The non-sterile products are subjected to two tests, microbial enumeration test and test for specified microorganisms. The microbial enumeration test has some limits, and the specified microorganisms are expected to be absent. Testing of nonsterile products for specified microorganisms mentioned in the pharmacopoeia is not sufficient. Because it is identified that there are chances of objectionable microorganisms that have greater risk to the pharmaceutical products. The absence of specified microorganisms in a product does not indicate that it is free from objectionable microorganisms.
The microorganisms recovered in the total microbial count may or may not be objectionable microorganism. An objectionable microorganism can either cause illness or degrade the product. The FDA code of federal regulations recommends that each drug product lot that has the potential for microbial contamination that is objectionable must be subjected to microbiological tests. The laboratory must define appropriate testing procedures to prevent objectionable microorganisms in nonsterile products.
How to identify them?
But how does any pharmaceutical company know which organisms are objectionable and how do they ensure their products do not have them? To determine if an organism is objectionable, all the microorganisms recovered in the microbial enumeration tests must be identified and evaluated. The manufacturer must conduct a risk assessment to define their own microorganisms that are objectionable depending on their products. Factors to take into consideration for the risk assessment are…
- Characteristics of the microorganisms
- Route of administration of the drug
- Nature of the drug
- Intended recipient of the drug
Identify the microorganisms isolated from the raw materials, product, and the environment using phenotypic or genotypic methods. Maintain a library of the microorganisms identified from different resources. Then, assess the microorganism for its potential harm using different resources available. The information can be found in the “Bad Bug Book” published by the USFDA. Click the button below to download the book.
Risk Assessment
First, understand if the identified microorganism is a pathogen. If it is a pathogen, and the route of infection of this pathogen is the same as the route of administration of the drug, the organism is likely to be objectionable. Find as much information as possible about the organism. Check if the microorganism can produce toxins, which will harm the patient even the microorganism is not present. Keep an eye on product recalls from other companies that make similar products.
Different microorganisms carry different risks depending on how it is administered to the patient. Some drug products carry a higher risk with some microorganisms. For example, Candida albicans pose a higher risk for oral and vaginal products and Burkholderia cepacia for nasal sprays.
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The nature of the product contributes by allowing the microorganisms to grow within the product. This happens when there is water content in the product and the time of exposure to the environment is greater. Suspect the product if the total aerobic microbial count is more than usual. Higher counts in total microbial count indicate that the preservative is not working sufficiently as it is supposed to.
Elderly people and immune-compromised patients are more susceptible to microorganisms.
If an objectionable microorganism is detected, the rejection or acceptance of the product lot is completely based on the risk assessment. The risk assessment should include the points that we have discussed so far. This requires knowledge of product characteristics like pH, water activity, and mode of action.
