How to allow pharmaceutical companies to reasonably build pharmaceutical workshops within a certain funding budget, so that the workshops can meet GMP standards, have complete functions and reserve space for future development, is the topic we are discussing today. This article takes the pharmaceutical solid preparation production workshop as an example. Through analyzing the characteristics of a solid preparation workshop and the requirements of the GMP design of the workshop, the draft of the solid preparation production workshop design is obtained. Commonly used solid dosage forms are divided into: powders, granules, tablets, capsules, dripping pills, films, etc., which account for about 70% of pharmaceutical preparations. Compared with liquid preparations, solid preparations have the advantages of good physical and chemical stability and lower production costs.

Analysis of the characteristics of a solid preparation workshop

The workshop mainly produces three dosage forms of granules, tablets and capsules, and the three dosage forms are products with different ingredients. If all types of products are solid preparations, the construction cost can be reduced by merging the same sections during design. According to the new version of my country's GMP, because the three dosage forms require the same production cleanliness level, they are all Grade D, and the previous granulation processes, namely crushing, sieving, granulation, drying, and total mixing, are the same, so they can be shared collectively. The subsequent processes are different in tablet compression, coating, and capsule filling, and they need to be arranged in blocks. The final packaging process is also partially the same, and it can also be set up collectively. It is achievable that the three preparations are in parallel in the same workshop, so the utilization rate of the equipment can be improved by integrating the common process equipment and the area of the clean area can be reduced. Thereby saving construction funds.

Design reference standard for solid preparation workshop

The legal basis for the design of solid preparation workshops is the new version of GMP and its appendices, "Specifications for the Design of Clean Workshops in the Pharmaceutical Industry" and national regulations on construction, fire protection, environmental protection, and energy. GMP requires the layout of the workshop to follow the following characteristics: reasonable layout, strict division of areas, prevention of cross-contamination, and convenient operation and production.

The design of the flow of people and logistics in the solid preparation workshop

The layout of the workshop should meet the relevant standards and norms of process production, GMP, safety, waterproofing, etc., as far as possible to ensure that the separation of people and logistics is not crossed, the process route is smooth, the logistics route is short, no backflow, and no circuitous. It should be insisted that the operators and materials entering the clean area cannot share the same entrance, and the entrance and exit channels for the operators and materials should be set separately. It is best to set up the entrance of people flow and logistics in the opposite direction or position. For example, if the entrance of people flow is arranged on the east side of the production plant, consider arranging the entrance of people flow on the west side of the production plant; when the entrance of people flow and logistics is set in the same direction, both A relatively long distance should be maintained between them, and mutual influence and interference should not be allowed.

Judging from the current level of domestic pharmaceutical equipment, it is impossible for the production of solid preparations to achieve fully enclosed, fully mechanized, and fully pipelined transportation. Mass transportation operations cannot do without human handling. The handling and delivery of a large amount of materials, intermediates and inner packaging materials is done manually, that is, people take the materials away. In the layout, the flow of people and logistics are unavoidable, but the concept of cross and cross contamination is not the same. Even if the flow of people and logistics are separated, there will still be cross-contamination between people and things, so there is no need to overemphasize the problem of non-intersection of people flow and logistics. Nevertheless, the rational arrangement of the flow of people and logistics is always a major issue in the process layout, especially for multi-dose integrated production plants.

Design of material purification system for solid preparation workshop

Materials and carriers attach to dust particles and microorganisms. The movement and transformation of materials will cause changes in air turbulence and produce dust particles. Therefore, materials entering the clean room should be purified. The clean room needs to set up an independent material purification room, which generally includes packaging cleaning, outsourcing, and buffer airlock (transfer window or buffer room). The raw and auxiliary materials and the inner packaging materials that directly contact the drugs will not cause pollution to each other. If the process is reasonable, there is no need to set up two inlets, and one inlet can be used. The storage area is determined according to the output. In the material purification process, transfer windows or air showers are generally used in the design. Since the production capacity of the solid preparation workshop and the packaging volume of the raw and auxiliary materials are very large, the size of the transfer window cannot be too large, and it cannot play its due role. It is recommended to use a cargo shower or buffer room, the door should be a double-door interlocking structure, and the air conditioner should supply air. In the design of the clean area, special outlets for materials and wastes that are likely to pollute the environment generated during the production process should also be set up to avoid pollution of raw materials and inner packaging materials.

