While not all organisms are harmful, minimizing viable contaminants is generally desirable. Such contamination may include bacteria, fungi, algae, protozoa, and viruses. Some viables that may be present in the manufacturing environment can cause infectious disease and/or produce toxins. Minimizing viable contaminants in medical applications is a given as they can also impact metal-working fluids, process baths, and a host of other products. As medical devices and pharmaceutical products change and become more complex, assuring that a manufacturing process controls viable and non-viable contamination is essential to a successful terminalsterilization process and maintenance of sterility assurance.
VIABLE CONTAMINATION SOURCES
Contamination can result from personnel-, environmental-, and process-related activities (Figure 1). Viable contamination is more complex than particulate contamination in that a colony-forming unit (CFU) may originate from a single micro-organism or from a cluster. Also, a particle may contain one or manypotential sources of microbial contamination.
For critical applications, current sterility and bioburden test protocols are capable of detecting most forms of bacteria and fungi, including the presence of the most resistant microbes (Bacillus spores, Mycobacteria, and fungi), that is, microbes that are resistant to the terminal sterilization process.
Figure 1: Potential Sources of Viable and
Non-viableContamination
STANDARDS AND GUIDANCE
Industry has developed a number of standards, such as ISO, EU, and PDA (Parenteral Drug Association), and methods to assist manufacturers in establishing specificationsfor the cleanroom including the level of acceptable viable contamination.
Here are examples of relatively recent U.S. and international standards and guidance documents. They replace and expand the now-retired Federal Standard 209. Many are useful in establishing protocols to control and minimize viable contamination.
ISO 14644 1-9 provide guidance for classifying controlled environments for particles (0.1 to 5 µm). While not used to determine the nature of viable particles, they can be coordinated with other standards.
ISO 14698-1 establishes basic methods for monitoring and controlling viable airborne, surface, textile, and liquid bio-contamination.
ISO 14698-2 provides guidance on evaluation of microbiological data, monitoring and record keeping, and liquid biocontamination.
ISO 14698-3 is expected to provide guidance in bioconta-mination control, including methodology for measuring the efficiency of cleaning and/or disinfection processes of inert surfaces bearing biocontaminated wet soiling or biofilms. The 1997 Revision of the Annex to the EU Guide to Good Manufacturing Practice – Manufacture of Sterile Medicinal Products classifies devices, products relative to end use requirements and for each class indicates appropriate levels of airborne, surface (floor), and personnel glove viables. U.S. USP 116 provides other classifications of product and viablecontamination limits.
OPTIMAL MONITORING AND CONTROL
Understanding the sources of contamination will enable the proper monitoring program as well as alert and action limits to be established. While it is not always feasible to set limits on viable contamination early on, it is far preferable that alert and action limits be established during the validation process. The new guidance offers valuable information that will provide the manufacturer with a systematic approach to validating a cleanroom environment that will emphasize control of the viable contaminants and allow for the appropriate level of cleanliness (non-viable and viable contamination) tobe consistently maintained.
Barbara Kanegsberg and Ed Kanegsberg are independent consultants in critical and precision cleaning,surface preparation,and contamination control.They are the editors of Handbook for Critical Cleaning,CRC Press.Contact them at BFK Solutions LLC., 310-459-3614;[email protected];www.bfksolutions.com.
John J. Broad, SM, (NRM) is a Senior Consultant for NAMSA Advisory Services,and a registered microbiologist with the American Society for Microbiology (ASM).He can be reached at (949) 699-6212; [email protected].
