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FY 2008 OSEL Division Descriptions

 

DIVISION OF BIOLOGY (DB)

DB participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of biological sciences. Specifically, DB conducts research to support the Center’s mission to assure the safety and effectiveness and promote the improvement of medical devices in the areas of biological risk assessment, biosensors/nanotechnology, genomic and genetic technologies, infection control and sterility, tissue-device interactions, toxicity/biocompatibility, and radiation bioeffects.  Through laboratory studies, researchers evaluate the potential adverse effects of medical devices on host biological systems and, in collaboration with engineering divisions, identify the source and impact of product degradation on organ systems both under acute and chronic conditions. The Division staff develops measurements methods and analytical procedures to characterize and evaluate devices and products, studies molecular and cellular mechanisms and bioeffects of biomaterials, and supports the Center’s enforcement and product testing activities.   

The DB staff members are primarily biologists, chemists, and biomaterials scientists.  

Laboratories
  • Biological Risk Assessment
  • Biomolecular Mechanisms
  • Biotechnology
  • Cardiovascular and Interventional Therapies
  • Toxicology

DIVISION OF CHEMISTRY AND MATERIALS SCIENCES (DCMS)

DCMS participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of chemistry and materials sciences. Specifically, the DCMS focus is on the developing experimental data, test methods and protocols for regulatory and scientific activities involving multicomponent mass transfer, reaction kinetics, absorption and swelling of network polymers, polymer processing, modeling of physiological processes, and materials degradation. Research conducted in the division includes polymer synthesis; synthesis of polymeric nanocomposite materials; sensors; thermodynamics; thermal transitions and phase stability; hydrogel and biopolymer synthesis and characterization; polymer formulation; separations; spectroscopy; small-angle x-ray and neutron scattering; and shelf-life and service life prediction. DCMS tests the performance of chemical processes of importance to medical devices, such as mass transfer through membranes used in dialysis and blood oxygenation, and manufacturing processes used to fabricate materials.

The technical disciplines of the DCMS staff include physical chemistry, chemical physics, polymer science, pharmacology, materials science, and biomedical and chemical engineering. 

Laboratories
  • Active Materials
  • Materials Performance

DIVISION OF ELECTRICAL AND SOFTWARE ENGINEERING (DESE)

DESE participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of electrical engineering and software. Specifically, the DESE works in the application of electronics, software engineering, and systems engineering body of knowledge to the regulation of medical devices and electronic products that emit radiation. The Division addresses the cutting edge of medical devices through all phases of the product life cycle and all aspects of the product manufacturer’s business, from research and development through procurement, production, and ongoing customer support. DCMS hosts the following resources and capabilities: analog and digital circuit design, data acquisition and display, embedded microprocessor and PC-based systems, software-based virtual instruments, quality management and risk management as applicable to electronics and software, testing for hazards arising from the use of electrical and electronic technology in medical products, and electronic design including components, circuits, and analytical techniques for controlling high voltages and/or currents.

DESE staff members are primarily electronics engineers, physicists, biomedical engineers, and general engineers.

Laboratories
  • Electrical Engineering
  • Software
  • Systems Engineering

DIVISION OF IMAGING AND APPLIED MATHEMATICS (DIAM)    

DIAM participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of medical imaging and applied mathematics. Specifically, DIAM provides scientific expertise and carries out a program of applied research in support of CDRH regulation of radiation-emitting products, medical imaging systems, and other devices utilizing computer-assisted diagnostic technologies. Medical imaging research encompasses ionizing and non-ionizing radiation from data capture through image display and observer performance. The computer-assisted diagnostics work of DIAM is focused on the appropriate mathematical evaluation methodologies for sophisticated computational algorithms used to aid medical practitioners interpret diagnostic device results. The Division is charged with developing and disseminating performance assessment methodology appropriate to these modalities. DIAM operates a calibration laboratory for ionizing radiation detection instruments and participates in a full range of programs in support of the Public Law 90-602 mission of the Center. 

DIAM staff members are primarily physicists, mathematicians, and physical science technicians. 

Laboratories
  • Image Analysis
  • Imaging Physics  
  • Ionizing Radiation Metrology 

DIVISION OF PHYSICS (DP)

DP participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of physics. Specifically, DP conducts research and engineering studies to support the Center’s mission to assure the safety and effectiveness of medical devices and electronic products, and to promote their improvement. Scientific and technical specialties in the division include optical physics and metrology, sensors, fiber optics, electromagnetics, electromagnetic compatibility and electromagnetic interference, electrophysics and electrical stimulation technologies, electrophysiology, radiofrequency/microwave metrology, and minimally invasive optical and electromagnetic technologies. The Division develops measurement methods, instrument calibration capabilities and analytical procedures to characterize and evaluate devices and products, and supports the Center’s enforcement and product testing activities. DP evaluates interactions of electromagnetic and optical energy with matter, analyzes implications for the safety and effectiveness of devices and products, and develops and evaluates procedures for minimizing or optimizing human exposure from such devices.

