One of the important processes in sterile production is process validation in drug production. This process has been a legal requirement since past years. Process validation is required not only by the Food and Drug Administration (FDA) or USFDA, but also by international authorities such as the World Health Organization (WHO), European Union (EU), Pharmaceutical Inspection Collaboration Plan and others.
Most pharmaceutical manufacturers invest in this process for both economic and regulatory reasons. This is because it is an important process that demonstrates that a manufacturer is operating under defined standard conditions to produce a sterile product free from microorganisms, pyrogens, particles and with an extremely high standard of quality and purity. The ultimate goal for validation of a sterilization process is to ensure zero presence of any microbial contamination.
Compared to other dosage form specifications, the sterility specification is an absolute value. The product produced is either non-sterile or sterile. The Food and Drug Administration (FDA) has established guidelines for the general outline of process validation. One such key principle is the inability to rely solely on end-product sterility testing to determine the sterility of a product. However, greater emphasis must be placed on process validation in the manufacture of sterile products.
Process validation tends to reduce the dependency of end product testing alone and therefore three principles apply in process validation for sterile products. The principles are to restore sterility to a product, to ensure that sterilization and processing methods have proven sterility across all units of a product line, and to provide support and greater assurance for final product sterility test results.
The process of microbial destruction includes lethality through radiation, chemical, heat to kill organisms. However, microorganisms will die based on the logarithmic relationship between the population or concentration of living cells and the radiation or exposure time. The relationship is either linear or non-linear. The D value is the only quantitative expression that indicates the rate at which microorganisms are killed. This value is affected by the type of microorganism, pH, surface and gas concentration, temperature or radiation dose, and formulation components. The Z and F values are applied in the validation of a heat sterilization process. The z-value allows calculation of effective time exposure, while the f-value measures equivalent time, but not click time. The non-sterile probability is also applied to identify sterile products free of microbial contamination.
The basic principle in the validation of sterile products is to be systematic in theoretical approaches. Theoretical approaches include written documentation, production parameters, test parameters, in-process controls and final product testing.
Sterile products are sterilized using the following methods: Heat, moist heat/steam or dry heat from a tunnel or oven, gas or ethylene oxide, peracetic acid, hydrogen peroxide (vapor phase), chlorine dioxide, radiation via gamma rays, beta, ultraviolet rays or microwave, light pure bright and filtration.
The five main steps are selection of desired product attributes, specification of preferred attributes, selection of appropriate equipment and processes, development and execution of tests that monitor and evaluate personnel, processes and equipment, and results analysis to determine their reliability and accuracy. in process validation in pharmaceutical manufacturing.