Scott Sutton, Ph.D.
A review article on Bioburden Contamination Control was recently published in the American Pharmaceutical Review. This review article, entitled Bioburden Contamination Control: A Holistic View (Amer Pharm Rev. Endotox Suppl July/Aug 2015 pp 20-24) offers a perspective on contamination control that has utility in understanding and teaching CGMP. It starts by describing areas that are of critical importance to bioburden control, including:
- Buildings and facilities
- Exclusion of microorganisms from areas of risk
- Sanitization of the areas of potential product risk
It is no coincidence that these are also major areas of CGMP (see 21 CFR 211). Perhaps of greater interest is how the topic of control itself is handled.
This review presents three main components to Contamination Control:
- Validation of Equipment/Processes/Facility (training/proficiency of personnel)
This component is critical to demonstrate that the facility, process, personnel, etc are suitable for the intended purpose and is the obvious first step. Until you have confidence in the basic mechanisms of your facility, there really is no point in being concerned about anything else.
- Control Activities
Control activities are active. For example, if you increase the frequency or extent of a sanitization program, you would expect to see a change in the bioburden makeup or numbers in the facility. If you change the design of the facility, you may increase or decrease its ability to exclude microorganisms from the aseptic core.
- Monitoring Activities
Monitoring activities do not have a direct effect on the bioburden measured. These monitoring activities are critical to the determination of the state of control of the facility or process, etc. However, they are not going to change those numbers or improve the state of control. For example, increasing the frequency of environmental monitoring sampling is not going to improve the bioburden levels in the facility, it will merely give you more data on those levels.
A critical consideration in bioburden control is the acquisition of solid data. Microbiological data is notoriously variable. Add to this the uncertainty associated with trying to extract information from measurements far in the noise range of the plate count assay and with these considerations, the question of how to handle and interpret environmental monitoring (EM) data becomes very challenging. This review article discusses methods to address the efficient extraction of information by trending the EM data and some different methods of trending that might be of use.
This article is recommended for those interested in Quality Control concerns in the regulated industries. This might include:
- Quality Assurance Professionals
- Regulatory Affairs Professionals