Biomaterial is a material that has been created to take on a shape that may be employed alone or in conjunction with other sophisticated systems to manage interactions with biological systems to guide the course of any therapeutic or diagnostic technique. The state of art and potential of biomaterials, in biomedical engineering and pharmaceutical sciences is very well examined. These biomaterials are gradually being included into controlled drug delivery systems, tissue engineering, minimally invasive biomedical products, diagnostics, and artificial organs. Agencies like FDA, EMA, and American Society for Testing and Materials (ASTM) has consciously developing standards for biomaterial. However, the rapid and consistent development of biomaterial based products brings challenges to regulatory agencies for its approval. Biocompatibility, irritation and sensitization are of utmost concern in clinical adoption of biomaterial based products. Moreover, toxicological testing is a critical tool for studying the safety and biological effects of bio material. On the other hand, it is difficult to capture repeated and long-term toxicity. The application of regulatory science to biomaterials and associated medical products presents additional difficulties. Thus, biomaterials-based regulatory science system has been established to address safety concern and clinical needs. The chapter delve into the critical aspects of regulatory concerns associated with biomaterial toxicity, highlighting the importance of rigorous safety evaluations in the development and approval of biomaterials for clinical use.