A case study on the design of GMP comprehensive workshop for solid preparations

Abstract: Based on the analysis of the characteristics of the comprehensive preparation workshop of solid drugs, the design case is studied Conclusion: due to the complexity of production process, detailed analysis and research must be carried out to make the design conform to GMP Key words: solid preparation; comprehensive production workshop; design; GMP hardware construction, such as the transformation or construction of factories and facilities, is the basis for drug manufacturers to implement GMP Generally, the enterprise puts forward the requirements according to the production process of specific varieties, the design unit designs the drawings, solicits the opinions of the enterprise, and submits them to the enterprise for implementation after demonstration However, due to the lack of deep understanding of the production process and GMP of the enterprise by the design unit, and the lack of understanding of the design process by the drug manufacturing enterprise, many design schemes seem to meet the GMP, but many situations conflict with the actual production process or site Many design schemes, taking the existing workshop mode as the sample, can not be well combined with the specific varieties or the actual situation of the enterprise In the actual operation process, they can not reach GMP at all, leaving a hard injury to the GMP transformation or construction of the enterprise, which has to be paid great attention to Taking a factory as an example, this paper discusses the GMP design of the comprehensive workshop for solid preparations The workshop of the enterprise is a comprehensive workshop of solid preparations, which mainly produces three dosage forms of tablets, capsules and granules, and three dosage forms are products with different ingredients Because it is all solid preparation, the enterprise hopes to reduce the construction cost by merging the same section and other ways According to the GMP of 1998 edition in China, the three dosage forms require the same level of production cleanliness, which is 300000, and the previous stage of granulation process, i.e crushing, screening, granulation, drying and total mixing processes, are the same, so they can be used collectively In the later process, tablet pressing, coating and capsule filling are different, which need to be arranged in blocks The Zui post packaging process is also partially the same, and can be set centrally It can be concluded that it is feasible to produce three dosage forms in the same workshop, and through the integration of common process equipment, the utilization rate of equipment can be increased, the area of clean area can be reduced, and the construction funds can be saved But the main problem is how to design it reasonably, so that it can meet GMP while saving money, so as to ensure the quality of drugs In this paper, through the analysis of the characteristics of the solid workshop and the requirements of GMP design, the design draft is obtained 2 Analysis of the characteristics of the comprehensive workshop of solid preparations 2.1 in the same process in the previous stage, the workshop mainly produces three dosage forms of tablets, capsules and granules, which are common solid dosage forms of Zui, with large production and use No matter what kind of production process is adopted, the granulation process of tablet, capsule and granule before production is basically the same, such as mixing, granulation, drying and whole granule, etc Therefore, the production lines of tablet, capsule and granule are arranged in the same clean area, which can improve the utilization rate of equipment, reduce the area of clean area, and save construction funds 2.2 there are many kinds of materials involved Because the workshop mainly produces three dosage forms of tablets, capsules and particles, and three dosage forms are products with different ingredients, it can be seen that the workshop involves many kinds of materials, and material confusion can be avoided by setting temporary storage and transfer stations for materials, clarifying the separation of people flow, strengthening personnel management and other measures 2.3 the process of producing dust is easy to produce a lot of dust in the production process of Multi-Solid preparation If not handled properly, it will have a great impact on the quality of drugs Necessary dust catching and dedusting devices shall be designed for crushing, screening, pelletizing, drying, pelletizing, general mixing, tablet pressing, filling and other sections with large dust generation In addition, the former process areas that produce a lot of dust should be combined to form the former process areas, so as to facilitate dust treatment 2.4 the small batch and multi variety solid preparation comprehensive workshop can produce tablet, capsule, granule and other dosage forms Because of the multi variety production, the production space of each dosage form is reduced and the output is low, so it is suitable for the production of small batch and multi variety products The solid preparation comprehensive workshop can not produce multiple products at the same time, each product requires different personnel and shifts, so the same process in the previous section should be divided into equipment compartments of different sizes for different production In the production of multiple dosage forms and varieties, the site must be strictly cleared between batches to ensure the quality of drugs Enterprises should attach importance to the management of personnel 3 Analysis of the design idea of the comprehensive solid preparation workshop The basis of the regulations for the design of the comprehensive solid preparation workshop is GMP 1998 and its appendix, the code for the design of pharmaceutical industry clean workshop (gb50457-2008) and the national code for building, fire protection, environmental protection, energy and other aspects GMP requires that the plane layout of the workshop should follow the following characteristics: reasonable plane layout, strict division of areas, prevention of cross pollution, and convenient operation and production 3.1 under the condition of meeting relevant standards and specifications of process production, GMP, safety and waterproof, the layout of the design workshop of human flow and logistics should be as separate as possible, with smooth process route, short logistics route, no return flow and no detour It should be insisted that the operators and materials entering the clean area cannot share the same entrance, and the access for operators and materials should be set separately Zui should be able to set people flow and logistics entrances in the opposite direction or location If people flow entrances are arranged in the east of the production plant, it can be considered to arrange logistics entrances in the west of the production plant When people flow and logistics entrances are set in the same direction, they should be relatively far away from each other, and they should not affect and hinder each other From the current level of domestic