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OCD FY2006: FDA Goal 2 - Increasing Access to Innovative Products and Technologies to Improve Health

CDRH Logo - Small

A critical aspect of protecting and promoting public health is facilitating access to innovative medical devices. To achieve this objective, CDRH is developing better ways to predict earlier in the review process which new products are likely to be safe and effective. CDRH is also promoting scientific innovation in product development and focusing device research using cutting-edge science.
 

 Approved/Cleared Devices

FDA does not test new medical devices to determine whether they are safe and effective before they are sold in the United States. Instead, FDA gives guidance to manufacturers on what tests they should conduct. CDRH evaluates the scientific test data manufacturers submit for review prior to making a decision whether the devices are allowed to be marketed.

Manufacturers wishing to sell a new type of medical device - or market an approved device for new uses that represent a high risk to public health - must submit a premarket approval (PMA) application to CDRH. A PMA must include valid scientific evidence showing that the product does what it claims to do (is effective) and that the benefits of using the product outweigh the risks (is safe). Examples of PMA devices include: mechanical heart valves, implantable pacemakers, intra-ocular lenses, and cochlear implants.

Most new medical devices are similar to products already on the market and do not represent a high risk to public health. Manufacturers wishing to sell these products must submit a premarket notification [also called 510(k)]. This process is for lower-risk devices that require less rigorous testing and evaluation. A 510(k) must include information demonstrating that the new device is very similar (substantially equivalent) to another device already on the market. Some applications for devices with well-established records of safety and use receive no review. Examples of 510(k) devices include: non-invasive blood pressure monitors, ventilators, and daily wear soft contact lenses.

Medical devices successfully evaluated through the PMA process are approved; devices successfully evaluated through the 510(k) process are cleared.

During FY 2006, CDRH approved and cleared a significant number of medical devices which exemplify advanced device technologies that have a valuable impact on patient care. A comprehensive list of approved medical devices is available at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/default.htm.
 

LeadCare® II Blood Lead Test System
http://www.accessdata.fda.gov/cdrh_docs/pdf5/k052549.pdf

The LeadCare II Blood Lead Test System is used to screen children and adults for harmful levels of lead using a finger stick or venous whole blood sample. It is performed while the patient is present in as little as three minutes. The rapid result means a second sample for confirmatory testing can be obtained quickly, reducing the need for a follow-up visit. Because the test is simple, accurate, and reasonably free of harm, CDRH broadened access to the test system by granting a Clinical Laboratory Improvement Amendment (CLIA) waiver. The waiver permits widespread distribution of the test system to nontraditional laboratory sites that have CLIA certification.
 

STAN® S31 Fetal Heart Monitor
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm078446.htm

The STAN® S31 Fetal Heart Monitor is a new type of fetal monitor that uses the fetal electrocardiogram (ECG) obtained through a fetal scalp electrode during labor to help the doctor or midwife decide whether to allow the mother to continue to labor or to intervene and deliver the baby. The new monitor is used when there is concern that the fetus might be at increased risk for metabolic acidosis.
 

X STOP® Interspinous Process Decompression System
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm078378.htm

The X STOP® Interspinous Process Decompression System (X STOP) is used to relieve symptoms of lumbar spinal stenosis, a narrowing of the passages for the spinal cord and nerves. The titanium implant that fits between the spinous process of the lower (lumbar) spine may relieve some or all of the symptoms of lumbar spinal stenosis and may improve a patient’s ability to function.


Avian Influenza A/H5 (Asian Lineage) Virus Real-Time RT-PCR Primer and Probe Set
http://www.accessdata.fda.gov/cdrh_docs/pdf6/k060159.pdf

The Avian Influenza A/H5 (Asian Lineage) Virus Real-Time RT-PCR Primer and Probe Set provides preliminary results on suspected H5 influenza samples within four hours once testing begins. This is in contrast to previous testing technology which required at least two to three days for results. If the presence of the H5 strain is identified, then further testing is conducted to identify the specific H5 subtype (e.g., H5N1).
 

UniCel® DxC 600i Synchron® Access® Chemistry-Immunoassay System
http://www.accessdata.fda.gov/cdrh_docs/pdf6/k060256.pdf

The UniCel® DxC 600i Synchron was cleared as the only system of its kind with closed-tube sampling (CTS) and closed-tube aliquotting (CTA) capabilities. By eliminating the de-capping and re-capping steps in the laboratory process, these features help increase lab efficiency and enhance operator safety. The system offers a throughput up to 990 chemistry tests per hour and up to 100 immunoassay tests per hour.
 

