USP-NF 1072 Disinfectants and Antiseptics

The standard "USP-NF 1072 Disinfectants and Antiseptics," published by the United States Pharmacopeia (USP), addresses requirements for the selection of appropriate chemical disinfectants and antiseptics, the demonstration of bactericidal, fungicidal, and sporicidal activity, the application of disinfectants in sterile pharmaceutical production areas, and regulatory and safety issues. Biofilm formation and its relationship with disinfectants are outside the scope of this standard.

Controlled environments used in the production of pharmacopoeial products require a robust cleaning and disinfection program to prevent microbial contamination of these products. Sterile drug products can be contaminated through pharmaceutical ingredients, process water, packaging components, the production environment, processing equipment, and production operators. Current good manufacturing practices emphasize the size, design, construction, and location of buildings and construction materials, and appropriate material flow to facilitate cleaning, maintenance, and proper operations for the production of drug products.

When disinfectants are used in a manufacturing environment, care must be taken to prevent contamination of the drug product with chemical disinfectants due to the inherent toxicity of the disinfectants. Aseptic processing requirements include easily cleaned floors, walls, and ceilings with smooth, non-porous surfaces, particle, temperature, and humidity controls, and cleaning and disinfection procedures to produce and maintain aseptic conditions.

The cleaning and disinfection program must meet specified cleanliness standards, control microbial contamination of products, and be designed to prevent chemical contamination of pharmaceutical ingredients, product-contact surfaces or equipment, packaging materials, and ultimately, drug products. These principles also apply to non-sterile dosage forms, where microbial contamination is controlled by selecting appropriate pharmaceutical ingredients, excipients, manufacturing environments, robust equipment cleaning procedures, products specifically formulated to control water activity, the inclusion of appropriate preservatives, and product packaging design.

In addition to disinfectants, antiseptics are used to decontaminate human skin and exposed tissue and can be used by personnel before entering the production area. Chemical sterilizers can be used to decontaminate surfaces in production and sterility testing areas. Additionally, sterilizers can be used to sterilize pharmacopeial substances, and UV irradiation can be used as a surface disinfectant.

For the purposes of this standard, the following terms and definitions apply:

• An antiseptic is a substance that inhibits or destroys microorganisms in living tissues, including the skin, oral cavities, and open wounds.
• A chemical disinfectant is a chemical substance used on inanimate surfaces and objects to destroy infectious fungi, viruses, and bacteria (but not necessarily their spores). Sporicidal and antiviral agents can be considered a special class of disinfectants. Disinfectants are generally categorized by medical groups as high-level, intermediate-level, and low-level based on their effectiveness against various microorganisms.
• A cleaning agent is a substance used to remove product residues that may render disinfectant agents ineffective or harbor microorganisms from facility and equipment surfaces.
• Decontamination is the removal of microorganisms through disinfection or sterilization.
• A disinfectant is a chemical or physical substance that, when applied to a surface, destroys or removes vegetative forms of harmful microorganisms.
• A sporicidal agent is an agent that, when used in sufficient concentration for a specified contact time, destroys bacterial and fungal spores. It is expected to kill all vegetative microorganisms.
• A sterilant is an agent that destroys all forms of microbial life, including fungi, viruses, and all bacterial forms and spores. Sterilants are liquid or vapor-phase agents. Microorganisms vary widely in their resistance to disinfectant agents. The order of resistance of clinically important microorganisms to chemical disinfectants is listed in the table, from most to least resistant.

Chemical disinfectants are classified by chemical type, including aldehydes, alcohols, halogens, peroxides, quaternary ammonium compounds, and phenolic compounds.

The effectiveness of a disinfectant depends on its intrinsic biocidal activity, the concentration of the disinfectant, the contact time, the nature of the surface being disinfected, the hardness of the water used to dilute the disinfectant, the amount of organic matter present on the surface and the type and number of microorganisms present.

The Environmental Protection Agency (EPA) registers chemical disinfectants marketed in the United States and requires manufacturers to provide product information regarding use dilution, type of microorganisms killed, and required contact time. Specific liquid chemical sterilizers intended for use in critical or semi-critical medical devices are defined and regulated by the U.S. Food and Drug Administration (FDA).

In the hospital setting, hands and surgical sites are disinfected to reduce resident flora and to remove transient flora (e.g., Streptococcus pyogenes) and methicillin-resistant S. aureus and P. aeruginosa, which are implicated in hospital-associated infections. The use of antiseptics to disinfect hands has been shown to be more effective than soap and water in reducing bacterial counts on skin. Repeated use of antiseptics further reduces these counts. These principles can be applied to cleanroom operators in the pharmaceutical industry.

When selecting a disinfectant for use in a pharmaceutical manufacturing area, the following points should be considered:

• Number and types of microorganisms to be controlled
• Activity spectrum of commercially available disinfectants
• Claims as a sterilizer
• Disinfectant or disinfectant supported by EPA registrations
• Concentration of disinfectant, application method and contact time
• The nature of the surface material being disinfected and its compatibility with the disinfectant
• The amount of organic compounds on the surface that can render the disinfectant ineffective
• Possibility of maintaining residual bactericidal activity of the disinfectant on the surface
• Corrosiveness of disinfectant to equipment upon repeated application
• Safety considerations for operators applying the disinfectant
• Compatibility of the disinfectant with cleaning agents and other disinfectants;
• Planned disinfectant rotation
• Steps to take to prevent disinfectant from contaminating pharmaceutical products

Our organization, which has been supporting businesses across all sectors for years through a wide range of testing, measurement, analysis, and evaluation activities, has a strong team of employees who closely follow global developments in science and technology and are constantly improving themselves. In this context, we also provide testing services to businesses in accordance with the "USP-NF 1072 Disinfectants and Antiseptics" standard.