The technical disciplines of DP staff include physics, mathematics, biophysics, biomedical engineering, electronics, and general engineering.

Laboratories
  • Electromagnetic and Wireless Technologies  
  • Electrophysiology and Electrical Stimulation
  • Optical Diagnostics   
  • Optical Therapeutics and Medical Nanobiophotonics

DIVISION OF SOLID AND FLUID MECHANICS (DSFM)

DSFM participates in the Center's mission by conducting research, participating in device review activities, developing consensus standards both domestic and international, developing regulatory guidance, testing forensic and regulatory samples, and providing educational programs in the area of solid and fluid mechanics. Specifically, the core responsibilities of this division involve issues for which mechanical interactions or transport are of primary concern, such as those involving motion; structural support, stabilization, or vibrations; device and material mechanical integrity; materials durability; and biologically relevant parameters of device and materials. The Division has expertise in the areas of fluid dynamics, solid mechanics and materials, acoustics and ultrasonics. DSFM develops measurement methods, instrument calibration capabilities, and analytical procedures to characterize and evaluate devices, device materials, and products, and supports the Center's enforcement and product testing activities. DSFM staff also evaluate interactions of ultrasound energy with matter and the implications of these interactions on the safety and effectiveness of devices and products. 

Technical disciplines of the DSFM staff include mechanical engineering, materials science, biomedical engineering, general engineering, and physics. 

Laboratories
  • Fluid Dynamics
  • Solid Mechanics
  • Ultrasonics

STANDARDS MANAGEMENT STAFF (SMS)

The Standards Management Staff (SMS) is responsible for facilitating the recognition of national and international medical device consensus standards. CDRH is invested in the development of medical device standards and participates significantly in the development process. SMS manages the Standards Program, a regulatory support activity consisting of cross-office teams within CDRH and FDA. This involves working closely with the Standards Developing Organizations (SDOs), advertising standards liaison representative positions, facilitating a Center recommendation to serve on a particular standards activity, and maintaining an appropriate standards database providing access to established standards for all CDRH staff, field inspectors, and industry. SMS continually updates currently recognized standards and coordinates the recognition of new voluntary consensus standards for medical devices and radiation-emitting electronic products. SMS ensures appropriate medical device standards are published in the Federal Register at least twice annually. The Standards Program was created as a result of the Food and Drug Administration Modernization Act (FDAMA) of 1997. Although CDRH had been involved in the development of medical device standards for decades, FDAMA formalized the process. 

Please refer to the following web page for additional information on the CDRH and FDA standards program: http://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/Standards/default.htm

MANAGEMENT SUPPORT STAFF (MSS)

MSS provides leadership and support to the Office of the Director, Division Directors, and laboratory professionals on all administrative, general management, and knowledge management issues. MSS is responsible for planning, developing, and implementing Center and OSEL programmatic matters concerning financial management, personnel, procurement, contracts, inter-agency agreements, employee training, and facilities.

MSS is also tasked with managing and administering OSEL resources designed to support on-going programs. The staff ensures the proper distribution of operating and payroll dollars, facility plans, procurement and property, travel requests and ADP needs. MSS advises the Office of the Director on potential issues that may affect resources, staffing, and management issues to comply with policies and avoid potential conflicts. In addition, MSS directs and conducts special assignments or projects for the Center as well as the Office Director.   

Office of Science and Engineering Laboratories

Research Laboratories and Selected Accomplishments   

 Active Materials (Division of Chemistry and Materials Sciences)

Scientists in the Active Materials Laboratory investigate materials used in devices in which the time dependence of materials properties is a key component of how the device's mode of action is provided. This includes combination products in which medical devices incorporate some material-based mechanism for drug delivery, such as drug eluting stents. It also includes nano-materials, in which the properties of the nano-particles are critical to delivery of expected results.  

Accomplishments 

Assessing the stability of nano-scale constructs Completed in-vitro testing to assess the impact of particle size distribution and environment on ion release.

  • Completed calculations in 1D.
  • Established toxicity and organ distribution of silver nano-particles (AgNP) in rat model (abstract submitted to Society of Toxicology for presentation in March 2009).
  • Extended computation model to 2D systems with complex geometry.
  • Demonstrated the validity of the model by establishing consistency between the model predictions and the in-vitro observations.   
  • Completed development and validation of a thermodynamically consistent 2D model that can be used to assess the impact of chemistry, size, shape, distribution, and environment of the electrochemical response of NP systems. 
  • Conducted simulations based on the model to elucidate the impact of NP geometry and environmental factors, such as substrate and solution chemistry, on ion release for AgNP systems.
  • Established micro-biological capabilities in laboratory and measured antimicrobial activity of AgNP on three different bacteria strains.
  • ICP-MS methods development for measuring silver content in low-concentration nano silver solutions in collaboration with the Center for Food Safety and Nutrition.  