LUMA™ Cervical Imaging System
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm078285.htm

The LUMA™ Cervical Imaging System is an optical detection system that helps the doctor identify areas on the cervix that are likely to contain precancerous cells. The doctor uses this device immediately after colposcopy (a high magnification evaluation of the cervix for women who have recently had an abnormal Pap smear) to decide where to take additional tissue samples (biopsies). The LUMA™ Cervical Imaging System will help improve the chances that the doctor does not miss an area that may contain precancerous cells.
 

DexCom™ STS™ Continuous Glucose Monitoring System
http://www.accessdata.fda.gov/cdrh_docs/pdf5/p050012a.pdf

DexCom™ STS® Continuous Glucose Monitoring System is a short-term sensor that wirelessly transmits glucose readings to a hand-held receiver to provide real-time continuous measurements. The system, used by adult diabetic patients at home and in health care facilities, detects trends and tracks patterns. The device aids in detecting episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments, which may minimize high and low blood sugar levels.

 

MonoPrep Pap Test
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm078291.htm

The MonoPrep Pap Test (MPPT) system is a device used to collect and prepare cell samples from a female patient’s cervix for Pap stain-based screening for cervical cancer, its precursor lesions, and other cytologic categories and conditions. Clinical trial results demonstrate that the MPPT system is safe and effective for preparing gynecological slides to screen for cervical abnormalities.
 

PhiCal™ Fecal Calprotectin Immunoassay
http://www.accessdata.fda.gov/cdrh_docs/pdf5/k050007.pdf

The PhiCal™ Fecal Calprotectin Immunoassay is a quantitative ELISA assay for measuring concentrations of human fecal calprotectin, a neutrophilic protein that is a marker of mucosal inflammation. The PhiCal™ test can be used as an in vitro diagnostic to aid in the diagnosis of inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, and to differentiate IBD from irritable bowel syndrome (IBS) when used in conjunction with other diagnostic testing and the total clinical picture.


Birmingham Hip Resurfacing (BHR) System
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm078189.htm

The Birmingham Hip Resurfacing (BHR) System is a metal on metal resurfacing artificial hip replacement system, surgically implanted to replace a hip joint. The BHR System relieves hip pain and improves hip function by replacing the parts of the hip that have been severely damaged by degenerative joint diseases (e.g., osteoarthritis, rheumatoid arthritis, traumatic arthritis, dysplasia, avascular necrosis). The BHR System is intended for patients who, due to their relatively younger age or increased activity level, may not be suitable for traditional total hip replacement due to an increased possibility of requiring future hip joint revision.
 

Xpert GeneXpert™ Dx Test For Group B Streptococcus
http://www.accessdata.fda.gov/cdrh_docs/pdf6/k060540.pdf

This qualitative in vitro diagnostic test is designed to detect Group B Streptococcus (GBS) DNA from vaginal and rectal swab specimens. The test rapidly identifies a GBS infection before and during labor and delivery. If passed from mother to child during birth, GBS can cause sepsis, pneumonia, meningitis, neurological damage, and, in a small percentage of newborns, even death.
 

Adept® Adhesion Reduction Solution (4% Icodextrin)
http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050011a.pdf

Adept® Adhesion Reduction Solution (4% Icodextrin) is a pale yellow fluid that contains icodextrin. The fluid is used during or after laparoscopic gynecological surgery to separate and protect tissues, and decrease the number of new adhesions after surgery. Adhesions are a common complication of gynecological surgery, and can cause pelvic pain, bowel obstruction, or infertility.
 

APTIMA Combo 2® Assay on the TIGRIS® System
http://www.accessdata.fda.gov/cdrh_docs/pdf6/k060652.pdf

The APTIMA Combo 2® Assay is cleared to detect Chlamydia infections and gonorrhea from a wide variety of sample types. These sample types include liquid-based ThinPrep Pap Tests and vaginal swabs, endocervical and urethral swab specimens, and female and male urine specimens.
 

Gore HELEX™ Septal Occluder
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm077730.htm

This new technology is an alternative to open heart surgery for pediatric and young adult patients. The device uses cardiac catheterization to position an occluder over a hole in the heart, allowing tissue to grow over the device, closing the defect, and making the device part of the wall of the heart.
 

