Animal Testing Recommendations for Dental Bone Grafting Materials (DRAFT)
This guidance provides recommendations for animal studies in support of 510(k) submissions for dental bone grafting material devices regulated under 21 CFR 872.3930. It covers synthetic, animal-source, and human-source bone grafting materials intended to fill, augment, or reconstruct periodontal or bony defects of the oral and maxillofacial region. The guidance excludes materials containing therapeutic biologics, minimally manipulated human DBM, and bone grafting materials for non-oral applications.
This is a draft guidance. Not for implementation.
What You Need to Know? 👇
What animal models are recommended for testing dental bone grafting materials in 510(k) submissions?
FDA recommends skeletally mature canine or porcine models over rodent models. Dogs and pigs have dental anatomy that more closely resembles human dentoalveolar architecture, while rodents experience continuous bone growth throughout their lifetime, hampering proper assessment.
How many evaluation time points are required for animal studies of dental bone grafting devices?
A minimum of 3 evaluation time points (e.g., 4, 8, and 12 weeks post-implantation) are recommended. This allows assessment of trends for graft resorption and new bone formation over time, as well as any inflammatory reactions.
Can cranial or orthopedic animal studies support dental bone grafting material devices?
No, cranial/calvarial or orthopedic animal studies are not generally sufficient. Intraoral environments have specific challenges like salivary flow, masticatory forces, food particles, pH changes, and unique micro-biota that are significantly different from other bone-associated environments.
What is the minimum sample size required for animal studies of dental bone grafting materials?
FDA recommends a minimum of 3 animals per treatment per evaluation time point. The animal study should be conducted on a minimum of 3 samples for each treatment group per time point to establish trends and account for potential animal loss.
Are radiography, histology, and histomorphometry sufficient to demonstrate biomechanical properties?
Yes, FDA believes that radiography, histology, and histomorphometry data are generally sufficient to demonstrate adequate biomechanical properties of newly formed bone without requiring direct biomechanical testing on explanted tissue samples from defect sites.
Can biocompatibility testing be combined with performance studies in the same animal study?
Yes, manufacturers can combine an animal study evaluating in vivo performance with biocompatibility evaluation of implantation endpoints. This approach can help reduce the total number of animals used while addressing both performance and biocompatibility requirements.
What You Need to Do 👇
Recommended Actions
- Consider Q-Submission to FDA for protocol review before conducting animal studies
- Select appropriate animal model (canine/porcine) and justify selection
- Design study to represent worst-case scenario for intended use
- Include minimum required number of animals and evaluation time points
- Implement comprehensive imaging and histological analysis protocols
- Consider combining performance and implantation biocompatibility testing if appropriate
- Prepare separate documentation for performance and biocompatibility results
- Ensure proper justification for any modified testing methods
- Include all required controls (predicate/reference device and empty defect)
- Document detailed methodology for all analyses (radiographic, histological, histomorphometric)
Key Considerations
Non-clinical testing
- Animal studies should be conducted using canine or porcine models rather than rodents
- Minimum 3 animals per treatment per evaluation time point
- Study should include minimum 3 evaluation time points (e.g., 4, 8, and 12 weeks)
- Critical size defect model required if indications don’t specify defect size
- Adequate healing period needed before creating defects (3-6 months)
- Control articles should include predicate device/reference device and empty defect control
- Study should represent worst-case scenario for intended use
Biocompatibility
- Can combine animal study with biocompatibility implantation testing per ISO 10993-6
- Other biocompatibility endpoints must be addressed separately
- Modified methods from ISO 10993-6 must be justified
Safety
- Radiographic analysis required to assess bone formation and graft resorption
- Histological analysis needed to evaluate tissue types and bone formation
- Histomorphometric analysis required for quantitative assessment
- Assessment of inflammatory response required
Other considerations
- Support for 3Rs principles (Replace, Reduce, Refine animal testing) when feasible
- Q-Submission Program recommended for protocol review
- Separate reporting of performance and biocompatibility data when combined
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Animal Testing for Medical Device Safety and Performance Evaluation
Related references and norms 📂
- ASTM F2721: Standard Guide for Pre-clinical In Vivo Evaluation in Critical Size Segmental Bone Defects
- ASTM F2603: Standard Guide for Interpreting Images of Polymeric Tissue Scaffolds
- ASTM F3259: Standard Guide for Micro-computed Tomography of Tissue Engineered Scaffold
- ISO 10993-1: Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
- ISO 10993-6: Biological evaluation of medical devices – Part 6: Tests for local effects after implantation