Tuesday 9 February 2021

Consideration of objectionable and harmful microorganisms in controlled environments that may impact product quality, efficacy or safety

As part of the profiling of microorganisms from environmental monitoring, consideration should given as to whether the identified microorganism is objectionable (as an indicator of something unusual from an unexpected source) or harmful (that is, if the microorganism entered the product it could cause spoilage or patient harm).

Objectionable microorganisms can be considered to be:

· Undesirable

· Detectable using conventional environmental monitoring methods


Capable of causing harm to the patient

· Could lead to degradation of the product and to product stability

· Could affect the processing or manufacturing environment.

There is no definitive list of objectionable microorganisms since the 'objectionable' nature depends upon the product and patient. However, pharmaceutical manufacturers should draw up a list of objectionable microorganisms of relevance to their product groups or manufacturing environments, using risk assessment methodologies. On this basis an objectionable microorganism can be defined as any organism having been determined to have an adverse effect on product, based on risk assessment.

Some examples include:

Gram-negative bacteria in high numbers are objectionable where an injectable product is manufactured due to potential for production of endotoxin.

Fungi are objectionable due to the possibility of spreading and resistance to certain disinfectants.

Risk assessment is also necessary when a listed objectionable microorganism is detected from environmental monitoring. Where objectionable or harmful microorganisms have been identified a risk analysis should be undertaken. The degree of risk that the microorganism poses will be dependent upon one or more factors. These are[i]:

a) The total number of microorganisms detected.

High microbial counts may indicate that the microorganisms could pose a risk to the product.

b) Type of microorganisms

The characteristics of the microorganism will indicate if the microorganism is objectionable. For example, the detection of Escherichia coli may indicate contaminated water.

The characteristics of the microorganism will also indicate if the microorganism is likely to cause harm to the patient if it were to enter the product and survive. Although any microorganisms in a sterile product is a concern, with non-sterile products the degree of harm relates to the route of administration. For example, a certain Pseudomonad in a topical cream may not be a risk, however the same type of Pseudomonad in an eye-drop would be of major concern.

c) Product characteristics

Some types of microorganisms pose a greater risk to a product that others. This relates to how the product is used and the intended patient population.

This also relates to what is contained within the product and whether the product contains any substances used by the microorganism for growth. Here it is important to evaluate the microorganism’s tolerance to unusual conditions: low or high pH high salt concentration high sugar concentration (osmotic conditions), low water activity, growth temperature and so on.

A further issue is whether the product contains a preservative and, if it does, whether the microorganism would still thrive and grow within the product.

[i] Sutton, S. 2006. Microbial Limits Tests: The Difference Between “Absence of Objectionable Microorganisms” and “Absence of Specified Microorganisms” PMF Newsletter 12(6):3-9

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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