Skip to content
Contact us

Navigating Microbial Contamination: The Importance of Organism Risk Assessment

Microbial contamination continues to be the leading cause of recalls of drug and cosmetic products, so, understandably, the first reaction to microbial recovery may be one of dread. However, as with most things in life, understanding what to do, and having a thorough plan, can alleviate at least some of the worries. Most people know that in addition to quarantining potentially affected lots, a thorough investigation needs to be conducted to assess risk. Part of this risk assessment needs to include the characterization of the organism(s) recovered – this is where many run into trouble. While occasionally the recovery may be one of the “named” objectionable organisms from USP, most of the time, the organism is identified to be something else. Should these organisms be considered objectionable? An Organism Risk Assessment (ORA) needs to be conducted to find out. While the specifics of an ORA can vary between industries, and be influenced by the specifics of the situation.

An ORA will virtually always consist of several key pieces:

  • General Information:

    Often the organism identified is not one we are immediately familiar with. Begin with a basic literature search, to get a good general overview of the organism identified. This search can include basic biochemical characterization, ecology, and particularly distinctive information about the organism. 

  • Survival Potential of the Organism in the Product:

    It is crucial to determine the likelihood that the organism can survive in the product. This evaluation often involves looking back at Antimicrobial Effectiveness Testing (e.g., USP <51>) data. Investigatory testing of sample retains, new samples from the same or related lots, etc. may also be appropriate. The goal is to determine if the organism recovered is likely to rapidly die, or if it may survive (or worse, survive and grow), in the product. 

  • Maximum Exposure:

    What level of contamination is the consumer likely to be exposed to? For dose-limiting drugs, this can be a somewhat straightforward calculation. For products that are not dose-limiting, including cosmetics, etc., the maximum exposure assessment may be more abstract. A risk-based decision – typically based on “worst case scenario” considerations may need to be made.

  • Pathogenicity:

    The most critical question that must be answered is whether exposure to the organism is likely to cause infection and/or disease. It is rare that this is a straightforward answer. Often, the organism recovered is not a primary pathogen but may be an opportunistic pathogen. Determining whether such an organism should be considered objectionable requires consideration of a number of factors. Who is the intended consumer? Might they be immunocompromised? How is the product intended to be used? Topically? Inhaled? Injected? Understanding how the product is used, and who will be using it, can help determine the risk of an opportunistic pathogen.

  • Capability of Producing a Consumer Noticeable Defect:

    Even if it has been determined that an organism is not likely to lead to infection or disease, microbial contamination is still “adulteration”. Consideration should be given to whether the microbial contamination could cause a product defect that the consumer might notice. Microbial contamination often causes issues such as swelling of primary packaging, off-colors, off-odors, or even visible colony growth (particularly in the case of mold contamination). While these incidents may not cause a health risk to consumers, a manufacturer may wisely consider this risk objectionable, to protect brand integrity. 

  • Regulatory/Recall History:

    While lack of a formal regulatory position or recalls associated with a particular organism, are not in themselves a reason to not deem an organism objectionable, the opposite is quite telling. If there have been a number of recalls, particularly of similar product types as your product, it gives an indication of what a regulatory agency may consider appropriate. However, even if you find recalls/regulatory statements that suggest that deeming the organism objectionable is appropriate, this does not absolve the firm from conducting a full risk assessment/OOS investigation of their own. 

Ideally, an ORA would be conducted by a qualified microbiologist. Minimally, the person conducting the risk assessment should have significant microbiology training so that they are competent not only to interpret the wide array of literature that will be evaluated throughout the assessment process but also in how to apply that information to the specifics of the individual contamination event. It is also crucial to understand that regardless of what information is uncovered during the ORA process, a full risk assessment/OOS investigation is required. Not all companies have this expertise in-house. Q Labs Consulting has decades of experience in performing a variety of microbial risk assessments including ORAS, and we are happy to lend our team of experts to help! Visit us online to learn more!