Features and functions of the "three-in-one" equipment for filtration, washing and drying used in the production of new GMP sterile raw materials
In recent years, due to the occurrence of various drug incidents, my country's drug regulatory system and manufacturers have paid more and more attention to the production of sterile drugs, especially the recent new GMP standards are basically consistent with the EU, and the requirements for production equipment have also been further improved. Generally speaking, the production of sterile raw materials is usually completed by combining the final product refinement and aseptic process in the production process as a one-step operation unit in the production process. Sterility and contamination of insoluble particles are the two main features that distinguish sterile raw materials from non-sterile raw materials, so the "three-in-one" equipment for sterile raw materials (the functions of the original multiple devices are concentrated and optimized to one device) It is directly related to the production process and quality of the product, and is the main equipment guarantee used in the production of sterile raw materials.
Introduction of "three-in-one" equipment for filtration, washing and drying used in the production of sterile raw materials
Filtration, washing and drying devices are commonly called "three-in-one" equipment, which is the key equipment commonly used in the production of raw materials. The tank body of the tank-type "three-in-one" equipment is similar to a large suction filter. The chassis is made of metal sintered The filter screen (stainless steel and titanium are mainly made of two materials), the support plate and the heating plate are combined. The tank body has a jacket for heating and cooling, and inside the tank there is an agitator that can move up and down. The agitator is a hollow structure, and the medium is used for heating and cooling, which plays a major role in the drying stage. The container can be protected by inert gas, which is composed of "input/output" interface system, working system, sampling system, CIP and SIP system.
The "three-in-one" process of filtration, washing and drying used in the production of sterile raw materials can be briefly described as follows:
(1) First seal the entire unit system, fill it with sterile inert gas (such as N2 gas) for protection, add crystallization liquid to be processed from the crystallizer to the "three-in-one" through the automatic valve, and close the feed valve after reaching a certain volume.
(2) Pass in inert gas to pressurize, and realize the solid-liquid separation of the crystallization liquid through the large metal filter plate at the bottom.
(3) After the solid-liquid separation of the crystallization solution, spray and wash the filter cake.
(4) After washing, the stirring device is lowered by the hydraulic device for stirring, and at the same time, the heating pipeline system inside the stirring is used to heat the material layer, and the temperature of the drying process is strictly controlled, otherwise the degradation and failure of the drug will be caused. While heating and drying, vacuumize the system to make the solvent evaporate quickly, and at the same time start the dust collector to work automatically to ensure the normal ventilation of the vacuum system.
(5) After the material layer is dried and qualified (sampling test or automatic process analysis can be used), stop the vacuum and enter the automatic discharge program.
(6) Automatic discharge: lower the stirring device, control the stirring speed and the descending speed of the stirring blade to carry out the scraping and feeding action, so that the powdery material can quickly enter the silo through the discharge valve, and stop when the stirring is close to the metal filter plate layer Stir and descend, and then inject inert gas instantly to blow all the bottom materials to the silo.
If the high-pressure sterile inert gas (such as N2 gas) is introduced near the discharge port, the silo is connected, and at the same time, vacuuming and weighing can also realize the whole process of filtering, washing, drying and packaging of medicines.
Most of the "three-in-one" equipment in China has solved many problems, but there are also some defects or imperfections in practical applications: (1) The material residue in the equipment, when each batch of material is discharged, there are 5%~10 % of the material cannot be automatically discharged from the equipment, even if the air knife or the barrel is tilted, the problem cannot be solved, which is the biggest problem of this "three-in-one".
(2) It integrates the functions of filtration and drying, but the efficiency of filtration and drying is lower than that of centrifuges and dryers, which is also a problem that most domestic manufacturers cannot overcome at present.
Wuxi ZhangHua Machinery Co., Ltd. aimed at the main problems of the above three-in-one, combined with foreign advanced technology, carried out a lot of design and development work, and finally successfully developed a multifunctional cylinder-cone reaction filter dryer integrating filtration, washing and drying. , and successfully applied for a patent (patent number: ZL201721560677.6.), which has greatly improved the technical performance of the equipment. From structural design to application, it closely follows the corresponding regulatory requirements of the pharmaceutical industry and the new GMP requirements. The equipment has three main functions of filtering, washing and drying, and also has many functions such as reaction, extraction, crystallization, concentration, evaporation, mixing and crushing, which belongs to the improved multifunctional equipment.
