Manufacturers must determine the appropriate sterilization method to use for their medical device. There are two factors to determine the sterilization method. The first factor is whether the manufacturer will deliver the device as sterile, or the end user will sterilize the device. If the end user is responsible for sterilizing the device, the most common methods used by hospitals are:

1. Steam sterilization ISO 17665-1:2024
2. Hydrogen peroxide sterilization- ISO 22441:2022
3. EO sterilization –ISO 11135:2014

On the other hand, if the manufacturer is responsible for delivering the medical device as sterile, the most common methods used by the manufacturer are:

1. EO Sterilization Method (ISO 11135)
2. Gamma Irradiation Sterilization Method (ISO 11137)
3. The Steam Sterilization Method (ISO 17665)

The general outline and benefits of these validation processes are:

EO Sterilization Method

1. Equipment IQ/OQ/PQ (installation Qualification, Operational Qualification and Performance Qualification)
2. Fractional cycles with products and biological indicators
3. Half and full cycles with biological indicators
4. Validation support testing

Ethylene oxide (EO), a colorless gas is used in ETO sterilization method to sterilize various medical devices.

EO sterilization enables medical devices to be sterilized in their final packaging due to gas permeation into sealed packages and cartons. Large volume products can be sterilized together in the chamber. EO is compatible with many materials and will not corrode plastic, metal and rubber.

Gamma Irradiation Sterilization Method

1. Dose mapping study
2. Determination of product bioburden (bioburden test method validation)
3. Verification dose resistance experiment

Gamma irradiation uses Cobalt-60 to kill bacteria and other microorganisms by breaking down their DNA. The Gamma irradiation sterilization method takes medical devices in their sealed packages and cartons and places them in specific totes or pallets where they pass through a specifically designed cell on a conveyor. They are then exposed to high-energy gamma rays produced from the Cobalt-60 radioactive decay.

Gamma rays have a high penetration power, so materials can be sterilized after being placed in their final packaging. Another advantage of using this sterilization method is that it’s reliable and accurately controlled. Gamma irradiation can also effectively sterilize various products with different variations in dose requirements, densities, and packaging.

The Steam Sterilization Method

1. Equipment IQ/OQ/PQ
2. Temperature profiles of the product during sterilization cycles
3. Fractional cycles with the product and biological indicators
4. Half cycles with the product and biological indicators
5. Sterility testing of product and biological indicators

Steam sterilization works by exposing the device to saturated steam under pressure. The steam kills microorganisms by reducing the time and temperature needed for the proteins to survive. It’s crucial to ensure the device’s steam sterilizer chamber reaches and stays at a certain temperature for the recommended amount of time. Recommended temperatures for steam sterilization are 250° F (121° C), 270° F (132° C), and 275° F (135° C).

Steam sterilization is a non-toxic and low-cost sterilization method. The equipment is fast and capable of seamlessly processing heat and stable moisture materials compared to other sterilization methods.

We have defined the sterilization methods above. Now let’s look through the sterilization validation requirements.

Sterilization Validation Requirements

Medical device sterilization requires validation of processes. The two main objectives of this validation are:

1. To verify the sterilization process will achieve consistent sterility,
2. The sterilization process does not have a negative effect on the device.

Validation includes several sterilization elements:

• Sterilization cycle development ensures that the sterilized load is actually sterilized. And verifies the load will sterilize consistently.
• Biological and physical measurement controls verify if the necessary conditions are present to neutralize a specific number of microorganisms for an identified sterilization process.
• Empty chamber studies are performed to establish uniform heat distribution.
• Loaded chamber studies are aligned with empty chamber studies, the loaded chamber studies identify if sterilization was achieved across the entire load without any over-processing.
• Routine use / ongoing monitoring
• Validation maintenance / Change control / Revalidation

Sterilization validations have five stages:

• process development,
• installation qualification,
• operation qualification,
• performance qualification, and
• process control

Validation Documentation

Sterilization validation documentation includes validation protocol, validation report and if necessary final report. Let’s see the contents of the protocol and reports.

Validation protocol

The validation protocol objective is to specify the procedure and tests to be conducted during the validation process and to determine which data to be collected. In general, a validation protocol will have the following element:

1. Identification of the product (i.e., the medical device),
2. Purpose and objective,
3. Equipment to be used,
4. Tests to be performed,
5. The test methods,
6. Acceptance criteria of the method,
7. Approvals.

Validation report

Validation report must include:

• Purpose and objectives,
• Equipment,
• Tests performed and rationale,
• Detailed test methods,
• Acceptance criteria,
• Approvals,
• Effective date,
• Supporting documentation.

Validation Final Report

This report provides a high degree of assurance that a particular process will provide consistent results and is also required by the FDA and includes:

• Equipment assessment
• Process testing results
• Deviations and rationale for determining impact on the validation study
• Meeting of acceptance criteria
• Established processing parameters

The sterilization verification process is a complex and comprehensive process. As Medloft team, we have the team that can perform sterilization, verification and documentation for your specific medical device, suitable for your needs. If you are looking for support in your sterilization verification process, we will be happy to assist you.