History and Scope of Biomaterials

1. History and Scope of Biomaterials J. L. Ricci, Ph.D. Department of Orthopaedics, UMDNJ

2. Biomaterials Characterization Website www.rci.rutgers.edu/~moghe/622.htm

3. What is a biomaterial? Who uses biomaterials?

4. Biomaterial — A biomaterial is a nonviable material used in a medical device intended to interact with biological systems.

5. Device — an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article. including any component, part, or accessary, which is... • as defined in Medical Device Amendments of 1976

6. (1) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them, • (2) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or

7. (3) intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its principal intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its principal intended purposes.

8. Examples of Devices • prescription lenses and frames, hearing aids, intrauterine devices, surgical instruments, cardiac pacemakers, etc.

9. Biomaterial — A biomaterial is a nonviable material used in a medical device intended to interact with biological systems. (see biocompatibility)

10. Biocompatibility — The ability of a material to perform with an appropriate host response in a specific application.

11. Host Response — The response of the host organism (local and systemic) to the implanted material or device.

12. What are biomaterials used for? • Dentistry, surgery, drug delivery...

13. Short-term implants • Catheters (including balloon catheters) • IVs

14. Long-term implants • Dental fillings, caps, crowns... • Opthalmic implants (lenses) • Orthopaedic total joint replacements (hips, knees, fingers, shoulders, ankles) • Pacemakers, defibrillators, etc... • Cardiovascular stents

15. Federal Food and Drug Administration Regulation • Federal Food, Drug, and Cosmetic Act of 1938 — Drug premarket approval, removal of fraudulent devices, proper labeling. • Medical Device Amendments of 1976 — regulation of development, testing, production, distribution, and use. Three classes of devices, Class I (least regulated) to Class III (most regulated).

16. Safe Medical Devices Act of 1990 — expanded FDA authority in premarketing and postmarketing stages. Established tracking for some devices. • Biomaterials Access Assurance Act of 1998 — limits liability of biomaterials suppliers.

17. Classes of Devices • Class I — General controls. A device for which controls other than standards and premarket approval are sufficient to assure safety and effectiveness. • Examples — dental floss, tongue depressor, surgeon’s glove

18. Class II — Performance Standards. General controls are insufficient but there is sufficient information for establishment of a performance standard. • Examples — Oxygen mask, blood pressure cuff, ultrasound imager.

19. Class III — Premarket Approval (PMA). Insufficient information for reasonable safety and effectiveness, required to have approved premarket approval application. • Examples — Intraocular lenses, replacement heart valves, most orthopaedic and dental implants.

20. Premarket notification for new or substantially modified devices — The 510(k) rule — substantial equivalence to a device already on the market prior to the 1976 amendments.

21. New devices — Premarket Approval (PMA) applications — nonclinical and clinical information establishing safety and effectiveness. • Investigational Device Exemption (IDE) — needed to conduct clinical studies — nonsignificant or significant risk.

22. Voluntary Standards • American Society for Testing and Materials • Examples — ASTM F-4 committee — implant devices • Materials — ASTM F75 standard for cast cobalt-chromium-molybdinum alloy • Test Methods — ASTM D638M Test method for tensile properties of plastics

23. Additional Voluntary Standards • AAMI — Association for Advancement of Medical Instrumentation • ANSI — American National Standards Institute • ISO — International Standards Organization

24. Biomaterials — A Historical View • Four generations of devices

25. First Generation Implants • “ad hoc” implants • specified by physicians using common and borrowed materials • most successes were accidental rather than by design

26. Examples — First Generation Implants • gold fillings, wooden teeth, PMMA dental prosthesis • steel, gold, ivory, etc., bone plates • glass eyes and other body parts • dacron and parachute cloth vascular implants

27. Examples — First generation Implants • breast implants • titanium dental implants • plaster of paris bone cements

28. Second generation implants • engineered implants using common and borrowed materials • developed through collaborations of physicians and engineers • built on first generation experiences • used advances in materials science (from other fields)

29. Examples — Second generation implants • titanium alloy dental and orthopaedic implants • cobalt-chromium-molybdinum orthopaedic implants • UHMW polyethylene bearing surfaces for total joint replacements • heart valves and pacemakers

30. Examples — Second generation implants • Most current implants fit this category • Many represent second generation versions of first generation implants

31. Third generation implants • bioengineered implants using bioengineered materials • few examples on the market • some modified and new polymeric devices • many under development

32. Fourth generation implants • tissue engineered implants designed to regrow rather than replace tissues • Integra LifeSciences artificial skin • Genzyme cartilage cell procedure • some resorbable bone repair cements • many new products under development —genetically engineered “biological” components (Genetics Institute and Creative Biomolecules BMPs)

33. Biomaterials Development and Marketing vs. Biomaterials Characterization • market pressures for new materials and devices • cost of development and characterization

34. Corporate biomaterials research • characterization of new and licensed technologies for product development • quality control (GMP)

35. Academic biomaterials research • development of new materials and application of advanced materials to biomedical applications • new tissue engineered materials • technology transfer