Integrated control system for clean room process supplies

Abstract

The application provides a clean room process auxiliary material integrated control system, which comprises a reaction tank, a control system and a processing system installed on the reaction tank; the control system comprises at least one of the following: a stirring control unit, a CIP / SIP control unit, a temperature control unit, a liquid level control unit, a flow control unit, a PH control unit, a dissolved oxygen control unit, a material transfer control unit and an emulsification control unit; and the processing system comprises at least one of the following: a homogenizer, a centrifuge, an ultrafilter, a chromatography column and a nanofilter.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of process auxiliary material integrated control, in particular to a clean room process auxiliary material integrated control system. BACKGROUND

[0002] In the production of pharmaceuticals, the pollution of the production environment and the production conditions generally includes microorganisms, dust, particles, corrosion, errors and cross-contamination. The prevention and control of pollution in the production of pharmaceutical equipment contains two meanings, the first is that the equipment itself does not pollute the drugs and does not pollute the environment, and the second is that it should have effective means of controlling pollution. Therefore, GMP has made a number of guiding provisions for pharmaceutical equipment directly involved in the production of pharmaceuticals, the basic point of which is to ensure the quality of pharmaceuticals, prevent various pollution that may be caused to drugs in the production process, and factors that may affect the environment and endanger human health. Therefore, the design of pharmaceutical equipment should meet the requirements of GMP, reduce pollution factors, and have good prevention and control of pollution.

[0003] The pharmaceutical liquid preparation system is mainly used for liquid preparation, filtration, and cleaning and sterilization of various solid and liquid preparation equipment. It is connected with traditional solid preparation equipment products in the pharmaceutical process, and participates in the whole pharmaceutical process, which has a crucial influence on the quality of pharmaceuticals.

[0004] The existing automatic liquid preparation device has many deficiencies. One of them is that the overall structure and shape are not simple enough, the overall equipment and the exposed part (including some visible parts) are too complex, the concave-convex, groove, and table in the conventional design of the equipment are not flat and simple enough, and dust and dirt are hidden to some extent, which is not easy to clean. After adding the concentrated solution of the medicament, a small amount of liquid remains on the inner wall of the pipeline, causing the unqualified liquid preparation structure.

[0005] The production and assembly automation degree of the existing traditional pharmaceutical liquid preparation system product is not high, the production equipment is not advanced enough, and the assembly link is mainly manual, which has high labor cost. At present, many links in the above production process are completed by hand, which easily mixes microorganisms, leading to the scrap of the whole batch of injection products, and also easily causes uneven liquid preparation, resulting in poor quality uniformity of each production batch of injection. SUMMARY

[0006] The purpose of the present application is to provide a clean room process auxiliary material integrated control system. In order to solve the technical problems existing in the background art.

[0007] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0008] The clean room process auxiliary material integrated control system comprises a reaction tank, a control system installed on the reaction tank and a processing system, wherein the processing system comprises at least one of the following: a stirring control unit, a CIP / SIP control unit, a temperature control unit, a liquid level control unit, a flow control unit, a PH control unit, a dissolved oxygen control unit, a material transfer control unit and an emulsification control unit; and the processing system comprises at least one of the following: a homogenizer, a centrifuge, an ultrafilter, a chromatography column and a nanofilter.

[0009] In some embodiments, a plurality of parallel pipelines are arranged above the reaction tank, and an electromagnetic valve is arranged on each pipeline.

[0010] In some embodiments, the tank body of the reaction tank adopts a vertical double-layer structure, and the reaction tank comprises an outer tank body and an inner tank body.

[0011] In some embodiments, an outer layer of heat preservation plate is attached to the surface of the outer tank body.

[0012] In some embodiments, a spiral belt is wound on the surface of the inner tank body, steam water or cooling water is injected into the spiral belt, and the inner tank body is attached to a filled polyurethane heat preservation material.

[0013] In some embodiments, the bottom head of the inner tank body is of a concave-convex type, the top of the tank body is provided with a water inlet, a backflow port, a sterilization port, a cleaning ball, a hole filling port and a breathing port, and the bottom of the tank body is provided with a condensate outlet, a discharge port, a blowdown port, a sampling port, a temperature probe and a liquid level sensor.

