Mycological Analysis as an Effective Method of Pharmaceutical Production Control: Investigation of a Case of Infection of an Immunoglobulin Preparation

A case of industrial contamination by microscopic fungi of a human recombinant immunoglobulin as a solution for injection was investigated. Flaky fragments of fungal mycelium were present in the test vials. The study was conducted by light microscopy, agar plating, and DNA analysis. Three isolates were identified including Cladosporium cladosporioides (occurring in plant debris and soil), Fomitopsis pinicola (wood-destroying fungus), and an ascomycetous fungus from the order Helotiales (saprotrophs and woody plant parasites). The appearance of these species in the pharmaceutical product could not result from biocontamination of the production line but might be caused by external contamination. Thus, it was found that outdoor air entered the sterile preparation bottling room. An internal investigation conducted at the production site established that employees once rudely violated the rules of aseptic conditions by opening a window in the bottling room. Accurate identification of the fungal contaminant species allowed plant downtime to be avoided and the root cause of the problem to be established.