 Regulations, Standards, and Guidance

CDRH is responsible for setting and enforcing FDA regulations and performance standards for medical devices and radiation-emitting electronic products. To describe FDA’s interpretation of policy on regulatory issues, CDRH staff prepare guidance documents for regulated industry and the general public. Regulations, standards, and guidance documents are intended to assist manufacturers improve the quality of premarket submissions, expedite the FDA review process, and speed consumer access to life-saving medical devices.

During FY 2006, CDRH cleared 20 regulations, reviewed and coordinated the Agency’s actions with regard to 16 Citizens’ Petitions, and cleared 46 guidance documents - which is a 59 percent increase from FY 2005.

CDRH Standards Program

The Standards Management Staff (SMS) develops and manages the standards used for regulatory assessments and facilitates the participation of CDRH and other FDA staff in developing national and international standards. In addition, the SMS manages CDRH’s process for the recognition of voluntary consensus standards for medical devices and radiation-emitting electronic products. As part of this responsibility, the staff annually publishes lists of recognized standards, consistently increasing the number of available standards. During FY 2006 CDRH withdrew 10 standards considered “no longer appropriate”; withdrew 80 additional standards and recognized new editions of each; incorporated 66 changes to existing recognized standards; and recognized 43 new voluntary consensus standards. The new standards address newly developing technologies to improve the quality of future submissions.

Guidance Documents

CDRH worked with industry and other stakeholders to develop best practices, policies, and guidance documents to make premarket applications more consistent, complete, and less subject to multi-cycle reviews. Below are examples of guidance documents issued during the FY 2006.

  • Draft Guidance for the Review and Inspection of Premarket Approval Applications under the Bioresearch Monitoring Program was developed and issued in collaboration with FDA’s Office of Regulatory Affairs.
  • Draft Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials provides a flexible alternative framework to classical clinical trial design for sponsors of innovative new devices.
  • Draft Guidance for Pharmacogenetic Tests and Genetic Tests for Heritable Markers was issued to facilitate progress in the field of pharmacogenomics and genetics by helping to shorten development and review timelines, facilitate rapid transfer of new technology from the research bench to the clinical diagnostic laboratory, and encourage informed use of pharmacogenomic and genetic diagnostic devices.
  • Draft Guidance Class II Special Controls: Bone Sonometers supports the reclassification of bone sonometers into class II (special controls) devices. Class II devices are exempt, subject to certain limitations, from the premarket notification requirements. Bone sonometers transmit ultrasound energy into the human body to measure the acoustic properties of bone that indicate overall bone health and fracture risk.
  • Final Guidance for Keratome and Replacement Keratome Blades Premarket Notification [510(k)] Submissions will assist industry in preparing premarket notification submissions for keratomes and replacement keratome blades. The intended use of the device is to shave tissue from sections of the cornea for a lamellar (partial thickness) transplant. Keratomes, originally used during cornea transplant surgery, are now widely used during the laser refractive surgical procedure known as laser-assisted in situ keratomileusis (LASIK).
     

 Quality Review Program for Premarket Submissions

The purpose of CDRH’s Quality Review Program for Premarket Submissions is to evaluate the quality and consistency of the Center’s scientific review process. During the fiscal year, CDRH expanded the program to five review areas: biocompatibility, sterilization and packaging, statistical analysis, software, and clinical reviews. The expanded program allows CDRH to improve the quality of its reviews in key scientific areas, ensuring that reviewers consistently ask the right questions at the right times to minimize review time.
 

 Advisory Committees

CDRH held 10 Federal Advisory Committee panel meetings in fiscal year 2006. These panels of external experts reviewed and made recommendations to FDA on six premarket approval (PMA) applications, three reclassifications, one classification, and three general issues. Among the topics addressed at the panel meetings were issues associated with significant breakthrough technologies for facial fillers, breast cancer detection, implanted telescope for macular degeneration, and cervical disc system for the treatment of degenerative disc disease.
 

 Premarket Critical Path

Examples follow of CDRH’s Critical Path initiative to address innovative medical therapies and support product development that is more predictable, efficient, and less costly:

  • Established a collaboration with the Juvenile Diabetes Research Foundation to promote the development of an artificial pancreas;
  • Established collaborative interactions with other government entities and external stakeholders to advance the development of new biomarkers for diseases; and
  • Developed guidance to foster the development of new technologies in the area of genetics, pharmacogenomics, and drug/device co-development.
     

