ASTM F1983-23

5.1?This practice is a guideline for a screening test of candidate materials or assessment of local tissue response to absorbable medical devices which are expected to undergo complete absorption within three years.

5.2?This practice is similar to those for studies on candidate materials or medical devices that are not absorbable, such as those specified in Practices F763, F981, and F1408; however, analysis of the host response must take into account the effect of degradation and degradation products on the inflammatory response at the local tissue site and on subsequent healing of the implantation site, as well as the potential for adverse distal tissue effects.

5.3?For testing of absorbable medical devices, the test article for implantation should be in the final finished form as for intended use, including packaging and sterilization (if applicable). Configurations specific to the animal study may be needed. The test articles surface-area-to-body mass or mass-to-body mass ratios within the animal model should be established by calculating based on surface-area-to-body mass or mass-to-body mass ratios in humans during the devices intended clinical use. Worst-case clinical dose should be considered in the study design. For implantation studies incorporating evaluation of both local tissue responses and systemic toxicity, exaggerated material surface area or mass-to-body mass ratios (for example, a 2X to 10X safety factor to assess implant safety for regulatory submissions) compared to clinical use (for example, largest device size, maximum number of devices) should be considered, unless otherwise justified. For example, implantation of exaggerated doses may not be feasible in the selected animal model. For some devices, additional animal group(s) for exaggerated conditions should be considered if dose response information is needed. Additionally, for some devices, exaggerated dose at a specific implantation site can also be used to evaluate local tissue responses.

5.4?Materials that are designed for use in devices with 1.1?This practice provides experimental protocols for biological assays of tissue reactions to absorbable biomaterials for implant applications. This practice applies only to absorbable materials with projected clinical applications in which the materials will reside in bone or soft tissue longer than 30 days and less than three years. Other standards with designated implantation times are available to address shorter time periods. Careful consideration should be given to the appropriateness of this practice for slowly degrading materials that will remain for longer than three years. It is anticipated that the tissue response to degrading biomaterials will be different from the response to nonabsorbable materials. In many cases, a chronic inflammatory response may be observed during the degradation phase, but the local histology should return to normal after absorption; therefore, the minimal tissue response usually equated with biocompatibility may require long implantations.

1.2?The time period for implant absorption can depend on variables of chemical composition, implant size, implant location, and animal models. Therefore, the selected time points for assessing tissue effects may be selected based on the rate of absorption.

1.3?These protocols assess the effects of the material on the animal tissue in which it is implanted. They do not fully assess systemic toxicity, carcinogenicity, reproductive and development toxicity, or mutagenicity of the material. Other standards are available to address these issues.

1.4?To maximize use of the animals in the study protocol, some aspects of systemic toxicity, including effects of degradation products on different organs and tissues downstream of or surrounding the target site, can be addressed with this practice.

1.5?Because animal models are not identical to human biology, this practice cannot account for all potential biological hazards, for example the effect of the oligosaccharide a-Gal (Gala 1,3-Galb1-4GlcNAc-R), known as the a-Gal epitope present in xenogeneic materials on humans. See ISO 22442.

1.6?This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

1.7?This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.