Materials Performance (Division of Chemistry and Materials Sciences)

Scientists in the Materials Performance Laboratory investigate materials used in devices in which the physical/chemical properties of a material impact its performance and the long-term behavior of these properties affect the device's safety or effectiveness. For example, the long-term performance of implanted electronic devices, such as cochlear implants or pacemakers, depends on the continued hermiticity of the devices' casings. Intraocular lenses used in cataract and other surgeries need to maintain their optical properties over time. Finally, mechanical performance and degradation of hydrogel materials, such as hyaluronic acid, may affect the safety and effectiveness of adhesion barriers and other devices. 

The use of new materials and processing technologies is a challenge to the regulation of new medical devices. The knowledge gap between the Center’s understandings of existing materials used in devices evolving technologies will tend to increase the time required for the review of these submissions, as our staff “comes up to speed” in these areas. Through directed research activities, it is the goal of this laboratory to develop such expertise and insights into the behavior of new materials used in devices and the effects of manufacturing on their safety and efficacy. 

Hermiticity in Active Medical Devices

  • Early experimental results for the moisture penetration through conformal polymeric coatings suggested that water was able to penetrate the coating in 1 – 5 days depending upon the coating thickness and substrate surface morphology. 
  • Successfully initiated research collaborations with leading experts in the field of molecular transport in polymer films in order to understand these results and have undertaken experiments that utilize time resolved ATR spectroscopy to assess the water transport properties of vapor deposited parylene films. This is the first time that this technique has been applied as an evaluative tool to assess the barrier properties of vapor deposited polymer films. 
  • Augmented the existing parylene coating system by constructing a new gas inlet baffle to ensure that we are producing the highest quality specimens for these cutting edge experiments. This addition allows for the deposition of a higher quality, more uniform, and defect-free parylene film.
  • Successfully developed methodology to produce selectively parylene coated ATR crystals, essential for water diffusion measurements, by utilizing a liquid silicone rubber molded mask/gasket. 
  • Performed thermal characterization (DSC), water diffusion measurements, and complementary structural studies via both wide angle (WAXS) and small angle X-ray scattering (SAXS) to explore how the structure and transport properties of parylene films are affected by thermal history. By varying the specimen temperature in an in-situ, small-angle scattering experiment, researchers observed a marked increase in the sharpness and intensity of the scattering peaks consistent with the 020 and 110 reflections of parylene’s monoclinic phase. Additionally, scientists observed the evolution of a peak consistent with the formation of parylene’s phase as a function of temperature. Thus, the crystalline structure of parylene films increases and changes with moderate annealing (24 hours, 180oC). Experiments are currently underway to quantify how these structural changes affect the transport of water through parylene films. 
  • Conducted the chemical characterization of these films, both annealed and unannealed using micro-Raman spectroscopy.

  Biological Risk Assessment (Division of Biology)  

Risk assessment is the process of determining the extent of human health hazard relative to exposure conditions. Staff in the OSEL Laboratory of Biological Risk Assessment: 1) conduct research to address CDRH’s regulatory need for improved methods of detecting and quantifying risks associated with chemical compounds, microbial agents, and radiation released from medical device materials; and 2) conduct risk assessments to inform risk management decisions in the Center.  Research is focused the following areas:

1. Safety of reprocessed medical devices: Research in this area includes the assessment of the toxicity of residual disinfectants/sterilants and the efficacy of methods to remove residual bioburden on reprocessed devices.

2. Development of clinically relevant biomarkers and preclinical animal models: Research in this area was identified as being central to the FDA Critical Path Initiative.

3. Bioeffects of ultrasound and ultrasound contrast agents: Involves an assessment of the extent of the vascular endothelial and smooth muscle damage by microbubble-based ultrasound contrast agents and its role in the pathogenesis atherosclerotic changes. 

  Biomolecular Mechanisms (Division of Biology)

New genomic and genetic technologies are expected to impact CDRH in major ways. The Center is beginning to receive submissions of genomic and genetic diagnostic microarray devices and expects more--some in co-development with drug or biological therapeutics. In addition, these technologies will be used to evaluate the safety of products such as implants and materials (toxico-genomics). However, considerable technical uncertainties impede the acceptance of these products and data. The Genomics Laboratory is providing support to the Center via 1) prioritization of the technical issues affecting microarray data that impact product review, and 2) application of the new technologies to both new and long-standing problems, including medical device adverse events, identification of medical device pathogen contaminants, and safety evaluation of products. Additionally, the Cell Biology Laboratory is investigating immunotoxicity related to particular patient susceptibility, in regards to biomaterials and devices that contact patient blood.

  Biotechnology (Division of Biology)

The biotechnology laboratory’s mission is to study various aspects of microbial pathogen contamination of medical devices and to reduce the risk of microbial infection from contaminated medical devices and to study the biocompatibility of nanoparticles. The laboratory’s main research projects are focused on evaluation of nanoparticles properties and on microbial detection and analysis, using an interdisciplinary research approach that integrates engineering and molecular biology.

