FDA proposes animal study requirements for dental bone grafts

The US Food and Drug Administration (FDA) on Thursday issued draft guidance for sponsors of dental bone grafting devices that offers advice on using animal studies to meet special controls requirements for such devices. The agency said the guidance is meant to augment and, in some circumstances, supersede previous related guidance.

FDA explains that dental bone grafting devices are materials used to fill, augment, and reconstruct the area around a patient’s jaw and face, and notes that that it typically requires sponsors to conduct animal studies to prove they are safe and effective.

FDA lays out its special controls requirements for the devices in a separate guidance entitled, Class II Special Controls Guidance Document: Dental Bone Grafting Material Devices. In some situations, the agency said the draft guidance would supersede requirements in the dental bone grafting guidance when finalized. The agency also said the draft guidance would supplement – but not supersede – its guidance entitled, General Considerations for Animal Studies Intended to Evaluate Medical Devices.

FDA generally recommends that sponsors include data from animal studies for 510(k) submissions for bone grafting material devices to address the safety and performance in vivo independent of how the predicate device has shown to perform and details why such studies are necessary in the guidance.

“Providing an explanation of the history of the safe use of similar devices alone is generally insufficient due to the potential impact of differences in proprietary manufacturing and technological characteristics (e.g., graft shapes and sizes, surface topography, porosity) on the in vivo behavior of the bone grafting material devices,” said the agency. “As a result, FDA does not recommend extrapolating the in vivo behavior of a proposed bone grafting material device from the known in vivo behavior of a predicate bone grafting material device.”

“Also, in vivo behavior of the bone grafting material typically cannot be adequately evaluated by bench testing methods alone, such as chemical and physical characterizations, because of specific challenges and anatomical differences in replicating the intraoral environment that include, but are not limited to, salivary flow, masticatory forces, food particles, pH and temperature changes, and environment containing unique micro-biota, oral mucosal epithelium and oral musculature,” the agency added.

While FDA typically requires animal testing for such products, it said sponsors should try to replace, reduce and/or refine such testing when feasible, or as the agency calls it, the “3Rs.” If sponsors have methods that they would like to use that don’t require animal testing that they think would be suitable and feasible, the agency recommends they discuss the methods with regulators early on using its Q-Submission Program.

In determining the right kind of animal studies to conduct, the draft guidance outlines FDA’s thinking on the types of animal models and study designs that sponsors should consider.

“We recommend the use of skeletally mature canine or porcine models, over rodent models, for studying the in vivo performance of dental bone grafting material devices,” said FDA when determining the right kind of animal model. “Canine and porcine models are recommended since the dental anatomy of dogs and pigs more closely resemble human dentoalveolar architecture than that of smaller animals.”

“Moreover, rodents experience continuous bone growth throughout their lifetime, which FDA believes would hamper proper assessment of devices intended to form bone over time,” the agency added. “Also, rodents are too small to allow for placement of a sufficient amount of graft material in an intraoral defect site, particularly for resorbable bone grafting material devices that contain granular components. In contrast, periodontal tissues and the size of the teeth in dogs or pigs are, in general, similar to those in humans.”

To show there is substantial equivalence between the intended patient and the animal used in the study, FDA said sponsors should enroll enough animal test subjects to establish trends and consider the loss of animals during the study. Broadly speaking, the agency recommends enrolling a minimum of 3 animals per treatment per evaluation time point.

The guidance also delves into what sponsors should consider if they plan to combine an animal study with the evaluation of the device's biocompatibility and adds additional recommendations that are already outlined in its dental bone grafting material devices guidance.

Stakeholders can comment on the guidance on www.regulations.gov under docket no. FDA-2024-D-1242 until 28 May for FDA to consider their comments before the guidance is finalized.

FDA draft guidance

FDA proposes animal study requirements for dental bone grafts

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