Disinfectant Rotation and the Frequency of Use of a Sporicidal Agent

Wendy Hollands - Contec, Inc.

History

Historically, the term rotation was applied to alternating the type of daily disinfectant selected. The thought was that microbes could adapt to one disinfectant chemistry and the disinfectant would no longer remain effective, similar to the development of microbial resistance to antibiotics. Two patterns selected were to 1) alternate high pH and low pH chemistries or 2) alternate disinfectants with different modes of action. However, the adaptation of microbes to disinfectants has not been supported by the literature.¹

USP states: “The development of microbial resistance to antibiotics is a well-described phenomenon. The development of microbial resistance to disinfectants is less likely to occur at significant levels, as disinfectants are more powerful biocidal agents than antibiotics. In addition, they are normally applied in high concentrations against low populations of microorganisms usually not growing actively, so the selective pressure for the development of resistance is less profound.²

PDA provides: “Concerns for the possible resistance of organisms to these products are based on a theoretical relationship to resistance found with antibiotics. To date, there is no conclusive published test data proving such development of resistance by organisms to these agents.”³

Current Use

Currently, the term “rotation” is commonly used to describe the alternating use of a daily intermediate disinfectant with a sporicide. USP <1072>defines a sporicide as: 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.²

It can be argued that the term “rotation” could be substituted with routine use of a validated broad-spectrum disinfectant and periodic use of a sporicide. Sporicides are required for the possible appearance of sporeformers, such as Bacillus sp., in environmental monitoring sampling. In addition to periodic use, a sporicide should be used when restoring a facility after an excursion or a shutdown.

Regulatory Expectations

FDA’s position on rotation also refers to establishing a frequency schedule. “Therefore, a sound disinfectant program also includes a sporicidal agent, used according to a written schedule and when environmental data suggest the presence of spore forming organisms.”⁴

While USP does not regulate manufacturers, FDA can point to its general chapter guidelines. “It is prudent to augment the daily use of a bactericidal disinfectant with weekly (or monthly) use of a sporicidal agent. The daily application of sporicidal agents is not generally favored because of their tendency to corrode equipment and because of the potential safety issues with chronic operator exposure.”²

PDA guidance on cleaning and disinfection states: “Based on this, the pharmaceutical and biotechnology industries have moved away from the rotation of two disinfecting agents. This formerly common practice led to high residue levels and subordinate efficacy performance. Today, most firms use a system whereby a disinfectant is rotated with a sporicide to more effectively reduce the bioburden levels. The rotation of a disinfectant with a sporicide is superior to the rotation of multiple disinfectants.”³

The current EU GMP draft revision of Annex 1 v12 states, “More than one type of disinfecting agent should be employed to ensure that where they have different modes of action their combined usage is effective against all bacteria and fungi. Disinfection should include the periodic use of a sporicidal agent.” This phrase is slightly misleading and there have been comments returned to the working group requesting the removal or clarification on the use of disinfectants with different modes of action.

There is general agreement that rotation should be based on the results of risk-based environmental monitoring for example a broad-spectrum disinfectant being used daily, with the periodic but regular use of a sporicide.⁵

Frequency of Sporicidal Use

Sporicides can be aggressive chemicals and can potentially cause corrosion of environmental surfaces with repeated use. It is good practice to follow sporicidal and broad-spectrum disinfectant use with a rinse once the appropriate contact time has been met. Rinsing not only removes residue but can also reduce rouging or corrosion in the long term due to reduced exposure.

A robust risk-based environmental monitoring program will provide the data needed for establishing the frequency of sporicidal use.⁶ If sporicides are used daily and environmental monitoring history does not show the presence of spores, a case can be made to reduce the frequency of use to weekly. An intermediate disinfectant can be substituted for daily use. Likewise, if sporicides are used weekly without a history of spore presence, a case can be made to use sporicides biweekly. A risk assessment should be performed in association with the review of the environmental monitoring data.³

Summary

Rotation previously applied to alternating the chemistry type of daily disinfectants used as part of a sanitization program. It now commonly applies to alternating a daily broad-spectrum disinfectant with a sporicide. Regulatory expectations are to base the frequency of sporicidal use on a risk-based environmental monitoring program and an overall risk assessment.

References

1. Sutton SVW. Disinfectant Rotation - A Microbiologist’s View. Controlled Environments Magazine, 2005; 8(7):9-14
2. USP <1072> “Disinfectants and Antiseptics”, US Pharmacopeia, Rockville, MD
3. PDA Technical Report No. 70 Fundamentals of Cleaning and Disinfection Programs for Aseptic Manufacturing Facilities, 2015
4. FDA Guidance for Industry Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice, September 2004
5. Draft Revision of Annex 1, Manufacture of Sterile Medicinal Products, v12
6. PDA Technical Report No. 13 (Revised) Fundamentals of an Environmental Monitoring Program, 2014

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