3D printing holds great potential for the medical industry. Advantages range from small batch products that would have been too costly to produce via conventional means, to customized implants and products tailored to the specific end-user. These same advantages can lead to turbulent waters with product validations and charting a course to successfully bringing a product to market.

A holistic view from the beginning is critical for successfully bringing a product to market. For 3D printing, this can become more challenging as there may be unknowns. Perhaps the filament material or formulation is proprietary and unknown. Or perhaps there is historical use of the material, but there is now a need for sterilization. Charting a regulatory course starts with understanding the path.

However a product is sterilized, it will require a validation. Most sterilization validations are based on validating batches of product. But the challenge for 3D printing is, how is a validation performed when there is only a single product tailored to the end user? In most cases, that is where a documented family grouping is necessary. Sometimes this may mean simulated products. In other situations, this could mean creation of a worst-case product. In all situations, the rationale needs to be built on why that sterilization method is representative for that product. This is often a balancing act to ensure a representative test, without making the challenge overly burdensome.

In addition to a sterilization validation, a package validation must be performed. A sterilization validation demonstrates the product is able to achieve an appropriate sterility assurance level, and a package validation ensures that sterility can be maintained up until the point of use. A package validation shares a similar challenge to the sterilization validation: How is a package validation performed on a packaging system that has the potential to encounter an unlimited variety of 3D-printed products?

First and foremost, the product and packaging must be constructed of materials that are compatible with the sterilization modality. Additionally, materials must be robust enough to withstand potential damage caused by the device or distribution and handling. Typically, packaging defects occur due to product/package interactions after the product is sealed. Unprotected sharps, unrestrained devices, and improperly sized packages all create a higher risk for the sterile barrier to be breached. The variety in 3D-printed products may prove challenging to create a “one size fits all” sterile barrier system (SBS).

Once an appropriate SBS is identified, validation strategy should also consider a worst-case approach. Worst-case product should present the highest challenge to the SBS, or in other words, the representative product should be most likely to cause damage to the SBS. Additionally, this worst-case approach should be applied to the sterilization validation.

One of the keys to a successful validation is the family group. It is important to consider the characteristics for creating a sterilization family and a packaging family are different. All characteristics must be considered and will vary depending on the sterilization method and the SBS. As an example, radiation sterilization is bioburden-based. 

For such families, the worst case would be the product with the highest bioburden. By contrast, the worst case for a packaging system may be the heaviest or have geometries that damage the SBS. Another common approach for the creation of family groups is bracket of product by size. The bracket will commonly consist of the smallest and largest sized products. If this bracketing approach is utilized, it can be applied to the packaging family as well, assuming the materials are consistent across the different package sizes.

The next consideration for 3D-printed products would be functionality. Functionality can be affected by sterilization modality. As an example, 3D-printed plastics may become brittle after irradiation. Additionally, 3D-printed products tend to be porous and could be a challenge for residuals from gaseous sterilization. Typically, functionality is evaluated post-sterilization and post-distribution. 

Prior to initiation of a validation, consider beginning with initial feasibility/functionality testing to ensure the product and SBS are compatible with the chosen sterilization modality. When this step is not performed before validation activities, potential risks include wasting valuable time, money, and product on testing, only to find that the product is not suitable as intended. 

The path to regulatory approval of 3D-printed products includes attention to sterilization modality, SBS, family groups, worst cases, bracketing, and product functionality. A plan with forethought given to these activities allows for smoother sailing in these uncharted waters.

Logan Luke graduated with a degree in microbiology and has five years of experience working at Nelson Labs. He has worked in the sterilization, IDs, and packaging departments. Luke has extensive knowledge in the packaging section, as he has aided many customers with their package testing needs, from the benchtop to trouble shooting and validation design. He is well versed in a broad spectrum of packaging tests, from lot release package testing for pharmaceutical products to full package validations, including shipping and distribution. Luke is also a member of the PDA.

Bryce Telford is a recognized authority and industry leader on radiation sterilization, bioburden, microbiology, and tissue processing. He has over 15 years of experience working in laboratory functions in research, test design, media formulation, medical device, and tissue industries. Telford works with clients in all areas of the world to speak, train, and consult on failure investigations, bioburden issues, establishing bioburden alert and action levels, product family grouping, product adoption, radiation sterilization, and tissue validations.