Design example study of GMP integrated workshop for solid preparations
Electronic Burglary Safes
Electronic burglary Safes are safes that have passed Chinese 3C certification and use digital password lock systems.
Details:
They are convenient, safe and easy to use;
The safes provide high levels of security;
The Passwords can be changed easily to prevent theft and they`re also quite convenient for official usage because the personnel turnover in the office is normal, hence changing passwords is necessary;
3 times wrong passwords will cause alarm;
The emergency supply can be used when the electricity is off or in case of a black out or EMP Surge;
They possess elegant designs hence they not only provide protection but also serve as decoration pieces.
Electronic Mini Safe,Electronic Safe Box,Electronic Security Safe,Electronic Lock YONGFA INTELLIGENT TECHNOLOGY SECURITY CO., LTD. , https://www.yongfa-safe.com
Key words: solid preparation; integrated production workshop; design; GMP
The reconstruction or construction of hardware construction such as factories and facilities is the basis for the implementation of GMP by pharmaceutical manufacturers. Generally, the enterprise puts forward the requirements according to the production process of the specific variety, and the design unit draws the design drawings, solicits the opinions of the enterprise, and submits the arguments to the enterprise for implementation. Because the design unit does not have a deep understanding of the production process and GMP of the enterprise, the pharmaceutical production enterprises do not understand the design process. Although many design schemes seem to satisfy the GMP, many situations contradict the actual production process or the scene. Many design schemes use the existing workshop mode as a sample to modify the application. They cannot be combined with the specific varieties or the actual situation of the enterprise. In the actual operation process, GMP cannot be achieved at all, and the GMP transformation or construction of the enterprise is left. Under the hard injury, this has to attract people's attention. This article takes a certain manufacturer as an example to discuss the GMP design of the solid preparation workshop.
1 Introduction of the problem The company's workshop is a solid preparation workshop, which mainly produces three types of tablets, capsules and granules, and the three dosage forms are products with different compositions. Because it is all solid preparations, the company hopes to reduce construction costs by merging the same sections. According to China's 1998 edition of GMP, since the three types of dosage forms require the same cleanliness level, they are all 300,000 grades, and the granules in the front section are crushed, sieved, granulated, dried, and the total mixing process is the same, so it can be concentrated. Share. In the latter stage, the tableting, coating and capsule filling are different, and it needs to be arranged in blocks. The post-zui packaging process is also partially the same, and can also be set centrally. It can be seen that it is feasible to produce three dosage forms in the same workshop, and it is possible to increase the utilization rate of the equipment and reduce the area of ​​the clean area by integrating the common process equipment, thereby saving construction funds. But the main problem is how to rationally design, so that it can also meet GMP while saving money, to ensure the quality of drugs. In this paper, the design draft is drawn by analyzing the characteristics of the solid workshop and the requirements of the workshop GMP design.
2 Characteristics analysis of solid preparation workshop 2.1 The same process in the previous stage The workshop mainly produces three kinds of tablets, capsules and granules. These three kinds are common solid dosage forms of Zui, and the production and use amount is large. Regardless of the production process, the granulation process in the pre-production stage of tablets, capsules and granules is substantially the same, such as mixing, granulating, drying and granulating, so that the production line of tablets, capsules and granules is arranged In the same clean area, this can increase the utilization rate of equipment and reduce the area of ​​clean areas, thus saving construction funds.
2.2 There are many types of materials involved. Because the workshop mainly produces three kinds of tablets, capsules and granules, and the three types of products are different components, it can be known that the workshop involves many kinds of materials, and can be set up by means of temporary storage and transfer stations. Clear the separation of people's logistics and strengthen the management of personnel to avoid material confusion.
2.3 Dust-producing process A large amount of dust is easily generated during the production of multi-solid preparations, which may have a great impact on the quality of the drug if not handled properly. It is necessary to design necessary dust-collecting and dust-removing devices for the sections such as crushing, sieving, granulating, drying, granulating, total mixing, tableting and filling. Moreover, the pre-process areas where a large amount of dust is generated should be joined together to form a pre-process area, thereby facilitating dust treatment.
2.4 Small batch, multi-species solid preparation integrated workshop can produce tablets, capsules, granules and other dosage forms. Due to the production of multiple varieties, the production space of each dosage form is reduced and the yield is low, so it is suitable for small batches and varieties. Production of products. The solid preparation integrated workshop cannot produce a variety of products at the same time. Each product requires different personnel and different shifts. Therefore, the same process in the previous section should be divided into different compartments for different production. The production of multi-dose multi-species must be strictly cleared between batch and batch to ensure the quality of the drug. Enterprises must pay attention to the management of personnel.
