Microbial Ecology of the Human Skin.

This review article on the skin microbiota was written in response to recent advances that transitioned from culture methods to PCR amplification and sequencing of bacterial and fungal genes as a result of the Human Microbiome Project. This transition enables the investigation of the full diversity of microorganisms inhabiting human skin. The skin provides a range of habitats with different microbiota associated with the three major regions of the skin, namely the moist axilla, perineum, and toe webs; oily or sebaceous head, neck, and trunk; and dry forearms and legs. These new culture-independent tools are revealing the diversity of the human skin microbiota in the different locations of the body and with skin depth. These tools should lead to a better understanding of the state of homeostasis between the microbiota and the host and the overall functionality of that microbiota.

Do Plant Isolates Have a Role in Method Suitability and Growth Promotion Testing in the Microbiology Laboratory? Is It a Matter of Science versus Compliance?

In response to regulatory citations for not including plant isolates in method suitability and growth promotion testing of microbiological culture media, the authors make the case that the compendial designated cultures meet the requirements of the official tests and are sufficiently representative of the most frequently identified environmental isolates. It was our conclusion that this compliance request lacks scientific justification. The scope of this review was largely directed to the growth promotion and suitability testing requirements for USP <60>, <61>, <62>, and <71>. Other microbiological tests such as USP <51> Antimicrobial Effective Testing, media fill validation, and water and environmental monitoring are discussed.

Microbial identification strategies in the pharmaceutical industry.

A commonly discussed question amongst pharmaceutical microbiologists, and the quality assurance organizations they serve, is what microbial isolates from the many microbial monitoring programs at a manufacturing facility need to be characterized, identified to genus, identified to species, or strain-typed? This article discusses the overall strategies that may be successfully applied to microbial identification in support of microbial monitoring of utilities, pharmaceutical ingredients, the manufacturing environment, and finished products. Emphasis in the article is given to the justification of the microbial identification program, selection of identification methods, and use of speciation in successful product failure investigations.

Managing the microbiological quality of pharmaceutical excipients.

The microbiological quality of the pharmaceutical excipients used to manufacture pharmaceutical and over-the-counter drug products may significantly affect the outcome of individual processing steps and the microbiological attributes of the final drug products. Unlike active pharmaceutical ingredients, excipients are purchased from multiple suppliers and in many cases are produced for the food, cosmetics, consumer products, photographic, and paint industries and not specifically for the pharmaceutical industry, so the management of their microbiological quality is less straight- forward. This article discusses the qualification of suppliers, excipient production methods, compendial standards, regulatory controls, and microbial limits testing of excipients. Emphasis is given to risk assessment associated with pharmaceutical excipients.

Justification for the use of aseptic filling for sterile injectable products.

This review article will provide general guidance to product development scientists for the justification for the use of aseptic filling for sterile injectable products in the place of terminal sterilization using moist heat. The discussion is centered on the position of U.S. and European regulatory agencies on aseptic processing versus terminal sterilization, and regulatory actions-that is, 483 observations, warning letters, and product recalls-associated with a lack of sterility assurance of aseptically filled injectable products. Also discussed are the sterility assurance levels achieved using terminal sterilization and aseptic processing, sterilization processes used for terminal sterilization, compatibility of different product, product packaging and delivery systems with terminal sterilization, physicochemical stability of product during a terminal sterilization process, and storage during the product shelf life. The author believes that a better understanding of the options surrounding terminal sterilization will result in fewer products being aseptically filled.

Bacterial endotoxin requirements for dry powder inhalants and their excipients: are they critical quality attributes?

This review article considers whether bacterial endotoxin levels are a critical quality attribute for dry powder inhalants and their major excipient Lactose, NF. Based on international no-effect levels for workplace endotoxin exposure, the technical literature, typical indoor and outdoor airborne endotoxin levels, and manufacturing capabilities for Lactose, NF and dry powder inhalation products, a strong case is presented that bacterial endotoxin is not a critical quality attribute and endotoxin specifications are not required for inhalation products and their excipients.

Equivalence of quality control strains of microorganisms used in the compendial microbiological tests: are national culture collection strains identical?

The pharmacopoeias list a number of microorganisms to be used in the compendial microbiological tests for confirming the growth-promoting, indicative, and inhibitory properties of the media and demonstrating the suitability of the test for a specific test article. Major national culture collections are specified as the sources for these test strains based on their history of deposition and maintenance and use in the compendial tests. Using these microorganisms, it has long been assumed that these strains are interchangeable and that sourcing the strains from different culture collections has no impact on the result of the media quality control and method qualification tests. In order to evaluate whether this assumption is correct and to add more certainty to the procedures, we investigated whether there are detectable differences among isolates of the same strain sourced from different culture collections. Using various phenotypic and genotypic identification and strain typing methods, nine major pharmacopoeial species were analyzed. As expected, most of the species showed very uniform patterns across the isolates, indicating that the strains were indeed identical. Surprisingly, the strains of Salmonella enterica subsp. enterica serotype abony showed distinct differences at both the genotypic and the phenotypic level, suggesting that the strains sourced from the different culture collections were not identical strains, or that they have undergone detectable genetic shift from the time they were derived from the original depositor. Irrespective of the level of genotypic or phenotypic homology identified here, there are no practical consequences on their performance in compendial assays. It is concluded that the compendial strains investigated in this study are indeed equivalent and will perform identically in compendial tests, making it safe to base pharmaceutical quality control procedures on the strains sourced from any of the recognized national culture collections.