Table 2.
Brief overview of United States FDA pathways for wound healing products (medical devices).
| Device classification/Risk | PHS 361: HCT/Ps low | 510 K Class II/moderate | PMA Class III/high |
|---|---|---|---|
| Review standard | No pre-market review Not required to demonstrate safety or effectiveness |
Substantial equivalence in safety and effectiveness to a legally marketed predicate device | Approval requires that the safety and effectiveness of the device be established with valid scientific evidence, i.e., high-quality clinical data |
| Requirements | Minimally manipulated Intended for homologous use No systemic effect/not dependent on metabolic activity of cells Manufacturers follow good tissue practice to prevent the introduction, transmission, and spread of communicable diseases |
Non-clinical laboratory studies for safety (performed under GLP conditions) Clinical investigations not typically required Quality Systems in place prior to interstate commerce Manufacturing not reviewed pre-approval |
Non-clinical laboratory studies for safety (performed under GLP conditions) Clinical investigations (such as performed under an Investigational Device Exemption) Detailed Quality Systems in place Pre-approval of manufacturing facility with inspection |
| Regulatory burden | Low | Medium | High |
| Wound healing products | TheraSkin® GraftJacket® DermACELL® EpiFix® |
Oasis® Integra®* Promogran™ Tegagen™, Algisite™ Algi-Fiber Talymed® Hyalomatrix® |
Apligraf® Dermagraft® Integra™* |
Pre-market approval (PMA); Human cells, tissues, or cellular-based products (HCT/Ps).
Although initial PMA was received in 1996, in April 2001, the FDA approved Integra™ Dermal Regeneration Template for marketing in the treatment of life-threatening full-thickness and/or deep partial thickness thermal injuries. Because the treatment of thermal injuries poses a significant risk, medical devices developed to treat burns are considered Class III devices that support of sustain human life. These products require a PMA submission accompanied with clinical data demonstrating safety and effectiveness. A separate 510(k) submission was filed for Integra™ Bilayer Matrix Wound Dressing, which was cleared for marketing in August 2002 for the management of a broad range of wound types, including partial, and full-thickness chronic wounds, surgical wounds (donor sites/grafts, post-Mohs surgery, post-laser surgery, podiatric, wound dehiscence), trauma wounds (abrasions, lacerations, second-degree burns, and skin tears) and draining wounds. Both Integra LifeSciences products are composed of cross-linked bovine tendon collagen with glycosaminoglycan and a semi-permeable polysiloxane membrane. With the 510(k) clearance, the Bilayer Matrix Wound Dressing is marketed to manage a broad range of wound indications, whereas the PMA limits indications to thermal injuries. However, as recently as January 2016, the Integra™ Dermal Regeneration Template was approved for indications including partial and full thickness neuropathic DFUs based on submitted clinical data.