3 Design Ideas of the Solid Preparation Workshop The regulatory basis for the design of the solid composite workshop is the 1998 version of GMP and its appendix, the “Code for the Design of Cleanrooms for the Pharmaceutical Industry†(GB50457-2008) and the national aspects of construction, fire protection, environmental protection, energy, etc. Specification. GMP requires that the layout of the workshop follows the following characteristics: reasonable layout, strict division of areas, prevention of cross-contamination, and ease of operation [1].
3.1 People flow logistics design workshop layout should meet the relevant standards and specifications of process production, GMP, safety, waterproof, etc., as far as possible, people and logistics should be separated, the process route is smooth, the logistics route is short, and the flow is not returned. , don't go back. Operators and materials that should adhere to the clean area should not use an inlet. Operators and material access points should be set separately. Zui can set up the flow of people and logistics in the opposite direction or position. For example, if you arrange the flow entrance to the east of the production plant, you can consider arranging the logistics entrance on the west side of the production plant; when setting the flow of people and logistics from the same direction, both The distance between them should be relatively long and should not affect each other and hinder [2].
From the current level of domestic pharmaceutical equipment, it is impossible to achieve full-closed, fully mechanized, full-pipeline transportation of solid preparations, and a large number of transportation operations are inseparable from human handling. The handling and transfer of a large amount of materials, intermediates and inner packaging materials is done manually, that is, people carry materials. The intersection of people and logistics in the layout is inevitable, but cross and cross-contamination are not the same concept. Even if people flow and logistics are separated, cross-contamination still occurs between people and things, so there is no need to over-emphasize the problem of cross-flow between people and logistics [3]. Despite this, reasonable arrangements for people flow and logistics are always major issues in the process layout, especially for multi-agent integrated production plants.
3.2 Material Purification System Design The dust particles and microorganisms attached to the material and the carrier itself, the movement of the material and the conversion process will cause changes in the air disturbance and generate dust particles. Therefore, the materials entering the clean room should be purified. The clean room needs to set up an independent material purification room, which generally includes the outer package cleaning, outsourcing, buffer air lock (transfer window or buffer room) and so on.
The raw materials and the materials in direct contact with the drug do not pollute each other. If the process is reasonable, it is not necessary to set two inlets. One inlet can be used, and the storage area determines the area according to the output. In the material purification program, the transfer window or the air shower is generally used in the design. Since the production capacity of the solid preparation workshop and the packaging volume of the original auxiliary materials are large, the transfer window size cannot be too large and does not function as it should. It is recommended to use a cargo shower or buffer room. The door should be a double door interlocking structure, and the air conditioner can supply air.
When designing in the clean area, special outlets for materials and wastes that are likely to pollute the environment generated during the production process should be set up to avoid contamination of the raw and auxiliary materials and the inner packaging materials.
3.3 Personnel purification facilities design According to statistics, the pollution of pharmaceutical companies' clean workshops is mainly microbes and dust particles, and these pollutions are mainly from people, accounting for 35% [4]. Therefore, in order to reduce the pollution of personnel, personnel entering the clean room (area) must be purified. The clean room should be set up with an independent personnel to clean the place. Under normal circumstances, the personnel cleaning place is composed of rain gear storage, shoe change, storage, washing, wearing clean overalls, air brake or air shower room, etc. Compatible with the incoming production area.
The workshop only produces solid preparations, only 300,000 functional zones and two functional zones of the general functional zone, so two personnel locker rooms can be set up, simplifying the dressing process and reducing pollution.
Before the personnel cleaning process, it must pass through the air lock chamber or the air shower room. When the air showers, it is necessary to consider whether to set the bypass door according to the number of operators in the clean area. The door of the air lock chamber should pay attention to the double door interlock, which prevents simultaneous opening. Measures.
Since the operator has a long operating time in the clean area and the working environment is not very good, a water dispenser should be installed in the air lock room before the person enters the clean area to facilitate the employee to drink water.
