Although the information in the guide is written for the cleanroom environment, many of the principles are applicable to

Manufacturers are being held to a high

standard when it comes to product sterility, and regulatory agencies are increasingly asking for validation data to support sanitization and disinfection procedures. Regulatory authorities now expect evidence of the efficacy of disinfection agents against environmental isolates.

The FDA Guideline for Aseptic Processing states, “the suitability, efficacy, and limitations of disinfecting agents and procedures should be assessed. The effectiveness of these disinfectants and procedures should be measured by their ability to ensure that potential contaminants are adequately removed from surfaces.”

Basic knowledge regarding the effectiveness of different chemical agents against vegetative bacteria, fungi, and spores will aid in selecting chemical agents.

A good understanding of test methods used to assess disinfectant effectiveness also is important. Most methods are adaptable allowing the user to customize the methods to their specific requirements.

Selection Procedure

In pharmaceutical, biotechnology, and associated industries, the selection of one sanitizer, one or two disinfectants, and one sporicide is typical. More than one type of chemical agent is needed to obtain the proper balance of effective microbial control and minimal surface damage because products vary in spectrum of activity and formulation. Currently, most facilities select one or two disinfecting agents to use on a routine basis and supplement with a sporicide, which is used on a less frequent routine basis to address spores that may not be destroyed by the routine disinfectant.

More than one type of chemical agent is needed to ob­tain the proper balance of effective mi­crobial control and minimal surface damage because products vary in spec­trum of activity and formulation. Cur­rently, most facilities select one or two disinfecting agents to use on a routine ba­sis and supplement with a sporicide, which is used on a less frequent routine basis to address spores that may not be destroyed by the routine disinfectant.

All three product types should be evalu­ated for effectiveness with appropriate test methods. Typical agents used in cleanrooms are:

Sanitizers: 70 percent v/v Isopropyl Alcohol (IPA); 70 percent v/v Ethanol.

Disinfectants: Phenols; Quaternary Ammonium Compounds; Hydrogen Peroxide, 3 percent Sodium; Hypochlorite < 0.10 percent 70 percent v/v; Isopropyl Alcohol (IPA) 70 percent v/v Ethanol.

Sporicides: Sodium Hypochlorite > 0.3 percent; Hydrogen Peroxide > 6 percent; Peracetic Acid Chlorine; Dioxide Vaporized Hydrogen Peroxide.

Sanitizers play a role in a cleanroom disinfection program. Isopropyl alcohol has good broad-spectrum efficacy, but in the manner which it is used routinely, minimal product contact time and flammability are of concern. Classifying 70 percent IPA as a decontamination or residue control agent is more appropriate, since it is often used dur­ing cleaning operations, as a sanitizer dur­ing manufacturing, and for removal of residues left from other antimicrobial agents.

It is important to choose a disinfectant that incorporates a surfactant in its formu­lation to help clean surfaces. Occasionally,

the choice will be made to rotate two dif­ferent disinfectants. These agents are de­signed for frequent use.

Sporicidal formulations typically contain highly reactive chemicals (for example, sodium hypochlorite or oxidizers) and may cause damage to surfaces, even stainless steel, if used too frequently. However, they are a necessity in the cleanroom since rou­tine disinfectants are not effective against bacterial endospores or resistant mold spores such as Aspergillus niger.

Typically, they are not used on a daily basis to avoid damage to substrates and re­duce the potential for irritation to cleaning personnel.

Critical Factors in Selecting Chemical Agents

One of the first steps in selection of a chemical agent is to collect all pertinent and available information from the potential supplier. This would include EPA registra­tion, technical data sheets, MSDS, recom­mended directions for use as well as data on substrate compatibility, stability, and mi­crobiocidal efficacy performed according to acceptable standards.

Cleanroom Bioburden: A review of environmental monitoring data is necessary to determine the number and types of mi­croorganisms to be controlled. Not all chemical agents are effective against all microorganisms and not all are sporicidal. Knowing the types of microbial flora in the area to be disinfected aids in selecting an appropriate disinfectant with the desired spectrum of activity. From this informa­tion, a facility can determine what efficacy is needed and identify potential product candidates.

Contact Time: For a disinfectant to be effective, a surface must remain wet for a defined period of time. The contact time may vary depending on the target microbial contamination, air temperature, as well as the type of surface being treated.

Preparation: Products can be purchased in concentrate form or a ready-to-use form. If a concentrated product is selected, dilu­tion will be necessary. The accuracy of preparation of a use-dilution is critical for optimal performance.

Regulatory standards require that disin fectants used in cleanrooms are sterile; therefore it may be necessary to purchase the agent sterile or sterilize it in-house. The kind of water available for dilution is also important. Water hardness or softness can interfere with the action of some disinfec­tants. It is recommended that purified water or better be used to dilute the concentrate.

Safety and Toxicity: The product MSDS should be reviewed to determine special storage and handling requirements and to identify any potential hazards to per­sonnel working with the agent. Appropriate regulations should be reviewed regarding disposal.

Compatibility: Some disinfectants are incompatible with others and can cause problematic residues. Performance of dis­infectants can be decreased if they are in­compatible with cleaning agents used in the area. Additionally, compatibility with surface types in the cleanroom should be evaluated. FSM

Source: ASTM E2614-08, Standard Guide for Evaluation of Cleanroom Disin­fectants. To download the full standard, go to www.astm.org/Standards/E2614.htm.