Pharmaceutical freeze-drying machine is composed of freeze-drying box, shelf, condenser and other large containers plus refrigeration system, heat medium circulation system, vacuum exhaust system, CIP/SIP system, recompression system, hydraulic pneumatic system, control system, etc. composition. Its main function is to freeze the dried medicinal liquid at low temperature, and to sublimate and remove the water in it under vacuum.
The freeze dryer ensures two purposes, one is to remove moisture in an appropriate manner in a sterile state, and the other is to not cause microbial contamination. According to its particularity, it is determined that the freeze dryer must have special conditions. Inspectors need to be familiar with the working principle and key operating parameters of freeze dryers. When inspecting pharmaceutical freeze dryers, they should pay attention to the following aspects:
1. The environment where the freeze dryer is located: enough space is reserved for the environment where the freeze dryer is located to facilitate the aseptic operation of personnel, the transfer of semi-stopped products into and out of the box to the freeze-drying box, and the operation area of the freeze-dryer out of the box. The environmental cleanliness level and environmental monitoring situation;
2. Design of freeze-drying machine: The design of the freeze-drying machine is suitable for its function. During inspection, pay attention to the key parameters of the freeze-drying machine or the alarm device for the failure of the freeze-drying cycle, the air blocking device of the drainage system, the sterilization method of the equipment, and especially the gas filter. Sterilization methods, measures to prevent oil contamination, etc.;
3. Confirmation of freeze dryer: There are many key operating parameters of freeze dryer, and appropriate and sufficient key operating parameters should be selected for verification. During the inspection, attention should be paid to the verification of the temperature uniformity of the shelf, the sterilization verification of the gas sterilization filter, the water capture ability test, the sublimation rate confirmation, the gas filter integrity test, and the vacuum leak rate inspection;
4. Cleaning, disinfection and sterilization of lyophilizers: equipment cleaning, disinfection and sterilization operations should be verified, and attention should be paid to the coverage of cleaning methods and confirmation of cleaning time during inspection; sterilization/disinfection cycle, sterilization effect Sterilizing filtration of disinfectants used to assess the situation (e.g. using biological indicators);
5. Personnel operation risk: For the manual feeding and discharging of freeze-dried products or the semi-automatic feeding and discharging system, there should be a time limit for verification, and manual dry operation should be minimized instead of mechanical operation. During inspection, attention should be paid to the operation of personnel entering and leaving the box.
