In the medical device industry, ensuring that products are sterile and remain so until use is a critical requirement. Packaging plays a crucial role in maintaining the sterility and integrity of medical devices. The interplay between packaging and sterilization is complex. As the industry moves away from ethylene oxide (“EtO”) to replacement modalities such as vaporized hydrogen peroxide (“VHP”) and supercritical carbon dioxide (“scCO₂”), careful consideration to ensure compatibility and effectiveness is required. This blog explores the essential factors that medical device manufacturers must consider when selecting a packaging configuration that meets their requirements and is suitable for the chosen sterilization method.

How Are Packaging and Sterilization Intertwined?

Packaging and sterilization are intrinsically linked in the medical device industry. The packaging material must be able to chemically withstand the chosen sterilization process, while allowing for sterilization to occur and the physical integrity of the barrier seals to be maintained. Each sterilization method has unique requirements and effects on packaging materials.

Each sterilization method is compatible with some subset of commonly used packaging materials (Tyvek®, paper, foil, polymers, etc.) and the adhesives used to construct the packages. For example, certain plastics, such as PTFE, cannot be used with gamma radiation because they become brittle and/or change color. Despite this fact, gamma radiation is more advantageous over other sterilization modalities when considering moisture sensitive products because it does not require gas permeable packaging to achieve sterility. Supercritical CO₂ is an extremely effective sterilization method for products that have complex designs or include biological components, but scCO₂ requires gas permeable packaging to achieve sterility. Supercritical CO₂ has benefited from compatibility with established packaging solutions used for ethylene oxide sterilization.

Packaging evaluations should begin early in the product development process because the packaging design must allow the sterilizing agent to penetrate and effectively sterilize the device to meet regulatory standards. This dynamic relationship means that both packaging and sterilization need to be considered together to ensure the efficacy and safety of the medical device.

When Should Packaging Be Addressed During Product Development?

Packaging should be considered early in the product development cycle, ideally during the initial design phase. Early consideration allows for the integration of packaging and sterilization requirements into the overall product design, reducing the risk of costly redesigns or delays later in the process.

The decision on whether to select the packaging configuration or the sterilization method first can depend on various factors, including the type of device, the materials involved, and regulatory requirements. However, a holistic approach that considers both aspects simultaneously is often the best practice.

• Device-Centric Approach: In some cases, the nature of the device and its materials might dictate the sterilization method. For instance, delicate or heat-sensitive devices may not withstand one of the traditional sterilization methods (EtO, Radiation, or Steam) and may require a novel low-temperature sterilization method such as VHP or scCO₂.  
• Packaging-Centric Approach: In other scenarios, the availability of specific packaging materials might limit the choice of sterilization methods. For example, if a particular material is necessary for its barrier properties, the sterilization method must be compatible with that material.

Ultimately, an integrated approach, where both the sterilization method and packaging configuration are considered in tandem, ensures the best outcome for device sterility and integrity.

Key Considerations for Packaging and Sterilization:

1.) Expectations

When selecting a packaging configuration, companies should be prepared for several key considerations:

• Multiple Packaging Iterations: The first choice for packaging may not be suitable for the selected sterilization method. It’s important to be flexible when settling on a packaging configuration and a sterilization method that work together. Be prepared to iterate the packaging configuration multiple times.
• Validation and Testing: Extensive testing and validation are required to ensure that the packaging maintains sterility throughout its lifecycle. This includes integrity testing, microbial barrier testing, and stability studies.  
• Regulatory Compliance: Packaging and sterilization processes must comply with regulatory standards that specify packaging requirements for terminally sterilized medical devices.
• Supply Chain Integration: The chosen packaging must fit seamlessly into the existing supply chain and manufacturing processes, including compatibility with sterilization facilities and transportation logistics.
• Cost Implications: Both the packaging material and the sterilization method can impact the overall cost. Companies must balance the need for high-quality, effective sterilization with cost-efficiency.