  Cardiovascular and Interventional Therapeutics (Division of Biology)

The Laboratory of Cardiovascular and Interventional Therapeutics (LCIT) investigates the safety and effectiveness of a range of interventional therapeutics, including cardiovascular and minimally invasive devices and related adjunctive agents. This includes the application of emerging imaging technologies to guide the delivery of novel therapeutic devices and agents. Local delivery of therapeutic devices alone or in combination with other agents via percutaneous catheters or direct surgical access has shown great clinical promise for the treatment and prevention of vascular disease and cancer. The laboratory’s Research Program includes both normal biology and the pathologic basis for disease and device failure at the genetic, molecular and tissue levels and the development of animal models that are predictive of clinical safety and effectiveness.

The focus is on studying existing models and developing more predictive models of device use and related failure modes including identification, evaluation and development of more optimal clinical treatment algorithms for image-guided interventions and drug delivery, such as tumor ablation. In addition, retrospectively, the models have been used to support applications for vascular devices. The in vivo models under study include both normal swine and swine models of human disease, i.e., those with vasculopathy induced by diet (atherogenic high fat/high cholesterol diets), mechanical manipulation (iatrogenic injury from balloon angioplasty or stenting), hormonal manipulation (castration, hormone replacement therapy), hemodynamic alterations (vascular ligation, fistulas) and/or metabolic manipulation (diabetes mellitus). These preclinical animal studies address the problem of identifying and assessing regulatory science issues associated with novel interventional and combination therapeutics and delivery technology including image guidance tools for the treatment of vascular disease and cancer. 

Toxicology ((Division of Biology)  

This is an interconnected program of laboratory research, risk assessment, and standards development activities designed to provide a scientific basis for regulatory decision making in CDRH. Researchers evaluate the potential adverse effects of medical device materials and chemicals, including nano-sized particles, using in vivo and in vitro experimental models and approaches. Scientists use data to reduce uncertainties in assessing risks to patients exposed to physical and chemical exposures, and ultimately protect their health. 

A primary focus of the program in 2006-07 was evaluating bioeffects of nanoparticles. The unique properties of nanoparticles (very small size, large surface area, increased biological activity) drive the current explosion in nanotechnology innovation in health care delivery. FDA-regulated products expected to utilize nanotechnology include implants and prosthetics, sensors for disease diagnosis, and drug delivery and personal care products. In contrast, these same properties may impart negative or undesirable effects on biological systems. Attempts to understand the potential adverse effects of nanoparticles are limited, and very few resources have been committed to research needed to address and understand risks to patients.

Accomplishments 

Evaluation of the biological effects of titanium nanoparticles (25-nm) in vivo and in vitro

  • Established working collaborations with CDER, NCL-NCI, and the University of Maryland.
  • Characterized TiO2 particles by dynamic light scattering spectrometry prior to experimental use, and by electron microscopy and energy dispersive X-ray scattering to visualize particles (or aggregates) in tissues after exposure.
  • In vivo studies – Determined the tissue distribution of aggregates, histopathology, distribution time course, blood cell changes, and production of inflammatory cytokines. Specifically, results have shown: 1) route of administration (intravenous vs subcutaneous) affects tissue distribution; 2) observed a re-distribution but no clearance of clumps of nanoparticles up to 6 months post-exposure; and 3) observed minimal toxic responses to titanium nanoparticles after 6 months exposure.
  • In vitro studies - Increased production of reactive oxygen species and loss of cell membrane integrity was observed at higher TiO2 doses and longer exposure times in cultured J774 macrophage cells. Cytokines released from cells included TNF-a, IL-1b, IL-6, and GM-CSF with increasing dose and exposure time to TiO2.  These data suggest macrophage accumulation of TiO2 aggregates may result in cytokine release and potential cytotoxicity in cells and tissues responsible for TiO2 clearance from circulation. 

Evaluation of silver nanoparticles (5-40-nm) in vivo:

  • Established working collaborations with University of Florida (tissue silver analysis via ICP-MS) and The George Washington University.
  • Initiated studies of placental transport of silver nanoparticles into mouse embryos after exposure of pregnant dams. A Zetasizer (Malvern Instruments Co) has been purchased to measure size and surface charge for the characterization of each batch of particles. Researchers have detected silver from treated mice in embryonic tissues and adult tissues.

Evaluation of silicon nanoparticles in vitro:

  • Established working collaborations with University of Maryland and NIST to produce well characterized, sterile, endotoxin-free silicon nanoparticles.
  • Observed apparent intracellular uptake of fluorescent silicon (4-nm) particles by murine macrophage cells, a cell line relevant to measure potential inflammatory responses to particles.
  • Determined intracellular uptake occurs without resulting cytotoxicity.
  • Effect of particle size on biological effects--Measured tumor necrosis factor-α, interleukin-6, and nitric oxide production by macrophages in the presence of silicon nano- and micro-sized particles. 

  Electrical Engineering (Division of Electrical and Software Engineering)

Electrical engineering is an enabling technology for many, if not most, classes of medical devices. Devices that incorporate this technology are inherently complex and require that engineers must be able to skillfully peel back many layers of abstraction from the underlying mathematical and physical models that govern device operation, to their hardware and software realizations, and down to the physical characteristics of component parts.

