The raw material drug production workshop not only has the requirements of safety, sanitation and environmental protection, but also meets the requirements of the raw material drug GMP. Many domestic API manufacturers pay more attention to the GMP requirements of final refining, drying and packaging of APIs, but do not fully understand the GMP requirements in the early stage of API production. It should be controlled according to GMP requirements from the beginning of the introduction of the raw material starting materials into the process.
1. When arranging the raw material drug production workshop, not only the GMP requirements for the refining of the raw material drug should be considered, but also the GMP requirements for the synthetic reaction of the raw material drug should be considered. Relatively independent storage areas for raw and auxiliary materials, dry storage areas for reaction intermediates, etc. should also be set up in the synthesis reaction area of raw materials to avoid cross-contamination of materials.
2. Avoid cross-contamination and contamination between raw materials, auxiliary materials, intermediates and semi-finished products, and finished raw materials.
3. The route for sending finished raw materials to intermediate storage or storage areas should be reasonable, and should avoid passing through heavily polluted areas.
4. The raw material drug production area should be arranged on the windward side of the dominant wind direction, and the raw material drug synthesis area should be arranged on the downwind side of the dominant wind direction.
5. In the man-cleaning setting of the raw material drug production workshop, it is not only necessary to set up human-cleaning facilities for capable personnel in accordance with GMP requirements, but also the personnel in the raw material drug synthesis reaction post should also have a unified changing and shower system, especially for the sterile raw material drug workers. Clean settings, and it should be considered as much as possible that the personnel in the lean package and the personnel in the synthesis reaction post must enter their respective production posts separately to reduce cross-contamination of personnel.
6. The flow of personnel and logistics ports in the lean and dry package area should be as small as possible to facilitate the control of the cleanliness of the entire workshop.
7. Process water, compressed air, nitrogen, etc. are purified according to process requirements.
8. Arrange the direction and shaft of various concealed pipelines. The pipelines can be combined with ventilation sandwich walls and technical corridors.
9. The air-conditioning room should be close to the clean area, so that the ventilation duct line is the shortest, and the return air duct is reasonably arranged to play a clean air-conditioning effect.
10. Rooms with the same cleanliness level should be combined as much as possible to facilitate ventilation and make the air-conditioning arrangement reasonable. The cleanliness level requires different rooms to be connected with each other to have anti-pollution measures, such as air locks, air showers, buffer rooms and transfer windows.
11. In factory buildings with windows, rooms with high cleanliness requirements should generally be arranged on the inside or in the center, and the sterile clean room can also be arranged on the outside, but a closed outer corridor is added for buffering.
12. The common system used in the raw material drug production workshop is relatively complicated. There are not only refrigerant systems with different temperature requirements, but also steam and heat source systems with different temperatures. Energy saving and consumption reduction should be fully considered to meet the requirements of clean production. For example, the chilled water (7℃～12℃) system can be considered to use the circulating water system in winter, and the single cooling water system mode of the chilled water system in summer, so that the two sets of water systems share the same set of pipelines, and the switching is realized through valves. Effectively save energy and reduce pipeline layout. The steam condensate system should be recycled and reused.
