USP <795> states compounders are responsible for ensuring compounded drug products are of acceptable strength, quality, and purity. The chapter also directs compounders to USP <1163> for recommended quality control procedures.
USP <1163> specifies the appropriate microbiological tests of non-sterile products:
- USP <61> Microbial Enumeration Tests
- USP <62> Tests for Specified Organisms
- USP <51> Antimicrobial Effectiveness Testing
The Food and Drug Administration (FDA) also refers to language from USP <1163> in its 483 citations to compounding pharmacies not performing microbiology testing of non-sterile products. Specifically referring to USP <61> to provide an estimate of viable aerobic organisms and USP <62> to demonstrate freedom from designated microbial species.
It is important pharmacists ensure non-sterile drug products meet quality specifications before releasing compounded preparations.
USP <61> Microbial Enumeration Tests
USP <61> is often called a "Bioburden" or "Microbial Limits" test. This test determines how many microorganisms are present in non-sterile drug products.
During a USP <61> test, a sample is prepared and plated on two types of growth media (Soybean-Casein Digest Agar and Sabouraud Dextrose Agar). The plates are incubated at a defined temperature and duration. The number of colonies present on the plates are then counted and the results are calculated. Results are compared to USP acceptance criteria provided in USP <1111>.
USP <1111> provides acceptance limits for microorganisms present based on sample type (raw material or finished drug product) and route of administration.
In addition to USP <1111> Table 1, the significance of other microorganisms recovered should be evaluated in terms of:
- The use of the product: hazard varies according to the route of administration (eye, nose, respiratory tract)
- The nature of the product: Does the product support growth? Does it have adequate antimicrobial preservation?
- The method of application
- The intended recipient: risk may differ for neonates, infants, the debilitated
- Use of immunosuppressive agents, corticosteroids
- The presence of disease, wounds, organ damage
USP <61> is critical to ensure non-sterile drug products meet quality control criteria.
USP <62> Tests for Specified Organisms
USP <62> results determine if objectionable microorganisms that could cause patient harm based on the route of administration are present in non-sterile drug substances or products. The microorganisms of concern listed in USP <62> include:
- Staphylococcus aureus
- Pseudomonas aeuginosa
- Salmonella
- Escherichia coli
- Bile-tolerant Gram-negative Bacteria
- Clostridia
- Candida albicans
A USP <62> test is initiated similar to USP <61> but uses microorganism specific growth media. At the conclusion of incubation, a result of "Pass" or "Fail" is generated. A passing result indicates the absence of the tested specified microorganism. USP <1111> provides absence of specified microorganism criteria based on sample type (raw material or finished drug product) and route of administration.
USP <62> is critical to ensure dosage forms do not contain specific microorganisms of concern.
For more information on USP <61> and USP <62> testing, contact ARL at info@arlok.com or (800) 393-1595.
References:
- USP <61> Microbial Enumeration Tests
- USP <62> Tests for Specified Organisms
- USP <795> Pharmaceutical Compounding-Nonsterile Preparations
- USP <1111> Microbiological Examination of Nonsterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use
- USP <1151> Pharmaceutical Dosage Forms
- USP <1163> Quality Assurance in Pharmaceutical Compounding