Pharmaceutical, biotech, and medical device clean-rooms today are faced with the increasing prevalence of molds that can lead to environmental monitoring excursions. Over the years, we have noticed mold issues associated with cleanrooms, cold rooms, door kick plates, incubators, and cleanroom startups. Molds, such as Aspergillus, have come from many sources in the cleanroom, such as bags, boxes, markers, intervention equipment, and cart wheels. These occurrences seem to be more prevalent. Aspergillus, Penicillium, Trychophyton, and other molds have, in some cases, caused significant microbial excursion issues that have resulted in adverse impacts on production.
STEP 1: Gather all data and information
The first step in selecting a chemical disinfectant is to collect all the pertinent and available information from the supplier(s). This should include technical data sheets, material safety data sheets, and recommended directions for use. All available testing on substrate compatibility, stability, and microbial efficacy (bactericidal, fungicidal, sporicidal, and virucidal) should also be reviewed, and these tests should have been performed according to accepted standards such as AOAC, ASTM, or EN. The disinfectant should also be manufactured in accordance with local, state, and country regulations. Each lot should have a certificate of manufacture/analysis and the supplier’s change control policies should be audited to ensure that customers will be notified of any significant changes in the product. Whether comparing products from the same suppler or different suppliers, it is critical to review all documentation provided and to request additional information from the suppler as needed to ensure proper selection of chemical disinfectants and sporicides.
STEP 2: Test the disinfectants for effectiveness in your cleanroom
Several factors are known to influence the effectiveness of active ingredients in biocides including but not limited to: concentration, type of surface, contact time, pH, the presence of organic soil, bioburden, water hardness, and temperature. For this reason, it is difficult to identify specific actives for use against fungal spores, as many of them are fungistatic or fungicidal depending upon the factors mentioned above, particularly concentration and contact time.
Futhermore, general disinfectants (pheno-lics, quaternary ammonium compounds, and chlorine) may not be effective in controlling mold outbreaks. Because of these factors, it is critical to perform in-house disinfectant effectiveness testing on agents to be used in cleanrooms.
Sound cleaning and disinfection procedures are critical to controlling fungal contamination in the cleanroom. A series of tests to demonstrate the efficacy of a disinfectant/sporicide against fungal spores within the pharmaceutical manufacturing cleanroom environment is necessary as many agents that are effective against vegetative fungi are not effective against fungal spores. Specifically, the following testing methods and comparisons should be considered:
- Suspension tests. While varying to some degree in their methodology, most of the proposed procedures tend to employ a standard suspension of the microorganism in appropriate dilutions of the test disinfectant. Suspension tests are valuable for determining the time necessary to achieve an acceptable log reduction of organisms, but they do not address the variations in efficacy that occur when a disinfectant is applied to different surface types.
- Carrier tests. These tests are useful in evaluating the antifungal properties of potential hard-surface disinfection agents under conditions that simulate a specific facility’s application. Most of the methods use stainless steel carriers, but in reality, all surfaces within a cleanroom will be exposed to the disinfectant/sporicide. The choice of test surfaces is matched to the types of surfaces present in cleanroom where the test disinfectant will be used
- Statistical comparisons: Suspension tests and surface tests give a fairly reliable evaluation of disinfectant efficacy under laboratory conditions, but cannot guarantee efficacy in the actual cleanroom environment. Therefore, it is necessary to perform a statistical comparison of the frequency of isolation and the numbers of organisms isolated before and after the implementation of a new cleaning and disinfection program.