Depyrogenation vs. Sterilization For Medical Devices
What is sterilization, and why is it essential for medical products?
Sterilization keeps patients safe from toxins and microbial illnesses when therapies or devices are consumed or used. Sterilization is any process that removes, kills, or deactivates all forms of life. Under the strictest definition of sterility, an item or product is sterile when there is the complete absence of viable microorganisms (bacteria, yeasts, viruses, and molds). For regulatory purposes, sterility is defined by acceptance criteria based on calculated contamination probability. An acceptable level of contamination risk for most items is the probability of a single contaminated product out of a million manufactured products. However, sterility criteria may be more stringent or lax depending upon the intended use of the medical device or product.
Sterile products that undergo sterilization are often chemical, heat, or filter sterilized. Sterilization kills any microorganisms products collect during manufacturing. For chemical and heat sterilization, sterilization occurs after the product is placed in its final packaging. The product is often filtered and then aseptically filled into a sterile container for sterilization by filtration.
What is depyrogenation, and why is depyrogenation needed for sterile products?
Parenteral products must be sterile and pyrogen-free. Even if a product is sterile, it can still contain pyrogens. Depyrogenation is a process that removes pyrogens. The most prevalent and problematic pyrogens are the bacterial endotoxins found in the outer cell walls of gram-negative bacteria. Thus, depyrogenation is a process that will either destroy or remove bacterial endotoxins. Products can accumulate pyrogens from raw materials or other parts of the manufacturing process. The best pyrogen removal or destruction processes are product-dependent. Standard depyrogenation methods are dry heat, rinsing, and filtration.
What are pyrogens, endotoxins, and lipopolysaccharide (LPS)?
Pyrogens are molecules or substances that cause a feverous reaction when they enter the human body. Endotoxins are the most common type of pyrogen. Endotoxins come from the cell walls of gram-negative bacteria. The endotoxins themselves are molecules with both fat components and complex sugar components. The presence of fat and sugar components is why endotoxins are also known in scientific literature as lipopolysaccharides (LPS). LPS is the biologically active portion of an endotoxin. In other words, LPS is the part of the endotoxin that triggers the innate immune system and causes illness in humans. Parenteral products and devices are contaminated with endotoxin through Gram-negative bacterial cells or cell wall fragments containing LPS. Lipopolysaccharide’s structure allows it to stick to hydrophobic (water-repellant) and hydrophilic (water-loving) surfaces. Thus, LPS components easily attach to molecules and proteins in solutions or material surfaces, causing endotoxin contamination. LPS also sticks to itself to form LPS chains known as aggregates.
What is dry heat sterilization?
Dry heat sterilization is a heat-based sterilization method that kills microorganisms by denaturing proteins within the cells at temperatures of 170◦C or higher.
What is steam sterilization (moist heat sterilization)?
Sterilization by moist heat (also known as steam sterilization) destroys microorganisms in a product with pressurized steam. Sterilization by moist heat is the most common method for medical device and medical product sterilization. However, autoclaves cannot sterilize medical devices with heat and humidity-sensitive materials.
What is gaseous (e.g., ethylene oxide) sterilization?
Gasses can be used as a form of sterilization. Ethylene oxide (EO or ETO) is the most used gas for sterilization. Ethylene oxide is a potent and highly penetrating alkylating agent. These characteristics make it an extremely effective sterilizing agent. However, at certain levels, ethylene oxide is also capable of causing cancer. Sterilization by ethylene oxide kills microorganisms through exposure to ethylene oxide gas under vacuum and humidity. EO is used either as one hundred percent EO or in combination with carbon dioxide.
What is sterilization by filtration?
Sterilization by filtration is a “cold” method of sterilization that removes microbes instead of killing them. Since sterilization by filtration works by removing microbes, sterilization by filtration (also called sterile filtration) is the only sterilization method that doesn’t rely on an elevated temperature, toxic chemicals, or another form of energy (such as gamma radiation) to destroy microorganisms. Sterile filtration is excellent for products that cannot be sterilized with heat or products containing a biological agent, such as an antibody or enzyme.