Personnel purification facility design of solid preparation workshop

According to statistics, the pollution in clean workshops of pharmaceutical companies is mainly microbes and dust particles, and these pollutions mainly come from personnel, accounting for 35%. Therefore, in order to reduce the pollution of personnel, the personnel entering the clean room (area) must be purified. The clean room should set up an independent personnel purification place. Under normal circumstances, the personnel purification place consists of rain gear storage, shoe changing, outer clothing storage, washing, wearing clean overalls, air locks or air shower rooms, etc. The cleanliness requirements of the personnel purification room Adapt to the production area entered. The workshop only produces solid preparations, with only D-level functional areas and general functional areas, so it can be divided into two changing rooms for personnel, thereby simplifying the changing procedures and reducing pollution. Personnel must pass through the air lock room or air shower room before the air shower. When passing the air shower, consider whether to install a bypass door according to the number of operators in the clean area. Pay attention to the double door interlock to prevent simultaneous opening of the door through the air lock room. Measures. As 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 airlock before the personnel enter the clean area to facilitate the employees to drink water and wash the clean clothes. The factory is a Class D solid preparation factory. The laundry room can be located in a clean area or a non-clean area, and the clean clothes after washing and drying are sent to the clean area through the transfer window. When cleaning in a non-clean area, it should be considered in the laminar flow purification workbench and stored in a storage cabinet in a clean workroom after being sealed. The storage cabinets of clean work clothes should not be made of wooden 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, engineering plastics, etc., should be used.

Layout design of production equipment for solid preparation workshop

The production equipment should be reasonably arranged according to the technological process, and the round trips and roundabouts should be reduced as much as possible. Generally, linear, U-shaped or L-shaped layouts can be considered. The plant is a comprehensive workshop for solid preparations, and the amount of materials involved is large. Therefore, the production processes should be arranged in the order of the process flow around the intermediate station. The connection between the processes is convenient and fast, and the upper and lower processes are arranged adjacently. The production area must have an area and space suitable for the scale of production to arrange production equipment and materials to ensure a reasonable connection between production operations and prevent the confusion and cross-contamination of raw and auxiliary materials, intermediate products, semi-finished products, and finished products. Auxiliary facilities should be able to meet production needs at the same time , Does not interfere with production operations.

Special requirements for related processes in the solid preparation workshop

1. Material preparation room

The company is a multi-dose comprehensive workshop with many types of materials and packaging materials involved. In order to facilitate management and avoid confusion, a material preparation room should be set up. When materials are used in the production area, special personnel are required to register and distribute materials to ensure that raw and auxiliary materials are used and reduce or avoid losses caused by personnel misoperation.

2. Weighing room

The weighing room in the production area should be set up separately, and the weighing scale should be arranged under a laminar flow hood with curtains or local exhaust air and dust removal to prevent cross-contamination caused by dust escape. In the past, the separate setting of the weighing room was not taken seriously, and it was often weighed in the material preparation room. It was easy to store the remaining raw and auxiliary materials on the spot, which was easy to cause cross contamination and confusion.

3. Dust removal and front room

Centralizing equipment with large dust production and noise can not only centralize dust removal, but also facilitate the management of the workshop. If the positions of crushing, sieving, tablet pressing, and filling with a large amount of dust cannot be fully enclosed, in addition to the necessary dust catching and dust removal devices, the front room should be designed to avoid adjacent rooms or sharing Pollution in the walkway. In addition, for posts with large heat dissipation and moisture dissipation, such as slurry preparation and container cleaning, in addition to the design of the dehumidification device, the front room can also be designed to avoid the large area of moisture dissipation and heat dissipation affecting the operation and environmental air conditioning of the adjacent clean room. parameter. Return air and exhaust air are set in the dust removal room at the same time. The air volume is the same. All exhaust systems in the workshop are interlocked with the corresponding air supply system. That is, the exhaust system can only be opened after the air supply system is running to avoid incorrect operation. Ensure that the clean area has a positive pressure relative to the outside. When the process produces dust, open the dust collector and close the return air; when no dust is produced, open the return air and close the exhaust air. All control switches are located in the operating room. The front room has a positive pressure relative to the clean corridor, and a positive pressure relative to the working room. This ensures that the clean corridor air does not flow through the studio, and 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 spread of indoor noise to the outside world. The exhaust air in the room should be exhausted from the side, and the air exhaust should be set in the downwind direction of the dust generating equipment. Otherwise, not only will there be an air dead zone in the room, but also the process equipment or operations on the upwind side will pollute the process equipment or operations on the downwind side. The dust collector or dust removal room should be arranged nearby the dust generating process equipment.

