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
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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
DePuy LCS Knee
Polyethylene Tibial Insert
DePuy LCS Knee
Titanium Alloy Tibial Component
DePuy LCS Knee
Titanium Alloy Tibial Component
DePuy LCS Knee
Titanium Alloy Tibial Component
DePuy LCS Knee
Cobalt Chrome Femoral Component
DePuy LCS Knee
Cobalt Chrome Femoral Component
Feldmuhle Ceramic Hip Ball
• Manufacturing flaw
– large grain size in ceramic ball
Feldmuhle Ceramic Hip Ball
Feldmuhle Ceramic Hip Ball
Feldmuhle Ceramic Hip Ball
Feldmuhle Ceramic Hip Ball
Feldmuhle Ceramic Hip Ball
DePuy ACS Cup
• Design flaw
– Inadequate stress analysis of hip acetabular
component
DePuy ACS Cup
Polyethylene Insert
DePuy ACS Cup
Polyethylene Fragments
DePuy ACS Cup
Titanium Alloy Shell
DePuy ACS Cup
Cobalt Chrome Head
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
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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
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 overstressed 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?
ACS Cup (continued)
• Thousands of lawsuits resulted, some seeking punitive
damages for callous disregard by the manufacturer of the
dangers inherent in this product after they were fully aware of
the problems. To date, all suits have been settled out of court.
• Who is to blame? manufacturer, design engineer, his
supervisors, employees who became aware of the problem,
surgeons for using an unproven product, FDA for allowing
the use of an unproven product, the law, the hospitals for
allowing surgeons to use an unproven product, lawyers?
Effect of Radiation Sterilization
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Radiation in air embrittles polymers.
This has been known since 1950s.
Polyethylene components radiated in air.
Are manufacturers responsible for early
implant failures from poly damage?
Guidant Heart Defibrillators
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Ventak Prizm 2 DR and Contak Renewal.
28,900 implanted.
February 2005 - failed at 1/month.
March to May 2005 - 2 deaths.
Circuit flaw found, but sold for months after.
June 2005 - recalled after 45 reported failures.
J&J to purchase at $76/share.
November 2005 -Deal renegotiated to $63/share.
January 2006 - Boston Scientific at $80/share.
Issues for Discussion
• What can be done to prevent the introduction of
potentially dangerous products yet not completely
stop innovation?
• Can FDA be better insulated from political
pressure?
• Should we change the law? (Tort Reform)
• What is the professional responsibility of the
employee?
• How do we protect the employee from retribution
when problems are reported?
Issues for Discussion
• Should the FDA regulate the practice of medicine?
• Biomaterials Access Assurance Act of 1998.
Federal pre-emption of state law.
• Weigh decreased cost for manufacturers vs
protection for patients
• Punitive damages
• Payment by insurance companies for experimental
procedures
• Long wait for FDA approvals