Risk assessment in development of technical requirements for designing fermentation equipment in accordance with requirements of good manufacturing practice

Abstract

The object of research is the risks arising at the stage of cultivation of biological agents in fermentation equipment. The starting point of the life cycle of equipment, including fermenters, is the terms of reference, which defines all the necessary requirements that must be taken into account in the design, manufacture, installation and qualification. One of the most important and important stages of the equipment life cycle is the formation of a holistic and complete technical specification, which would allow taking into account all critical process parameters already at the stage of developing the design of the fermenter in accordance with the requirements of good manufacturing practice. It is important to note that the regulatory documents of the pharmaceutical industry (good manufacturing practices, good engineering practices, etc.) do not form specific requirements for equipment and processes, but only define general approaches to ensuring the quality system. The study used the principles of risk management, which are advisable to use throughout the entire life cycle of the equipment. The analysis of the stages of sanitary preparation (washing, disinfection and rinsing), sterilization of the fermenter and the cultivation process made it possible to determine the risks arising at the corresponding stages of production and ways to solve them. The approach to the analysis of critical parameters proposed in this work can be used to improve the development of technical specifications for a fermenter. Thanks to this, at the initial stages, a comprehensive approach to risk management is provided, which in turn will prevent the negative impact of external factors on the final product. Another aspect of using the research results is the possibility of forming fermenter validation protocols. The results obtained in this work can also be used in the development and scaling of the cultivation process for the production of active pharmaceutical ingredients in biopharmaceutical production.