4. Capsule shell storage

The capsule shell is easy to absorb moisture, and it is easy to stick after absorbing moisture and cannot be used. It should be stored in an environment with a temperature of 18~24℃ and a relative temperature of ≤65%. It 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%, and a dehumidifier should be installed to avoid the influence of temperature on the filling. Capsules are particularly susceptible to temperature and humidity. High humidity can easily change poorly packaged capsules. Soft, sticky, swelling and conducive to the growth of microorganisms, so the storage of finished capsules should also be set up for dehumidification storage.

5. Exhaust

When the aluminum-plastic packaging machine is working, it produces PVC burnt odor, so exhaust air should be set. The exhaust air is located above the heat-sealing position of the aluminum-plastic packaging.

6. Explosion-proof

A large amount of organic solvents are used for coating. According to safety requirements, the efficient coating studio should be designed as an explosion-proof area with a door bucket for explosion-proof. The explosion-proof area adopts all exhaust air, no return air, and the explosion-proof area is relatively negative in the public corridor of the clean area.

7. Auxiliary Room

The container cleaning room, container storage room, sanitary ware cleaning room, sanitary ware storage room, intermediate laboratory, mold storage, as well as the dust removal room and explosion-proof room mentioned above should be arranged in the main work room as close as possible to the application site. These auxiliary rooms are in close contact with drugs, so their air cleanliness should be the same as the air cleanliness of the place where they are used. The cleaning room and storage room should be arranged to avoid secondary pollution of equipment and appliances, and unidirectional flow arrangement can be adopted.

8. Clean corridor

The clean corridor designed in the clean area should ensure that it directly reaches every production post, transit or inner packaging material storage room. The operation room or storage room of other positions cannot be used as a passage 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 the flow of operators. And try to reduce the middle aisle, so as to avoid the spread of dust through people, turnover barrels, etc., avoid bringing dust to other work sections, and control and avoid cross-contamination. At the same time, due to the particularity of the production of solid preparations and the continuous improvement of process formulas and equipment, clean corridors should be appropriately widened to reduce collisions with partitions during transportation and the partitions must be removed or destroyed during equipment replacement.

Advantages of solid preparation workshop design scheme

①Pedestrian flow and logistics: separate entrances and exits, smooth production processes without roundabouts, and reverse L-shaped logistics. Each function is clearly divided by area, and functional blocks are relatively independent from each other and connected by clean corridors. It eliminates the probability of crossing between people and things from the hardware.

②Equipment: The same equipment can be used in the same process (pay attention to cleaning verification and personnel management) to increase the utilization rate of the equipment; arrange the equipment according to the production volume to reduce the idle rate of the equipment.

③Function room: The size of the function room is set in consideration of production volume and equipment to meet the actual production needs; the arrangement of the function room meets the requirements of the process flow.

④ Clean area: The general control area is separated from the clean area, and the areas with high cleanliness requirements, such as capsule filling and tablet compression, are all close to the air conditioning purification system; because the same work sections are merged, the layout structure is compact, and the area of the clean area is reduced.

⑤Cost: Reduce costs in terms of improving equipment utilization rate and reducing clean area area to meet enterprise requirements.

⑥Quality: Separate personnel and logistics, reduce material confusion and pollution, increase dust removal and dust catching rooms and other measures, so that the production workshop as a whole is more in line with GMP requirements, and the quality of medicines can be guaranteed.

When an enterprise bids for the construction of a GMP workshop, it must look for a company with three best “qualifications”, “experiences” and “reference cases”. Such companies will have comprehensive control over the planning, design, engineering, and supporting aspects of the project. CEIDI Xidi is a professional integrated service provider specializing in providing planning, design, decoration, furniture and supporting engineering integrated services for laboratories, clean rooms, animal rooms, and operating rooms. It has a third-level qualification for general contracting of construction engineering, electromechanical Level 3 Qualification, Level 3 Qualification for Environmental Protection, Level 1 Qualification for Purification, Level 3 Qualification for Steel Structure. In the field of GMP purification workshop and industrial decoration, it has built landmark projects for more than 1,000 companies, with a cumulative construction area of more than 2 million square meters. It is still worth investigating and understanding. Related case: Pharmaceutical laboratory engineering R&D room GMP construction project-Yangtze River Pharmaceutical.