Custom Implant Sterilization and Patient Safety: A Critical Guide for Surgeons

In the world of patient-specific custom implants, one of the most crucial factors in ensuring successful surgical outcomes is sterilization. As surgeons, patient safety is the ultimate priority, and we need to be acutely aware of the processes that our custom implants undergo before they are placed in the human body. In this article, we’ll explore how biological contamination affects custom implant sterilization, the regulatory requirements for bioburden analysis, and the different sterilization methods available. Moreover, we will underscore why autoclave sterilization is strictly forbidden for permanent implant devices and discuss which sterilization techniques are safe, efficient, and legally compliant under MDR/745 and 510(k) regulations.

While the previous article discussed physical contamination from the manufacturing process, today we focus on biological contamination—an equally important topic that influences both short-term healing and long-term patient safety.

Biological Contamination: A Hidden Threat

The concept of biological contamination is often misunderstood. Some may think that if no live microorganisms are detected after sterilization, the implant is safe for use. However, this oversimplified view overlooks the reality of endotoxins—toxic remnants of bacterial cell walls that can remain on the implant even after sterilization. Endotoxins trigger inflammatory responses in the patient, leading to compromised healing, chronic inflammation, or even implant failure.

According to regulatory guidelines such as MDR/745 and 510(k), manufacturers are required to conduct bioburden analysis to quantify the level of biological contaminants present on an implant before sterilization. This analysis ensures that the implant achieves a Sterility Assurance Level (SAL) of 10??, meaning there is less than a one in a million chance that a single microorganism survives on the device post-sterilization. This standard is non-negotiable for ensuring that patient safety is not compromised.

Cleanrooms and Bioburden Control

To reach this SAL level, implants must be manufactured, handled, and sterilized in controlled environments such as ISO 6 cleanrooms. At Boneeasy, for example, all our implant production and handling occurs in such environments to minimize biological contamination before sterilization. The importance of cleanrooms cannot be overstated: without them, achieving low bioburden levels is nearly impossible. This is especially crucial in custom implants where every product is unique and exposed to various environments during the manufacturing process.

The Graveyard Effect: Why Sterilization Isn’t Always Enough

It is critical to understand that while sterilization is meant to kill microorganisms, it does not necessarily remove all biological material from the implant surface. Even dead microorganisms can leave behind endotoxins, which can initiate an overblown inflammatory response in the body, delaying or preventing proper healing. This "graveyard effect" underscores the importance of controlling bioburden from the very beginning, not just relying on sterilization to mitigate all risks.

Surgeons must be aware that even the most meticulous surgical techniques won’t guarantee success if the implant they are using is biologically contaminated. This emphasizes the need for manufacturers to provide bioburden analysis reports alongside their custom devices, ensuring that endotoxin levels are within acceptable limits.

Autoclave Sterilization: A Forbidden Method for Custom Implants

One of the most pressing concerns in implant sterilization is the improper use of autoclave sterilization. Autoclave sterilization, which uses steam and high pressure to kill microorganisms, is commonly used for many medical devices, especially reusable surgical tools. However, it is strictly forbidden for permanent custom implants, especially those made from materials like titanium.

The reason for this is twofold:

1. Physical contamination: The high-pressure steam used in autoclaves causes water to come into contact with the implant surface, and this water can deposit metallic ions, leading to physical contamination. This is particularly problematic with implants that have rough surfaces designed for osseointegration—the intentional roughness can trap water and contaminants, rendering the implant less effective or even harmful.
2. Material degradation: Repeated autoclave cycles can degrade the mechanical properties of certain materials, particularly 3D-printed metals, which are becoming increasingly common in custom implants. This not only weakens the implant but also raises concerns about long-term performance.

The autoclave method should only be used for temporary devices or short-term implants, such as osteosynthesis plates, but never for long-term permanent custom implants.

Sterilization Methods for Custom Implants

For custom implants, the appropriate sterilization methods are ethylene oxide (ETO), plasma sterilization, and radiation sterilization. Each of these methods offers specific advantages and is aligned with internationally recognized standards for medical devices. Let’s take a closer look at these methods and their corresponding ISO standards:

1. Ethylene Oxide (ETO) Sterilization

• ISO Standard: ISO 11135:2014
• ETO sterilization is a gas-based method that is particularly well-suited for sensitive materials and complex geometries, such as custom 3D-printed implants. ETO is highly effective in penetrating porous materials and does not leave behind significant residues that could compromise the implant.
• One of the main advantages of ETO is that it operates at low temperatures, reducing the risk of material degradation. However, it does require post-sterilization aeration to remove residual gases, making the process longer.

