Scott Sutton, PhD, was a well-respected and influential thought leader in the microbiology industry. He was a consultant and trainer in CGMP, investigations, environmental monitoring, and contamination control for pharmaceutical companies for over 30 years. He gave many presentations on these topics, and received multiple awards for his publications in microbiology journals and industry trade publications. For the past 22 years, Dr. Sutton served on the United States Pharmacopeia committee on Microbiology, serving as Vice-Chair from 2000 through 2010.
Dr. Sutton passed away on October 19, 2015. Shortly before his passing, Dr. Sutton published an article regarding the process of controlling bioburden contamination in a manufacturing facility. In memory of this great contributor to the microbiological and pharmaceutical industries, we have highlighted a few key points from this recent article. To read the full article by Dr. Sutton, please click here.
Bioburden contamination is an aspect of product manufacturing that must be considered for all medical devices and pharmaceuticals. Processes to attempt to control the contamination through validations and monitoring in each phase of production should be in place to ensure the bioburden contamination remain at an appropriate level. Maintaining control of the bioburden is far too complex for a single individual or even department to accomplish by themselves, so training and adherence to these processes is vital in ensuring any bioburden contamination stays at a manageable level.
Building Design & Control: Bioburden control in a facility should optimally begin with the design and construction of the building. Areas in a facility that are able to be tightly controlled should be surrounded by areas that are not as easily controlled. An important part of this design is the placement of air filters to ensure the pressure differential between areas allows the aseptic air to be pushed out. An argument can be made that the placement of filters in a terminal location allows for better air cleanliness, however, the ease of monitoring and maintenance should also be considered when placing filters. Facilities should also be designed to prevent personnel and materials from using the same paths to minimize cross-contamination. This type of building design works best when airlocks and pass-through chambers are put in place, as they help maintain bioburden barriers.
Water Systems: The water system of a facility also contributes to the control of bioburden contamination in a building. The properties of water make it an easy avenue for microbial contamination. Because water is often used as a raw material and a utility, frequent maintenance and monitoring are necessary to contain the bioburden resulting from the use of water. The last design element Dr. Sutton discusses is the location of the product when it will be at its most vulnerable point in the manufacturing process. Protection of the environment around the product at this point by an isolator or other environmental controls aids in maintaining control of the bioburden.
Equipment: Once the design of the facility is in place, the next factor to analyze is the equipment being used. In addition to the tasks the equipment is required to perform, the ability to clean and sanitize the equipment should also be considered. Choosing equipment and placing it in locations that allow for easy cleaning and sanitation aids in the exclusion of microorganisms from coming in contact with the product. Fill lines and equipment should also be organized in a way that will not allow for mix-ups or cross contamination between filled products and raw materials. One way to minimize contamination is to eliminate the human factor, and utilize equipment to fill the product.
Cleaning Processes: The sporicides and sanitizers that are used in bioburden control processes need to be tested to show their efficacy against the microorganisms in a facility; generally, this is a four-step process. The first step is a suspension test. This test analyzes the effectiveness of a sanitizer against indicator organisms as well as other organisms found in a facility. This test aids in selecting the best sanitizer for your product and also determines the most resistant microorganism. The second step is a coupon study, performed on materials present in the facility. This study evaluates the effectiveness of the chosen sanitizer against the organisms found in the suspension test. The third step is a “mock” sanitation study to provide real-world analysis of the effectiveness of the sanitizer. The last step of testing the sanitizer is ongoing environmental monitoring. This is usually done by the annual trending of the environmental monitoring to show the bioburden is being adequately controlled.
Personnel: The main source of bioburden contamination during manufacturing process comes from the personnel involved. It is estimated that an individual at complete rest sheds about 10,000 particles per cubic meter. Any movement or activity increases this number exponentially. Because of this, it is important to be careful in selecting gown material and also gowning methods. Simulated trainings, proficiency testing, and monitoring of the operators and their involvement in the manufacturing process are vital to make sure human contamination of the product is limited. Use automation in manufacturing to avoid the chance of mix-ups causing cross-contamination and limit the need for human intervention. To assist in monitoring the bioburden in these processes, bioburden testing should be performed on all material coming into a facility, and checked against existing bioburden acceptance criteria prior to use.
Process Monitoring: Monitoring activities and processes to control bioburden are indirect, so it is important to partner with a reputable testing facility that is knowledgeable on current industry standards in creating and carrying out these procedures. USP has recently released a chapter to help break down laboratory operations into a series of systems, that when paired with other USP chapters are useful in determining the best practices for a facility.
Thank you, Dr. Scott Sutton, for your contribution to the microbiology community.
Need Additional Guidance? Nelson Labs employs many scientists who actively participate in the creation and modification of industry standards who can help interpret the standards and apply them to specific products and facilities.