Sterilization concepts can be a confusing and formidable challenge for companies looking to establish a sterilized product. For those looking for assistance with establishing a sterilization process for their product, LexaMed can help. LexaMed has the in-house expertise and laboratory testing capabilities to help manage all aspects of sterilization process validations. 

For many types of medical devices and pharmaceuticals, a sterile condition is required for obvious infection prevention reasons. The definition of sterile means the absence of viable microbial organisms. While this is a simple definition, the determination or measurement of whether a product is “sterile” is not as simple. Since microorganisms are too small to be seen with the naked eye, a sterile condition cannot be detected by visual inspection. A test for sterility on every sterilized item is impractical due to its destructive nature. Therefore, the state of being sterile can only be described in terms of the probability that viable microorganisms are present. 

Sterilization process validation using any sterilization method involves three essential steps. These steps include defining the level of probability for microbial survival, defining the methods to achieve this level, and demonstrating that equivalent lethal conditions are achieved throughout the full load of commercial products. LexaMed has the resources to assist manufacturers with these three aspects through comprehensive project management, protocol and report authorship, and ISO 17025 accredited laboratory testing. 

Useful guidance for defining the level of probability for microbial survival, also known as the sterility assurance level (SAL), can be found in ANSI/AAMI ST67:2019, Sterilization of Health Care Products – Requirements and Guidance for Selecting a Sterility Assurance Level for Products Labeled Sterile. In the United States, most devices and pharmaceuticals labeled as sterile from terminal sterilization processes will require a minimum SAL of 1 potential non-sterile unit in 1,000,000 processed. In mathematical terms, this can be stated as a 1 X 10^-6 probability of a non-sterile unit. This SAL will apply to items that are invasive or implanted in the body, have contact with the blood stream, and/or have contact with compromised tissue. Some devices, however, may not be able to withstand the physical stress of a terminal sterilization process required to achieve a SAL of 10^-6 and may need an alternate sterile claim.   In these cases, a thorough assessment of alternate manufacturing materials or design, modifications to the sterilization process or approach to validation, and consideration of alternate sterilization modalities must be documented before a risk assessment is made to justify support for an alternate sterile claim greater than 10^-6 (10^-5 or 10^-4). 

There are options available for methodologies to demonstrate a validated sterilization process. For a gaseous sterilant such as Ethylene Oxide, commonly used strategies are the ‘overkill’ and ‘BI/Bioburden’ methods. These procedures are detailed in nationally recognized documents such as the ethylene oxide standard, ANSI/AAMI/ISO 11135:2014, Sterilization of Health Care Products – Ethylene Oxide – Requirements for the Development, Validation, and Routine Control of a Sterilization Process for Medical Devices. The foundation of these two methods requires establishing a log₁₀ linear death rate kinetic for a biological indicator (BI) placed into the most difficult to sterilize location of a worst-case challenge device, also known as a master challenge device (MCD). In either method, the BI is used as a surrogate for the natural bioburden and must first be shown to have equivalent or greater resistance to the sterilization process compared to the product’s bioburden. LexaMed can provide a detailed rationale for selection of the MCD and BI placement site as well as help determining the optimal procedure for establishing a linear death rate within a custom and comprehensive validation protocol. 

Radiation sterilization processes are commonly conducted with gamma, E-beam, or X-ray energy.  All three of these modalities use a bioburden-based approach to process validation. Linear death rate curves have been experimentally developed for many microorganisms by subjecting them to varying levels of radiation. All organisms were found to follow a similar model that allows a prediction for microbial survival based on exposure level. This facilitates the prediction of SAL for a particular bioburden level when exposed to a specific radiation dose. A few variations in radiation validation methods are available and are detailed in ANSI/AAMI/ISO 11137-2:2013/(R)2019, Sterilization of Health Care Products – Radiation – Part 2: Establishing the Sterilization Dose. 

The final important step for sterilization validation involves demonstrating that similar lethal conditions exist within all points of the entire product load to be processed. This is a physical aspect that typically involves measurement of critical variables of a process such as energy dose, temperature, humidity, or sterilant concentration. These variables are affected by the product’s materials of construction, density, packaging, loading, and distribution within the sterilization chamber or energy field. To measure the physical aspects which impact the lethality of a sterilization process, sensors or monitors are distributed throughout the load in all areas. This data can then be analyzed to ensure that equivalent lethal conditions have been reached across the entirety of a product load.

No matter the sterilization process selected for a particular medical product, LexaMed can help make the process of establishing a sterilization process for your product less daunting. LexaMed offers expert management services that enable a timely completion of your sterilization project and offer consulting to resolve any issue that may arise during processing or testing. LexaMed also offers protocol and report services to provide you with thorough documentation which is essential for smooth navigation through regulatory waters. These documents will include the necessary rationales regulatory officials and notified body auditors are looking to ensure a valid sterilization process has been achieved. 

If you have an upcoming sterilization validation project, and you’re not sure where to start, reach out to us at [email protected] and we’d love to help you navigate the world of sterilization validations.