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Medical Device Evaluation and Validation. Harold Alexander, Ph.D. Orthogen Corporation Springfield, NJ Halexander@orthogencorp.com. Introduction. Vast experiment underway 20 million people (1 in 14) in USA with implants Vast experiment with no data collection
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Medical Device Evaluation and Validation Harold Alexander, Ph.D. Orthogen Corporation Springfield, NJ Halexander@orthogencorp.com
Introduction • Vast experiment underway • 20 million people (1 in 14) in USA with implants • Vast experiment with no data collection • With exception of occasional reports of clinical failures, little is know about biomaterials performance in the human clinical environment
No good, long term, systematic studies have been performed. • A registration system for implants and biomaterials? • When we consider issues of long-term survival of biomaterials in vivo, the lack of attention to epidemiology and physiology are key issues. Researchers must become more careful and observant of clinical performance. • A national database of clinical data is essential to this effort.
Materials Selection • Currently used materials are survivors of a trial and error process. • Materials borrowed from other industries • Cost prohibitive for development of unique biomaterials. • Industry, until recently, could not afford it • Less than optimal materials.
Unique Biomaterials? • Few new candidate materials waiting for adoption. • Medical-legal environment argues for unique biomaterials. • Tissue Engineering Efforts.
Biologic Safety • ASTM F 981-87: Standard Practice for Assessment of Compatibility of Biomaterials • Tripartite Biocompatibility Guidance
Animal Functional Tests • In use simulation • Safety • Efficacy
Clinical Studies • Initial Studies, Short term safety • Clinical Protocol • Prospective, Controlled, Randomized • Multi-Center • Assess mid-term safety and efficacy • Marketing Application • Long term follow-up (post-market?)
Regulatory Primer • Device Law passed in 1976. • Methods to introduce new medical devices: • Investigational Device Exemption Application • Clinical trials • Premarket Approval Application. or • 510(k), substantial equivalency application.
Device Retrieval & Analysis (DRA) • Devices that fail in service are not routinely analyzed • Studies address device in absence of clinical data • Clinical studies focus on patient, ignoring device issues
DRA (Continued) • Knowledge from small, non-random sampling. • Need to study 10% of devices that fail. • Greater need to study 90% that do not fail!
Sample Cases • Manufacturing flaw • Excess blast material on a total knee replacement • Manufacturing flaw • large grain size in ceramic ball • Design flaw • Inadequate stress analysis of hip acetabular component • Manufacturing procedure flaw • Residual machine oil on hip acetabular component
DePuy LCS Knee • Manufacturing flaw • Excess blast material on a total knee replacement
Feldmuhle Ceramic Hip Ball • Manufacturing flaw • large grain size in ceramic ball
DePuy ACS Cup • Design flaw • Inadequate stress analysis of hip acetabular component
Sulzer Acetabular Component • Manufacturing procedure flaw • Residual machine oil on hip acetabular component
Ethical Concerns • Professional Status • Professional status creates special obligations to use one's specialized skill and knowledge to promote significant social values (e.g., health), to protect the interests of those (clients) who will use the products you design and build, and to be a loyal employee.
Professional Obligations • Professional obligations take many forms, including: • a. using care in design to make sure that devices are safe and effective (promoting health); • b. protecting consumer autonomy, the right to make informed choices about health problems; • c. promoting and protecting your employer's legitimate interests.
One of the vexing problems of professional ethics is that these areas of obligation are often in conflict, requiring ethical judgment about how best to balance these conflicting demands!
Sample cases • Bjork-Shiley artificial heart valve • Pedicle Screw Spinal Fixation • DePuy ACS Acetabular Cup • Effect of Radiation Sterilization
Bjork-Shiley artificial heart valve • unexpected defects in the welding of the valve led to catastrophic failure in a small percentage of them; • about 2/3 of those experiencing valve failure will die; • Shiley failed to warn patients, who were then unable to make informed decisions about their possibly defective heart valves; • there is evidence of poor manufacturing techniques at Shiley; what were the obligations of those who were aware of them?;
Bjork-Shiley Valve (continued) • Who should inform patients of possible defects? The patient's physician? The manufacturer? The Food and Drug Administration • What should patients be told? Only scientifically valid and reliable research? Reports of poor manufacturing techniques? • What if bioengineers are aware of a defective design or poor manufacturing techniques but the company is not responsive the their concerns? • What policies should guide these issues concerning medical devices and the patients who receive them?
Pedicle Screw Spinal Fixation • Adjunct to spinal fusion surgery. • Old hook and rod systems did not provide rigid fixation and required multiple level fixation. • Pedicle screw fixation, developed in Europe, could be used in single spinal unit (one level) or more and provided more rigid fixation. It was hypothesized that this would result in higher fusion rate. • Application to FDA for 510(k) allowance denied for lumbar pedicle fixation because of concerns of nerve damage, broken hardware, clinical efficacy. • FDA required IDE-PMA studies. These studies were started, but never concluded. • Manufacturers applied for 510(k) allowance for sacral, long bone or anterior screw fixation; a pre-1976 application. This was allowed by FDA.
Pedicle Screws (continued) • Using the argument that the FDA does not regulate the practice of medicine, manufacturers encouraged surgeons to use devices for posterior lumbar fixation, a non approved application. This was done. It became standard practice in USA. • Injured patient sued manufacturers, surgeons and hospitals claiming the improper promotion and use of an unproven, unsafe product. • 10s of thousands of lawsuits resulted against Smith & Nephew Richards, Danek Medical, Acromed, and a number of smaller companies.
Pedicle Screws (continued) • At one time, Danek alone was spending a million dollars a week pursuing the defense of outstanding lawsuits. • Acromed settled globally and others are both litigating and settling cases. Total cost of this litigation will probably be 2 billion dollars. • Who is at fault? FDA, manufacturers, their employees, surgeons, hospitals, the law, lawyers?
DePuy ACS Acetabular Cup • This is a hip acetabular component where the polyethylene insert was designed with a thin lip that tended to be over-stressed and fractured in some sizes. • The device was designed by a novice engineer who had been a draftsman for the manufacturer and had recently earned his BS degree. He had no biomedical engineering or biology training and was unfamiliar with the research literature on the appropriate design characteristics of an acetabular insert. • The acetabular shell was porous coated for bone attachment without cement; an IDE-PMA product. However, the manufacturer applied for, and obtained, 510(k) allowance for cemented use; a pre-1976 application. Consequently, the device was never subjected to rigorous clinical testing.
ACS Cup (continued) • As failures started to occur (typically 25% have failed within four years) the manufacturer embarked upon a crash redesign project hoping to phase out the old product and phase in the new product without publically admitting the defective design. However, pressure from surgeons using the product prompted a recall before the switch was accomplished. • A letter was written to selected surgeons and distributors announcing the recall. However, a number of patients were implanted with the product during the phase-out, phase-in period and even after the recall because of its incomplete notification. Additionally, patients with early stage failures were not promptly diagnosed because of incomplete notification to orthopaedic surgeons. Should all implanted patients have been informed?
