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Unlike many therapeutic antimicrobials (such as antibiotics), most biocides are provided in formulation with other ingredients as products. Formulation may be defined as the combination of ingredients, including active (biocides) and inert ingredients, into a product for its intended use (e.g., cosmetics, antiseptics, and disinfectants). Inert (or excipient) ingredients include water, nonaqueous solvents, emulsifiers, chelating agents, and corrosion inhibitors. The functions of these various ingredients are summarized in Table 1.26.

TABLE 1.25 Examples of standards and guidelines for antisepsis, disinfection and sterilization

Referencea	Title	Summary
Standards
ISO 14937	Sterilization of Healthcare Products—General Requirements for Characterization of a Sterilizing Agent and the Development, Validation and Routine Control of a Sterilization Process	Basic requirements for any sterilization process, including characterization of the sterilizing agent and validation of specific sterilization processes
ISO 11137-1	Sterilization of Healthcare Products—Requirements for the Development, Validation and Routine Control of a Sterilization Process for Medical Devices—Radiation—Part 1: Requirements	Requirements and tests for radiation sterilization processes, including radionucleotides, X rays, and electron beams
EN 285	Sterilization: Steam Sterilizers. Large sterilizers	Requirements and tests for large steam sterilizers primarily used in health care facilities
ISO 13408-1	Aseptic Processing of Healthcare Products. Part 1: General Requirements	Requirements and guidance for processes, programs, and procedures for the validation and control of aseptically processed health care products in cleanrooms and barrier isolator systems
Guidelines
FDA 21 CFR880.6885	Guidance on the Content and Format of Premarket Notification (510(k)) Submissions for Liquid Chemical Sterilants/High Level Disinfectants, and User Information and Training	Guidance on the requirements for the registration of a liquid chemical sterilant/high-level disinfectant with the FDA
HC-HPFBI (2001)	Process Validation: Moist Heat Sterilization for Pharmaceuticals	Guidelines for the steam sterilization of pharmaceutical dosage forms
TGO-TGA	Guidelines for the registration or listing of disinfectants and sterilants in Australia
EPA, DIS-TSS 01	Disinfectants for Use on Hard Surfaces	Efficacy data requirements for the registration of disinfectants for use on hard surfaces with the EPA (01 and associated guidelines)
EC Council Directive 98/8/EC	Biocidal Products Directive	Requirements for the use of biocidal products in the European Union, including disinfectant and preservative safety and efficacy
APIC	Guideline for Hand Washing and Hand Antisepsis in Health-Care Settings	Guidelines on the types and uses of various antiseptics in health care applications
WHO, 1999	Infection Control Guidelines for Transmissible Spongiform Encephalopathies	Guidelines for infection control practices against prion diseases, including decontamination

^aISO, International Standards Organization; EN, European Norm, from the CEN (European Committee for Standardization);APIC, Association for Professionals in Infection Control and Epidemiology (United States); EPA, U. S. Environmental Protection Agency; FDA, U. S. Food and Drug Administration, HC-HPFBI: Health Products and Food Branch Inspectorate of Health Canada; EC, European Commission;TGO-TGA, Therapeutic Goods Order-Therapeutic Goods Administration, Australia;WHO, World Health Organization.

The formulation of a biocide can be a complex task to ensure the optimization of antimicrobial efficacy, compatibility, required characteristics, and aesthetics of the final product. The first consideration is the choice of the biocide itself, which must have an optimal range of concentration, pH, temperature, solubility, stability, and spectrum of activity. It is also clear that the desired performance attributes of the product also need to be considered during its formulation (e.g., the effect of water quality if the product is diluted prior to use, compatibility with surfaces, and improved antimicrobial activity by synergy with other biocides or excipients). These considerations allow the choice of various formulation ingredients (Table 1.26). The basic components of many formulations are water and other solvents (such as alcohols); although many biocides and other excipients are soluble (ionic or hydrophilic) in water, many are insoluble (hydrophobic). Biocides are therefore often mixed with emulsifiers, including soaps and detergents, to increase their solubility or dispersion in a formulation. Emulsifiers form micelles, which are aggregated units of surface-active molecules (Fig. 1.26). Soaps are water-soluble salts or fatty acids, which are made by reactions of fats and/or oils with an alkali (e.g., sodium hydroxide). Detergents are mixtures of surfactants, which are defined as surface-active agents. Surfactant molecules act in low concentrations to change the properties of a liquid at its surface or interface with a surface. This increases the wettability of the liquid by breaking its surface tension, the force that holds the surface molecules together, and allowing it to spread over a surface better. Surfactants are further defined as nonionic (no charge), anionic (negatively charged), cationic (positively charged), and amphotheric (positively and negatively charged), and many possess antimicrobial activity (see section 3.16). Surfactants form micelles (Fig. 1.26), which are useful for the solubilization, dispersion, or emulsification of incompatible materials, as well as aiding in cleaning processes by the removal and dispersion of hydrophobic soils from a surface.

TABLE 1.26 Various constituents of formulated biocidal products

Ingredient	Purpose	Examples
Biocide	Antimicrobial or preservative activity	QACs, phenolics, biguanides
Solvent	A solvent is a substance (usually liquid) that is capable of dissolving other substances, with water being the most common. Solvents are used for dissolution and dilution of the biocide and other ingredients.	Deionized water, isopropanol, propylene glycol, urea
Emulsifiers, surfactants	Emulsifers are ingredients (including surfactants) that allow the formation of stable mixtures (emulsions) of water- and oil-soluble ingredients. Surfactants (“surface-acting agents”) can be used as emulsifiers. but also to reduce surface tension, improve wettability of a surface, disperse contaminants, and inhibit foam formation.	Sodium lauryl sulfate, potassium laurate, lecithin, nonionic and other surfactants (see section 3.16)
Thickeners	A substance used to increase the viscosity of a formulation	Polyethylene glycol; polysaccharides, like pectin, gums, and alginates
Chelating agents or sequestrants	Binding metals (like calcium and magnesium) and inhibiting their precipitation; water softening and prevention of mineral deposition	Ethylenediamine, EDTA, EGTA
Alkali or acid	pH stabilization. Alkalis are used as “builders” to optimize the activities of surfactants, including emulsification of soils. Acids are also used to prevent mineral deposition and for water softening.	Alkalis (NaOH, KOH, silicates); acids (acetic acid, citric acid, phosphoric acid)
Buffer	Maintaining pH over time and increasing alkalinity	Disodium phosphate
Corrosion inhibitors	Reducing the corrosion rates and protecting the surfaces of metals	Nitrates, phosphates, molybdates, ethanolamine
Others	Aesthetic qualities	Colors and fragrances

FIGURE 1.26 Basic structures of surfactants and soaps and micelles (a water-in-oil micelle is shown).

Other formulation ingredients, including thickeners, buffers, chelating agents, and fragrances, allow further optimization of the stability, efficacy, and compatibility of the product. Due to the variety of ingredients that can be present in a given formulation, the preservative and/or antimicrobial activity can vary considerably. For this reason, users should pay close attention to the instructions (or labeling) provided with the product for its intended use, including the shelf life, application, dilution (if required), contact time for antimicrobial efficacy, spectrum of activity, safety, and compatibility.