 MDUFMA

In 2002, the Federal Food, Drug, and Cosmetic Act was amended to provide FDA important new responsibilities, resources, and challenges. The Medical Device User Fee and Modernization Act of 2002 is commonly referred to as MDUFMA.

One particularly significant provision of MDUFMA permits FDA to collect user fees for certain premarket reviews received on or after October 1, 2002. The additional funds obtained from user fees will enable FDA to improve the medical device review process in order to meet MDUFMA performance goals.

To meet these progressively challenging performance goals, CDRH consulted with its stakeholders, developed guidance documents, and implemented new review processes and process improvements. Key MDUFMA-related accomplishments for FY 2006 follow.

Progress in Meeting MDUFMA Performance Goals

CDRH met, or is on track to meet, most of the MDUFMA performance goals for fiscal years 2003 through 2006 receipt cohorts, and maintained review performance in areas not covered by official performance goals. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ MedicalDeviceUserFeeandModernizationActMDUFMA/default.htm

MDUFMA Third Party Inspection Program

CDRH continued implementation of the MDUFMA authority to accredit third parties to conduct inspections of eligible manufacturers of Class II and Class III medical devices, which will help FDA focus its limited resources on higher-risk inspections and give medical device firms operating in global markets an opportunity to more efficiently schedule multiple inspections.

FDA issued guidance to implement the new authority and published criteria for Accredited Persons (AP) in the Federal Register. The FDA review board received, reviewed, and rated AP applications which resulted in 16 third parties being selected to participate in the program.

Industry use of the Third Party Inspection Program for 510(k) submissions in FY 2006 increased 18 percent over use of the program in FY 2005. CDRH received 287 510(k) submissions reviewed by Accredited Persons and made final decisions on 268, up from 250 in FY 2005. This review option may be faster than reviews performed exclusively by FDA staff and gives manufacturers access to specialized expertise by third parties. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/ ThirdPartyInspection/ucm125418.htm

MDUFMA Guidance Document Development

CDRH issued six MDUFMA guidance documents during FY 2006. The guidance documents addressed reprocessed single-use medical devices, combination products, small business qualifications, Section 301 compliance (mark of manufacturer on single-use devices), premarket approval application (PMA) inspections, and the Bioresearch Monitoring (BIMO) Program. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm

MDUFMA Stakeholders Meetings

In November 2005, CDRH held the third Annual Stakeholders Meeting on the Implementation of MDUFMA. In addition to addressing the Agency’s progress in implementing the various MDUFMA provisions, meeting participants discussed the current qualitative performance goals, participation of eligible manufacturers in the inspection program, and the current requirements for reprocessing single use devices. The meeting gave stakeholders an opportunity to provide information and share their views on the implementation of MDUFMA.

A MDUFMA Public Stakeholders meeting was also held in May 2006 to consult with stakeholders and to determine whether the following two goals are appropriate for implementation in FY 2007:

  • 50 percent of PMA applications will have an FDA decision in 180 days;
  • 80 percent of premarket notifications [510(k)s] will have an FDA decision in 90 days.

MDUFMA Public Notices and Reports

CDRH issued 14 Federal Register notices and three reports to Congress: FY 2005 MDUFMA Performance Report, FY 2005 MDUFMA Financial Report, and FY 2005 Office of Combination Products Report.

MDUFMA Small Business Determinations (SBDs)

CDRH received, evaluated, and responded to 717 Small Business Determinations (SBDs) under the meaning of MDUFMA, and granted 698, an increase of 8 percent over FY 2005. (Establishments judged to be a small business are eligible to receive a reduced or waived user fee for premarket reviews.) CDRH completed all SBDs within 7 days of the allowable 60-day timeframe.
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ MedicalDeviceUserFeeandModernizationActMDUFMA/ucm109195.htm


 

 Applied Research

Research findings improve the predictability, efficiency, and effectiveness of premarket reviews and the development of new device technologies. Following are CDRH applied research-related accomplishments during FY 2006.

Nanotechnology in Medical Devices

CDRH took major steps to assure its readiness to address future nanotechnology products and issues. Steps included building a knowledge base and developing experimental expertise and collaborative research with other key participants in the field, and discussing regulatory processes and standards coordination issues. A major Center strength is the availability of scientists from many disciplines - some with significant prior experience with nanotechnology. Other activities in progress include coordination of standards activities, identification of regulatory issues/gaps, and training of staff.

