USP <61> and USP <62> Microbial Tests for Non-Sterile Products

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:

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