At PBL we hear a lot of questions from medical device clients regarding FDA material and chemical characterization requirements. To address, and hopefully alleviate some of this confusion, we’ll be delving into material and chemical characterization – what these terms mean, what the ISO standards say, what the FDA requirements are, and when certain types of testing are necessary.
Chemical Characterization Background
Historically, assessing the safety (or biocompatibility) of a new medical device has been done primarily through in vivo biocompatibility testing. This testing looks at whether device components, or extracts from a device, have the capacity to cause irritation, damage, or toxicity in an animal system. This method of testing produces data that has been shown to correlate strongly with human biocompatibility.
However, with the advent of more sensitive analytical equipment, and more robust analytical methods, the FDA and other regulatory bodies are increasingly asking for data on the material and chemical components of devices to complement in vivo biocompatibility studies. By analyzing the device components, and by looking at the types and amounts of chemicals that may migrate from a device to a patient during use, potential toxicities can be predicted. We can then examine these potential toxicities, as well as the in vivo testing data, and better assess overall biocompatibility.
Thus, characterization studies are ultimately performed in order to gain a more complete understanding of a device, and of the risk factors associated with using a device. This also explains why the FDA is placing a greater emphasis on these studies – to better ensure patient safety.
Material Characterization vs. Chemical Characterization and Leachables and Extractables
Material characterization refers to identifying all the component materials of a device. This can include colorants, plasticizers, specific metals, and ceramics, for example. Often, specific information and data on materials can be obtained from material manufacturers. In fact, the ISO 10993 standards, a series of standards on methods to be used to determine the biocompatibility of devices, recommend that as much data as possible be gathered from material manufacturers. Preexisting data can significantly reduce the amount of chemical characterization testing needed.
Chemical characterization is analogous to leachables and extractables, and these two terms are often used interchangeably in device testing. These studies look at what chemicals may come out of the device in both typical usage (leachables) and when challenged (extractables), and these studies are most often conducted according to ISO 10993-17 and 10993-18.
As mentioned previously, a user of the device may be exposed locally and/or systemically to these chemicals, and it is important for the safety of the potential user to know whether use of the device may produce harmful effects. Once the composition of a device is fully known, a qualified toxicologist can conduct a risk assessment to thoroughly characterize patient risk from exposure to device materials.
ISO 10993 Standards for Characterization Studies
Several sections of the ISO 10993 standard cover aspects of material and chemical characterization studies:
- ISO 10993-9: Framework for identification and quantification of potential degradation products
- ISO 10993-13: Identification and quantification of degradation products from polymeric medical devices
- ISO 10993-14: Identification and quantification of degradation products from ceramics
- ISO 10993-15: Identification and quantification of degradation products from metals and alloys
- ISO 10993-16: Toxicokinetic study design for degradation products and leachables
- ISO 10993-17: Establishment of allowable limits for leachable substances
- ISO 10993-18: Chemical characterization of materials
- ISO 10993-19: Physico-chemical, morphological and topographical characterization of materials
Although there are multiple sections of ISO 10993 which address material characterization specifically, the standards clearly state that gathering data from the manufacturer is the best way to characterize a material. For instance, ISO 10993-13, section 5.2 (regarding polymeric materials) states:
“The initial material characterization shall address the bulk polymer and the residuals and additives present in the final device. Because of the difficulties of retrospective analysis, this information is best obtained from the supplier or manufacturer of the material [emphasis mine]. It is important to fully characterize the purity of the polymer and the additives used in the formulation.”
Because it is likely that the majority of material characterization data will be obtained from the manufacturer, subsequent posts will focus more specifically on chemical characterization, how this data can best complement in vivo biocompatibility data to inform on the overall toxicity profile of a medical device, and how this data can be used to assess the potential impact of manufacturing or materials changes.
Pacific BioLabs performs Biocompatibility testing of medical devices, including chemical characterization. More information on our chemical characterization services can be found here: https://pacificbiolabs.com/chemical-characterization-devices.