[0014] In some embodiments, an air breather and a stirring system are installed in the breathing port.

[0015] In some embodiments, a high-temperature wastewater discharge system is connected to the bottom of the reaction tank.

[0016] Advantages

[0017] Compared with the prior art, the present application has the following advantages:

[0018] The clean room process auxiliary material integrated control system can realize automatic liquid preparation, stirring and mixing, can relieve the shortage of operation personnel for liquid preparation in the production of injections, can make the liquid preparation more accurate and standardized, and can guarantee the sterility and safety of the automatic liquid preparation system through the perfect combination of CIP cleaning and SIP sterilization. The unique tank body structure, the combination of the upper and lower oval heads and the standard sandwich jacket, has a large jacket space, a large heating area, reduced welds, a flat inner container to prevent material from sticking to the wall, an attractive appearance and a simple and durable structure. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1is a schematic diagram of a clean room process auxiliary material integrated control system related to the embodiment;

[0020] Figure 2 is a schematic diagram of a control system related to the embodiment;

[0021] Figure 3 is a schematic diagram of a processing system related to the embodiment;

[0022] Figure 4 is a schematic diagram of a clean room process auxiliary material integrated control system related to the embodiment. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical scheme and advantages of the present application clearer, the present application will be further described in detail below in combination with the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and do not limit the present application.

[0024] On the contrary, the present application covers any substitution, modification, equivalent method and scheme defined by the claims on the essence and scope of the present application. Further, in order to make the public better understand the present application, some specific details are described in detail in the following detailed description of the present application. The present application can also be completely understood without the description of these details by those skilled in the art.

[0025] The following will be combined with Figures 1-4 A clean room process auxiliary material integrated control system related to the embodiment of the present application will be described in detail. It should be noted that the following embodiments are only used to explain the present application and do not limit the present application.

[0026] As Figure 1 shown, a clean room process auxiliary material integrated control system includes a reaction tank 110, a control system 120, a processing system 130; the control system includes at least one of the following: stirring control unit 121, CIP / SIP control unit 122, temperature control unit 123, liquid level control unit 124, flow control unit 125, PH control unit 126, dissolved oxygen control unit 127, material transfer control unit 128, emulsification control unit 129; the processing system includes at least one of the following: homogenizer 131, centrifuge 132, ultrafilter 133, chromatography column 134, nanofilter 135.

[0027] In some embodiments, the reaction tank is connected with a high-temperature wastewater discharge system at the bottom.

[0028] In some embodiments, the entire device is divided into various functional modules with independent functions according to the functions of each group; each module is divided into various standardized constituent components according to different implementation modes, specifications and structures of the functions; each functional module and constituent component constitutes a module library of the enterprise; various process requirements of users can be met through dynamic combination of each functional module and constituent component; non-standard products are converted into standardized production; the quality and stability of the device and the manufacturing efficiency are greatly improved; the stability of the production process is ensured; and the operation and maintenance are simpler.

[0029] In some embodiments, when the clean room process auxiliary material integrated control system of the present application is working, water for injection can be automatically added to the reaction tank through a pipeline first; the mechanical stirrer is started under the control of the stirring control unit; the material is added; the auxiliary material is added after being dissolved in advance; the stirring is performed to dissolve everything; the PH value is adjusted by the PH control unit; then the water for injection is added to the full amount; the stirring is continued; the activated carbon is added for needle; the stirring and adsorption are performed; and the decarburization is performed through the self-circulation of the filter such as the ultrafiltration machine and the nanofiltration machine of the treatment system.

[0030] After the self-circulation solution is clarified, the sampling detection is qualified, the reaction tank is connected with the nitrogen gas filtered through the sterilization filter, the liquid medicine is filtered through the related filter of the serial treatment system to the sterile storage tank or directly enters the emulsification tank to start the next process.

[0031] After the preparation of a batch of liquid medicine is completed, the reaction tank starts the tank body cleaning; first, the CIP (cleaning in place) online cleaning is performed, which mainly removes the non-biological pollutants; then, the SIP (steam in place) steam wet hot air disinfection is performed; the production wastewater and the steam condensate water are connected to the high-temperature wastewater discharge system through the pipeline at the bottom of the tank body.

