**1. Introduction**

Bacteria, fungi (yeasts and molds), mycobacteria, prions, protozoa, and viruses are common pathogens infecting humans and animals. They typically exist within the host or in the environment. It has been observed that these microorganisms exhibit a notable difference in the natural survivability in the environment, as well as susceptibility to chemical and physical inactivation. For example, under ambient and dried conditions, human coronaviruses seem to lose their infectivity in a matter of several hours to several days [1], whereas endospores and prions may remain infectious for years to decades or even indefinitely [2, 3].

As more and more data have become available regarding the survivability and susceptibility of pathogens to microbicides, it has been observed that the pathogens seem to demonstrate an order of susceptibility to chemical and physical inactivation. E. H. Spaulding first proposed a classification system for the sterilization and disinfection of medical instruments based on the infection risk in 1939 [4]. On the basis of this classification, the concept of a hierarchy of pathogen susceptibility was proposed, in which microorganisms are placed into several groups and ranked from least susceptible to most susceptible. In this hierarchy concept, bacterial spores were ranked the least susceptible, followed by mycobacteria, non-enveloped viruses, fungi, vegetative bacteria, and enveloped viruses. The susceptibility hierarchy was also believed to be related to the biochemical and biophysical characteristics of a pathogen [5, 6].

This hierarchy concept has been slightly modified and expanded over the years. For example, prions were added and considered less susceptible to inactivation by microbicides than bacterial spores; small non-enveloped viruses were considered less susceptible than large non-enveloped viruses; and the order between mycobacteria and small non-enveloped viruses was sometimes reversed (**Figure 1**) [7–10]. Additionally, it has been suggested that the hierarchy concept may be applied either "vertically" (i.e., ranking of susceptibility *between* classes of pathogens) and/or "horizontally" (i.e., ranking of susceptibility *within* a class of pathogens) [11].

The hierarchy concept has been quite useful for enabling scientists to better understand the innate difference among various types of pathogens. In the case of newly emerged pathogens, especially, the hierarchy concept has helped stakeholders design and implement a disinfection strategy swiftly with a reasonable level of confidence. The concept also helps the contaminant control for food, pharmaceutical, and biopharmaceutical products, as it is impractical to test every possible contaminating pathogen, and a robust infectivity assay system may be lacking for certain pathogens (e.g., hepatitis E virus).

Despite its usefulness, the hierarchy concept should be interpreted with caution, as it may oversimply the differences and trending of pathogen susceptibilities. Further examination and refinement of the concept may be necessary; and several important questions should be answered. For example, how often do exceptions to the hierarchy occur and what are the underlying reasons? Could a trending be specific to a given type of chemistry? Is the hierarchy the same between susceptibility to both chemical and physical inactivation? Why do pathogens in the same

#### **Figure 1.**

*Proposed hierarchy of susceptibility of pathogens to microbicides. Note: slightly different versions of the hierarchy concept have been proposed in the literature. Mycobacteria have been placed above small non-enveloped viruses, and molds have been placed above large non-enveloped viruses in certain versions. In some versions, the small and large non-enveloped viruses are combined; and yeasts and molds may be combined.*

*Variability and Relative Order of Susceptibility of Non-Enveloped Viruses to Chemical… DOI: http://dx.doi.org/10.5772/intechopen.102727*

group, or even the same family or genus, sometimes exhibit striking differences in susceptibility? Is there a way to identify and separate reliable/consistent trending versus blurred/variable trending? A deeper look at the efficacy data for various types of microbicidal actives, especially for non-enveloped viruses, may help stakeholders understand the scope, reliability, and limitation of the hierarchy concept so that it can be best utilized.

This chapter reviews the inactivation efficacy data from the literature against non-enveloped viruses for several commonly used types of chemistries, either in formulated or unformulated form, in an effort to generate a separate relative order of susceptibility among these non-enveloped viruses for each type of chemistry and to differentiate consistent versus variable trending. Physical inactivation approaches are not covered in this chapter, although a significant degree of variation also exists for physical treatments. It is not clear that the physical inactivation approaches, in general, are governed by the same hierarchy to susceptibility as is observed for chemical inactivation approaches [12].