The focus of CDRH research projects is primarily to address mechanistic understanding of nanoparticles behavior from physical, chemical, and biological aspects. The other major focus is on advancing the knowledge regarding the characterization of nanoparticles. The knowledge and data developed in these projects would help address potential questions related to:

  • Available methods/technologies for characterization of nanoparticles and their limitations;
  • Physico-chemical stability/interaction of nanoparticles;
  • Physical, chemical, and biological interaction of nanoparticles;
  • Toxicity and behavior of nanoparticles in in-vitro and in-vivo environment; and
  • Test methods to assess biocompatibility of nanoparticles’ exposure to blood elements.

Device Safety in Magnetic Resonance Imaging (MRI) Environments

CDRH developed a new standard practice for marking medical devices and other items safe in the magnetic resonance environment. The revised system replaced the old system and its confusing MRI compatible terminology, which may have resulted in patient injuries. CDRH measured and modeled implants in MRI radio frequency fields to develop data on induced heating. These data will aid in the formulation of guidance and standards for MRI compatibility of implants.

Relationship Between Bone Cement Dose and Mechanical Strength after Vertebroplasty

CDRH conducted research to determine whether bone mineral density (BMD) can be used to predict mechanical strength and stiffness of the vertebral body after cement injection. Vertebroplasty has been reported to have high success rates in providing pain relief, but the procedure is not without serious risks. Adverse events associated with cement leakage have been reported, including persistent pain, paralysis, loss of sensation, and death. Laboratory results suggest that there may be significant differences between osteoporotic and non-osteoporotic patients in terms of the relative improvement in strength and stiffness that larger cement volumes can offer. In general, laboratory study suggests that clinicians may be able to select an appropriate cement volume and to make predictions about the expected improvement in mechanical stability after vertebroplasty for a specific patient based on his or her bone mineral density.

Exposure to Electromagnetic Fields and the Effect on Implanted Devices

CDRH measured and modeled exposure to electromagnetic fields and the effects on implanted devices from hand-held and walk-through security systems, cellular telephones, hand-held computers, and MRI systems. This research included models of the head for evaluation of cellular phone exposure and models of pregnant women representing nine fetal gestational ages to evaluate heating during MRI. This effort resulted in the standardization of specific absorption rate (SAR) across multiple systems. Results of this work include:

  • Nine journal articles and 14 proceedings and other presentations during the past year;
  • Support from the Federal Aviation Administration (FAA)/Transportation Security Administration (TSA) for the security system studies; and
  • Establishment of a Cooperative Research and Development Agreement (CRADA) to further the virtual family modeling.

Modeling of the heating effects of MRI upon implanted pacemakers, implantable cardioverter-defibrillators (ICDs), neural stimulators, and cardiac stents helped define the parameters for acceptable application of MRI for individuals with these implanted medical devices and has a potentially large impact on public health as industry uses the information to improve device safety.

Test Methods for Intraocular Lenses (IOL)

CDRH developed a significantly more accurate and applicable confocal laser method for testing intraocular lenses (IOL) diopter power. Precise measurement is critical for evaluating the effectiveness and safety of IOLs, which are implanted during cataract surgery. The test method has been used to evaluate samples of new IOL designs and on IOLs on regulatory hold because of questions about the labeled power. This work resulted in a pending patent, 4 journal articles, and more than 10 proceedings publications and presentations during the past year.

CDRH also developed accelerated testing procedures to identify IOL materials that are prone to the formation of “glistenings” (fluid filled ellipsoidal voids within the lens). Both of these testing procedures ensure the effectiveness and safety of a device for the treatment of cataracts that is critical to an aging population.

Combined Approach to Evaluate Circulatory Assist Devices

CDRH developed a combined approach of review and laboratory expertise to evaluate proposed ‘subtle’ design changes to critical components of life-sustaining mechanical circulatory assist devices. Design of the blood path in these devices is critical for avoiding damage to blood components, stroke, and embolism. CDRH’s new combined approach for review significantly reduces the review burden while reducing the uncertainty of evaluations.

Effects of Optical Energy

CDRH evaluated the effects of optical energy on cellular and intracellular structures and components. This resulted in improved understanding of the effects of light on energy production in cells. CDRH developed a new confocal fiber-optic nano-biosensing system that enables measurements at resolutions better than the theoretical half wavelength limit, resulting in work below the 200 nanometer range. This work, supported in part by an interagency agreement with the Air Force Office of Scientific Research, resulted in 4 journal articles, numerous proceedings and presentations during the past year, and a proposal to the Army’s Telemedicine and Advanced Technologies Research Center to evaluate optical methods of stimulation that may enhance the field of neuro-prostheses.

