Biofilm formation in process equipment presents challenges and may lead to serious consequences in GMP related manufacturing. The presence of a biofilm, which may consist of Gram-positive, Gram-negative bacteria, mold, and bacterial spores on process equipment can affect the safety, identity, strength, quality, or purity of products manufactured with this equipment. Such effects can lead to adulterated product which may pose risks to consumers, and lead to regulatory action.
Understanding Biofilm Lifecycle and Remediation Procedures
The FDA regulation on microbial contamination is:
"21 CFR 211.113 Control of Microbiological Contamination"
(a) Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile, shall be established and followed.
(b) Appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and followed. Such procedures shall include validation of all aseptic and sterilization processes."
Microbial contamination of products can often lead to product recall. An example of recent product recall due to microbial contamination is shown below.
"The company states that a "small percentage" of its products that were manufactured between August 1, 2017 and April 2018 tested positive for microbial contamination. In July 2018, the company announced it was recalling four lots of Aquaflora Candida HP9, Lymph Detox, and Baby Teething liquids because Pseudomonas brenneri, Pseudomonas fluorescens, and Burkholderia multivorans were found during a routine FDA inspection."(1)
The FDA regulation and product recall example cited above demonstrate that microbial contamination is clearly a concern with pharma packaging machinery manufacturers and regulators. It is expected that any microbial contamination issues on site need to be dealt with promptly, with thorough investigations and implementation of robust corrective and preventive actions.
This article looks at the lifecycle of biofilm, conditions or factors that can lead to the formation of biofilm, and the methodology for biofilm remediation. Understanding these factors enables manufacturers to pro-actively ensure suitable procedures are in place to minimize the risk of biofilm.
Biofilm Lifecycle
Microorganisms have primarily been characterized as planktonic, i.e., unattached or freely suspended single cells, and characterized based on their metabolic and physical growth characteristics in culture media. More recently it has been shown that microorganisms are seldom found in natural settings in this planktonic state, rather they can and do attach to and grow on exposed surfaces in complex microbial communities, which led to studies revealing the nature of surface-associated microorganisms (biofilms).
What exactly is biofilm? Biofilm is generally composed of multiple micro-organisms encased in slimy complex matrix of polysaccharides, nucleic acids and proteins known as extracellular polymeric substances (EPS).
There are three main stages in the biofilm lifecycle (refer to diagram 1: Biofilm Lifecycle below).
Diagram 1: Biofilm Lifecycle
Stage 1: Attachment
Free-floating, or planktonic, bacterial cells can attach to surfaces in moist environments and start to excrete the slimy, glue-like substance known as EPS. The microorganisms attached to the surface can be a single bacterial species, or more commonly are comprised of multiple species of bacteria, as well as fungi, algae, yeasts, protozoa or other microorganisms, along with cellular debris and corrosion products.
Stage 2: Growth
Excretion of EPS allows biofilm community to develop quickly into a complex, three-d...
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