The role of microbiology in the design and development of pharmaceutical manufacturing processes

Abstract

The role of microbiologists in pharmaceutical development and manufacturing has become more visible in recent years due to the QbD and risk-based approaches promoted by regulatory authorities and industry [1]. Microbiology, microbiological control and contamination control are indispensable in the manufacture of sterile and nonsterile products as well as biologic drug substances, as evidenced by multiple conference presentations and publications. Terms such as objectionable microorganisms, organisms of concern, alert and action limits, environmental monitoring and sterility are dominating our daily work. Lack of sterility assurance is the number one reason for recalls of sterile drug products, and presence of objectionable organisms is the number one reason for recalls of nonsterile products [2,3]. While no one disputes the role of microbiologists in the design and development of pharmaceutical manufacturing processes, microbiologists still appear ‘confined’ in the laboratory of the manufacturing facility long after a process has been established and approved. They are not visible as equal partners in the development process along with chemists and pharmacists. However, microbiology issues frequently arise and critical decisions must be made. The science of microbiology and its applications have a large impact on microbiological and contamination-control strategies for robust and consistent processes with infrequent failures and contaminations. End-product testing is no longer considered acceptable for assuring product quality. Back to the basics When expectations and practices seem to drift away from science and reach scientifically unjustifiable terrain, we need to go ‘back to the basics’ and the science of applied microbiology. This is even more necessary when regulatory expectations impose scientifically insupportable requirements and expectations. Training and mentoring microbiologists in the basic principles of microbiology is critical. Microorganisms do not visit facilities out of nowhere; there is a source associated with their origin and introduction into a facility and manufacturing process. Once introduced, favorable conditions are required for a microorganism’s growth. Such conditions must be evaluated to understand whether this microorganism could represent a hazard to the product and patient. Microbiological control centers primarily on preventing the introduction of microorganisms into a manufacturing process. If introduction cannot prevented, then control is achieved by destruction, removal, inhibition of microorganisms, or a combination of these approaches. Drug product sterility is based on destruction or removal of microorganisms and is indicated for products that bypass the human body’s natural defenses (e.g., parenteral administration). In the case of nonsterile products, APIs, excipients and biologic drug substances, small amounts of microorganisms are acceptable provided that they do not replicate in the final material during storage and provided that these microorganisms are not pathogenic and do not create other objectionable conditions. Nonsterile drug Pharmaceutical Commentary