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U.S. Department of Health and Human Services

About FDA

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FY 2001 Artificial Organ Replacements And Assists

Advances in the development of artificial organs and organ assists will be driven by the continuing dearth of natural donor organs. The products in this category are among the most complex that the Center evaluates, and their public health significance is often profound. OST's projects are directed toward elucidating the underlying mechanisms by which these devices interact with the body so as to provide methods for addressing key issues of safety and effectiveness. These activities are targeted to identify key scientific questions early in the Total Product Life Cycle for new technologies, and to provide meaningful techniques to answer those questions.

OST's Division of Physical Sciences (DPS) has a number of issues under investigation related to the successful use of artificial organs and organ assists including 1) damage to blood induced by cardiovascular devices, 2) the safety and effectiveness of prosthetic heart valves, 3) the consistency in performance of cerebral spinal fluid shunts, 4) the optical quality of intraocular lens implants for refractive corrections of otherwise healthy eyes, and 5) issues related to neural stimulation. In each case, the goal is to develop information that will assist Center decision-making in the timely assessment either of manufacturer's submissions or of unforeseen problems following introduction into commerce.

Many of these projects are directly coupled into regulatory guidance and standards-setting activities. For example, the need for better designs fuels a steady stream of heart valve submissions to the Agency. The goal of the laboratory effort is to provide reliable, easily interpreted methods for evaluating new heart valve designs. DPS also has a long history of working with both national (ANSI) and international (ISO) standards groups to develop standards on refractive implants. Current laboratory work examines the performance of new intraocular lenses (IOLs) being developed for the correction of myopia and hyperopia. These phakic IOLs are implanted in otherwise healthy eyes and the natural crystalline lens is left intact. This new wave of phakic IOLs implanted in otherwise healthy eyes, addresses patients with severe corrections that are difficult to treat with spectacles, contact lenses or laser surgery. DPS' laboratory studies develop test methods and performance standards for assessing the optical quality of these new IOLs. Laboratory work on electrical stimulation has been used to help formulate regulatory guidance for spinal cord stimulators, and to revise national standards for nerve stimulators. Additionally, this research serves as a basis for the pre-market review of a number of investigational sense-organ replacement devices, including cochlear and middle ear implants as well as artificial retinas.

Assessing Blood Trauma in Medical Devices

Key words: hemolysis, blood damage, medical devices

Prior to their use in patients, medical devices are evaluated for their potential to damage or activate blood elements by a battery of laboratory tests. One aspect of this hemocompatibility evaluation includes determining that both the materials used in the device and the device itself, when operated at its maximum conditions, do not cause excessive damage to red blood cells (i.e., hemolysis). In the past year OST scientists continued to standardize the assessment of chemically and mechanically induced blood trauma in medical devices.

OST worked with manufacturer testing laboratories to upgrade and evaluate the testing methodology in the document "Standard Practice for Assessment of Hemolytic Properties of Materials (ASTM F756)" for use in national and international standards. To test for chemically induced blood damage in this standard, medical device materials and their extracts are exposed separately to rabbit blood under static test conditions. Interlaboratory round-robin testing using positive and negative control materials and extracts showed consistent results within each laboratory. However, the more variable results between laboratories are being used to determine precision and bias for the test system.

OST scientists also joined researchers from the University of Pittsburgh Medical Center and the Cleveland Clinic Foundation in conducting a workshop exploring flow-induced blood trauma in medical devices in September 2001. The presentation topics included testing for red blood cell mechanical fragility on the bench, identifying factors which affect hemolysis testing (e.g., animal-to-animal variability, hematocrit, temperature), and evaluating medical device testing from a regulatory perspective. Important areas of research identified by the workshop participants included the effects of medical devices on white blood cells and platelets, blood clot formation and release from devices (i.e., thrombosis and embolization), visualization of flow around devices, and the increasing role of computational fluid dynamics in complex medical device design.

Interlaboratory Comparison of Heart Valve Fluid Mechanics

Key words: prosthetic heart valves, left heart simulator, pulse duplicator, fluid dynamics

The evaluation of prosthetic heart valve hydrodynamic performance relies on the use of a left heart simulator also known as a pulse duplicator. Manufacturers and test centers have developed various pulse duplicators and associated instrumentation. Recently, the concurrent need to update both the FDA premarket review guidance and the existing ISO international standard for prosthetic heart valves have prompted a study of the current test technology. The goal of this study is to understand the interlaboratory consistency of current test technology associated with the two primary hydrodynamic measures of heart valves -- pulsatile flow pressure drop and regurgitation. These measures are necessary in order to compare the performance of different valves or valve designs.

The collaboration, coordinated by OST labs, includes the pulse duplicators used by several manufacturers and test centers in addition to two left heart simulators maintained by OST. OST has developed and finalized protocols. These call for a round-robin evaluation of test valves. The test valves used to evaluate the measurement systems were obtained from the participating manufacturers and then first evaluated by OST. They will be circulated to all participating laboratories for testing and then tested again by OST. OST will perform the analyses and report the results.

Design and Optimization of a Flexible System for Digital Particle Image Velocimetry Fluid Flow Analysis

Key words: flow visualization, Digital particle image velocimetry (DPIV), standard test method, validation

Digital particle image velocimetry (DPIV) is a flow visualization tool that provides for a quantitative 2-D velocity vector mapping of flow patterns. The technique uses clear plastic models to examine the effect of specific medical devices upon blood flow in the body. This measurement technique can identify zones of flow stagnation or high shear stress, either of which can lead to adverse effects. Flow stagnation can cause thrombosis, embolism, and stroke. Excessive shear causes hemolysis, that is, ruptured red blood cells.

DPIV requires two high-intensity light pulses to illuminate fluorescent beads flowing through the region of interest. These pulses are separated in time by a fraction of a second. The changes in bead positions observed in the two images provide the information needed to compute fluid velocity. Short intense pulses are needed to freeze the motion of the particles. Laser pulses coupled to the model by fiber optics provide the most practical method of illuminating the model system. However, the intense pulses approach the damage thresholds of the fiber optics.

Three commercially available solid silica core fiber optic links were evaluated for providing a flexible laser illumination sheet for DPIV applications. In addition, the peak power density damage threshold was determined. The damage threshold varied from 2.1 GW/cm² for the smallest 100 m m fiber to >3.3 GW/cm² for the largest 365 mm high power delivery fiber. These three fibers are marginally useful for DPIV applications. To improve power delivery, OST began testing a new fiber link with potentially better laser power delivery capability. Scientists used a hollow glass taper coupled to a specially coated hollow fiber waveguide with a hollow air core diameter of 300 mm and coated for transmission @ 532 nm. This new fiber technology can handle peak power density levels in excess of 10 GW/cm².

Safety of Electrical Stimulation to Neural Tissue

Key words: nerve, brain, computer model, high frequency, neurology, electrical stimulation

Many organ-assist devices employ electrical stimulation to alter physiology and treat pathologies. Recently, a number of developing electrical stimulation devices initiated paradigms for rapid-rate neural stimulation. The safety of such stimulation, which is beyond the physiological range of neuronal activation, has not been studied. In FY 2001, OST scientists examined the effects of rapid-rate stimulation in computer-modeled and real nerve cells. Stimulation at these rates will induce nerve depolarization and the irregular firing of nerve impulses. This was shown by the model and by actual experiments. The work positioned the Center to anticipate safety issues early, and it was applied to a broad number of regulatory reviews, several international standards, and several FDA guidance documents.