Sterile parenteral product microbial contamination

Any material introduced into the body, human or animal, parenterally (that is para-enteron or beyond the gut ) must be sterile because the body defenses have been bypassed. This concept is absolute in the sense that one cannot have partially sterile —a product is either sterile or not. Sterility means rendered free of living microorganisms (The Shorter Oxford Dictionary, 1993) or, quoting the United States Pharmacopeia (USP) 28 (2005), completely free of viable microbial contamination. ... 

Preservatives In addition to those processing controls mentioned above (Section 3.1.4.3), the sterility of a product may be maintained through the addition of antimicrobial preservatives. Preservation against microbial growth is an important aspect of multidose parenteral preparations as well as other formulations that require preservatives to minimize the risk of patient infection upon administration, such as infusion products [52], Aqueous liquid products are prone to microbial contamination because water in combination with excipients derived from natural sources (e.g., polypeptides, carbohydrates) and proteinaceous active ingredients may serve as excellent media for the growth [57], The major criteria for the selection of an appropriate preservative include efficiency against a wide spectrum of micro-... 

The microbiological contamination of products (bioburden) is minimal prior to sterilization. There is a working limit on contamination immediately before sterilization that is related to the efficiency of the method to be used and the risk of pyrogens. All solutions, in particular large-volume parenterals, are passed through a bacteria retentive filter, if possible immediately before the filling process. Where aqueous solutions are held in sealed vessels, any pressure-release outlets are protected, e.g., by hydrophobic microbial air filters. 

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