What is radiation (e.g., gamma, e-beam) sterilization?
Sterilization by radiation is a non-thermal sterilization method that functions by destroying microorganisms in a product with gamma radiation, beta particles (electron beam), x-ray, or ultraviolet light. Other than sterile filtration, sterilization by radiation is the only other sterilization method that doesn’t rely on elevated temperature to sterilize. Sterilization by radiation is an excellent alternative for products that cannot be sterilized with heat or chemicals.
Which sterilization type should I use for my medical device or sterile product?
Dry heat and steam sterilization are the easiest to use. Steam sterilization is more popular, as materials sterilized via dry heat must be able to withstand temperatures of 170◦C or greater. Temperature-sensitive materials that cannot withstand high heat, or are humidity sensitive, should be sterilized with radiation or ethylene oxide. If products are biologics, protein therapies, or other drugs with components susceptible to radiation damage or ethylene oxide toxicity, sterile filtration should be used for sterilization. Many sterilization techniques also provide depyrogenation. However, depyrogenation via dry heat and filtration requires special conditions compared to traditional sterilization techniques.
What is depyrogenation by rinsing?
Depyrogenation by rinsing is the process of destroying bacterial endotoxins through warm pressurized water exposure.
When should you use depyrogenation by rinsing?
If medical devices or products cannot undergo the high temperatures used for dry heat depyrogenation, depyrogenation by rinsing is recommended.
What is depyrogenation by dry heat?
Depyrogenation by dry heat is the process of destroying endotoxins through exposure to high temperatures.
When should you use depyrogenation by dry heat?
If the materials from a medical device or product can withstand high 250◦C or above temperatures without losing functionality, dry heat depyrogenation is recommended.
What is depyrogenation by filtration?
Depyrogenation by filtration removes endotoxins from solutions through adsorption and size exclusion.
When should you use depyrogenation by filtration?
Depyrogenation filtration processes are for liquids (e.g., solutions, suspensions, emulsions, and the like). Nearly all solutions containing proteins and peptides have their pyrogens removed by filtration.
What are the differences between sterilization and depyrogenation processes?
For most sterilization processes (e.g., steam, ethylene oxide, radiation), the sterilization process is lethal enough to destroy both microbes and pyrogens. Thus, depyrogenation and sterilization processes may be the same. However, extra precautions must be taken for filtration and dry heat sterilization. Some dry heat temperature levels will not depyrogenate products. Thus, a temperature of 250°C or above must be used for dry heat processes to perform both sterilization and depyrogenation. For filtration, traditional two-micron membrane filters will not depyrogenate products. Thus, one-micron filters, charged filters, ultrafiltration, or other methods must be used to depyrogenate solutions, emulsions, and suspensions via filtration.
Summary
Medical devices, products, and therapies must be sterile and pyrogen-free. Sterilization is any process that removes, kills, or deactivates microbes, whereas depyrogenation is a process that eliminates pyrogens. The most prevalent and problematic pyrogens are the bacterial endotoxins found in the outer cell walls of gram-negative bacteria. Sterilization is achieved through steam, dry heat, gases (like ethylene oxide), radiation, and filtration. Many sterilization techniques also provide depyrogenation. However, depyrogenation via dry heat and filtration requires special conditions compared to traditional sterilization techniques. All in all, ensure you choose a contract testing organization that can provide appropriate sterility testing, bacterial endotoxin testing, and depyrogenation for your product needs.
Ethide Labs is a contract testing organization specializing in Sterilization Validations and Bacterial Endotoxin Testing. Ethide Labs also offers Microbiology Testing, Bioburden Testing, Sterility Testing, EO Residual Testing, Cytotoxicity Testing, Environmental Monitoring & Package Integrity Testing services for medical device companies and allied industries. Ethide is an ISO 13485 certified facility.
References
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