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U.S. Department of Health and Human Services

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FY 2008 OSEL Regulatory Support Activities

Research conducted in the OSEL supports the regulatory activities of the Agency as follows: 

  1. Providing a scientifically sound basis for responding to current needs and anticipating future regulatory challenges; and
  2. Providing technical consults in support of the Center’s pre-market, post-market, and compliance activities.

Both activities are coordinated within OSEL so as to best meet the Center’s regulatory science needs. Laboratory research is the cornerstone of the Office’s regulatory support function. (The research is described in subsequent sections.) It is largely based on investigations related to the mechanistic understanding of device performance or test procedures, enabling the Center and device manufacturers to gain an improved understanding of issues related to safety and efficacy. The scope and goals of OSEL research span a wide range of device types and goals.  Some research is directed toward issues identified at the pre-market review phase, addressing topics of significant interest to both regulators and device developers.  Other OSEL investigations originate from problems identified via use experience after introduction into commerce. The findings of the laboratory are then used not only to help resolve the on-going identified problems but are also fed into the standards and guidance development to refine premarket clearance requirements associated with products of that type.

The regulatory support function of the Office is also provided through consults supporting both pre-market decisions and post-market actions using expertise developed in the laboratory. A consult is a request for expert advice or information. Consults provide information that contribute to sound regulatory decisions. They are often based on acknowledged scientific/engineering principles or on independent data generated in OSEL laboratories.

Through these consults and other related means, OSEL staff supports the Center’s regulatory mission in the following ways:

  • Provide scientific and engineering reviews and analyses of pre-market submissions (IDE, HDE, PMA, 510(k));
  • support compliance actions through review of material submitted by sponsors or collected through field investigations;
  • draft and refine guidance documents;
  • conduct laboratory investigations of product performance;
  • assist health hazard evaluation/health risk assessments or in device determinations/classifications;
  • participate in inspections of medical device establishments;
  • conduct forensic reviews and investigations;
  • provide training to FDA and industry; and
  • contribute to Center-wide Matrix teams on issues identification as well as science-based analysis of post-market device performance.    

The reviews and investigations conducted by OSEL independently assess the claims made by manufacturers or other parties concerning safety or effectiveness. In other cases, OSEL reviews may assess the adequacy of a design, a failure investigation, a production process, or a quality process employed by the manufacturer. OSEL laboratory investigations may be undertaken in instances where the veracity of a performance claim needs to be independently verified by testing.

Developing standards and measurements methods is a significant activity of this office. OSEL continues to provide innovative solutions to public health problems by constructing generic techniques that lead to the creation of national and international standards that will enhance product safety and effectiveness. OSEL staff actively participate in developing standards at the national and international levels by performing research to establish standard procedures and by shouldering standards committees responsibilities to manage, develop, and support.

Office of Science and Engineering Laboratories 2008 Highlights

Active Materials (Division of Chemistry and Materials Science)

Contaminants in the Heparin Supply 

DCMS was actively involved in issues surrounding oversulfated chondroitin sulfate (OSCS) contamination of the heparin supply used in medical devices. The Division worked with CDRH, the Center for Drug Evaluation and Research (CDER) and outside academic institutions to assess the impact of this contamination on the safety of medical devices and risk/benefit assessments required to avoid shortages where immediate replacement was not feasible. DCMS continues to assist the Office of Compliance in screening incoming lots of heparin to avoid further potential adverse events. Based on dialogues with faculty at the Massachusetts Institute of Technology, MIT, a protocol was postulated for testing the potential of surface-bound OSCS in heparin derivatives to stimulate the contact system in blood and elicit the same anaphalactoid responses seen in patients on anti-coagulant therapies. This test allowed CDRH to rationally permit certain products to remain on the market while the supply chain was decontaminated. In addition, the Division worked with the CDRH Office of In Vitro Diagnostic Device Evaulation and Safety (OIVD), the National Institutes of Health (NIH), and CDER to assess the impact of OSCS contamination on blood tests where the blood was drawn into contaminated tubes. These results are currently being developed into a publication and will provide further guidance to the IVD industries.   

Electromagnetics and Wireless Technologies (Division of Physics)

Security System Exposures to Medical Devices.

DP performed a large-scale study of high priority medical devices for electromagnetic compatibility (EMC) with modulated emissions in the Industrial, Scientific, Medical (ISM) radio frequency band at 902 MHz. The OSEL EMC-wireless laboratory is widely recognized for expertise and experience in performing medical device EMC research and was sought out by other federal agencies such as the Department of Homeland Security (DHS) to investigate concerns about security system exposures to medical device users.

