Author: Steven K. Pollack, Ph.D. (Carbon, Inc.)
“First, a little about myself. I am currently a Research Scientist at Carbon, Inc. a Silicon Valley-based additive manufacturing company. Carbon brings both a unique approach to traditional SLA-type polymer printing and a family of resins with true engineering properties. Prior to joining Carbon, I was Director of the Office of Science and Engineering Laboratories at the FDA’s Center for Devices and Radiological Health. One of my key roles was working to have the Agency understand the ramifications and opportunities additive manufacture bring to the development of Medical Therapies. My role at Carbon is in the technical and regulatory aspects of the use of our materials and printers in the Life Sciences and working with companies to realize those opportunities. The most common question we are asked is “do you have a biocompatible resin?” This short piece is to help clarify what that does and does not mean.”
Biocompatibility is a term the FDA uses to signify a set of tests (described by the international standards ISO 10993) that assure that a final medical device will be safe and effective for its indicated use. Therapeutic compatibility of a material (usually referred to as USP VI) has to do with whether a material used in the manufacture, storage and delivery of pharmaceutical and biological will not negatively impact the therapeutic or the patient. This blog will focuses on medical devices. The FDA Center for Devices and Radiological Health follows a guidance (https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm348890.pdf), which relates the level of sophistication (and cost) of these tests to the anticipated risk. At a minimum, tests for cytotoxicity (local cell damage), dermal irritation (local inflammation) and sensitization (a developed allergic response) are required. If the device spends more that 24 hours in contact, further tests on systemic toxicity, genetic toxicity (related to potential to cause cancer) are required.
The phrase “FDA Approved” often shows up in marketing for 3D printing materials. With the exception of certain classes of materials used in dentistry, FDA does not regulate materials and does not confer any certification for materials. If a provider of 3D printing resins submits their materials for these tests, they are in a position to assure a buyer that they have a good stating place from which to work from. But stating that they have any stamp of approval from the FDA is purely marketing.
Materials used for denture bases, surgical guides, splints, orthodontic devices, sleep apnea and anti-bruxing devices (to prevent teeth grinding) are directly regulated. For short term contact (like surgical guides), the bar for testing is relatively low, and the material can go to market with very little cost to the manufacturer. For repeated use and prolonged contact time (> 24 hours), more extensive tests are required and the manufacturer/distributer of these resins is required to obtain a 510(k) document to legally market their product in the US.
Photo Credit: Rodion Kutsaev
Put simply, these tests answer the question “will anything in the product do harm. “ These tests are both chemical and biological. For traditional manufacturing materials, the FDA reviewers will have had extensive experience with materials, but biocompatibility testing of just the resin will typically be insufficient for the FDA reviewers, as subsequent manufacturing process can potentially introduce new contaminants that could be harmful. For 3D printing, the FDA experience is limited and the agency has put forth relatively conservative guidance on what manufacturers using 3D printing will be expected to do to assure the safely of the device (https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM499809.pdf). This guidance is still in draft form and as such is only a glimpse into the thinking of the Agency. It addresses the printing process, post-processing, formulation of resins and any software changes that effects the physical and chemical properties of the final printed object.
The bottom line is that the ultimate responsibility for the safely of most materials lies with the end-manufacturer. For most applications, this is the end-user of the printers. In the case of dental materials, it’s the printer manufactures and/or their suppliers. Carbon and many other providers of resins for additive manufacture gather biocompatibility data to provide a starting point and level of assurance that the use of our product will service to improve patients health.