Considerations for Choosing a Cleanroom Disinfectant

To ensure the quality of the products they produce, pharmaceutical, biopharmaceutical and medical device manufactures must disinfect as well as clean the cleanrooms in which their products are made. The choice of disinfectant¹ and the frequency of disinfectant rotation, which includes a sporicidal¹ agent, are based on an Environmental Monitoring Program and Quality Risk Assessment (QRM) at each manufacturing site. It is essential that disinfection selection be based on Environmental Monitoring results

Considerations When Choosing an Anti-Microbial Agent

The efficacy of the disinfectant or sporicidal agents against the microorganisms present in the facility as determined by the Environmental Monitoring Program.

Contact times required to kill the microorganisms. The shorter the contact time, the greater the chance for compliance. If a long contact time is required, the surface must be re-wetted, leading to increased chemical costs. Contact times under 5 minutes are ideal, as they do not usually require re-wetting of the surface.

One step cleaning and disinfecting. The EPA states: ”An antimicrobial agent identified as a “one-step” cleaner-disinfectant, cleaner-sanitizer, or one intended to be effective in the presence of organic soil must be tested for efficacy by the appropriate method(s) which have been modified to include a representative organic soil such as 5% blood serum.”³  Some commonly used sporicidal agents such as sodium hypochlorite (bleach) and some hydrogen peroxide/peracetic acid blends are effective only on pre-cleaned surfaces. Pre-cleaning adds both chemical costs and labor costs to the disinfecting process and downtime to the facility.

Material compatibility. Stainless steel compatibility is an issue in many life science cleanrooms. Most of the processing equipment is stainless steel. If corrosive products such as sodium hypochlorite (bleach) are used frequently, pitting can occur. The pits can harbor bacteria and other harmful microorganisms, leading to product contamination, costly replacements and possible FDA citation.

Residue. Both viable and non-viable particles must be controlled in cleanrooms. Antimicrobial agents which leave residues can contribute to potential product contamination. Also, harmful residues such as chlorine ions can cause stainless steel corrosion.

Ready-to-use or concentrate. Ready-to-use disinfectant products eliminate hazards associated with handling and pouring highly acidic and caustic solutions, eliminate the potential for improper blending and the cost of quality control, and eliminate the labor cost of blending and handling solutions. These risks and costs should be weighed against the possibly higher with higher chemical costs of the ready-to-use solution.

Phenols, quaternary amines, alcohol, and hydrogen peroxide are some of the active ingredients found in disinfectants. Sodium hypochlorite and hydrogen peroxide/peracetic acid blends are typically used as sporicidal agents. A good overview of the various chemistries used in disinfectants and sporicidal agents can be found in an article by Strickland.²

The EPA and Labeling

All disinfectants and sporicidal agents sold in the US must be registered with the EPA (US Environmental Protection Agency). EPA approved labels include valuable information such as the EPA registered microbial claims and contact times, directions for use, hazards, precautions, and storage and disposal. Here you will also find the conditions under which the product was tested (for example with a 5% serum load at a certain temperature) and if pre-cleaning is required. It is a violation of US federal law to use a disinfectant in a manner other than in the way it is stated on the label. Please consult with your local authorities for requirements for disinfectant labeling and registration in countries other than the US.

Steps for Successful Disinfection

The steps to ensure successful disinfection after a disinfectant or sporicidal agent is validated for use in the facility include: 

1. Always follow label directions and site SOPs.
2. Don appropriate personal protection equipment (PPE).
3. Pre-clean the surface if required. The use of proper wiping techniques is critical to ensure successful disinfection.
4. Apply the disinfectant or sporicidal agent by spraying, wiping or mopping, making sure the entire surface is covered.
5. Leave disinfectant or sporicidal agent on the surface until its wet contact time is achieved.
6. Remove residue with approved residue removal agent, if necessary. It is important to always be cognizant of residues as they build up overtime. In some instances, a residue removal step can be immediate or done on a periodic basis. Residues are most commonly rinsed with 70% Isopropyl Alcohol, Water for Injection, Hydrogen Peroxide, and/or a detergent.  

Consistent environmental monitoring results are the goal of a disinfectant program. Validating the disinfectant or sporicidal agent is the first step for successful bioburden control. Following the label directions and site SOPs, applying the solutions properly and adhering to required contact times are all important factors to ensure compliance. 

Contec's Technical Services Group offers several options for Contamination Control Assessments for contamination control guidance for all cleanroom areas.

Article was written by Kathy Miscioscio.

References:

¹USP <1072> “Disinfectants and Antiseptics”, US Pharmacopeia, Rockville, MD
²Lisa Strickland, Microorganism Contaminants – Unique, Insidious and Dangerous^©, CleanRooms magazine, June 2008.
³EPA DIS/TSS-2 Jan 25, 1979, Efficacy Data Requirements, Supplemental Recommendations

Disinfectant - A chemical or physical agent that destroys or removes vegetative forms of harmful microorganisms when applied to a surface.
Sporicidal Agent - An agent that destroys bacterial and fungal spores when used in sufficient concentration for a specified contact time. It is expected to kill all vegetative microorganisms.