The US Pharmacopeia (USP) lists methodologies, standards, and requirements for microbiological tests used in assessing the quality of pharmaceutical
and biotechnological products. These requirements are enforceable by the US Food and Drug Administration in compliance investigations.
USP does not provide clear suggestions on how to perform these tests, however.
The first edition of Microbial Limit and Bioburden Tests provided a much-needed manual with practical instructions for carrying out the USP tests. Author Lucia Clontz described the compendial tests in a format familiar to practicing microbiologists.
Microbial Limit and Bioburden Tests: Validation Approaches and Global Requirements, second edition, Lucia Clontz, CRC Press,
Boca Raton, FL, 2008, 280 pp., ISBN: 13-978-1-4200-5348-7.
The second edition of the book reflects the advances that have occured during the past several years, including the results
of the efforts undertaken by USP, the European Pharmacopoeia, and the Japanese Pharmacopoeia to harmonize microbiological
requirements and testing. The collaboration has provided industrial and regulatory microbiologists with uniform tests and
reduced their workload.
Each of the chapters from the first edition has been brought up to date to conform to the new requirements, which include
the modification of various testing procedures. For example, Salmonella is now tested using a different media than before. Also, the amount of sample needed for microbiological testing was changed
from 10 g to 1 gm, with the exception of Salmonella testing. The harmonized text also includes a special exception for products that are only available in exceptionally small
quantities and that are expensive, especially for biotechnological products.
New chapters have also been added to the book. The chapter titled "Biofilms" covers the pharmaceutical and biotechnological
production equipment and materials susceptible to biofilm formation. The author provides practical advice for controlling
and preventing the formation of biofilms by various means. One shortcoming, though, is the chapter's section on the qualification
of chemical sanitization using biofilm cells, which would be more appropriate for a research environment than for a quality-control
A chapter titled "Pharmaceutical Waters" provides a complete protocol for microbiological testing. The author deals in detail
with sampling programs and sample collection and preservation. The section about recovery media is particularly well written.
The chapter also discusses topics such as endotoxins testing of waters and the establishment of alert and action levels for
microbiological bioburden and endotoxin levels.
Illustrations and simple diagrams are provided throughout the text to help microbiologists perform each test and procedure.
In addition, separate sections provide advice about interpreting and validating each test. The procedures, interpretation
of results, and validation guidelines follow the requirements in USP monographs, general chapters, and information chapters.
Several organizations market rapid methods for microbiological testing such as the identification of isolated microorganisms
and the determination of microbial bioburden. Younger microbiologists often specialize in these rapid methods because they
are automated and quicker than classical methods, which are labor-intensive and require days of incubation.