Microbial risks to pharmaceuticals
The risk to people from spoiled or otherwise adulterated pharmaceuticals has been appreciated for many centuries. However, it was only during the late nineteenth and the early twentieth centuries that the particular role played by microorganisms in this
process was understood. Even here, the steps taken to minimize the risk of contamination were relatively gradual, and these steps have progressed in tandem with increased knowledge. For example, it was not until the 1970s that cleanrooms, originally conceived for the development of nuclear weapons, became commonplace within pharmaceutical facilities in order to provide a clean air barrier to protect the product.
Microbial contamination and spoilage of pharmaceuticals will not only alter the
esthetic qualities of a product (color, smell, texture, and so forth); such contamination may also render the product dangerous to the user; or it may also nullify any intended therapeutic value of the product. Here the infection risk presented by pharmaceuticals varies according to the route of application of the product, the health status of the user and the nature of the contaminating microorganism (to take some of topics first raised in Chapter 2). Thus, those products which are injected directly into blood vessels or tissues (injections and infusions), and those that are applied directly to the eyes and ears (contact lens solutions, eye drops, etc.) represent a greater infection risk than
products that are taken orally or applied to intact healthy skin. The infection risks
from injected products and eye products are sufficiently great that all such products must be manufactured in such a way that they are completely free from all types of microorganism (i.e., they are classed as “sterile products”). In contrast, oral and topical products may contain a small number of certain types of microorganisms (excluding specific pathogens) . The assessment of pathogenic microorganisms is important for the risk assessment of nonsterile products, and, in general, monitoring microbial distribution and identifying the predominant isolates are part of good manufacturing practices . Those or ganisms assessed as dangerous to the patient must be assessed and specified. Although indicator organisms can be used, and it is sensible to include such organisms as a part of method qualification, the list of organisms must be based on what could actually present a risk to the product or process. For such analyses, phenotypic or genotypic microbial identification systems are required . In relation to the patient population, individuals who are immunodeficient, either through clinical disease or through use of immunosuppressive drugs are at a greater risk of infection than young healthy individuals. Damaged skin (burns, cuts, spots, etc.) is more easily infected than healthy intact skin, and special care must, therefore, be taken with products that might be applied to broken or burnt skin.
22.3 Microbial challenges to process environments
The environment where pharmaceuticals and healthcare products are prepared presents a potential vector for contamination (as Chapter 16 demonstrates). With envi-
ronment, examination of air for microbial content can be demonstrated by exposing dishes containing agar media directly to the air (settle plates) or through drawing in a fixed volume of air through a device that can capture a proportion of the microorganisms in the air-stream (volumetric air-samplers) . Microorganisms falling onto the surface of the agar or deposited upon it produce visible colonies on incubation.
It is not straightforward to generalize about the number of microorganisms present in air, since this varies markedly with location. Air samples taken from within occupied buildings will tend to have a greater bacterial content than those taken outdoors; how- ever, outside fungal cells predominate over bacteria. Typically, total microbial counts of air, taken from occupied rooms, vary between 10 and 104 microorganisms per liter. High values are likely to be associated with activities such as milling, hay-making, and so forth. In an uncontrolled laboratory environment, counts typically fall between 100 and 500 cells per liter. Numbers would be appreciably smaller for a cleanroom environment with adequate air filtration. This descending level of contamination tends
Types of spoilage, factors affecting the microbial spoilage of pharmaceutical products, sources and types of microbial contaminants, assessment of microbial
contamination and spoilage. Preservation of pharmaceutical products using antimicrobial agents, evaluation of microbial stability of formulations. Growth of animal cells in culture, general procedure for cell culture, Primary, established and transformed cell cultures. Application of cell cultures in pharmaceutical industry and research.