Washing of clean clothes, China's 1998 edition of the GMP appendix stipulates that "clean work clothes in areas above 100,000 levels should be washed, dried, and cleaned in clean rooms (areas), and should be sterilized as required when necessary." The plant is a 300,000-class solid preparation plant. The laundry room can be set in a clean area or in a non-clean area. The cleaned and dried clothes are sent to the clean area from the transfer window. When cleaning in non-clean areas, it should be stored in the laminar flow purification workbench, sealed and stored in the storage Cabinet of the clean work room. The storage cabinets of clean overalls should not be made of wood materials to avoid mold growth or deformation. Materials that are not dusty, non-corrosive, easy to clean and resistant to disinfection, such as stainless steel and engineering plastics, should be used.
3.4 Production equipment layout design The production equipment should be arranged according to the process flow, and the round-trip and round-trip should be minimized. Generally, linear, U-shaped or L-shaped layout can be considered. The plant is a solid preparation comprehensive workshop, and the amount of materials involved is relatively large. Therefore, each production process should be arranged in the order of process flow around the intermediate station, requiring convenient and fast steps between the processes, and the upper and lower processes are adjacently arranged. The production area should have the area and space suitable for the production scale to arrange production equipment and materials, to ensure the reasonable connection of production operations [1], to prevent confusion and cross-contamination of raw and auxiliary materials, intermediate products, semi-finished products, finished products, auxiliary facilities should be able to meet production At the same time, it does not hinder the production operation.
3.5 Special requirements for the relevant procedures of solid preparations 3.5.1 Preparation room The enterprise is a multi-dosage comprehensive workshop. There are many types of materials and materials involved. To facilitate management and avoid confusion, a preparation room should be set up. The materials used in the production area shall be registered and distributed by special personnel to ensure the use of raw materials, reducing or avoiding the losses caused by the misoperation of personnel.
3.5.2 Weighing chambers in the production area of ​​weighing chambers should be set separately. Weighing should be arranged under the laminar flow hood with curtains or local exhaust and dust removal to prevent cross-contamination caused by dust. In the past, the symmetrical measuring chambers were not individually attached, and were often weighed in the preparation chamber. It is easy to store the remaining raw materials in situ, which is prone to cross-contamination and confusion.
3.5.3 Dust removal and the front chamber will concentrate the dust-producing and noisy equipment together, which can not only concentrate dust removal, but also facilitate the management of the workshop. If the dust is large, the crushing, sieving, tableting, filling and other positions, if not fully closed, in addition to designing the necessary dust collection and dust removal devices, the front room should be designed to avoid neighboring rooms or sharing. The walkway produces pollution. In addition, such as dispensing, container cleaning and other places with high heat dissipation and large amount of moisture, in addition to designing the dehumidification device, the front chamber can also be designed to avoid the operation of the adjacent clean room and the environmental air conditioning due to the large area of ​​moisture and heat dissipation. parameter.
The return air and exhaust air are set at the same time in the dust removal room, and all air exhaust systems in the workshop are interlocked with the corresponding air supply system, that is, the air exhaust system can be opened only after the air supply system is operated, to avoid incorrect operation, Ensure that the clean area is relatively positive outside the room. When the process produces dust, the dust collector is turned on, and the return air is turned off; when the dust is not generated, the wind is turned back, and the exhaust is closed. All control switches are located in the operating room. The front chamber is positively pressed against the clean corridor and is positively pressed against the studio. This ensures that the clean corridor air does not flow through the studio, while the dust-producing air does not flow to the clean corridor, avoiding cross-contamination from the airflow organization. At the same time, it can reduce the indoor noise to the outside. The exhaust air in the room should adopt the side lower air exhaust mode, and the air exhaust port should be set in the wind direction under the dust generating equipment. Otherwise, not only will there be an air dead zone in the room, but it will also cause the upwind side process equipment or operation to pollute the downwind side process equipment or operation. The dust collector or dust removal room should be placed close to the dusting process equipment.
3.5.4 Capsule shell storage Capsule shell is easy to absorb moisture, easy to stick after moisture absorption can not be used, should be stored in the temperature of 18 ~ 24 ° C [2], relative temperature ≤ 65% environment, can be controlled by a constant temperature and humidity machine. The relative temperature of hard capsule filling should be controlled within the range of 45%~50%[2]. Dehumidifier should be installed to avoid filling due to temperature. Capsules are particularly susceptible to temperature and humidity. High humidity tends to make packaging poor. Capsules become soft, sticky, and swell and are beneficial to the growth of microorganisms. Therefore, the storage of finished capsules should also be set up for dehumidification storage.
3.5.5 Exhaust aluminum-plastic packaging machine produces PVC burnt odor when working, so exhaust should be set. The exhaust is located above the heat sealing position of the aluminum-plastic package.
