A view of the ongoing effort, means and challenges, detecting, identifying, and controlling bioburden in laboratories, pharmaceutical and medical device manufacturing, and the environment.

MICROBIAL MONITORING OF CONTROLLED ENVIRONMENTS and the medical products produced in those environments is often a regulatory requirement. [1-6] However, the environmental monitoring program is often established as a stand-alone program where only the numbers of organisms collected and enumerated determine whether environmental control is being maintained. For ISO Class 7-9 environments, [4,5] there is often little planning as to what data may be important for the products manufactured in those environments, and how to capture, trend, and evaluate critical data before product problems arise. In many cases, once a product problem occurs, the determination of root cause is hampered because important related objective evidence has not been captured even though data was collected. The pharmaceutical industry has progressed rather well in many of these areas, and serves as an exemplary example, particularly in aseptic manufacturing operations. The capture of related objective evidence by the burgeoning medical device companies isgenerally far behind their pharmaceutical counterparts.

21 CFR Part 820.70 states, “Where environmental conditions could reasonably be expected to have an adverse effect on product quality, the manufacturer shall establish and maintain procedures to adequately control these environmental conditions.” [1] The two phrases that must be addressed by manufacturers are “...could reasonably be expected...” and “...adequately control...” We recognize that without measurement there cannot be control. The reality is that if product problems never arise, one has collected more data than necessary, and if problems do arise, the documented data often provesinsufficient.

Manufacturing medical products aseptically or for terminal sterilization requires that one monitor and control microorganisms. However, these are not the only types of products where product bioburden and environmental control may be required. For instance, “...it is a cGMP requirement to exclude objectionable microorganisms from non-sterile pharmaceutical products.” [9]The microbes and how they may adversely affect product quality attributes will depend on the product, its intended or potential application, method of manufacture, and sterilization if applicable. If an organization manufactures multiple products in a single facility, each product may have different associated microbes with the potential to produce undesirable product results. Product bioburden may arise from numerous sources including: components, materials, personnel, processes, utilities (e.g. water and compressed air), or the facilities. Potential contaminants may involve hundreds or thousands of species most of which never become associated with product, or when they do, no quality attribute problems are created. How can a medical product manufacturer be responsibly proactive in preventing deleterious effects from these potential contaminants? Any program approach to this challenge should be systematic and must consider the value (cost/benefit) of start-up and long-term maintenance. The potential impact of these sources for contaminationcan be evaluated in the product risk assessment and the specific test programs can be modified based on the assessment of baseline test results. Capturing and trending data from the test programs will provide the means for proactive improvements in manufacturing operations, cleaning regimens, control limits,and test methods or programs.