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Learn more about Sterility assurance level
- Apr 19, 2018 -

Sterilization is defined as the process of killing all microorganisms, including viruses. A sterility-assurance level (SAL) is defined as the probability of an item being nonsterile after it has been exposed to a validated terminal sterilization process. Implantable medical devices are terminally sterilized to achieve a SAL of 10−6, which implies a probability of finding not more than one viable microorganism in one million sterilized items of the final product [77]. Additionally, sterility assurance must be supported by sterility testing using validated and verified test methods, such as those found in the United States Pharmacopeia (USP) Chapter 71. An ADM labeled as “sterile” meets these requirements and is labeled with the SAL [77].
Terminal Sterilization
Radiation is the most effective and widely validated sterilization process in industry [65]. The sterilization energy operates by either disrupting the cell wall of bacteria and viruses or destroying the nuclear DNA of the microbiological organism. Penetrating radiation can have the negative effect of breaking collagen bonds, while simultaneously crosslinking the collagen chain [78]. Radiation types include gamma ray or electron beam (beta ray). Either type is performed at a radiation dose level demonstrated to penetrate the sealed, finalpackage containing the ADM. Currently, typical doses of sufficient irradiation for collagen range from 5 to 25 kGy, with lower doses less likely to induce damage to the material [65,78].
Ethylene Oxide
Ethylene oxide (EtO) gaseous treatment is accomplished at elevated humidity to reactivate any spore form of the microorganisms. The hydrated organisms react with the EtO to disrupt the cell wall, destroying the organism. Ethylene oxide gas will also react with the collagen molecules of the ADM creating a significant change in surface chemistry. A major advantage of EtO treatment over irradiation is that it can be performed at relatively low temperatures, which is important in avoiding denaturation of collagen [65,78].
Terminal Sterilization Optimization
Although sterilization procedures free ADMs of viable microorganisms, the effects of terminal sterilization can affect biomechanical properties and material stability [78]. However, no consensus exists on the definitive effects of sterilization methods, since testing is performed on various collagen constructs using a multitude of sterilization conditions including radiation doses and environmental settings [78]. Additionally, the tests used to evaluate the effects are often in vitro enzymatic digestions, with the results needing to be interpreted carefully since they cannot reflect the in vivo situation completely [65]. Optimization of sterilization conditions for ADMs can be performed to achieve the appropriate SAL and limit or minimize the negative effects, including collagen denaturation or foreign body reaction postimplantation.
Aseptic Processing
To avoid potential negative effects and lengthy studies to optimize terminal sterilization, an alternative to terminal sterilization is aseptic processing of the dermal tissue. Aseptic processing occurs in clean room facilities with controlled procedures and environmental conditions. ADMs processed aseptically must meet the USP standards for sterility assurance; however, while these products are in fact sterile, as mandated by the FDA, they cannot be labeled as sterile, but only as aseptically processed and sterility tested [54,79].