Streamlining Sterilization Validation Processes for Faster Market Entry

Sterilization is a pivotal component in the delivery of medical devices and other products that require sterility to function safely. However, sterilization is not merely a final step before a product hits the market, it is an integral part of the entire lifecycle of product development — from the selection of materials to the design of packaging, and even the calculation of lifecycle product costs. As the costs associated with traditional sterilization methods such as ethylene oxide (EtO) and gamma irradiation continue to rise, alternative methods like electron beam (E-Beam) and X-ray sterilization are gaining traction. These newer methods not only offer cost benefits but also present opportunities for companies to streamline their sterilization validation processes, potentially accelerating time-to-market.

Sterilization is becoming more integrated into product development as devices evolve

Sterilization impacts nearly every aspect of product development. Material selection, for example, must consider the compatibility of those materials with the chosen sterilization method. Packaging design must ensure that the sterile barrier is maintained throughout the product's shelf life, and that the chosen sterilization modality can effectively reach the product. Additionally, the cost associated with sterilization plays a material role in determining the overall lifecycle cost of a product. As EtO and Gamma sterilization costs rise due to increased regulatory scrutiny and limited facility availability, there is a growing interest in exploring alternative sterilization methods such as E-Beam, which can provide faster processing times and reduced costs.

E-Beam sterilization is an increasingly attractive option for manufacturers looking to reduce time-to-market while maintaining high standards of safety and efficacy. This method uses high-energy electrons to penetrate the product, effectively sterilizing it without the need for long exposure times or harmful chemicals. E-Beam sterilization is also more environmentally friendly, producing no harmful emissions and requiring less energy compared to traditional methods. However, transitioning to E-Beam sterilization requires careful planning, especially in the validation stage, where the goal is to prove that the sterilization method consistently produces a sterile product without compromising its integrity or functionality.

The importance of early sterilization consideration

One of the most significant challenges in the sterilization validation process is that it is often considered too late in the product development cycle. This can lead to costly and time-consuming rework, as well as potential delays in bringing the product to market. To mitigate these issues, it is crucial to adopt a design for sterilization approach, where the sterilization modality and validation strategy are considered from the very beginning of the product development process.

Designing for sterilization involves selecting materials that are compatible with the chosen sterilization method, designing packaging that will maintain its integrity throughout the sterilization process, and anticipating the regulatory requirements for validation early on. By selecting sterilization processes with good availability and long-term sustainability, and then choosing materials that are compatible with these modalities, device manufacturers can avoid sterilization supply problems or the need for redesign and additional testing later in the process.

Moreover, the design of the product and shipper-level packaging should consider the sterilization process. Complex geometries or densely packed components can present challenges for sterilization, as they may create shadowed areas where the sterilizing agent — whether EtO or radiation — cannot reach effectively. Designing the product with sterilization in mind can help ensure that all parts of the product are adequately exposed to the sterilizing agent, reducing the risk of non-sterile areas and minimizing the need for revalidation.

Leveraging software tools to predict sterilization performance

A strategy for streamlining the radiation sterilization validation process ahead of time is the use of software tools, such as virtual dose mapping (VDM) applications that can help simulate the sterilization process, allowing companies to identify potential issues before physical testing — or the construction of physical prototypes — begins. This can reduce the need for multiple rounds of testing and revalidation, saving both time and money. Beyond just predicting feasibility, these VDM tools can be used to optimize the placement of products within shipper boxes for maximum processing efficiency.

Another critical aspect of designing for sterilization is understanding the regulatory requirements for validation. Different sterilization methods have different validation protocols, and regulatory bodies such as the FDA have specific guidelines that must be followed. By considering these requirements early in the design process, companies can streamline the validation process and avoid delays caused by the need for additional testing or documentation.

Streamlining the validation process

The sterilization validation process can be time-consuming, especially because it must be managed across multiple parties — sterilizer, microbiology laboratory, and manufacturer’s engineering, operations, and quality teams. However, there are several strategies that companies can adopt to streamline this process, particularly when using E-Beam sterilization. These strategies include adjusting the sequence of testing, leveraging software tools, and adopting a more integrated approach to product development and validation.

One way to streamline the validation process is by adjusting the sequence of testing. Traditionally, testing is conducted in a linear fashion, with each phase of testing building on the results of the previous phase. However, this approach can be time-consuming, as each phase must be completed before the next can begin. By adopting a more parallel approach to testing, where multiple phases of testing are conducted simultaneously, companies can significantly reduce the time required for validation. For example, bioburden testing, which assesses the initial microbial load on a product, can be conducted in parallel with other types of testing, such as dose mapping, which determines the appropriate radiation dose for sterilization. By overlapping these tests, companies can reduce the overall validation timeline. We provide an example timeline below for E-Beam sterilization validation, which suggests that an entire sterilization validation could be completed in eight weeks if managed proactively with responsive service providers.

Graphic courtesy of NextBeam

Conclusion

In conclusion, adopting strategies to streamline the sterilization validation process can provide significant benefits, particularly when using E-Beam sterilization. By considering sterilization early in the product development process, selecting modalities that offer rapid validations (like E-Beam), leveraging software tools, and parallelizing/actively managing these processes, companies can reduce the time required for sterilization validation to weeks, not months, lower costs, and accelerate time-to-market. Moreover, these strategies can enhance product quality and safety, ensuring that the final product meets all regulatory requirements and is safe for human use.

As the costs associated with traditional sterilization methods continue to rise, and as the demand for faster time-to-market increases, it is more important than ever for companies to adopt a proactive approach to sterilization validation. By streamlining the validation process, companies can not only reduce costs and accelerate time-to-market but also enhance the overall quality and safety of their products, ensuring that they remain competitive in an increasingly demanding marketplace.