2.) Optimizing the Selection Process

To optimize the selection of packaging materials and ensure robust testing and validation, companies can follow these best practices:

• Early Collaboration: Engage with packaging and sterilization experts early in the product development cycle to identify potential issues and solutions.
• Material Selection: Choose materials with proven performance in similar applications. Consider multi-layer films that offer enhanced barrier properties and durability.  High pressures and deep penetrating characteristics of novel sterilization modalities, such as scCO₂, can present unique stress on packaging materials historically acceptable for other sterilization modalities.
• Prototype Testing: Develop prototypes and conduct preliminary testing to identify potential weaknesses and areas for improvement.
• Simulated Transport Testing: Perform simulated transport tests to ensure packaging can withstand handling and shipping conditions without compromising sterility.
• Continuous Monitoring: Implement a monitoring system to track packaging performance over time and make necessary adjustments based on real-world data.

3.) Material Compatibility

When choosing a sterilization method, several packaging considerations need to be addressed to ensure compatibility:

• Material Compatibility: The packaging material must be compatible with the sterilization method. For example, Tyvek® is commonly used for EtO sterilization due to its breathability and durability.
• Barrier Properties: The packaging must maintain a sterile barrier after sterilization. Materials should prevent microbial ingress while allowing sterilization agents to penetrate. Leveraging the established barrier properties of commonly used sterilization packaging materials enhances efficiency and effectiveness of material evaluations for alternative sterilization modalities. Tyvek® 1073B has historically been used with ethylene oxide sterilization, and it was adapted for use with scCO₂ sterilization since 2005.
• Thermal and Chemical Resistance: The packaging must withstand the temperature and chemicals involved in the sterilization process without degrading.
• Mechanical Strength: Post-sterilization, the packaging must remain intact and protect the device during handling, transportation, and storage.
• Permeability: For gas-based sterilization methods, the packaging should allow the sterilant to permeate effectively and then be aerated to remove residual sterilant.

4.) Function vs. Aesthetics

While functionality is paramount in medical device packaging, aesthetics also play a role, particularly in market acceptance and branding. Companies should aim to balance these considerations:

• Functionality First: Ensure that the packaging meets all functional requirements for sterility, protection, and compliance.
• Aesthetic Enhancements: Incorporate aesthetic elements such as branding, color, and design without compromising the packaging’s protective qualities. Also, ensure that the sterilization method does not negatively affect the aesthetic elements of packaging. Some sterilization methods can lead to film color changes, smearing of inks, and wrinkling of the packaging itself.
• User Experience: Consider the end-user’s experience with the packaging, ensuring it is easy to open, handle, and use while maintaining sterility.

5.) Levels of Packaging

When establishing a sterilization method, companies should consider various levels of packaging including:

• Primary Packaging: Directly contacts the device and must maintain sterility. It includes pouches, trays, and blister packs.
• Secondary Packaging: Provides additional protection and bundling, such as cartons and boxes.
• Tertiary Packaging: Used for bulk handling and transportation, such as pallets and crates.

Sterilization must be incorporated into the manufacturing and supply chain to ensure that each packaging level maintains its integrity and protective functions throughout the process. Often, the optimal solution is terminal sterilization in primary packaging. There are cases where sterilization may be performed in an industrial packaging material that gets used in a final aseptic fill manufacturing step. The supply chain understanding allows for trade-offs of viable packaging vs. sterilization modality.

6.) Risks

Failure to consider sterilization modalities when selecting packaging can lead to several risks:

• Compromised Sterility: Incompatible packaging can lead to sterility failure, posing significant health risks to patients.
• Material Degradation: Inappropriate packaging materials may degrade during sterilization, compromising the device’s functionality and safety.
• Regulatory Non-Compliance: Non-compliance with regulatory standards can result in product recalls, fines, and damage to the company’s reputation.
• Increased Costs: Unforeseen compatibility issues can lead to additional testing, validation, and redesign costs.

Streamlining Safety and Efficiency with the Right Medical Device Packaging 

Selecting the right packaging configuration for sterilized medical devices is a complex process that requires careful consideration of both the packaging materials and the sterilization method. By addressing compatibility issues, regulatory requirements, and cost implications early in the product development cycle, companies can ensure the safety, efficacy, and market success of their medical devices. Integrating best practices and maintaining a holistic approach will help navigate the challenges and achieve optimal outcomes in the packaging and sterilization of medical devices. Market interest in new biomaterials and medical devices will drive the collaboration between packaging suppliers, sterilization process development companies, and medical device/pharmaceutical companies.

NovaSterilis can help you achieve the desired outcomes in the packaging and sterilization of your medical devices. Contact our team to explore compatibility and testing solutions.