News | May 7, 1999

Water Activity: Its Role in a Comprehensive Microbiological Quality Assurance Plan

Robert R. Friedel, Perritt Laboratories

In a world of ever increasing pressures and diminishing resources, the need to strengthen microbiological quality assurance programs in the pharmaceutical and cosmetic products arena has not abated. In fact, there is more pressure than ever on the management of microbiological quality. The evidence is quite clear: One only needs to review the FDA GMP Non-compliance documents (FD483s) or review FDA Warning Letters cited in regulatory newsletters (e.g., Dickinson's FDA Review).

The consequences of microbiological failures, particularly as they relate to product recalls, can be very costly to say the least. Brand recognition and sales may ultimately suffer as a result of consumers associating the recall with other products manufactured by the same company. Salvaging product that has been shown to contain excessive contamination or pathogenic microorganisms is usually not possible and the contaminated product is normally destroyed.

One must remember that the microbiological analysis of a finished consumer product is merely a "post mortem" examination of its contents. Once the contaminants are packaged in the finished product, the manufacturer is, for all intensive purposes, "at the mercy" of the microbiology lab's analytical results. The FDA has long recognized this problem and has continually endorsed the benefits of building quality into a particular product during the planning stages including: raw material/excipient selection, preservation system, formulation, equipment design, manufacturing steps, cleaning/sanitization, packaging, etc. To the microbiologist, these are the primary areas of consideration when designing, developing, and implementing effective control strategies.

Very few intrinsic antimicrobial factors are as important as water activity (aw) in predicting the survival of microorganisms in a consumer product. This new analytical technique has gained wide acceptance by food microbiologists worldwide and has been the subject of a recent publication concerning its application in the pharmaceutical industry as well1. (The author has also written a second article addressing the issue of water activity and raw materials. The latter has been accepted by the United States Pharmacopeia's Pharmacopeial Forum for publication2).

The principle surrounding water activity is fairly simple: microbes live in aqueous environments and require a specific amount of "free" water to survive and replicate. Water activity instrumentation allows the measurement of free water versus "bound" water. The microbiologist can then predict the types of contaminants which could survive and possibly proliferate in a particular material (i.e. pathogenic Gram-negative bacteria need high levels of free water in order to survive, whereas organisms such as yeasts and molds may require much less free water). The food industry literature provides a comprehensive list of specific groups, as well as types of organisms and their associated water activity values.

The primary purpose for conducting water activity analysis is to proactively evaluate specific materials or products as part of a comprehensive microbiological quality assurance plan. This approach allows the microbiology laboratory to reduce testing costs by concentrating on areas which require additional monitoring due to higher contamination risk. At the same time, reduced testing frequencies for materials which have little, if any, microbiological risk may be implemented.

References

  1. Friedel, R.R. and A.M. Cundell. "The Application of Water Activity Measurement to the Microbiological Attributes Testing of Nonsterile Over-the-Counter Drug Products", Pharmacopeial Forum, Vol. 24, No.2, pp. 6087–6090.
  2. Friedel, R.R. "The Application of Water Activity (aw) Measurement to the Microbiological Attributes Testing of Raw Materials Used in the Manufacture of Non-Sterile Pharmaceutical Products", Accepted for Publication—Pharmacopeial Forum, May/June, 1999.

Robert Friedel is Quality Assurance Manager, Laboratory Research & Analysis Groups, at Perritt Laboratories (Hightstown, NJ). Perritt is an FDA-registered, independent testing laboratory specializing in microbiological testing using both standard and custom assays.

For more information: Robert R. Friedel, Perritt Laboratories Inc., 145 South Main St., Hightstown, NJ 08520. Tel: 609-443-4848. Fax: 609-443-5293. Email: rfriedel@perrittlab.com.