A large body of knowledge has developed within the electronics, embedded software, and systems engineering communities to assure successful application of these technologies. The mission of the Electrical Engineering Laboratory is to apply this body of knowledge to the regulation of electronic medical devices and electronic products that emit radiation.

The breadth of the engineering disciplines needed poses a significant challenge. The body of knowledge is segmented into numerous areas of specialization, power engineering, electromagnetic and static immunity, microminiaturization and signal processing. Within industry, large manufacturers typically have sizable organizational components to address those engineering segments (specialties) having most relevance to their needs. Small manufacturers typically have specialists in just a few key areas and rely on consultants or other external resources to augment their in-house capabilities.

The laboratory maintains a suite of special-purpose, computer-aided engineering tools and laboratory facilities having broad applicability to medical device electronics and embedded software and we rely on external sources for specialized capabilities that are needed on an occasional basis.  

Software (Division of Electrical and Software Engineering)

The scope of this laboratory’s activities is to support CDRH pre-market and post-market software evaluation activities by establishing relevant in-house expertise and identifying, qualifying, quantifying, and communicating conformity assessment techniques and criteria which the Center can use to fulfill its mission.

Software is one of the most ubiquitous enabling technologies for many, if not most, classes of medical devices. Devices that incorporate this technology are inherently extremely complex and require that engineers must be able to skillfully peel back many layers of abstraction from the underlying mathematical, behavioral and physical models that govern device operation, to their hardware and software realizations, and down to the physical characteristics of component parts.

A large body of knowledge has developed within the software engineering community, embedded software industry, and systems engineering communities to assure successful application of these technologies. The mission of the DESE Software Laboratory is to apply this body of knowledge to the regulation of electronic medical devices and electronic products that emit radiation.

An essential element of the program is to identify and develop in-house specialized analytical tools and laboratory facilities. We maintain a suite of special-purpose, computer-aided verification tools and laboratory facilities having broad applicability to medical device software and embedded software, and we continue to leverage external sources for specialized capabilities that are needed on an occasional basis.

Systems Engineering (Division of Electrical and Software Engineering)

This laboratory applies a systems engineering perspective to medical device regulatory issues.

With the advent of systems of devices, closed-loop devices, and intelligent devices, the fabric of regulation and FDA’s historic enforcement discretion policy needs to be continually revisited to determine its ongoing ability to get as many safe systems to market and to allow them to remain safe while there. The expertise developed through this laboratory is being used to educate reviewers across the Center and provide a basis for the evaluation and drafting of new classification regulations, guidance documents and enforcement policy.

  Electromagnetic and Wireless Technologies (Division of Physics)   

Research is focused on several concerns associated with medical devices that utilize or are affected by electromagnetic (EM) fields. The primary concern is to address the rapid deployment of wireless technology around and into medical devices, and to address the safety and effectiveness issues associated with electromagnetic interference (EMI) disruption of medical devices and the deposition of the electromagnetic energy in the human body. Another concern is to develop methods to evaluate medical devices used for ablation of body tissues and the measurement and evaluation of EM heating and the evaluation of devices used intentionally to hear body tissues. A principle goal of this effort is to develop standard techniques for the measurement and evaluation of RF heating for both high and low frequency electromagnetic devices. A third area involves the safety of patients undergoing magnetic resonance imaging procedures. Patients with implanted devices, and electrodes or other devices attached to the body, are being imaged by MRI, and some are being injured or even killed due to heating from the intense EM fields produced by the radiofrequency (RF) coils during clinical imaging procedures. Medical device manufacturers are submitting requests for approval of their devices as MRI compatible, e.g., allowed to be in or attached to the patient during MR imaging procedures

The wireless technology revolution together with a flood of new medical devices incorporating sensitive microelectronics is leading to a highly unstable situation. Dangerous malfunctions and numerous patient injuries have been induced in medical devices via electromagnetic interference (EMI) from electromagnetic fields emitted by wireless equipment. This equipment includes cellular phones, magnetic-field emitting security devices (such as airport metal detectors), radiofrequency identification (RFID) systems and other medical devices such as shortwave diathermy and magnetic resonance imaging (MRI). DP leads the FDA effort to make all electrically powered medical devices electromagnetically compatible (EMC) with the electromagnetic environment where they are used. In addition to EMC, concerns are continually raised by the public and the news media about the possible harmful effects of exposure to radio frequency (RF) electromagnetic fields (also known as non-ionizing RF radiation) from handheld wireless (cellular) telephones and other wireless personal communications devices.

Accomplishments

  • Developed new electromagnetic compatibility test method for implanted cardiac stimulation devices exposed to radiofrequency identification (RFID) emitters. Collaborated with medical device manufacturers and other researchers to draft a new ANSI/AAMI standard for testing.
  • Performed a large scale postmarket electromagnetic compatibility testing of medical devices for radiated susceptibility under the sponsorship of the Department of Homeland Security.
  • Developed detailed computer anatomical models (2 adults and 2 children) with 1 mm resolution for computational assessment of electromagnetic field exposure of personnel in collaboration with the Foundation for Research on Information Technologies in Society (IT’IS), Switzerland
  • Developed and published results of the first in-vitro method to assess MRI safety of passive and active implanted medical devices exposed to gradient fields from MRI systems. Drafted a new IEC/ISO standard for testing these devices.
  • Performed computer modeling and lab studies to assess a postmarket issue of widespread reports of patient burns from ground pads of electrosurgical units.  Discovered a flaw in the AAMI HF-18 standard test procedure.

