Micro-organisms found in pharmaceutical manufacturing

Common microflora

References for bench marking the most likely microfora found in pharmaceutical manufacturing can be hard to come by. In this posting some common micro-organisms along with some references are detailed. 

For a 2011 study by Sandle go to: benchmarking cleanroom microflora

The most commonly occurring micro-organisms from human skin (either commensurable or transient) are Gram-positive micro-organisms and common environmental fungi:

• Staphylococcus aureus
• Staphylococcus epidermidis
• Staphylococcus capitis
• Staphylococcus hominis
• Propionibacterium
• Micrococcus spp.
• Kocuria spp.
• Bacillus spp.
• Lactobacillus spp
• Corynebacterium spp
• Clostridia spp.
• Candida spp
• Aspergillus niger
• Trichophyton spp.
• Epidermophyton spp.

Whereas those associated with eyes, ears and mucus include Gram-negative micro-organisms, which can arise on rare occasions directly from the operator:

•  Pseudeomonas aeruginosa
• Ralstonia pickettii
• Comamonas acidovorans
• Escherichia coli 

References:

Emod, J. L. (2003): ‘Procedure and Area Specific Validation of Disinfectants’, paper to PDA Aseptic Processing Convention, Prague

 Jiminez, L. (2004): ‘Microorganisms in the Environment and their relevance to Pharmaceutical Processes’ in Jiminez, L. (ed): ‘Microbial Contamination Control in the Pharmaceutical Industry’, Marcel-Dekker , New York , pp8-9

In relation to this there are four main sources of contamination:

• People
• Room surfaces
• Room air
• Water 

The most common micro-organisms in clean rooms are Gram-positive bacteria. These micro-organism have a close phylogentic affiliation as indicated by comparative analysis of partial 16S rDNA studies (such as Gen-fu and Xiao-hua, 2007):

• Micrococci
• Staphylococci
• Corynebacteria
• Bacillus spp.
• Aspergillus spp
• Pencillin spp.

 (Sources: Favero, 1968; Jiminez, 2004; Gen-fu and Xiao-hua, 2007).

Gen-fu, W. and Xiao-hua, L. (2007): ‚Characterisation of predominant bacteria isolates from clean rooms in a pharmaceutical production unit’, Journal of Zhejiang University Science B, Vol. 8, No.9, pp666-672

Favero, M., Puleo, J., Marshall, J. and Oxborrow, G. (1966): ‘Comparative Levels and Types of Microbial Contamination Detected in Industrial Clean Rooms, Applied Microbiology, Vol. 14, No.4, pp539-551

For fungi specifically, a review by Bartnett et al (2007) concluded that the most common fungi in cleanrooms are: Aspergillus, Penicillium and Trychophyton.

Johnson (2003: 6.17) has stated that the types of micro-organisms recovered from clean rooms in the USA and Europe are very similar and would typically be Staphylococcus hominis, Staphylococcus epidermidis, Micrococcus spp., Bacillus spp., and yeast, from an aseptic processing area. 

Johnson, S. (2003): ‘Microbiological Environmental Monitoring’ in Hodges, N. and Hanlon, G.: ‘Industrial Pharmaceutical Microbiology: Standards and Controls’, Euromed Communications

For the genus Staphylococcus over 50% of the species are indigenous to humans with the most commonly found species being S. epidermidis and S. haemolyticus (Heikens et al, 2005: 2286).

Heikens, E., Fleer, A., Paauw, A., Florjn, A. and Fluit, A. C. (2005): ‘Comparison of Genotypic and Phenotypic Methods for Species-Level Identification of Clinical Isolates of Coagulase-Negative Staphylococci’, Journal of Clinical Microbiology, May 2005, pp2286-2290

Thermophiles and extremotolerant bacteria are not examined as these do not pose a risk to pharmaceutical cleanrooms (refer to LR1262). Literature also indicates that occurrences of such micro-organisms are very low (La Duc, 2007).

La Duc, M.T., Dekas, A Osman, S., Moissl,M., Newcombe, D. and Venkateswaran, K. (2007): ‘Isolation and Characterization of Bacteria Capable of Tolerating the Extreme Conditions of Clean Room Environments’, Appl Environ Microbiol. 2007 April; 73(8): 2600–2611

For a more recent 201 study by Sandle go to: benchmarking cleanroom microflora