Explant Imaging (i.e. radiography, microCT)

Prior to preparing devices for histomorphometric analysis, you should consider whether an analysis of the structural integrity of the device would assist in the determination of device safety.

Scanning Electron Microscopy (SEM)

FDA recommends the use of Scanning Electron Microscopy to fully characterize the implant device surface after explant of the device from animals.

Histomorphometric Analysis

Because proper interpretation of acute and chronic biologic responses is critical to FDA’s evaluation of safety, especially in the absence of clinical data, FDA recommends that you seek the expertise of board-certified veterinary or clinical pathologists when developing and executing methods for preparing tissues for histomorphometric analysis. FDA also recommends that you identify appropriate expertise to develop pre-specified objective methods for scoring and analyzing observations of injury and inflammation of all tissue. Specific assessments such as inflammation, vascularization, calcification, proteoglycan/collagen, and fibrin/thrombus, etc. should be considered in your evaluation.

FDA recommends that you report any non-standard tools and methods used to collect the tissues that contain the device as well as the methods of fixation, cutting, and staining. The reports should also include diagrams indicating the location of implants. The sectioning methods, including tissue and device orientation, should be detailed. When discussing the study results, you should include well-marked high resolution color images, each indicating the animal number, study group, tissue section, magnification, stain, and other important identifiers. Some sponsors find the use of pathology keys that further detail their grading system useful. Other important identifiers are experimental animal number and cohort as well as a scale on the photomicrograph.

Local and Downstream Tissue Assessment

FDA believes that most devices, including both implant and delivery system components, have the ability to embolize particulates or microthrombi from devices’ structural elements or coatings, resulting in adverse observations such as pressure necrosis and inflammation in surrounding tissue or upstream/downstream tissue if the device is in contact with blood. The calvarium should be opened and the brain sectioned if there is a risk of upstream emboli. If your risk analysis identifies this potential risk for your device, FDA recommends that your pathologic study include systematic descriptive evaluation of upstream/downstream and surrounding tissue. If foreign bodies are observed, you should provide a discussion of the amount of surface area affected as well as the methods utilized to calculate this affected area.

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