  Electrophysiology and Electrical Stimulation (Division of Physics)

Medical devices that rely on electrophysiology and electrical stimulation for safety and efficacy cut across all medical specialties. The most important examples are devices that work in the heart and nervous system including the following: cardiac pacemakers, defibrillators, retinal stimulators for blindness, brain stimulators (for Parkinson’s disease, pain, motor function, hearing), electroconvulsive therapy, magnetic brain stimulation, cochlear implants, middle ear hearing devices, spinal cord stimulators, vagus nerve stimulators, and peripheral nerve stimulators (including those for locomotion, breathing, bladder and bowel control). The less obvious examples are devices for the electrical detection of cancer (from breast, colon and cervix), the transdermal electrical extraction of glucose for monitoring, and a number of “complementary and alternative medicine” devices. The scientific discipline of electrophysiology forms a unified basis for the scientific evaluation of all of these devices. The scientific issues involve the basic electrophysiology of a number of body systems and the biomedical engineering of the devices.

The work ranges from research directly applied to a single device type (the retinal stimulator), to broader work that is relevant to a class of devices (cardiac stimulators for treating arrhythmias and heart failure), to far-reaching work on the development of optical stimulation of excitable tissue (supported extramurally). In addition to these areas of research, this laboratory is heavily involved in direct regulatory activities with staff performing as lead reviewers, expert consultants, subject matter experts to FDA Advisory Panels, authors of guidance documents and the revision of international medical device standards.     

Accomplishments

  • Developed software to model magnetohydrodynamic signals for the assessment of blood flow in heart failure. This is part of an FDA Critical Path project for the development of biomarkers of blood flow in heart failure.
  • Completed experiments showing depressed retinal function following certain levels of electrical stimulation of the retina.
  • Performed first use of optical stimulation to evoke nerve impulses in spinal cord dorsal root ganglion cells. This work is the first to show that the optical stimulation time constant is longer than electrical stimulation time constant.
  • Successfully grew rat neonatal heart cells on bioengineered flexible surfaces for testing arryhtmogenic effects of mechanical/electrical dysynchrony. This work is applicable to device therapies that attempt to synchronize electrical and mechanical activity.
  • Measured arrythmogenesis with multi-site optical recording from transmural preparation from a porcine model of sex differences in heart failure. This is part of an FDA Office of Women's Health-funded project in collaboration with the Uniformed Services University of the Health Sciences.
  • Implemented the use of an arbitrary waveform defibrillator (invented by Dr. Giovanni Calcagnini's laboratory at the Italian National Institute of Health) to study the safety of new defibrillation waveforms with multi-site optical recording from isolated rabbit heart.
  • Completed technique for analyzing optical and electrical cardiac excitation to discern sources of currents involved in cardiac excitation and arrhythmia formation.
  • Developed an animal model for testing cardiac ablation techniques and outcomes for the treatment of atrial fibrillation.

Fluid Dynamics

This laboratory studies the interaction of moving fluids with medical devices, such as evaluating blood damage caused by medical material.  

Accomplishments

  • Developed a platelet-counting protocol that includes a platelet fixation step to stabilize platelet number, so that the samples could be stored for 24 hours before analysis.  
  • Developed an Enzyme-Linked ImmunoSorbent Assay (ELISA) protocol for the analysis of a plasma platelet activation marker; serotonin. The consistency of this assay will be verified in the next year using both human and cow blood.
  • Started experiments on the relationship between platelet activation status by flow cytometry and platelet aggregability (by aggregometer) using chemical and mechanical activation. This will compare how the expression of platelet activation markers actually predicts platelet functionality.
  • Fabricated blood clots to aid in the in vitro assessment of the efficiency of vena cava filters to catch them. 
  • Developed and submitted an FDA Critical Path Initiative proposal with academic collaborators for Year 3 funding to evaluate computational fluid dynamic validation and accuracy for designing medical devices and assessing blood damage safety. 
  • Computational fluid dynamics (CFD) is increasingly being used in developing blood-contacting medical devices. However, the lack of reliable standardized techniques for assessing the validity of CFD models limits the use of this tool by industry and the FDA in the evaluation of new products. Through an FDA science initiative, participants from academia, industry, and the FDA began an interlaboratory study on a benchmark flow model (nozzle design) to determine the applicability and limits of current CFD simulations in evaluating medical devices.