[0032] In some embodiments, the preparation, CIP cleaning, SIP disinfection, medicine storage and production wastewater discharge of the entire preparation system are automatically performed through the PLC control program, and a series of parameters are printed through the set printer; whether the preparation of the preparation system is correct, the CIP cleaning and SIP disinfection are qualified, and whether the entire preparation system is sterile and safe are determined through the analysis of the parameters.

[0033] In some embodiments, the entire preparation system can have more than one tank body; one control secondary module can be set based on each tank body; multiple secondary modules can be parallelly arranged; and one main module is set to control the multiple secondary modules. Multiple functional submodules such as the dissolved oxygen module and the centrifugal module can be matched under the secondary module. The control interfaces are left between the main modules to provide a standardized control system for the automatic pharmaceutical production of multiple processes and lay a foundation for the establishment of the module library of the enterprise.

[0034] In some embodiments, the reaction tank is provided with several parallel pipelines above the tank, and each pipeline is provided with a solenoid valve. For example, the reaction tank is provided with several parallel pipelines above the tank, and the pipelines are connected with process materials (including auxiliary materials), drinking water, circulating chilled water, industrial steam, clean compressed air, and pure steam. The pipelines are provided with solenoid valves to realize automatic liquid preparation under joint control.

[0035] In some embodiments, the tank body of the reaction tank adopts a vertical double-layer structure, and the reaction tank comprises an outer tank body and an inner tank body. In some embodiments, the outer tank body is provided with an outer layer of heat preservation plate. In some embodiments, the inner tank body is provided with a spiral belt, and the spiral belt is filled with steam water or cooling water, and the inner tank body is provided with a filling polyurethane heat preservation material.

[0036] For example, the tank body adopts a vertical double-layer structure, and the inner tank body has a polishing precision of RaO.45. The inner cylinder is provided with a spiral belt through which steam is heated or cooling water is passed, and is filled with polyurethane material for heat preservation. The outer heat preservation plate adopts mirror or frosted polishing, and the tank body has consistent gloss. Moreover, only the components in contact with the liquid are made of 316L material, and the remaining components are made of 304 material.

[0037] In some embodiments, the bottom head of the inner tank body is of a concave-convex type, the top of the tank body is provided with a water inlet, a reflux port, a sterilization port, a cleaning ball, a filling port, and a breathing port, and the bottom of the tank body is provided with a condensate outlet, a discharge port, a blowdown port, a sampling port, a temperature probe, and a liquid level sensor. In some embodiments, the breathing port is provided with an air breather and a stirring system. For example, the bottom head of the inner tank body is of a concave-convex type, and the tank body is provided with a mechanical axial flow stirring, a water inlet, a reflux port, a sterilization port, a cleaning ball, a filling port, and a breathing port provided with a 0.22um air breather and a stirring system. The bottom of the tank body is provided with a condensate outlet, a discharge port, a blowdown port, a sampling port, a temperature probe, and a liquid level sensor. The tank body is provided with a control cabinet for operation, and the instrument displays the liquid temperature and liquid level, and provides upper and lower limit alarm functions. The tank body can be additionally provided with a nitrogen filling device and a pH meter.

[0038] In some embodiments, the tank body, valves, instruments, pipe materials, and pipe fittings of each system in contact with process materials are made of stainless steel, and can be configured according to the ASME BPE or ISO2037 standard, 304 or 316L material, surface mechanical polishing or electrolytic polishing treatment. The polishing precision reaches Ra0.45, and the transition between the barrel body and the upper and lower heads adopts a spinning R angle forming, which is flat, smooth, and has no sanitary dead angle, so as to ensure that the container is always in a sanitary and sterile state. The outer surface adopts polishing, sand blasting, frosted or cold-rolled original color matte surface treatment.

[0039] In conclusion, through the system of the present application, the automation of process auxiliary material integrated preparation and the intelligent operation can be realized, the efficiency and standardization are improved, and the risk of product pollution by liquid preparation operators is avoided. The structure of upper and lower elliptical head or lower reverse convex bottom and upper elliptical head ensures that there is no residue in the liquid delivery and the cleaning is thorough without dead angle. The cleaning and sterilization combination of IPCIP+SIP cooperates to complete the cleaning and sterilization process, which can ensure that the equipment pipeline cleaning and sterilization is thorough, and effectively prevent the pollution of harmful microorganisms (such as salmonella, listeria and escherichia coli).