Under this study, a unique microwave frequency emitter exposure system was developed for use in performing tests on several medical devices determined to be high priority for potential risks from electromagnetic interference (EMI). Over 30 high priority medical devices were obtained and used as samples including ventilators, automated external defibrillators, pain care administration pumps, infusion and insulin pumps, glucose meters, implantable neurostimulators, implantable cardiac pacemakers and cardiac defibrillators, transcutaneous electrical nerve stimulators, and powered wheelchairs and scooters. Potentially significant effects such as device malfunctions, critical alarms, and loss of function were observed in at least eight specific devices. To help determine the types of medical devices that would constitute the highest priority of concern, an extensive search of published medical and technical literature was performed that found over 200 publications about medical device EMC/EMI. Additionally, more than 120 medical device EMI-related adverse event reports over the last 3 years were located in the FDA databases. Further, a group of 22 FDA and other medical device experts were surveyed to assess device areas of most concern for EMI and obtain information about high priority devices and the risks posed if EMI were to disrupt the devices. 

Data and new knowledge from this major research project are being leveraged into pre- and post market regulatory work as well as national and international consensus medical device standards and guidance. FDA and the public health reap many benefits from this work, including the addition of sorely needed resources such as very specialized EMC contract engineers who helped develop special test systems that can now be used to evaluate EMC of many other RF emitters representing potential threats to medical devices and patient safety.

Electrophysiology and Electrical Stimulation (Division of Physics)

Arbitrary waveform defibrillator for cardiac electrophysiology research

An innovative arbitrary waveform defibrillator for animal research was developed and tested at OSEL by engineers from the Italian National Institute of Health in collaboration with OSEL. The system is capable of delivering electrical energy (up to 10 Joules) with any duration or shape defibrillator shock for animal experiments. The system is battery operated, has an isolated output, and is PC-controlled via LabView software (a commercial visual programming language used to facilitate communication between a computer and laboratory instruments). It is being used to test new waveforms by comparing them to traditional ones, in experiments with isolated and perfused rabbit hearts. Loads with impedance ranging from 15 to 75 ohms can be connected. A maximum of 380 V, 10A can be delivered to the loads. The use of a proper power supply and additional external resistors limit the power dissipated internally, so that up to 1.7KW can be delivered to the load. Starting from an estimation of the load impedance, a LabView application calculates the proper settings for the power supply and the additional resistors, if needed. Effective voltage and current are measured and collected in the PC. The design of this system has been presented at several cardiac electrophysiology meetings, and the system is being employed in testing the physiological effects of newly proposed defibrillator waveforms. 

Safety Studies of Optical Nerve Stimulation

Lasers have long-standing applications in clinical medicine as diagnostic and therapeutic tools.  More recently, it has been proposed that lasers emitting near infrared light can be used to stimulate neurons to evoke nerve impulses (action potentials). This optical stimulation (OS) may replace or supplement neural stimulation technologies that rely on the use of implanted metal electrodes. However, the mechanisms and safety profile of action for optical OS are still not well understood, and the basis for developing standards of safety and efficacy are still evolving. Collaborations with the Optical Diagnostics Laboratory (Division of Physics) and Professor Daniel Weinreich (University of Maryland) have resulted in the development of in vitro electrophysiological studies to (a) reproduce in vitro data demonstrating optical stimulation of peripheral nerves, and (b) identify stimulation parameters for OS that can be applied to the development of safety guidelines.

An excised rat sciatic nerve model was employed to explore optical conditions for eliciting nerve impulses, termed laser-evoked compound action potentials (L-CAPs).  Four different lasers, with peak emissions at different wavelengths, were shown to elicit L-CAPs. Common to all lasers tested was the finding that light doses (fluence) that evoke L-CAPs also produced nerve recoil. This recoil is attributed to pressure waves emanating from the light. Additionally it was found that fluence and repetition rate of laser pulses interact on L-CAPs.  At low fluences and repetition rates, the pulse-to-pulse amplitude of the L-CAPs gradually increased over time, which indicates activation of additional nerve fibers. In contrast, increasing fluence levels and repetition rates have the opposite effect: a gradual decrease in L-CAP amplitude over time. This decrement was histologically correlated with frank tissue destruction,h and the damaging effects may be due to temperature. The mechanism of OS is suggested to be due, in part, to a transient temperature rise in the tissue. As repetition rates increase, there is a higher probability that heat will accumulate in the tissue, increasing the probability of thermal injury. 

