Disinfectant rotation practices revolve around two schools of thought
By Richard Prince
This represents the inaugural column of “GMP Buzz” in CleanRooms magazine. This column will strive to provide perspective and insights into Good Manufacturing Practice (GMP) requirements as well as to highlight and comment on current debates on compliance issues within our industry. This month`s topic is disinfectant rotation.
Disinfectant rotation is a common practice in the pharmaceutical industry. A recent survey by the Parenteral Drug Association`s (PDA) Disinfectant Task Force found that 96 percent of the respondents rotate disinfectants as part of their environmental control programs. The PDA Survey also stated that 73 percent of the respondents had not encountered (microbial) resistance and, if they did, they used more potent sporicides to inactivate the offending microorganisms.
The premise behind disinfectant rotation is that it is necessary to prevent or circumvent the phenomenon of microbial resistance to chemical agents. While it seems like a good idea to rotate disinfectants on a theoretical basis, since one could argue that it is feasible for microorganisms to develop possible resistance to a particular chemical germicidal agent if subjected to it continuously, it has never been conclusively demonstrated that such chemical resistance occurs in the first place in pharmaceutical manufacturing settings. So, why have we, as an industry, adopted such a universal practice? It seems that some employ rotation because they have been asked this question by Food and Drug Administration investigators during GMP inspections. Some firms have apparently implemented the practice simply because other firms have established the practice. Some, as mentioned before, believe that there is good scientific reasoning in support of disinfectant rotation, i.e., prevent microbes from mutating into more resistant forms. The theory is akin to the established and well documented phenomenon of antibiotic resistance occurring in microorganisms owing to mutations in plasmids. Proponents also point out that disinfectant rotation is helpful in keeping microbial counts within acceptable levels.
Critics of disinfectant rotation, on the other hand, contend that science has not adequately proven that rotation prevents or reduces the phenomenon of microbial resistance to disinfectants in pharmaceutical manufacturing settings. And, as such, the practice is not required, and, therefore, an unnecessary expense. Critics also question the need for rotation in cleanrooms, given that such settings are typically quite clean, devoid of water and the other nutrients required for organisms to first replicate and mutate into a more resistant form.
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.
While the sporicide certainly would be expected to inactivate the vegetative organism, it could also be argued that the microbial strains capable of sporulation would themselves become resistant to the sporicide over time. So, where does this end? For example, let`s assume for a moment that you were able to prove that a resistant organism, say Staphyloccocus epidermidis, had become “resistant” to your commonly used disinfectant (perhaps, a phenolic or quaternary ammonium compound). Let`s further assume that the total counts were within your firm`s Action Level for viable particulates. What do you do with the information? What if the total count was over the Action Level, and you detected the presence of an organism you had never seen before? The mere presence of the organism showing up in the next environmental monitoring screen does not mean that it has become resistant to the currently used disinfectant. All it means is that it is physically present again unless proven otherwise.
Environmental isolations of microbes are point-in-time determinations and may not necessarily be representative of actual risks to final product quality associated with the aseptic filling process. Further, microbes are randomly distributed in nature as in cleanrooms. So, the presence of a putative (non-pathogenic) resistant organism means as much as the presence of a non-resistant organism. In the end, whether a bacterium is possibly resistant or not resistant to chemical germicidal agents, is not the overriding concern. The overriding concern should be in keeping your cleanroom environment in a proper state of control. If the use of a single disinfectant agent enables appropriate environmental control, there is no need to rotate with another chemical germicidal agent. If the disinfectant agent is not properly controlling microbial populations, based on a review of trended data, then it makes sense to rotate with either another disinfectant (with a broader range of efficacy) or with a sporicide. The sporicide would be expected to inactivate the endospore population and any resistant vegetative bacteria.
Some final words of caution: Before contemplating the need to rotate chemical germicidal agents, first be convinced that the environmental sample was properly acquired. Make sure that the personnel who collect the air and surface samples are properly trained. And, of course, make sure that you have implemented a suitable procedure covering the selection, use and control of disinfectants for your facility.
Richard Prince, Ph.D., is president of Richard Prince Associates, Inc. (Short Hills, NJ), a pharmaceutical-based consultancy. Prince has been providing contract testing and, now, consulting services to the pharmaceutical and allied industries for 12 years. He has a bachelor of arts degree in microbiology from Rutgers University and a doctorate in zoology and physiology from Rutgers. He can be reached at (973) 564-8565 or e-mail: [email protected].