[0040] Secondly, the tank body adopts a hygienic and sterile design, each pipe opening is subjected to drawing treatment to form a smooth transition, avoiding the dead angle caused by direct socket welding, and ensuring the reliability and stability of the production process. At the same time, the simplification of the overall structure and shape is emphasized, the overall equipment and the exposed part (including some directly visible parts) are simplified in the GMP view, which can make the concave-convex, groove and table in the conventional design of the equipment flat and simple, and can maximize the reduction of dust accumulation and dirt accumulation, and easy cleaning. The hierarchical control structure of the main module, the secondary module and the sub-module can accurately and efficiently control and manage the complex and multi-sequence liquid automatic program.

[0041] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. An integrated control system for cleanroom process auxiliary materials, characterized in that, This includes the reaction vessel and the control and processing systems installed on it. The control system includes at least one of the following: a stirring control unit, a CIP / SIP control unit, a temperature control unit, a liquid level control unit, a flow control unit, a pH control unit, a dissolved oxygen control unit, a material transfer control unit, and an emulsification control unit; The processing system includes at least one of the following: homogenizer, centrifuge, ultrafiltration machine, chromatography column, nanofiltration machine; The bottom of the reaction tank is connected to a high-temperature wastewater discharge system; The entire device is divided into functional modules with independent functions according to their respective functions; each module is further divided into standardized components according to the different implementation methods, specifications and composition of its functions; the functional modules and components together constitute the module library. When the cleanroom process auxiliary material integrated control system is working, water for injection is first automatically added to the reaction tank through pipelines. The stirring control unit controls the mechanical stirrer to start, add materials, and then add pre-dissolved auxiliary materials. Stir until they are completely dissolved. The pH control unit adjusts the pH value, then water for injection is added to the full volume, stirring continues, and activated carbon for injection is added and stirred for adsorption. The ultrafiltration and nanofiltration filters of the treatment system self-circulate to remove carbon. After the self-circulating solution is clarified, it is sampled and tested to ensure it is qualified. Then, sterilized filtered nitrogen is introduced into the reaction tank, and the drug solution is filtered through the filters of the series treatment system to a sterile storage tank or directly enters the emulsification tank to start the next process. After a batch of solutions is prepared, the reaction tank begins cleaning. First, online cleaning (CIP) removes non-biological contaminants, followed by steam sterilization (SIP). The resulting wastewater and steam condensate are piped to a high-temperature wastewater discharge system at the bottom of the tank. The entire solution preparation system—including solution preparation, CIP cleaning, SIP sterilization, reagent storage, and wastewater discharge—is automatically controlled by a PLC program. A series of parameters are printed out using a pre-programmed printer. Analysis of these parameters determines whether the solution preparation is correct, and whether the CIP cleaning and SIP sterilization processes are satisfactory, thus confirming the sterility and safety of the entire solution preparation system. The entire liquid preparation system is based on the tank body of each reaction vessel, with a control sub-module. Multiple tanks have multiple parallel sub-modules, while the entire liquid preparation system has a main module to control multiple sub-modules. This module is equipped with multiple functional sub-modules, including dissolved oxygen module and centrifugation module; control interfaces are provided between the main modules to provide a standardized control system for multi-process pharmaceutical automation; The reaction vessel has several parallel shared pipes above it, and each pipe is equipped with a solenoid valve. The reaction vessels all adopt a vertical double-layer structure, and the reaction vessels include an outer tank and an inner tank; The outer tank surface is covered with an outer insulation board; The inner tank surface is wrapped with a spiral strip, and steam or cooling water is injected into the spiral strip. The inner tank is also filled with polyurethane insulation material. The bottom end cap of the inner tank is concave-convex. The top of the tank is provided with a water inlet, a return outlet, a disinfection outlet, a cleaning ball, a packing inlet, and a vent. The bottom of the tank is provided with a condensate outlet, a discharge outlet, a sewage outlet, a sampling outlet, a temperature probe, and a liquid level sensor.

2. The integrated control system for cleanroom process auxiliary materials according to claim 1, characterized in that, An air respirator and a shaking system are installed inside the breathing port.

Images