Potential factors in unexplained mold contaminations of unused drugs and cosmetics

Detection of mold contaminants has been reported to underlie an increasing incidence of voluntary (FDA Class 2) drug and cosmetic recalls by manufactures. Mold contaminants rarely associate with adverse infections and disease but their presence may affect product availability and, indirectly, patient health. Occasionally, following extensive cleaning and sanitation efforts, sporadic- delayed recurrent contaminations or blooms may occur that cannot be correlated with quality assessments of the mold content of the general environment, raw materials and processing. It is recognized that classic species of molds not uncommonly identified with drug contamination are complexes of phenotypically similar but genetically distinct cryptic species. Molds phenotypically characteristic of the genera Aspergillus, Fusarium, Paecilomyces and Penicillium with capacities to produce dormant and heat-stress-resistant ascospores and chlamydoconidia are suggested as prominent in the unusual sporadic recurrent contamination episodes. Dormant resistant morphotypes of several cryptic species may be differentiated under insufficient cleaning and sanitizing stresses with potential sole or co-survival-colonization (biofilm), particularly in drains. Such molds with growth capacities at 37^oC and an established history for rare infections of a compromised host especially should be of concern in cleaning, sanitization, and environmental monitoring processes. Sanitizing procedures for equipment and process surfaces should not only include periodic chemical shock but also ongoing treatment to address recalcitrant populations (resistant morphotypes) found in biofilms, drain lines and fill tubing. Combinations of sanitizing and disinfection chemicals have shown efficacy against biofilms and need evaluation both in vitro and in-situ against resistant mold morphotypes.