Materials for production in clean workshop, such as raw and auxiliary materials, vials, aluminum caps, rubber plugs, finished product packaging cartons, product labels, etc., are first sent to the unpacking room in the clean area of each user post, and then sent to the post for use after the outer packaging of the materials is removed. Glassware that needs to be used in the freeze-drying production process should be cleaned before sterilization. Generally speaking, the glass containers used in the freeze-drying production process should be cleaned before sterilization It is repeated washing and washing, through the cleaning process can effectively remove all kinds of dirt and impurities attached to the surface of utensils.
In general, purified water is used to wash the surface of the vessel to avoid contamination of the container, and the final washing shall meet the requirements for water for injection; the vial is washed by washing bottle, distilled water and sterile air, and sent into the tunnel type dry heat sterilizer for continuous dry heat sterilization by unidirectional high-temperature airflow heating or far-infrared heating. The washed vials are placed at the entrance of the thermal sterilization equipment After sterilization, the outlet of dry heat sterilization equipment should be protected by level unidirectional flow clean air, and it will be automatically sent to the filling room after drying and sterilization.
The washing effect of the glass bottle, the cleanliness of the bottle after washing, and whether it has been re polluted before use after sterilization are mainly controlled by checking the cleanliness of the washing water and bottle. If necessary, the pollution challenge test in the washing process is used to control the quality. The main principle of rubber plug treatment is to use pure and pyrogen free water for injection, wash and remove the impurity particles on the rubber plug surface, and dilute the pyrogen substance on the rubber plug surface to below the detection sensitivity.
When the rubber plug is initially cleaned, the pollutants and insoluble particles adsorbed on the surface of the rubber plug are gradually cleaned down. As the cleaning process continues, the rubber plug surface is continuously damaged by friction. The longer the cleaning time is, the more serious the mechanical damage on the rubber plug surface. The cleaning method of the rubber plug determines the damage speed and degree of the rubber plug, so a non-destructive cleaning method should be selected Remove the outer package from the material storage room in the clean area, count the quantity and move it to the rubber stopper treatment room. Clean the inner package of the rubber plug with purified water and put it into the cleaning machine for rinsing, silicification, rinsing, and then sterilizing and drying.
In most of the freeze-drying process, the treatment process of the rubber plug contains silicification process. Silicification of the rubber plug is beneficial to reduce the adhesion of the rubber plug during sterilization and the delivery of the rubber plug during filling. Attention should be paid to the possible pollution caused by improper silicification. At the same time, the silicone oil used in the preparation of the rubber plug should meet the appropriate quality control standards; the container sealing system of freeze-dried sterile drugs should be able to prevent microbial invasion During the inspection of the final sealing products, any damaged or defective products should be found out and removed. Strict safety measures should be taken to prevent the products with defective sealing and pollution from being put into the market.
Poor adaptability of equipment and defects in the supply of containers and seals can lead to problems in the integrity of container sealing system. If some defects causing sealing problems are difficult to find, improvement measures should be taken as soon as possible to prevent and detect defective products. The final flushing medium of the inner packing container must be water for injection. Purified water can only be used in the initial cleaning stage of the inner packaging container. The purified water for washing can be recycled and recycled by pre filtering the water and using membrane filter with special pore size. After cleaning, the rubber plug should be sterilized and dried. At this time, the sterilization is usually carried out by wet heat sterilization. These steps can be completed separately or combined together, preferably at the same time. The rubber plug should be sterilized and dried in the filtered air protection of the high efficiency air filter.