USP 797: Microcleaning and the controlled environment - Part 2


By Douglas Theobald, CFM

Cleaning solutions and their use

Probably the most critical element of the controlled environment along with the actual practices observed while manufacturing and packaging the product, in this case CSPs, is the need for a routine cleaning and disinfecting of the environment and its components, equipment, etc. The primary purpose of the cleaning solution is to disengage contamination, isolate it and allow it to be removed. As this is accomplished, the optimum goal is also to disinfect. It is recommended that, before sterilizing a surface, a gross cleaning be performed to remove soiling. Without a gross cleaning, the effect would be to inhibit the disinfecting action by causing the cleaning solution to address the gross contamination more and the surface that requires the sterilization less. A good dual-effect cleaner will also neutralize the contamination.

Cleaning solutions vary in type, usage and, to some degree, method of application. Since the USP is in the process of revising the information on cleaning agents and specific recommended practices of use, we will attack this issue from the broader common industry uses and available data on performance. Technology today allows for comprehensive understanding of a large variety of cleaning solutions such as germicides, disinfectants, sterilants and detergent-type cleaners. An integral part of selecting a cleaning agent is taking the time to review information about its performance and application. Review any available laboratory studies and, when possible, testing that is relative to the specific product being manufactured. In some cases, you may actually have the capability of performing tests yourself, in conjunction with an outside laboratory testing facility. As we work through the following information, be aware that it is derived from experience and the findings of others. I will make reference to studies and information and of course I will give credit where it is due.

Choose your weapon

Two common types of disinfectants are quarternary and phenolic. The first thing to note is that the two do not mix; they are insoluble and will leave a sticky and/or hazy residue. There are varieties of both and, in the case of planning a disinfectant rotation (addressed more in depth later), keep it in the family. A sterile quaternary disinfectant should be gamma irradiated so it can be validated to ensure sterility. NPD™ is an excellent one-step cleaner and disinfectant for pharmaceutical facilities, usable on most hard, nonporous surfaces such as glass, vinyl floors, stainless and galvanized steel, porcelain tile, washable painted surfaces, etc. It has great germicidal, virucidal and fungicidal properties. You can verify the efficacy by reviewing any tests performed by the “Use Dilution Method” as specified by the AOAC (Association of Official Analytical Chemists) “Methods of Analysis.” In some cases the test methods may have been modified to meet EPA standards as well.

Similarly a sterile phenolic disinfectant, such as LpHst or Vesphene IIst, is a sterile, gamma-irradiated, germicidal detergent made from a non­alkaline formula. This has proven to be a high-level disinfectant, which is good for use on hard, nonporous surfaces such as hoods, barriers and isolators. A cold sterilant sporicide is an excellent broad-spectrum disinfectant; however, it should not to be used on instruments that are introduced directly into the body or normally sterile areas of the body, mucous membranes or the bloodstream. In extremely stringent environments, there may be a need for cleanroom-grade bleach. In any case, when a sporicide is used, follow the disinfecting process directly with a wipe-down of IPA and DI or purified water to terminate the inherent oxidizing effect.

Regarding rotation

As is the case with any good research, you often find things that are best said in the original language. Although he is not convinced of the efficacy of the rotation regimen, Richard Prince, PhD, president of Richard Prince Associates (Short Hills, N.J.), writes: “While disinfectant rotation is an industry norm, the rotation of disinfectants and sporicidal agents is apparently not as widespread an industry norm. This is unfortunate since the rotation of these two types of chemical agents-one type (i.e., disinfectant) targeted for vegetative cells and the other type (i.e., sporicide) targeted for endospores-would effectively inactivate all types of bacterial and fungal organisms from hard surfaces if used properly and in accordance with label instructions. The sporicide would be expected to inactivate the endospore population and any resistant vegetative bacteria.”1

Elaine Kopis Sartain, director of technical service for STERIS Corp. and a proponent of rotation, states: “The mode of action which results in the inactivation of the adherent organisms through a rotational application has not yet been well-defined. However, speculation suggests extremes in pH, contributed by the use of compatible alkaline and acidic phenolic disinfectants, augmented the ability of these antimicrobial agents to penetrate the surface-adherent bacteria. This study represents the strongest evidence thus far supporting a rotational approach to hard surface disinfection.”2

And so the debate goes on. Although there have been new developments in the efficacy of disinfectants, there are still those who doubt the necessity. Review the data on any cleaning agent as it pertains to your specifics and make your own determination.

Methods of application

Following the dilution instructions for the selected disinfectant is always recommended. The use of deionized or purified water is typical in all applications. Again, although there is some controversy about whether to use a squirt bottle or spray, you can choose the tool. I prefer the squirt bottle as I am wary about the ability of a spray bottle to atomize consistently. When wiping a surface, always apply the solution to the wipe as described in my last article on microcleaning (see CleanRooms, June 2005). Use straight and overlapping stokes. Allow the surface to be saturated. The standard contact time for a disinfectant is 10 to 20 minutes. This applies to any surface regardless of the method of application. For floors, walls and ceilings, use a cleanroom-certified sponge mop (many are rated by classification). A two- or three-bucket system is best, as this allows for a minimum of one rinse bucket to prevent reapplication of contaminants onto the cleaned surfaces. Again, observe the contact time.

In some cases there may be a need to address contamination in a facility by way of “fogging.” Based on the disinfectant and the fogging apparatus, follow the dilution instructions. Whenever fogging is performed, the procedure should be followed by a full clean with a solution of IPA and DI or purified water.

Update time

Next time, we’ll discuss the progress that’s been made on the latest revisions to USP 797 and how it more specifically defines the way in which sterile compounding should be performed.

Douglas Theobald is a consultant and general manager with Controlled Contamination Services LLC (San Clemente, Calif.). He can be reached at


  1. Prince, Richard. “Disinfectant rotation practices revolve around two schools of thought,” CleanRooms, January 1998.
  2. Kopis, Elaine. “Rotation of disinfectants to combat microbial resistance,” CleanRooms, October 1996.