8.4 Answer questions daily; 10 wealth points for each correct answer^_^

1) Moist heat sterilization; 2) Dry heat sterilization; 3) Radiation sterilization; 4) Gas sterilization; 5) Sterilizing filtration.

1) Moist heat sterilization; 2) Dry heat sterilization; 3) Radiation sterilization; 4) Gas sterilization

1) Moist heat sterilization; 2) Dry heat sterilization; 3) Radiation sterilization; 4) Gas sterilization; 5) Sterilizing filtration.

1) Moist heat sterilization; 2) Dry heat sterilization; 3) Radiation sterilization; 4) Gas sterilization; 5) Sterilizing filtration.

1. Sterilization process: 1. Aseptic drugs should be subjected to final sterilization by heating whenever possible; the probability of microbial survival in the finally sterilized products (i.e., the sterility assurance level, SAL) must not exceed 10-6. When final sterilization is carried out using moist heat sterilization, the standard sterilization time F0 value should generally be greater than 8 minutes; steam treatment does not constitute final sterilization. For heat-unstable products, aseptic production methods or alternative methods such as filtration sterilization can be employed. 2. Sterilization can be achieved using moist heat, dry heat, ionizing radiation, ethylene oxide, or filtration. Each sterilization method has its specific scope of application; the sterilization process must comply with the requirements set by regulatory approvals and must be validated. 3. Before any sterilization process is put into use, physical testing methods and biological indicators must be employed to verify its suitability for the products or items in question, as well as to ensure that sterilization is achieved in all areas. 4. The effectiveness of the sterilization process should be re-verified regularly (at least once a year). Re-validation is required after significant changes to the equipment. Records of re-verification should be kept. 5. All items to be sterilized must be treated in accordance with the specified requirements to achieve satisfactory sterilization results; the design of the sterilization process should ensure compliance with the sterilization requirements. 6. The loading method of the products and items to be sterilized in the chamber of the sterilization equipment should be confirmed through verification. 7. Biological indicators should be stored and used in accordance with the supplier’s requirements, and their quality should be confirmed through positive control tests. When using biological indicators, strict management measures should be implemented to prevent microbial contamination resulting therefrom. 8. There should be a clear method to distinguish between sterilized products and products awaiting sterilization. Each load (tray or other loading device) of products or materials should be labeled with the clear indication of the product name, batch number, and whether it has been sterilized. If necessary, moist heat sterilization indicator strips can be used to distinguish them. 9. A sterilization record should be kept for each sterilization process, and it shall serve as one of the bases for product release. II. Sterilization methods: 1. Thermal sterilization typically includes moist heat sterilization and dry heat sterilization, and it must meet the following requirements: (i) During validation and production, the temperature probes used for monitoring or recording should be separate from those used for control, and their placement locations should be determined through validation. The time-temperature curve of the sterilization process should be recorded for each sterilization cycle. Those that employ automatic control and monitoring systems must be verified to ensure compliance with the requirements of critical processes. The control and monitoring system should be able to record faults that occur during the operation of the system and the process, and it should be under the supervision of operators. The readings from the independent temperature display should be regularly compared with the graphs recorded during the sterilization process. (II) Chemical or biological indicators can be used to monitor the sterilization process, but they cannot replace physical tests. (III) The heating time required for each loading method should be monitored, and the sterilization time shall be calculated starting from the moment all the products or items to be sterilized reach the set sterilization temperature. (IV) Measures should be in place to prevent sterilized products or items from being contaminated during the cooling process. Unless it can be proven that any products or items with leaks can be removed during the production process, any cooling medium (liquid or gas) in contact with such products or items must be sterilized or decontaminated. 2. Moist heat sterilization shall meet the following requirements: (1) The parameters for monitoring the moist heat sterilization process shall include sterilization time, temperature, or pressure. A sterilization cabinet with a drain at the bottom of the chamber should have the temperature data at that point measured and recorded throughout the sterilization process, if necessary. For sterilization processes that involve vacuum pumping, the chamber should be regularly tested for leaks. (II) Except for products that are already sealed, the items to be sterilized should be properly wrapped using suitable materials; such materials and wrapping methods should facilitate the release of air and penetration by steam, while also preventing contamination after sterilization. Within the specified temperature and time, all parts of the items to be sterilized must be in full contact with the sterilizing medium. 