  Image Analysis (Division of Imaging and Applied Mathematics)

A wide variety of new digital imaging and display devices is under development by academia and industry, with a broad range of performance characteristics. The Center requires augmented support for the evaluation of such devices. To this end, OSEL scientists in this laboratory are developing a fundamental understanding of how these new devices operate and are developing a unified methodological approach for validating the applicability of these new diagnostic medical systems. The emphasis of the Image Analysis Laboratory is to understand the building block of computer software tools and develop assessment methodologies that appropriately estimate performance and improve clinical and non-clinical trial designs. Application areas include mammography, optical imaging, computed tomography, nuclear medicine, immunohistochemistry, computer-aided diagnosis, and gene expression. This program is located within the Division of Imaging and Applied Mathematics (DIAM).  

Accomplishments

  • Finished the development of a computer-aided diagnosis (CAD) algorithm for immunohistochemical (IHC) datasets.  Results from this work were presented at ISBI 2008 and have been accepted for publication in IEEE-TMI (April 2009 expected publication date).
  • Completed the development of a study protocol and design of a graphical user interface for a reader study that will assess whether the IHC CAD algorithm improves reader performance and agreement.  The study will be performed in 2009. 
  • CDRH held a public panel meeting to discuss the assessment of radiological CAD algorithms in March 2008. This project's scientists were contributors and presenters at this panel meeting. 
  • Completed a draft of a radiological CAD guidance document. This is currently being reviewed within CDRH, and it is expected to be released for public comment in the spring of 2009.    
  • Collaborated with professors at the University of Chicago on a hybrid-linear-classifier project.  Finished the theoretical derivation, algorithm implementation, and demonstration on simulated and real-world datasets. Results of this study were presented at SPIE 2008 and have been submitted for publication to IEEE-TMI.
  • Developed software for the assessment of classifiers in high-dimensional problems and demonstrated the applications of our methodology and software on the Micro-Array Quality Consortium MAQC-II genomic datasets. Two papers are being written and will be submitted to Nature Biotechnology in 2009 along with other manuscripts by colleagues in MAQC-II.
  • Developed software for the assessment of classifiers when (a) only a single dataset is available; (b) two datasets are available for training and testing the classifier. 
  • Participated in Inter-agency Oncology Task Force (IOTF) collaboration meetings and the IOTF Annual Meeting in December 2008. 
  • Completed phantom data acquisition of over 760 CT scans (4080 reconstructed) at our FDA facility as well as with collaborators at Washington University at St. Louis.
  • Announced the public release of a lung CT database at the 2008 RSNA meeting for lung nodule image analysis software benchmarking and reader training. All CT images will eventually be hosted on the National Cancer Image Archive (NCIA) for general public usage.
  • Developed a computer model for the CT acquisition process that allows simulated CT data sets to be produced. 
  • Initiated OSEL participation in the Quantitative Imaging Biomarker Alliance (QIBA). This is an RSNA-initiated consortium developing guidelines for industry on the use of imaging in drug trials.   

  Imaging Physics (Division of Imaging and Applied Mathematics) 

A wide variety of advanced imaging systems with solid state detectors and digital display devices are under development by academia and industry, with a broad range of performance characteristics. To support the Center’s need for assistance evaluating such devices, OSEL scientists are developing evaluation methodologies for diagnostic medical imaging systems such as mammography and fluoroscopy, computed tomography, nuclear medicine, diagnostic ultrasound, and magnetic resonance imaging, as well as for novel soft-copy display devices for viewing medical images. This program is located within the Division of Imaging and Applied Mathematics (DIAM).  

Accomplishments

  • The second version of MANTIS, a Monte Carlo code for simulation of x-ray, electron, and optical physics relevant for x-ray imaging, was made available to the scientific community. MANTIS incorporates a Monte Carlo package known as the PENELOPE code, through collaboration with one of the developers of this code, Dr. Josep Sempau of the Institut de Tecniques Energetiques, Universitat Politecnica de Catalunya in Barcelona, Spain. This accomplishment enables the combined x-ray/electron/optical simulation of radiation detection at the full energy range of interest in radiological imaging. 
  • Developed specific Monte Carlo simulation tools for 3D x-ray breast imaging systems using MANTIS.
  • Developed methods for the automated, quantitative evaluation of imaging phantoms for use in the objective assessment methods for digital radiography. These methods were validated using both a laboratory imaging system in DIAM as well as a clinical mammography unit at USUHS. 
  • Developed new methods for the efficient computation of objective metrics for image quality for linear imaging systems using feature extraction methods.
  • Developed efficient computation methods for determining the upper bound on imaging system performance for disease detection tasks in images with non-Gaussian, randomly-varying backgrounds. 
  • Developed a unique physical breast phantom consisting of PMMA balls with different sizes and different densities for use in validation of simulation tools and evaluation of 3D breast imaging systems. 

Developed analytical models for detector point response functions that will allow the accurate computational modeling of 3D breast imaging systems with reduced computation times. 

  Ionizing Radiation Metrology (Division of Imaging and Applied Mathematics) 

The scope of the Ionizing Radiation Measurements Laboratory (IRML) is to provide metrology support to the Center’s Radiological Health and Medical Device safety mission. IRML maintains measurement and calibration capabilities for ionizing radiation. The ISO17025-compliant laboratory provides traceability for standards-enforcement measurements, provides metrology expertise for pre- and post-market issues, performs evaluations of x-ray emissions from regulated products, performs evaluations of measurement methods, and represents the Center on appropriate consensus standards efforts.