Electrical stimulation with metal electrodes has traditionally been used in medical devices to restore neural function. These devices typically operate at stimulation frequencies over the kHz range. In the OSEL study, OS was tested at only a few (1-10) Hz. The parameter of laser inter-pulse interval to estimate the minimum time required for thermal relaxation could provide an index of the maximum repetition rate at which the irradiation dose would not produce thermal accumulation and injury. 

This work was supported in part by a grant from the U.S. Army Telemedicine and Advanced Research Center (TATRC). 

Fluid Dynamics (Division of Solid and Fluid Mechanics)

Fluid dynamics, as it applies to medical devices, can be broadly defined as the interaction of moving fluids with medical devices: both as the device affects the moving fluid and as the moving fluid affects the device. Often the moving fluid is blood, as in the flow of blood through a heart valve or through the filters and pumps of a renal dialysis apparatus. Damage to the flowing blood can result in serious clinical consequences, up to and including death. Prosthetic heart valves, ventricular assists, total heart replacements, grafts, stents, bypass pumps, hemodialysis systems, and oxygenators all must avoid placing unusual hydrodynamic loads on the body; they must avoid damaging the cellular components of blood; and they must minimize the activation of platelets that initiates the clotting cascade. Damage to a device, such as might be caused by cavitation in a heart valve, can lead to catastrophic device failure causing death. Accordingly, the Laboratory of Fluid Dynamics, located in the Division of Solid and Fluid Mechanics, maintains a research program focused on the fundamental factors governing the interaction of flowing fluids with medical devices and the development of test methodologies to objectively characterize such interactions and their consequences.

Accomplishments

  • Published acoustic method for cavitation detection in vitro. The method may benefit premarket testing and has clinical implication. A paper will be published in the American Society for Artificial Internal Organs, titled “A Novel Study of Mechanical Heart valve Cavitation in a Pressurized Pulsatile Duplicator” Wu, C; Retta, SM; Robinson, RA; Herman, BA; Grossman, LW (in press). 
  • Developed laboratory protocols for flow cytometry detection of two commonly used platelet activation markers: CD62P (P-selectin receptor) and PAC1 (activated GP IIb/IIIa receptor). The applicability of these two platelet markers to in vitro testing of medical devices was investigated using a cone-and-plate rheometer model. With this model, human blood experiments were conducted under different shear stresses, experimental temperatures, and using various anticoagulants.
  • Received an FDA Critical Path Initiative award to evaluate the suitability of CFD for assessing blood damage safety in submissions to the FDA. 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 evaluating of new products. OSEL was awarded the grant to address this problem. In collaboration with academic collaborators OSEL/DSFM developed  a benchmark flow model (nozzle design) to determine the applicability and limits of current CFD simulations in medical devices. Participants from academia, industry, and the FDA recently completed an interlaboratory study of CFD in predicting flow and blood damage in the model. Assembling and analyzing data from 29 groups from around the world is currently underway.
  • Completed characterizing the radial heating pattern from three axial symmetric high intensity focused ultrasound (HIFU) transducers using infrared thermography. 
Image Analysis (Division of Imaging and Applied Mathematics)

Advances in CAD Device Science

The year 2008 saw great progress developing consensus on the regulatory pathway for radiological computer-aided diagnosis (CAD) devices, and OSEL imaging scientists played a significant role in this effort.

CDRH convened a special FDA Radiological Devices Panel Meeting on Computer Aided Diagnosis Devices in early March 2008. The panel members included outside experts in radiology, computer algorithms, clinical trials, and statistics. The purpose of this panel was for these experts to provide feedback and recommendations to FDA on the regulation of CAD device submissions. The panel discussed and made recommendations on how to evaluate CAD algorithms and device performance. Preparation for this panel involved significant efforts from across CDRH, including the Office of Science and Engineering Laboratories (OSEL), the Office of Device Evaluation (ODE) and the Office of Surveillance and Biometrics (OSB). OSEL scientists made presentations to the panel in the areas of 1) overview of CAD devices, 2) colon CAD devices, and 3) lung CAD devices. OSEL research on the development of appropriate statistical methodologies for the assessment of CAD algorithms resulted in a number of presentations and publications during the year that will support the guidance development effort in this important public health product area.

Imaging Physics (Division of Imaging and Applied Mathematics) 

Phantom CT data as a public resource

DIAM has been conducting research sponsored in part by the FDA Critical Path Initiative related to improving the quantitative information that can be extracted from radiographic images, with the goal of developing imaging-based assessment of new drug therapies. Scientists in the group have written a review article on the state of the art with respect to lung nodule volumetry from CT data, titled “Volumetric Assessment of Non-Calcified Lung Nodules in Thoracic CT Imaging,” that will appear in the journal Radiology in early 2009.

