate of change of the error). The automatic control system may oscillate or even become unstable during the adjustment process of overcoming the error. The reason is that the controlled object with a large inertia link or lag has the effect of suppressing the error, and its change always lags behind the change of the error. The solution is to make the change of the error suppression effect "lead", that is, when the error is close to zero, the error suppression effect should be zero. The differential term can predict the trend of error change, so as to make the control effect of suppressing the error equal to zero or even negative in advance, thereby avoiding serious overshoot of the controlled amount and improving the dynamic characteristics of the system during the adjustment process.

[0049] PID control combines the advantages of the three: the timely and rapid proportional action, the ability to eliminate residual errors in the integral action, and the advanced control function of the differential action. As long as the control parameters of the three actions are properly selected, the advantages of the three control laws can be fully utilized to obtain a more ideal control effect.

[0050] For clean rooms where intermittent process filling equipment is installed, a main air-conditioning system and an auxiliary air-conditioning system are set up in consideration of the load characteristics of only heat dissipation and exhaust. The main air-conditioning system adopts the same air supply state point as other rooms regardless of whether the process filling equipment is running or not, and the supply and return air volumes are constant. When the process filling equipment is running, the auxiliary air-conditioning system is turned on in conjunction. In summer, the air supply state point is changed by cooling the fresh air to the indoor machine dew point and adjusting the reheat. In winter, the air supply state point is changed by adjusting the heating and humidification amounts.

[0051] In order not to disturb the ambient temperature and pressure of the room, the auxiliary air handling system adopts direct-flow fresh air air conditioning. The additional cooling load in the room is the heat dissipation Q of the process filling equipment, and the additional humidity load is zero. According to the design state point (In, Dn) of the room (In is the indoor enthalpy value, Dn is the indoor humidity content), a heat-humidity ratio line ε=Q / W=∞ is made from the indoor point on the enthalpy-humidity diagram. Given a suitable temperature difference, the air supply state point (Io, Do) is determined, and the air supply volume G is determined by the heat-humidity balance formula Q=G(Io-In).

[0052] The auxiliary air conditioning and air supply system operates in conjunction with the process filling equipment, and has no correlation with the main air conditioning and air supply system, which does not reduce the ventilation frequency of the room and effectively ensures the cleanliness of the room; while ensuring the room temperature and humidity design requirements and pressure coupling control effects, it avoids various drawbacks brought by traditional methods; the auxiliary air conditioning and air supply system operates in conjunction with the process filling equipment, and management and operation are flexible. In short, for clean rooms where intermittent process filling equipment is installed, while considering the heat and humidity load brought by the operation of the process filling equipment and the pressure coupling control problem of the room, the innovative approach of this article is more efficient and energy-saving than the traditional approach.

[0053] In a specific implementation example, take a process filling equipment set up in the project as an example. When the process filling equipment is not running, the VVA exhaust volume is 1200CMH (cubic meters / hour, the same below). When the equipment is running, the equipment exhausts 3500CMH. The auxiliary air supply volume of the air conditioning system is 3000CMH calculated by the heat and moisture balance, and the difference is 500CMH. At this time, by inputting the room pressure difference setting and PID parameter setting value into the variable air volume air valve PID control box (if it is a Venturi valve, it is set by the residual air volume balance), the variable air volume valve exhaust volume is adjusted to 1200-500=700CMH.

[0054] Auxiliary air conditioning system controller description: During operation, the room temperature and humidity detection feedback is compared with the room design state point preset by the auxiliary air conditioning system controller, and the auxiliary air conditioning system air supply is refrigerated, heated and humidified to make the room temperature and humidity meet the design requirements;

[0055] Variable air volume valve PID controller description: Through debugging, set the PID key control parameters suitable for the project needs. During operation, the room pressure is detected and the appropriate VVA air valve opening parameters are output through calculation, so that the room pressure changes meet the pressure stability time and fluctuation range required by the pharmaceutical process quality control.

[0056] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for simultaneously controlling the heat and moisture balance and the wind balance in a sterile drug filling room, characterized in that: The invention comprises a clean room and a main air conditioning and air supply system, an exhaust system, a variable air volume valve, a PID controller and an auxiliary air conditioning and air supply system connected to the clean room. A temperature sensor and a humidity sensor are also arranged in the clean room. The temperature sensor and the humidity sensor communicate with the control system of the auxiliary air conditioning and air supply system. The pressure detection end of the PID controller is arranged in the clean room. The signal output end of the PID controller is connected with the control end of the variable air volume valve. The implementation steps of the pressure and heat and humidity balance control in the clean room are as follows: (1) Determine the air supply volume and air supply status of the auxiliary air conditioning system based on the heat dissipation of process equipment and indoor environmental parameters; (2) Tune the parameters of the PID controller and determine the key control parameters; (3) When the process filling equipment is running, the auxiliary air conditioning system is started; (4) Monitor the pressure in the clean room using an air differential pressure gauge; (5) Control the exhaust air volume of the variable air volume valve through the PID controller; (6) The auxiliary air conditioning system adjusts the supply air temperature and humidity by receiving detection data from the temperature sensor and humidity sensor.

2. A method for simultaneously controlling heat and moisture balance and wind balance in a sterile drug filling room according to claim 1, characterized in that: Priority should be given to ensuring the cleanliness of the room without reducing the number of room ventilation times. Regardless of whether the process filling equipment is running or not, the air volume and air supply status of the main air conditioning air supply system are kept unchanged.

3. A method for simultaneously controlling heat and moisture balance and wind balance in a sterile drug filling room according to claim 1, characterized in that: The auxiliary air conditioning air supply system is a DC type fresh air air conditioning system.

4. A method for simultaneously controlling heat and moisture balance and wind balance in a sterile drug filling room according to claim 1, characterized in that: According to step (1), specifically, based on the design state points In and Dn of the clean room, a heat-humidity ratio line ε=Q / W=∞ is drawn from the indoor point on the enthalpy-humidity diagram, and the air supply state points Io and Dn are determined given a suitable temperature difference, and the air supply volume G is determined by the heat-humidity balance formula Q=G(Io-In); Among them, In is the indoor enthalpy value, Dn is the indoor humidity content, Io is the supply air enthalpy value, Q is the heat dissipation of the process filling equipment, and W is the wet load.

5. A method for simultaneously controlling heat and moisture balance and wind balance in a sterile drug filling room according to claim 4, characterized in that: The indoor pressure caused by the difference between the supply air volume G and the exhaust air volume G1 of the process filling equipment is controlled through steps (2) and (3).

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