3.5.6 Explosion-proof coating uses a large amount of organic solvent. According to safety requirements, the high-efficiency coating studio should be designed as an explosion-proof area, and the door is explosion-proof. The explosion-proof area adopts all exhaust air, does not return air, and the explosion-proof area is under negative pressure in the public corridor of the clean area.
3.5.7 Auxiliary room with cleaning room, container storage room, sanitary ware cleaning room, sanitary ware storage room, intermediate laboratory, mold storage, and the above-mentioned dust removal room and explosion-proof room should be placed as close as possible under the reasonable conditions of the main work room. Its application [6]. These auxiliary rooms are in close contact with the drug, so the air cleanliness should be the same as the air cleanliness of the place of use. The setting of the cleaning room and the storage room should avoid secondary pollution of equipment and appliances, and can be arranged in a one-way flow.
3.5.8 Clean corridors designed in clean corridors should be guaranteed to reach each production post, transfer or in-package storage room. Other post operating rooms or storage rooms cannot be used as access for materials and operators to enter this position, so as to effectively prevent cross-contamination of different types of drugs caused by material transportation and operator movement. And try to reduce the middle walkway, so as to avoid dust from spreading through people, turnover barrels, etc., to avoid bringing dust to other sections, to control and avoid cross-contamination. At the same time, due to the speciality of the production of solid preparations and the continuous improvement of the process formula and equipment, the clean corridor should be appropriately widened to reduce the collision or the replacement of the equipment during the transportation process. Therefore, the clean corridor is not only the passage of personnel and materials, but also the passage for equipment replacement.
4 Design results and comparisons After the above characteristics analysis, the design scheme (shown in Figure 1) is obtained, and compared with the original design scheme (as shown in Figure 2) prepared by the enterprise, the defects of the original design can be found as follows: : (1) Two sets of logistics systems are confusing and polluting; (2) Common areas are not merged, and construction costs are high; (3) Functional area size is not combined with actual production volume; (4) Two sets of systems are used There are problems in the design and operation of the air-conditioning purification system, which can not meet the purification requirements and energy saving; (5) the auxiliary room for reducing material pollution such as dust removal and exhaust is not set; (6) the auxiliary room such as the front chamber and weighing is not refined. Settings; (7) clean corridors are not set, etc.
After redesigning the adjustment, the new design (shown in Figure 1) has the following advantages:
(1) Flow of people and people: The entrance and exit are separated, the production process is smooth and unreturned, and the logistics trend is inverted L-shaped. Each function is clearly divided by area, and the function blocks and functions are relatively independent and connected through clean corridors. It eliminates the probability of human beings, people and things intersecting from the hardware.
(2) Equipment: The same equipment can be used in the same process (focusing on cleaning verification and personnel management) to improve equipment utilization rate; equipment is arranged according to the amount of production, and equipment idle rate is reduced.
(3) Function room: The size of the function is comprehensively considered in terms of production volume and equipment, etc., to meet the actual production needs; the function layout is in line with the requirements of the process flow.
(4) Clean area: The general control area is separated from the clean area, and the area with high cleaning requirements, such as capsule filling and tablet pressing, is close to the air conditioning purification system; because the same sections are combined, the layout is compact and the area of ​​the clean area is reduced.
(5) Cost: Reduce costs by improving equipment utilization rate and reducing clean area, and meet the requirements of enterprises.
(6) Quality: Separation of human logistics, reduction of material confusion, increase of dust collection and dust collection, etc., so that the production workshop as a whole is more in line with GMP requirements, and can better ensure the quality of medicines.
5 Conclusion For the specific situation of the enterprise, three production lines of tablets, capsules and granules are arranged in the same clean area. When layout is arranged, the production sections should be arranged as much as possible, such as the granulation section (mixed granulation, drying and Whole grain mixing, capsule section (capsule filling, polishing capsule), tablet section (tablet, coating) and inner packaging are relatively concentrated, which can reduce the mutual interference of each section, and is also conducive to air conditioning purification. The system is reasonably arranged. At the same time, the division of the functional area is consistent with the actual production volume and reserved amount of the enterprise, which not only conforms to GMP, guarantees the quality of the medicine, but also meets the requirements of the enterprise to save money and seek development.
This is not a special case. When designing factories and facilities that meet GMP requirements, we should consider the company's own situation, GMP and other laws and regulations, instead of copying it, so that we can truly design both GMP and GMP. The plan that the company expects.