During the course of this research effort, DIAM scientists have systematically collected thousands of CT datasets from an anatomically accurate chest phantom containing simulated lung nodules. This data is being used internally to assess how differences in CT acquisition parameters (e.g., CT dose and slice thickness) impact the ability to accurately and precisely estimate lung nodule volume. DIAM announced an initial public release of phantom data (over 1000 CT datasets) at the annual meeting of the Radiological Society of North America (RSNA) in December 2008. It is anticipated that this publically available data will serve as a resource to industry, academia and government agencies as they investigate and evaluate medical imaging systems, imaging techniques, and analysis software. Outside groups such as the Quantitative Imaging Biomarker Alliance (QIBA) are already taking advantage of this public resource.

Materials Performance (Division of Chemistry and Materials Science)

Lead in Dental Ceramics

A news broadcast by a television station in Ohio on February 27, 2008, brought to light a concern regarding the presence of lead in dental prosthesis. The story was based upon a consumer’s allegations of adverse health consequences associated with the apparent presence of lead in a ceramic dental restoration. CDRH created a special, multidisciplinary group of scientists, clinicians, and investigators to develop and implement a comprehensive program to determine whether lead was present in ceramic dental prostheses, and if so, what are the expected levels of exposure to the general public? CDRH’s Office of Science and Engineering Laboratories (OSEL), and specifically DCMS (in collaboration with ORA), became the focal point for the scientific and laboratory work that surrounds this investigation. FDA is consulting with the Center for Disease Control (CDC) to determine whether the current levels of lead in dental restorations present a health risk concern. At this time, the investigation is on-going. Currently, no quantitative toxic threshold level for lead in dental restorations is recognized by FDA or by a voluntary consensus standard. Information derived from the current scientific studies may provide a basis for determining whether a quantitative limit of lead in dental restorations should be considered.

Optical Therapeutics and Medical Nanobiophotonics (Division of Physics)

Development of Advanced Test Methods for Preclinical Evaluation of Intraocular Lens Implants  

Since the invention of the intraocular lens (IOL) in 1949, refractive cataract surgery using IOL implants has become one of the most commonly performed operations in medicine. More than 20 million Americans over age 40 have cataracts in at least one eye, and more than 3 million cataract surgeries are performed per year in the U.S. with an annual cost on the order of 3 billion dollars. The focal length (or dioptric power) is a fundamental parameter whose precise measurement is of critical importance for characterizing and evaluating the effectiveness and safety of IOLs. The effectiveness of most of the conventional methods used for IOL dioptric power testing is often limited in terms of high accuracy, dynamic range over which measurements can be performed, spatial sample alignment, and subjective image observation. Furthermore, new IOL materials and recently developed IOL designs, such as toric, multifocal, and aspheric, have introduced new problems which include difficulty in measuring precise IOL dioptric power.

CDRH is responsible for evaluating and approving implanted devices designed to improve human vision. The Center reviews IDEs and PMAs for IOL designs and materials on an on-going and continuous basis. The number of applications for new IOL designs and materials continues to increase. There is a continuing need for laboratory testing of the optical quality of some new IOL designs as a part of the review process. New standard test methods to precisely evaluate IOL dioptric power are also needed.

In order to support the Center's IOL regulatory activity, the OSEL/Division of Physics’ Laboratory of Optical Therapeutics and Medical Nanophotonics (OTMN) maintains laboratory capabilities for preclinical testing and evaluating the fundamental characteristics, performance quality and safety of IOL implants. This includes developing independent test methods for preclinical evaluation of IOL dioptric power. OTMN developed a novel confocal laser method (CLM) for precise IOL dioptric power testing, which is based on a simple apertureless fiber-optic confocal microscope approach. The key element is a single-mode fiber coupler that serves simultaneously as a point light source providing a collimated Gaussian laser beam profile, and a point receiver that is highly sensitive to spatial displacements of the focused backreflectance laser emission. This new method overcomes significant problems associated with previously used test methods. It ensures higher accuracy in spatially locating the focal point (£ 1 µm resolution) and in measuring the IOL dioptric power. It also provides FDA and the medical device community with a means for the accurate measurement of a wide range of IOL designs. Using the CLM technique, we tested various IOL samples with both positive and negative dioptric powers over the range from 0 diopter to greater than ±30 diopter, under both dry and in-situ simulated conditions.