Device-Tissue Interfaces

CDRH also worked towards developing a better understanding of the device-tissue interface for optical spectroscopy leading to improvements in the efficiency of spectroscopic methods for minimally invasive disease detection. This area has the potential to improve the detection of mucosal cancers and the monitoring of changes following therapeutic applications. This work resulted in journal articles and several presentations.

Better Animal Models and Biomarkers to Improve Public Health

CDRH conducted research to stimulate the development of new evaluation tools - biomarkers and clinically-relevant preclinical models - for assessing the safety and efficacy of new medical products. An animal model of subclinical renal insufficiency that was able to detect known nephrotoxicants at doses that were non-toxic in “healthy” control animals was developed and partially validated. The regulatory impact is significant in that adverse effects detected using the disease model would have been missed using healthy animal models typically used to test medical devices. CDRH also evaluated a new kidney toxicity biomarker, a kidney injury molecule that can be measured in kidney tissue and urine and appears to be more sensitive for renal injury detection than traditional clinical markers. The public health impact is significant in that the new biomarker may be useful to identify patients with subtle renal disease at an earlier stage and prevent pathogenesis of renal failure as well as reduce uncertainties in the preclinical assessment of FDA-regulated products.

Infection Control: Reuse of Single-use Devices and Cleaning Validation

CDRH developed cleaning and disinfection-sterilization methods to ensure that no microbial contamination remains on a reusable device. Improper cleaning can cause misdiagnosis due to tissue contamination and toxicity from residual detergents and sterilization agents. CDRH has determined that total organic carbon is an effective marker of residual soil from patients exposed to the devices and residual chemicals used in reprocessing on cleaned devices versus measuring total protein only as an endpoint of cleaning. The research will improve safety of patients exposed to single-use and reusable medical devices. Protein residual data from CDRH research have provided an endpoint for device reprocessors to meet requirements of supplemental validation submissions for single-use devices and aided CDRH review and inspection functions.

Drug Coated Stents: Drug Eluting Stents Associated Thrombosis

The drug eluting stents have been shown to exhibit late-stent thrombosis which may be mediated by an increased expression of tissue factor (TF) and decreased levels of thrombomodulin in endothelial cells that line the arteries. CDRH research on the treatment of endothelial cells with either rapamycin or paclitaxel resulted in a slight increase in coagulation activity. However, addition of vascular endothelial growth factor (VEGF) significantly augmented the coagulation cascade. Coagulation correlated with increased expression of TF in endothelial cells. Thrombomodulin expression was unaffected by either rapamycin or paclitaxel in the presence of VEGF. Data suggest that platelets and rapamycin/taxol may elevate TF expression. However, platelets themselves are not affected by either drug. These results suggest that anti-proliferative drugs exhibit prothrombotic effects which could be potentiated by VEGF. These findings imply that high levels of VEGF in atherosclerotic plaques could potentially contribute to thrombotic effects observed following drug eluting stent implants. Experimental and computational studies of model coatings have led to an understanding of the role of processing conditions on the rate of drug release. For example, increases in processing temperature leads to a decrease in the size of included drug particles and an increase in the rate of drug release. These observations have been used in evaluating proposed changes to manufacturing procedures in currently approved drug eluting stents.

Computational Fluid Dynamics of Left Ventricular Assist Device

CDRH laboratory scientists worked with an industry sponsor to assess the effect of a proposed design change to a left ventricular assist device (LVAD). The sponsor proposed making a change to the blood flow path within the pump that could have adversely affected hemolysis and thrombogenesis in the pump such that patient safety and/or device efficacy could have been compromised. It would have been extremely difficult, if not impossible, to validate the design changes using animal or human data. After discussions and a meeting with CDRH staff, the sponsor agreed to provide experimental (flow visualization, hemolysis) and analytical (computational fluid dynamics [CFD]) testing to support the design changes. CDRH experts recommended appropriate CFD models to the sponsors and analyzed the results.

