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USP <60>, Microbiological Examination of Nonsterile Products – Tests for Burkholderia cepacia Complex, describes a test procedure that evaluates the microbiological quality, specifically the presence of species of the genus Burkholderia, in non-sterile substances and preparations.  This is important, because Burkholderia is a potentially dangerous pathogen, especially for drugs or raw materials that are intended for inhalation use, and aqueous preparations for oral, oromucosal, cutaneous, or nasal administration. 

There are several clinical reasons why it is important to screen for this genus of microorganisms.  First, they are Gram-negative, indicating their presence will produce endotoxins, potentially triggering a pyrogenic effect in a patient.  Burkholderia is an opportunistic pathogen, commonly causing pneumonia in immunocompromised persons or those with existing lung diseases.  Lung infection from Burkholderia is dangerous, and is characterized by a steep decline in function, potentially resulting death.  According to Lyczak (2002), death rates can be nearly 5x higher in Cystic Fibrosis (CF) patients infected with Burkholderia vs non-infected CF patients.  This, combined with its ability to spread person to person via body fluids, generally results in strict isolation procedures if detected in the hospital setting.  Burkholderia are naturally resistant to many antibiotics, including aminoglycosides and polymyxin B.  Treatment generally requires a combination of several antibiotics.  Combinations of ceftazidime, doxycycline, chloramphenicol, and others have been used as successful treatment options.

Just as crucial as the sterile production of drug products is ensuring those same products are free of dangerous pyrogens - contaminants that induce febrile reactions in patients if introduced at high levels.

Relative to patient safety, the most concerning and common pyrogen is bacterial endotoxins. Pyrogens can be removed or destroyed by depyrogenation. A common method for depyrogenation is dry heat. Largely reproducible and easily controlled, dry heat depyrogenation is dependent on temperature and time to eliminate bacterial endotoxins. The depyrogenation process can be qualified and monitored with Endotoxin Challenge Vials (ECVs).

Ophthalmic medications must meet particulate matter test requirements. Particulate matter may come from foreign or product-related substances. Clinical exposure to unwanted particulate matter can cause a biological response in patients including blocking capillaries and arteries, introducing microorganisms and causing an infection, or causing an allergic reaction. 

A cleaning validation demonstrates a pharmacy, hospital, or outsourcing facility's cleaning procedure is effective and consistent in cleaning equipment and compounding surface areas. The Food and Drug Administration (FDA) expects firms to have written procedures (SOP's) detailing the cleaning processes used for various pieces of equipment. According to the FDA, 21 CFR Part 211, "Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements." A cleaning validation is how one proves their cleaning SOPs are sufficient.

United States Pharmacopeia published the revised <795> and <797> chapters November 1, 2022. These chapters become official November 1, 2023. Revisions to the chapters can be accessed through a subscription to the USP Compounding Compendium.