pharmaceutical equipment, it is impossible for solid preparation production to be fully enclosed, fully mechanized and fully piped A large number of transportation operations cannot be separated from human handling A large number of materials, intermediates and inner packaging materials are handled and transferred by manual operation, that is, people take materials with them It is inevitable that people flow and logistics cross in the layout, but cross and cross pollution are not the same concept Even if people flow and logistics are separated, cross pollution will still occur between people and things, so it is not necessary to overemphasize the problem that people flow and logistics do not cross However, the reasonable arrangement of people flow and logistics is always an important issue in the process layout, especially for the comprehensive production plant with multiple dosage forms 3.2 the material purification system is designed to attach dust particles and microorganisms to materials and carriers The movement and transformation of materials will cause changes in air disturbance and produce dust particles Therefore, materials entering the clean room should be purified An independent material purification room shall be set up in the clean room, which generally includes cleaning of outer package, unpacking, buffer airlock (transfer window or buffer room), etc Raw and auxiliary materials and internal packaging materials that directly contact with drugs will not pollute each other If the process flow is reasonable, it is unnecessary to set two inlets, and one can be used The area of the storage room is determined according to the output In the process of material purification, transfer window or air shower is usually used in the design Due to the large production capacity and packaging volume of raw and auxiliary materials in the solid preparation workshop, the size of the transfer window is unlikely to be too large to play its due role It is recommended to use cargo shower or buffer room, whose door should be double door interlock structure and air conditioning supply In the design of the clean area, special outlets for materials and wastes that are easy to pollute the environment during the production process shall also be set to avoid pollution to the raw and auxiliary materials and the inner packaging materials 3.3 according to the statistics of the design of personnel purification facilities, the pollution in the clean workshop of pharmaceutical enterprises is mainly microorganism and dust particles, and these pollution mainly comes from personnel, accounting for 35% [4] Therefore, in order to reduce personnel pollution, the personnel entering the clean room (area) must be purified The clean room shall be equipped with an independent personnel purification place Generally, the personnel purification place is composed of rain gear storage, shoes change, coat storage, washing, wearing clean work clothes, air lock or air shower room, etc the cleaning requirements of the personnel purification room shall be suitable for the production area The workshop only produces solid preparations, only 300000 level functional areas and general functional areas, so it can be divided into two personnel changing rooms, so as to simplify the changing procedures and reduce pollution Before the personnel purification process, they must pass through the airlock room or the air shower room When passing through the air shower, it is necessary to consider whether a bypass door should be set according to the number of operators in the clean area The door of the air lock room should pay attention to the double door interlock to prevent simultaneous opening Since the operators operate in the clean area for a long time and the working environment is not very good, the water dispenser should be set in the airlock room before the operators enter the clean area to facilitate the employees to drink water For the washing of clean clothes, the appendix of GMP 1998 stipulates that "clean work clothes in areas above 100000 level shall be washed, dried and sorted in the clean room (area), and sterilized as required if necessary" The factory is a 300000 level solid preparation factory, which can set the laundry room in the clean area or in the non clean area, and then send the washed and dried clean clothes to the clean area through the transfer window When cleaning in the non clean area, it should be considered to arrange in the laminar flow purification table and store in the storage cabinet of the clean clothing room after being sealed The storage cabinet of clean work clothes shall not be made of wood materials to avoid mildew, bacteria or deformation, and shall be made of materials that are dust-free, non corrosive, easy to clean and resistant to disinfection, such as stainless steel, engineering plastics, etc 3.4 layout design of production equipment production equipment shall be reasonably arranged according to the process flow to minimize round-trip and detour In general, linear, U-shaped or L-shaped layout can be considered The workshop is a comprehensive solid preparation workshop, which involves a large amount of materials Therefore, each production process should be arranged around the intermediate station according to the sequence of process flow It is required that each process is convenient, fast and adjacent to the next process The production area shall have the area and space suitable for the production scale to arrange production equipment and materials, ensure the reasonable connection of production operation, prevent the confusion and cross pollution of raw and auxiliary materials, intermediate products, semi-finished products and finished products, and the auxiliary facilities shall be able to meet the production needs without hindering the production operation 3.5 special requirements for relevant processes of solid preparations 3.5.1 material preparation room the enterprise is a multi dosage form comprehensive workshop, which involves many kinds of materials and packages In order to facilitate management and avoid confusion, a material preparation room should be set up The materials used in the production area shall be registered and distributed by a specially assigned person to ensure that the raw and auxiliary materials are received and to reduce or avoid the loss caused by the misoperation of personnel 3.5.2 the weighing room in the production area of the weighing room shall be set up separately, and the weighing scale shall be arranged under the laminar flow hood with a curtain or local exhaust shall be adopted for dust removal to prevent cross pollution caused by dust escape In the past, no attention was paid to the separate setting of the weighing room, which was often weighed in the material preparation room It was easy to store the remaining raw and auxiliary materials on the spot, resulting in cross contamination and confusion 3.5.3 the dust removal and front room will gather the equipment with large dust production and noise, which can not only collect dust, but also facilitate the management of the workshop Crushing and sieving with large amount of dust