3. Dry heat sterilization must meet the following requirements: (1) During dry heat sterilization, the air within the sterilization chamber should be circulated and kept at positive pressure to prevent non-sterile air from entering. The air entering the chamber should be filtered through high-efficiency filters, which in turn must undergo integrity testing. (II) When dry heat sterilization is used to remove pyrogens, the validation shall include a bacterial endotoxin challenge test. (III) The temperature, time, and pressure difference inside and outside the chamber during dry heat sterilization should be recorded. 4. Radiation sterilization shall meet the following requirements: (1) Radiation sterilization may be used only if it has been proven to have no adverse effect on product quality. Radiation sterilization shall comply with the Pharmacopoeia of the People’s Republic of China and the relevant requirements specified in the registration approval. (II) The radiation sterilization process shall be validated. The validation protocol should include radiation dose, radiation time, packaging material, and loading method, while also examining the impact of changes in packaging density on the sterilization effectiveness. (III) During radiation sterilization, dose indicators should be used to measure the radiation dose. (IV) Biological indicators can be used as an additional monitoring method. (5) Measures should be in place to prevent the mixing of irradiated items with unirradiated items. Each package should contain a radiation indicator sheet that undergoes a color change upon exposure to radiation. (VI) The total radiation dose limit shall be met within the specified time. (7) Records should be kept for radiation sterilization. 5. Ethylene oxide sterilization shall meet the following requirements: (1) Ethylene oxide sterilization shall comply with the Pharmacopoeia of the People’s Republic of China and the relevant requirements specified in the registration approval. (II) The sterilization process validation shall demonstrate that ethylene oxide has no destructive effect on the products, and that the exhaust conditions and times specified for different products or materials ensure that all residual gases and reaction products are reduced to the specified acceptable levels. (III) Measures should be taken to prevent microorganisms from being trapped within crystals or dried proteins, ensuring direct contact between the sterilizing gas and the microorganisms. It is necessary to determine the impact of the nature and quantity of the packaging materials for the items to be sterilized on the sterilization effect. (IV) Once the items to be sterilized have reached the temperature and humidity conditions specified by the sterilization process, the sterilizing gas should be introduced as soon as possible to ensure effective sterilization. (5) During each sterilization process, an appropriate number of biological indicators should be placed in different locations of the items to be sterilized in order to monitor the effectiveness of the sterilization; the results of such monitoring should be recorded in the corresponding batch records. (VI) The contents of each sterilization record shall include the time taken to complete the entire sterilization process, as well as the pressure, temperature, and humidity inside the chamber during sterilization, as well as the concentration of ethylene oxide and its total consumption amount. The pressure and temperature throughout the sterilization process should be recorded, and the sterilization curve should be included in the corresponding batch record. (7) Sterilized items should be stored in a controlled, well-ventilated environment to reduce residual gases and reaction products to specified levels. 6. The filtration sterilization of products that are not subject to final sterilization shall meet the following requirements: (1) Products that can be finally sterilized shall not have filtration sterilization used as a substitute for final sterilization. If the drug cannot be sterilized in its final packaging container, the drug solution can be filtered into a pre-sterilized container using a sterilizing filter with a filtration efficiency of 0.22 μm (or lower or equal). Since sterilizing filters cannot remove all viruses or mycoplasmas, heat treatment can be used to compensate for the limitations of sterilizing filtration. (II) Measures should be taken to reduce the risk of filtration sterilization. It is advisable to install a second sterilized sterilizing filter to filter the liquid medication once more; the final sterilizing filter should be as close as possible to the filling point. (III) After use, the sterility filter must have its integrity checked immediately using appropriate methods, with the results recorded. Common methods include the bubble point test, diffusion flow test, or pressure hold test. (IV) The filtration and sterilization process must be validated, during which the time required to filter a certain volume of the medicinal solution as well as the pressures on both sides of the filter must be determined. Any significant deviation from normal time or pressure should be recorded and investigated, and the results of the investigation should be included in the batch record. (5) The service life of disinfection filters of the same specification and model shall be verified, and it generally shall not exceed one working day

Moist heat sterilization, dry heat sterilization, radiation sterilization, gas sterilization, filtration sterilization, etc

Moist heat sterilization, dry heat sterilization, radiation sterilization, gas sterilization, filtration sterilization

1) Moist heat sterilization; 2) Dry heat sterilization; 3) Radiation sterilization; 4) Gas sterilization