Recommendations for evaluating specific types of risks are provided below.
1. Performance and Handling
FDA recommends that your animal study protocol simulate the clinical setting as much as possible. You should identify all steps required to deliver, implant, or use the device, and develop acceptance criteria for each of the steps. FDA recommends that you apply a semi-objective rating scale (e.g., Likert scale) to each acceptance criterion. If the device is delivered or used with ancillary equipment, the acceptance criteria should include elements evaluating system compatibility. Rating criteria should encompass steps between the preparation of the device through device placement or use, and also withdrawal and redeployment, if appropriate. If the device is surgically placed, all steps from entry through the body wall through the final device handling should be described.
2. Device Safety
- Physiological Response
Medical devices can cause mechanical or biologic stresses. FDA recommends that you identify key biologic response variables at regional sites, at locations adjacent to the implant site (if applicable), and along all paths to and from the point of implantation or use to develop active means of surveying the impact of your device on the body. FDA strongly recommends that you work with a pathology expert such as a veterinarian boarded by the American College of Veterinary Pathology to develop the study protocol.
- Unexpected Morbidity and Mortality
You should fully explain all observed instances of animal illness and death. The supporting rationale for any statements made regarding whether such events are or are not device-related should be thoroughly described. Retrospective testimonials or statements made by study directors, their designees, or their consultants that explain veterinary clinical outcomes should be supported by appropriate evidence, records, and reports. If the cause of death or illness could be indirectly attributed to the device, you should discuss the etiology of the condition. FDA recommends that you follow modern methods of animal health surveillance by having qualified veterinarians use problem-oriented veterinary medical records (POVMR) for the purpose of detailing wellness or morbidity, including the development of key assessments for systemic effects of device use. These assessments include postoperative, interim, and terminal clinical pathology, including but not limited to: serum chemistry, hematology, and coagulation profiles with laboratory reference range values; imaging reports; and case report forms for specialized evaluations (e.g., electrophysiological, behavioral, and neurological assessments).
- Downstream and Systemic Effects
FDA recommends that you evaluate whether or not the device can have effects remote from the site of placement or use. If you believe that your device has the potential for this type of risk, you should ensure that your study includes objectives to evaluate other tissue beds (such as downstream tissue for blood contacting devices or other relevant end organ tissue) for evidence of potential systemic problem(s) that might be part of the device and delivery system. Should these findings occur, you should develop a plan for assessing the quantity of tissue affected and whether there are any resulting functional disturbances.