Bacterial Endotoxin Testing vs. Environmental Monitoring
What is an endotoxin?
The “endo” in endotoxin refers to something that is within. The “toxin” component of endotoxin relates to something poisonous. Endotoxins can be deadly to humans and come from the cell walls of gram-negative bacteria. The endotoxins themselves are molecules with fat and complex sugar components (also known as polysaccharides). The fat and sugar components are why endotoxins are also known in scientific literature as lipopolysaccharides (LPS). Endotoxins are also considered pyrogens because they trigger the innate immune system and produce fever when released within the human body.
What is environmental monitoring for medical products & medical devices?
Environmental monitoring is the tools and techniques used to observe an environment, characterize an environment’s quality, and make sure that an environment meets established acceptance criteria.
How do endotoxins and environmental monitoring relate?
When it comes to medical products and medical devices, environmental monitoring controls the microbial acceptance criteria for the manufacturing environments throughout the entire lifecycle of the product, from raw materials to end-use or expiration. Microbial acceptance criteria impact the endotoxin concentration within a product. Though endotoxins are not gram-negative bacteria, gram-negative bacteria concentration during manufacturing impacts the endotoxin concentration of a medical product or device. Thus, the better an environment reduces microbial burden (particularly gram-negative microbial burden), the better protected a manufactured medical device or product is from high levels of endotoxin contamination.
What are the differences between bacterial endotoxin testing and environmental monitoring?
Bacterial endotoxin testing measures the presence and quantity of endotoxins in a particular sample. Sampling and testing (of the air, water, and surfaces) are key environmental monitoring components for microbial contamination. Microbiology testing for environmental monitoring rarely requires the complexity and specificity of identifying the species and genus of different microbes. In this way, environmental monitoring sampling and testing differs from other traditional microbiology assays that may test medical devices, product packaging, or products directly. Microbiology testing for environmental monitoring also differs from bacterial endotoxin testing as environmental monitoring testing does not test for endotoxins directly and often looks for total bioburden vs. gram-negative bacterial specifically.
Bacterial endotoxin testing uses the methodologies outlined in USP 85. Multiple USP guidance documents (USP 1211, USP 1115, USP 1116, etc.) govern environmental monitoring.
Why are both bacterial endotoxin testing and microbiology testing important?
Bacterial endotoxin testing is an important quality control step that detects the level of endotoxin contamination of a product at any stage, from initial product manufacture to final distribution. As microorganisms exist on every surface (including our body), bacterial endotoxins can be accidentally introduced during the manufacturing or packaging process in many ways. Some of the most common examples are contamination through the raw materials used, technicians, tubing/piping used to transfer product between development stages in a process, or the manufacturing environment itself. With such abundant sources of contamination, regular endotoxin testing supports the long-term control of manufacturing sites. Bacterial endotoxin testing is primarily for medical products or devices that will be inserted into the human body. Suppose bacterial endotoxins exist on the surface of a medical device or product or are present within an injectable product. In that case, the innate immune system of the patient exposed will be activated, causing fever, chills, and potentially death.
Environmental monitoring is an important quality control metric and is particularly critical for verifying your medical device or product is devoid of microbes during various phases of manufacturing, packaging, transportation, and storage. Sampling and testing are key components of environmental monitoring for microbial contamination. Thus, environmental monitoring is imperative for preventing product-induced infections and mitigating contamination risk in manufacturing environments, especially aseptic manufacturing environments. Aseptic manufacturing environments rely heavily on environmental monitoring because aseptic processing requires excluding microorganisms from the manufacturing methods.
Summary
Overall, bacterial endotoxin testing and environmental monitoring are imperative safety metrics for regulatory approval of a medical device or product. The combination of environmental monitoring and bacterial endotoxin testing ensures that medical devices and products are free of toxins so that patients will not be at risk of pyogenesis or infection following device exposure or product use. Ensure you choose a contract testing organization that can support you with appropriate environmental monitoring and bacterial endotoxin testing for your unique medical device or product needs.
Ethide Labs is a contract testing organization specializing in Bacterial Endotoxin Testing & Environmental Monitoring. Ethide Labs also offers EO Residual Testing, Microbiology Testing, Cytotoxicity Testing, Sterility Testing, Bioburden Testing & Package Integrity Testing services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
Bacterial endotoxins: biological properties and mechanisms of action. Mediators of Inflammation. 1993; 2(7): S11–S16.
Nalbantsoya A. et al. Determination of in vivo toxicity and in vitro cytotoxicity of lipopolysaccharide isolated from Salmonella Enteritidis and its potential use for production of polyclonal antibody. Food and Agricultural Immunology. 2011.
Kessel R.W.I. et al. Endotoxin Cytotoxicity: Role of Cell-Associated Antibody. Experimental Biology And Medicine. 1966.
United States Pharmacopeial Convention. <85> Bacterial Endotoxins Test. Rockville, MD, USA. 2021. (USPC <85>).
United States Pharmacopeial Convention. <1115> Bioburden Control of Non-Sterile Drug Substances and Products. Rockville, MD, USA. 2021. (USPC <1115>).
United States Pharmacopeial Convention. <1116> Microbiological Control & Monitoring of Aseptic Processing Environments. Rockville, MD, USA. 2021. (USPC <1116>).
United States Pharmacopeial Convention. <1211> Sterility Assurance. Rockville, MD, USA. 2021. (USPC <1211>).