Accomplishments

Calibration Laboratory Quality and Accreditation Activities

An internal audit was conducted by the senior staff members in the office with support from an external advisor. The calibration laboratory received separate reports from all three auditors. As part of the continuous improvement process, the CDRH XCL will work on incorporating all comments. No deficiencies were noted.  

IR Product Compliance and Field Support 

IRML provided instrumentation and logistics support to FDA and State inspectors for compliance testing of general radiography installations under the Radiation Control for Health and Safety Act (RCSHA), and the voluntary surveys under the Nationwide Evaluation of X-ray Trends (NEXT) program. This included 209 radiation calibrations of general diagnostic instruments for RCSHA and NEXT, 43 radiation calibrations of mammographic instruments, 131 electrical calibrations of radiation monitors, 21 calibrations of non-invasive kVp meters, and 14 calibrations of light meters.  

  Optical Diagnostics (Division of Physics)

The rapid proliferation of medical devices employing minimally invasive optical technology is revolutionizing modern health care. However, these devices also represent a significant new challenge to FDA. For many of these devices, guidance documents and reliable test methods are currently not available. Basic mechanism data is needed to facilitate the development of relevant evaluation criteria early in the regulatory process, thus enabling thorough and swift reviews of this cutting edge technology. The Optical Diagnostics laboratory works to generate this data through studies of light-tissue interaction mechanisms, device performance and tissue safety for a variety of optical technologies. This program is located within the Division of Physics (DP).

Accomplishments

  • Completed a post-market study on the optical and thermal output of adult and neonatal battery powered transilluminators, as requested by the Office of Surveillance and Biometrics. Presented the findings to, and discussed with, OSB. This work provided the Center with a scientific basis by which to assess the need for changes in the regulation of these devices. Furthermore, this study provided the Center with initial insights into a potential emerging safety issue – thermal and optical injury from devices employing ever more powerful light-emitting diodes (LEDs).
  • Completed a research study on the measurement of tissue optical properties – data which is critical for performing accurate computational modeling studies on the safety and effectiveness of optical spectroscopy/imaging devices for minimally invasive detection of mucosal neoplasia. Measured the bulk tissue properties of ex vivo porcine bladder, colon, and oral mucosa were measured, and compiled the results into a publication that was accepted by the scientific journal Optics Express.
  • Completed a research study on novel techniques for processing time-resolved fluorescence data. This work helps to elucidate the strengths and weaknesses of algorithms used by optical spectroscopy devices to generate cancer diagnoses.

  Optical Therapeutic and Medical Nanobiophotonics (Division of Physics)

Biophotonics is an emerging biomedical technology that is increasingly being applied in the extensive areas of life sciences and medicine. Minimally invasive biophotonics techniques have been recently developed as potential alternatives to conventional medical methods for diagnostics, monitoring and treatment of a variety of diseases, drug discovery, proteomics, and environmental detection of biological agents. These techniques offer a non-contact, effective, fast and painless way for sensing and monitoring of various biomedical quantities. Medical devices utilizing minimally invasive biophotonics technology are rapidly finding their way into the mainstream for early disease diagnosis and improved patient acceptance and comfort.

The Optical Therapeutics and Medical Nanophotonics Laboratory (OTMNLab) was established as part of OSEL’s Division of Physics in September 2006. OTMNLab is responsible for maintaining state-of-the-art knowledge of biomedical optics and laser field to assist the Center and Agency in the following:

  • Evaluating new medical therapeutics devices that employ the latest minimally invasive medical laser technology.
  • Evaluating critical fundamental parameters of key laser and fiber-optic components employed in recently developed optical therapeutics devices.  

Accomplishments   

  • Developed, experimentally tested and prepared a patent application for a novel independent test method for precise measurement of refractive-index and thickness of intraocular lens (IOL) implants
  • Demonstrated and published an alternative concept of fiber-optic confocal microscopy based on nonlinear optical frequency upconversion effects. This method provides a highly efficient upconversion multiphoton imaging of biological specimens in the visible spectral range at a near-infrared laser excitation.
  • Submitted a draft description of the recently developed in the OTMN Lab new confocal laser method for testing dioptric power of IOLs for incorporating into the ISO 11979 Standard “Ophthalmic Implants – Intraocular Lenses Part 2: Optical properties and test methods”
  • Established a new collaborative agreement with the Wilmer Eye Institute at Johns Hopkins University on investigation of safety and effectiveness of ultrashort femtosecond laser approaches in refractive surgery as well as  noninvasive optical imaging methods used in ophthalmology.
  • Investigated the functional role of laser induced hydrogen peroxide from human brain cancer, in-vitro, to yield "Bystander" effects. Quantified laser induced hydrogen peroxide kinetics from malignant human brain cancer, in-vitro.
  • Hosted a jointly sponsored meeting between the Academy of Laser Dentistry and the Food and Drug Administration on “Light Based Technology Utilization in Dentistry”.