Beth Zielinski, PhD Jeffrey Scott, PhD Biomaterials 2013

The Medical Implant Top Ten List 2012 US Implantable Cardioverter Defibrillators > Number of procedures: 133,262 > Total annual expenditure: $5.5 billion > Average cost per procedure: $40,000 > Major manufacturer: Medtronic (40%), St. Jude Medical, and Boston Scientific Artificial Hips > Number of procedures: 230,000 > Total annual expenditure: $10.5 billion > Average cost per procedure: $45,000 > Major manufacturers: Zimmer (24%), Stryker, DePuy/J&J, Biomet, Wright Medical Heart Pacemakers > Number of procedures: 235,567 > Total annual expenditure: $4.5 billion > Average cost per procedure: $20,000 > Major manufacturers: Medtronic (40%), St. Jude Medical, Boston Scientific Breast Implants > No. of procedures: 366,000 > Total annual expenditure: $992 million > Average cost per procedure: $3,351 > Major manufacturers: Allergan, Mentor Metal Screws, Pins, Plates, and Rods (Traumatic Fracture Repair) > Number of procedures: 453,000 > Total annual expenditure: $4.5 billion > Average cost per procedure: $2,000-$20,000 > Major manufacturer: Synthes (50%)

The Goals of this Course Basic pathophysiology of several conditions Repair and replacement options/devices Structures (including materials) and functions of these options/devices Relationships between hosts and devices Facialart.com

In More Detail Device What function is the device augmenting or replacing? What are the material design characteristics of the that lend the device as an appropriate alternative to native tissue/organ? Once in line with host tissue, how will the host tissue respond? How will the device respond to the new physiological environment? Will this marriage be a success?

History

What came first….. the chicken (device) or the egg (biomaterial)?

Historically… The materials existed before the device Available materials were used to fabricate necessary devices and implants. Dacron fibres from E.I. DuPont de Nemours & Company, Inc. were the first polyester fibres to gain acceptance by the Food and Drug Administration (FDA) in the U.S.A.-1950 Implanted by Dr. Debakey in 1957 Cleveland Clinic

Early Civilizations 2500+ years ago Egyptians, Romans, Chinese and Aztecs Gold, wood, ivory and gems to replace teeth and fill bone defects Discoverynews.com Homeopathicdentristy.com

1700-1800 1759 - Repair of lacerated brachial artery using wood and twisted thread 1804 – Steel pins 1860 - Development of aseptic techniques

Early 20th century 1914 – Steel plates 1924 – First assessment of biocompatibility of metals/alloys 1926 – Stainless steel (18-8) developed 1940 – Ti first used in pacemakers and heart valves First implanted pacemaker, Sweden, 1958

Early 20th century Explosion of new materials Jarvik-7 WWI WWII Celluloid – craniofacial plates Natural rubbers – synthetic grafts and artificial hearts WWII PMMA – craniofacial plates, ocular lenses, vascular grafts Silicone breast augmentation Silicone breast implant Jarvik-7

More recently… 1960 – Biomer (Lycra) – artificial hearts, catheters, ACL repair 1969 – PTFE (Teflon) 1971 – ePTFE – vascular grafts St. Jude Medical

Today Materials developed over last 40-60 years New materials are being designed with “nanofeatures” The goal is optimization of the host-material interface Many devices require combinations of different materials and include drug delivery components Natural, Synthetic, Combination Products, Regenerated Tissues

Rules and Regulations

According to the FDA… Medical devices have several components The FDA/Center for Devices and Radiological Health regulates companies that design, manufacture, repackage, relabel, and/or import devices but does not regulate how and which physicians use a device

Combination Products Therapeutic and diagnostic products that combine drugs, devices, and/or biological products Drug-eluting stent Nicotine patch ABCNews.com

Medical Device Law Pure Food and Drug Acts of 1904 did not include provisions for medical devices Medical Device Amendment of 1976

Medical Device Law Subsequent legislation includes: Safe Medical Device Act of 1990 Quality systems Post-market surveillance FDA Modernization Act of 1997 Automatic Class III designation Fee schedule for shorter reviews Medical Device User Fee and Modernization Act of 2002 Inclusion of pediatric experts FDA Modernization Act of 2007 Expanded MDUFMA

Medical Device Regulation Risk-Based Device Classification Class I -Simple, no risk (latex gloves, arm slings) Class II -Higher risk devices (catheters)/510(k) Class III -Highest potential risk (heart valves)/ PMA

Journey to Market FDA.gov Following approval based upon one of these pathways, devices can still be subject to post-approval studies

Medical Device Regulation Pathways for approval Investigational Device Exemption (IDE) Allows an investigational device to be used in a clinical study to collect data for safety and effectiveness This is required for a PMA and 510k Pre-market notification application (510 (k)) Medical devices mfg must provide data to demonstrate that the new devices is “substantially equivalent” to a legally marketed device Class I and II devices Premarket Approval (PMA) Medical devices that do not show SE Class III devices; extremely rigorous review process

510 (k) versus PMA

510 (k) versus PMA Annals of Internal Medicine

The Pipeline

Human Device Exemption Commercialization of Class III devices designed to address small markets Diseases or conditions that effect fewer that 4000 patients in the US/year Device is safe and probable benefits outweigh probable risks

In coming weeks….