Computer-Assisted Diagnostic Systems

CDRH developed new models and methods for assessing computer-assisted diagnostic (CAD) systems in the review of digital mammography systems, breast cancer screening, lung cancer screening, and computed tomography (CT) colonoscopy. The new assessment tools can be used with the most common clinical study design paradigms. The new assessment tools have been developed to improve the evaluation of reader variability and algorithm complexity for imaging and CAD devices by extending these assessment tools to the most common clinical study design paradigms. CDRH research has also lead to a better understanding of the impact of CAD used concurrently instead of as a second reader, and to the development of assessment tools for measuring CAD stand-alone performance. Having these tools and methods available has greatly assisted developers of these innovative imaging and CAD devices.

Tools for the Simulation of Imaging Physics

CDRH scientists have developed and made available to the scientific community, an advanced simulation package for studying radiation imaging systems. The code, developed in collaboration with scientists at the Universitat Politecnica de Catalunia in Spain, allows for the simulation of medical imaging systems involving x-rays, gamma-rays, electrons, and optical radiation, such as digital mammography, breast tomosynthesis, breast, and other flat-panel based CT. The tool will enhance the Center's understanding of the physics behind novel imaging technologies that are currently being considered by industry and possibly submitted to FDA for review in the near future.

Performance Testing of Pulse Oximeters

CDRH scientists and engineers have developed test methods for a range of non-invasive monitoring devices. CDRH laboratory studies on pulse oximeter performance, for example, enabled substantial improvements in the ISO/IEC standard and the CDRH Guidance Document. This testing facilitated the development of a single test protocol for SpO2 accuracy studies, which simplified the premarket evaluation process by unifying the basis for establishing substantial equivalence. The work has established the groundwork to enable the extensions of claims being made for perfusion measurements and established acceptable performance criteria.

Test Methods for High Intensity Focused Ultrasound

The lack of standardized methods to assess the acoustic and thermal characteristics of high intensity focused ultrasound (HIFU) has challenged the regulatory review of these devices, especially in the pre-clinical phase, and has been burdensome to the industry. In the past, CDRH scientists and engineers have developed measurement instrumentation and computational modeling techniques for characterizing other types of medical ultrasound devices such as diagnostic imaging and therapeutic ultrasound. This work has resulted in the creation of numerous regulatory guidance and standards documents. This expertise is being used to accelerate the review of submissions for HIFU devices. For example, in a device for the ablation of uterine fibroids, CDRH-developed computational modeling was used to predict the performance of the device under conditions that would have been difficult to investigate experimentally, thus shortening the review time.

Effect of RFID on Drug Potency

CDRH initiated, at the request of FDA, important new research to determine whether exposure to electromagnetic fields from radiofrequency identification (RFID) systems has any effect on the potency of pharmaceuticals. Of primary interest are exposures that are several times more severe than the anticipated worst-case field strengths and durations.

Reorientation of the CDRH Radiation Metrology Program

As part of the CDRH reorganization of the radiation health program, the CDRH X-ray Calibration Laboratory underwent significant changes. The laboratory continues to be accredited by the National Voluntary Accreditation Program (NVLAP). During the fiscal year, the laboratory provided 840 radiation calibrations of general diagnostic instruments, 202 radiation calibrations of mammographic instruments, 484 electrical calibrations of radiation monitors, 147 calibrations of non-invasive kVp meters, and 36 calibrations of light meters. In addition, the laboratory provided instrumentation and logistics support to FDA and Agreement-State inspectors for compliance testing of general radiography installations, mammography machines, and voluntary surveys under the Nationwide Evaluation of X-ray Trends (NEXT) program.

 Medical Device Fellowship Program

The Medical Device Fellowship Program (MDFP) provides select individuals the opportunity to get unique, hands-on experience helping to evaluate the safety and effectiveness of cutting-edge medical devices. MDFP fellows include student interns starting their careers in science and engineering and senior scientists and physicians with vast experience in academia and clinical practice. By increasing the range and depth of collaboration between CDRH and the outside scientific community, the MDFP helps ensure that CDRH decisions are based on the best scientific information and knowledge available. In 2007, MDFP fellows contributed expertise in ophthalmology, interventional cardiology, cardiac surgery, neurology, gastroenterology, biostatistics, and biomedical engineering.

The Center’s technology transfer program, managed through the MDFP, makes possible collaboration with people and programs outside FDA, augmenting CDRH expertise and resources. Government and academic partnerships (e.g., cooperative research agreements, grants, memorandums of understanding for academic partnerships, interagency agreements, material transfer agreements) result in scientific information being used to develop standards, guidance, and regulatory decisions.