The main technical characteristics of the "three-in-one" filtration, washing and drying used in the production of sterile raw materials by ZhangHua Machinery in Wuxi
1. Able to complete multi-unit operation functions on the integrated equipment. Filtration, washing, and drying "three-in-one" equipment replaces the original filtering equipment, which can complete the washing operation and realize the drying function; there is also a sub-packaging "three-in-one" equipment that realizes crushing, sieving, and weighing The function of continuous operation in a closed system fully reflects the practical significance of the "three-in-one" equipment.
2. The filtration, washing and drying "three-in-one" used in the production of aseptic raw materials by Wuxi ZhangHua Machinery is a closed system with a separate sampling system; the parts in contact with medicines are made of 316 stainless steel, and the coolant and lubricant have their own independent The operating system is completely separated from the medicine; the mechanical seal of the shaft part has a gas seal and a particle collection device or a lip seal imported from the United States.
Prevent particles from entering the tank or container to contaminate equipment; effectively reducing the chance of contamination. The design of the equipment has the function of reducing pollution, cross-contamination, confusion and errors; the material of the equipment, the lubricant used, the coolant and many other aspects will not increase the pollution of the product; the materials in and out, sampling, design and wear of mechanical seals Particle prevention and exclusion, etc., effectively prevent particles from entering the tank or container to contaminate equipment; greatly reducing the chance of contamination.
3. The "three-in-one" filtration, washing and drying used in the production of aseptic raw materials by Wuxi ZhangHua Machinery is equipped with manual and automatic operation procedures, a touch-type operation screen, easy to operate, and an automatic fault diagnosis function, which is convenient for maintenance; production process comparison Mature and stable products can be controlled by programming, equipped with pneumatic or electric valves, and implement one-button operation.
It reduces the cumbersome operating procedures that may lead to wrong operations, causing losses to production, and the convenient operation of maintenance can reduce the chance of equipment being contaminated during maintenance.
4. The "three-in-one" filtration, washing and drying used in the production of aseptic raw materials by ZhangHua Machinery in Wuxi facilitates thorough CIP and SIP, or parts in contact with drugs should be disassembled and cleaned and sterilized; it is also convenient for batches to draw boundaries to prevent contamination Batch residues pollute the next batch of materials, resulting in drug quality accidents. The "three-in-one" equipment currently used in the production of sterile raw materials has the functions of in-situ cleaning and sterilization of the tank, removal and cleaning of the discharge valve and sampling valve, and in-situ sterilization. The base with the filter plate can be Realize disassembly cleaning and steam sterilization together with the tank body, all parts in direct contact with medicines can be cleaned or disassembled and washed in place, and steam sterilized in place after assembly.
5. The "three-in-one" filtration, washing and drying used in the production of aseptic raw materials of Wuxi ZhangHua Machinery is made of 316L stainless steel, and most of them use CNC machine cutting, automatic welding, machine polishing, cleaning and passivation processes. The surface of the equipment is smooth, smooth, easy to clean or disinfect, and resistant to corrosion. It will not chemically react with or absorb drugs, or release substances into the drugs that will affect product quality and cause harm, and will not cause any harm to the drugs.
3. Pollution-free sampling can be realized
Most of the "three-in-one" equipment is designed with a safe and pollution-free sampling valve device. When sampling, it is not necessary to open the equipment cover or cabinet door, which avoids the contamination of drugs by impurities brought into the sampling tool.
4. Improve production efficiency and save operating costs
(1) Since the work completed by multiple equipment operations in multiple processes is completed by one equipment, the operation time is reduced and the production cycle is shortened; (2) The space occupied by the clean area is saved on site, and construction costs are reduced; (3) Also It saves operating costs such as air conditioning and refrigeration, and has certain effects on reducing costs, increasing efficiency, and saving energy.
The fully enclosed production process in pharmaceutical production has always been the best production method pursued by pharmaceutical manufacturers. In this way, the pharmaceutical production process is not affected by external or artificial impurities, pollution, etc., and the quality of pharmaceuticals can be guaranteed most effectively, and Production also has minimal environmental impact.
This production method is in line with the development trend of cleaner production in the world.
7. The "three-in-one" filtration, washing and drying used in the production of aseptic raw materials by Wuxi ZhangHua Machinery also focuses on the specific requirements of customers in terms of energy saving.