2. Plasma Sterilization (Low-Temperature Hydrogen Peroxide Gas Plasma)

• ISO Standard: ISO 14937:2009
• Plasma sterilization is another low-temperature option that is particularly useful for custom implants. This method uses hydrogen peroxide vapor, which is energized to form plasma. The plasma contains free radicals that destroy microorganisms.
• Plasma sterilization is fast, effective, and leaves no toxic residues, making it a preferred choice for sensitive devices like custom implants. Its short cycle times also make it ideal for time-sensitive applications.

3. Radiation Sterilization (Gamma or Electron Beam)

• ISO Standard: ISO 11137-1:2015
• Radiation sterilization, commonly done with gamma rays or electron beams, is widely used for shelf-stable medical devices like screws, plates, and mass-produced implants. While it is highly effective and can sterilize in bulk, it is not ideal for custom implants. The primary issue with radiation sterilization for custom implants is the delayed process time—because there are only a limited number of facilities that perform this type of sterilization, the logistics can cause significant delays.
• Additionally, certain materials used in custom implants, particularly those that are 3D-printed, may be sensitive to radiation, which can alter their physical properties, leading to brittleness or reduced strength over time. As such, radiation sterilization is not recommended for patient-specific implants.

Surgeons: A Vital Role in Ensuring Sterilization Compliance

While manufacturers are responsible for providing sterilized, safe implants, surgeons play a crucial role in ensuring compliance with sterilization standards. Surgeons must ask manufacturers for documentation proving that the implants they are using have undergone appropriate sterilization. Specifically, surgeons should request:

• Bioburden analysis reports showing compliance with SAL 10??
• Sterilization certificates for ETO, plasma, or radiation sterilization, depending on the method used
• Endotoxin levels testing to ensure there are no harmful residues

Additionally, surgeons should understand that manipulation of the implant during surgery is critical. They should avoid touching the implant’s rough surfaces with gloves or instruments to prevent contamination and ensure optimal osseointegration.

Conclusion: Custom Implants Demand Stricter Controls

Custom implants offer immense benefits to patients through personalized treatment, but they also come with unique challenges. Sterilization is one of the most important factors in ensuring these devices are safe for use, and both manufacturers and surgeons have a responsibility to maintain high standards. By understanding the limitations of different sterilization methods and ensuring that appropriate steps are taken to prevent both physical and biological contamination, we can improve patient outcomes and reduce the risk of complications.

Surgeons, the devices you use are only as safe as the processes they undergo. Stay informed, ask questions, and ensure that your custom implants meet the highest standards for sterilization and patient safety.

References

1. Nuno Cruz, M.I. Martins, J.D. Santos. (2020). Surface Comparison of Three Different Commercial Custom-Made Titanium Meshes Produced by SLM for Dental Applications. Materials, 13(2177). doi:10.3390/ma13092177.
2. European Parliament. (2017). Regulation (EU) 2017/745 on Medical Devices (MDR). Official Journal of the European Union, L117.
3. U.S. Food and Drug Administration (FDA). (2021). 510(k) Premarket Notification. Retrieved from FDA website .
4. 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.
5. ISO 14937:2009. Sterilization of health care products — General requirements for characterization of a sterilizing agent and the development, validation, and routine control of a sterilization process.
6. ISO 11137-1:2015. Sterilization of health care products — Radiation — Part 1: Requirements for the development, validation, and routine control of a sterilization process for medical devices.
7. ISO 14644-1:2015. Cleanrooms and associated controlled environments — Part 1: Classification of air cleanliness by particle concentration.
8. Endotoxin Testing and Regulatory Guidelines for Medical Devices. (2020). FDA Guidance.
9. Dempsey, E. et al. (2018). Bioburden Monitoring in Medical Device Manufacturing. Journal of Sterilization Technology, 21(3), 145-152.
10. Gil Mur, J. et al. (2017). The Role of Contaminants in Custom Medical Device Sterilization. Journal of Medical Materials, 16(4), 311-319.

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