Welcome to this month’s AM Focus: Medical. For the entire month of February, we are going to zoom in on the many possibilities that additive manufacturing is offering today to medical companies. In this article, Matthew R. Jorgensen, PhD, DABT, Chemistry and Materials Scientist at Nelson Labs, explains how testing 3D printed medical devices verifies biocompatibility in an industry where safety is paramount. Nelson Labs is the leading global provider of laboratory testing and expert advisory services for MedTech and pharmaceutical companies, and Dr. Jorgensen has expertise in areas such as the fabrication of structures with micro- and nano-patterning. Upcoming articles in the AM Focus will cover the medical segment from all angles, featuring highly innovative startups and giant multinational corporations. At the end of the month all the best content will be featured in 3dpbm’s Medical AM Focus 2020 eBook.
Additive manufacturing, commonly referred to as three-dimensional (3D) printing, allows access to materials and physical geometries that would otherwise be impossible to manufacture. 3D printed objects are infinitely customizable and able to replicate complex structures based on scanned information. The ability to reproduce 3D information into a tangible object has presented a massive opportunity for personalized medicine, which takes scans of patient anatomy obtained with instruments like an MRI and translates that into a computer model that a doctor can visualize, edit and print. A titanium knee replacement, for example, can be printed to fit a person’s bone structure exactly, or in cases of traumatic injury, cosmetic pieces can be printed to match complementary parts of the patient.
Before any device can be cleared for use as a medical treatment, it must be evaluated and proven to be safe from the perspective of biocompatibility. In other words, it must be shown that the device doesn’t cause unexpected, unintentional or unjustifiable adverse effects to the user. The roadmap for demonstrating biocompatibility is standardized in the ISO 10993 series and prescribes what biological risks must be evaluated for a device depending on the nature and duration of patient contact.
For non-invasive devices, like something that contacts intact skin only, it should be shown that the device doesn’t cause cellular damage (cytotoxicity), skin irritation or an allergic reaction (sensitization). More invasive devices are considered riskier and must be evaluated for more potential adverse effects that may develop over time, like causing damage to the user’s DNA or cancer.
For each potential biological risk, there is an animal or living cell based test that can be conducted. However, it is strongly encouraged by regulators to avoid unnecessary animal testing, so there are often alternative strategies to evaluate biological risks, like carefully conducting chemical analysis of a device and having that analysis interpreted by a toxicologist. At Nelson Labs we either provide or can coordinate all of the biocompatibility testing needed for a 3D printed medical device, including chemical analysis and toxicology.
From a testing perspective, and depending on the material used, 3D printed devices present a special challenge. The first challenge is defining and defending what is used as the test article. Because each 3D printed device is different, a device to be tested must be designed that is representative of all the forms that could be used in contact with a patient.
The test article should be the riskiest version of the device, which means that it would be the largest, most complex and most difficult to clean. The most common 3D printed medical devices in use today are titanium orthopedic implants, which are made with a technology that builds the implant by melting fine metal powder layer by layer. In these devices, residual metal powder can be a unique and significant biological risk; effort must be taken to ensure that cleaning procedures are adequate for powder removal deep within the internal surface of the device.
Other less common 3D printed medical devices are polymer based and involve either depositing melted plastic into the desired geometry or polymerizing monomers into the desired shape. Plastic 3D printed devices have potential problems from a toxicological perspective, because the materials are often designed with very tight chemical and physical technical parameters that accommodate the printing process and not necessarily patient wellbeing down the line. Plastic devices are also more commonly made from novel materials produced by the manufacturer of the 3D printer, which means the devices are likely to contain chemicals that are new and difficult to analyze and assess from the perspective of toxicology.
We have worked with most of the major manufacturers of 3D printers to help test and improve the biocompatibility of their materials. At the same time, other companies using those printers and materials are making specific devices that have come to us for biological evaluation planning, testing, toxicology and assessment. Over the last few years we have seen an increase in the number of 3D printed devices being evaluated and an increased awareness of biocompatibility by 3D printer material manufacturers. All of these positive changes enhance patient safety and bring us closer to a world more universally filled with personalized medical devices.