The sterility assurance of the product does not depend on the sterility inspection of the final product, but on the adoption of qualified processes, strict GMP management and a good overall quality assurance system in the production process. The formulation and determination of the process should comprehensively consider factors such as the nature of the object, the effectiveness of the method, and the economy, and the integrity and stability of the product.
Validation of procedures is an important prerequisite for sterility assurance. For products (including final containers and packaging), the methods must be validated for their procedures before they are actually used before they can be delivered for formal use. Verification includes:
⑴ Write and determine the verification scheme and formulate evaluation standards.
(2) Confirm that the technical data of the equipment are complete, installed correctly, and can be in normal operation (installation confirmation).
⑶ Confirm that the key control equipment and instruments can work normally within the specified parameter range (operation confirmation).
⑷ Use items or simulated items to repeat the test, provide the range of parameters, and confirm that the effect meets the requirements (performance confirmation).
⑸ Summarize and improve various documents and records, and write a complete verification report.
In daily production, the operation of the process program should be monitored to confirm that all key parameters (such as temperature, pressure, time, humidity, gas concentration and absorbed radiation absorbed dose, etc.) in the process are within the range determined by verification. ; Critical equipment and processes in the adopted procedures should be periodically revalidated. When there is a major change in the program and changes (including changes in the placement and loading methods and quantities of items in the cabinet), re-validation should be carried out.
The sterility assurance of products in this probabilistic sense cannot depend on the sterility inspection of the final product, but depends on the adoption of qualified processes, strict GMP management and a good overall quality assurance system in the production process. This means that monitoring of the batch manufacturing process will better reflect the sterility assurance level of the product than the batch sterility test results. The sterility assurance of the product is related to the degree of contamination of the previous product and the characteristics of the contaminating bacteria. Therefore, the level of microbial contamination and the tolerance of contaminating bacteria should be strictly monitored before the product, and various measures should be taken to reduce contamination in all aspects of production to ensure that microbial contamination is controlled within the specified limits.
Otherwise, necessary measures should be taken to reduce contamination and eliminate resistant strains, or even revalidate the process. Recontamination of existing items should be prevented. In any case, the container and its closure system should be required to ensure that the product meets sterility requirements during the expiry date.