In CY 2008, OTMN used this method to evaluate the dioptric power of regulatory samples of new IOL designs as well as official samples of IOLs on regulatory hold for questions about the accuracy of the labeled dioptric power. The laboratory obtained high levels of dioptric power testing repeatability which are significantly smaller than the tolerance limits specified in both the ISO and ANSI standards for dioptric power labeling. This is an essential CLM benefit when newly developed IOL products are tested. OTMN has also demonstrated the greater CLM potential for use in testing more complicated IOL designs such as multifocal and toric IOLs. Thus, the CLM operating principle and designs provide a simple, accurate, completely objective, quick and inexpensive method for measuring the dioptric power of various IOL implants.

The basic technical accomplishments and testing results associated with the CLM approach have been published in several peer-reviewed journals and reported at major international conferences. An international pending patent has been filed on the basic CLM principle. This independent test method has also been proposed as a standard test method in the currently discussed ISO 11979 Standard: “Ophthalmic Implants – Intraocular Lenses Part 2: Optical properties and test methods.” 

Software (Division of Electrical and Software Engineering)

Formal Methods Based Generic Patient Controlled Analgesia Pump Model

DESE researchers have developed a mathematical model for a generic patient-controlled analgesia (GPCA) pump as part of the infusion pump modeling project (RP1030A). The project uses leading-edge formal methods research to encapsulate core safety features of real-world pumps. The model reflects infusion pump usage in a hospital and home care environment. It may ultimately serve as a basis for manufacturer (software) safety certification and as a framework for capturing CDRH, industry, and academic domain knowledge. Such a capability may result in increased public safety and facilitate more efficient regulatory activities.

The GPCA model represents a rudimentary yet fully functional description of the basic operation and safety features of a PCA pump. DESE carried out a detailed hazard analysis study was to collect the specifications for the model. As part of this study, researchers consulted subject matter experts and identified a comprehensive list of hazardous situations that could lead to a malfunction, or endanger the patient in any way. Once these hazards were identified, safety characteristics could be defined for the pump, and common features could be derived to develop the core (generic) infusion pump model.

The model architecture consists of three main components: a graphical user interface (GUI) front-end, an executable state-machine representation of the pump control software, and a back end consisting of system models of the various pump (physical) components. The rationale for having three separate components for the GPCA pump model is to make it extensible and easily modifiable. Having a three-tiered architecture provides academics and manufacturers with a simple interface to replace the existing user interface and system components with their own specific models. Moreover, it allows them to easily extend the model by incorporating additional functionality, if needed. This is done simply by supplementing the current state machine with additional system states.

The GPCA model has been developed in-house in DESE, with collaborative input from the Fraunhofer Center for Experimental Software Engineering (CESE) and the University of Pennsylvania (UPenn). The current version of the model is hosted on UPenn’s website and is available for academics and manufacturers to extend and use for their purposes. By making this model open to academics and manufacturers, the goal is to consolidate a core set of safety features for infusion pumps and to encourage the use of formal modeling techniques in the medical device community.

Solid Mechanics (Division of Mechanics and Materials Science)

Engineers and scientists in the Solid Mechanics Laboratory help CDRH understand issues of concern related to the response of medical devices and  material to applied stress in both pre-market evaluations and post-market reported adverse events.  The materials of interest include traditional engineering materials like metals and polymers, materials of biological origin, and those used in tissue engineered medical products (TEMPs).  We have the capabilities to measure mechanical properties ranging from the tensile strength of sutures and medical glove materials, to the fatigue strength of total joint prostheses

Accomplishments

Strength retention of bioabsorbable polymers subjected to load

  • Developed protocols to measure the tensile properties, crystallinity, and thermal properties of bioabsorbable specimens.
  • Preliminary immersion of bioabsorbable polymer specimens under load suggest significant creep behavior.

Fatigue testing of PMMA bone cements

  • Tested specimens in accordance with ISO 5833-02 and related properties .
  • Presented data at Annual Meeting of Society for Biomaterials (San Antonio, TX)

Development of a standard test method to assess compatibility of personal lubricants with natural rubber latex condoms—(Part A) Tensile and airburst properties, (Part B) Viscoelastic properties

  • Completed first round of swelling tests, stress relaxation and tensile testing.
  • Completed first round airburst testing (Collaboration: FDA/WEAC).
  • Presented preliminary data and protocol to ASTM D11.40 Condom Task Group.  Task Group agreed to move forward with an interlaboratory study based on the tensile and airburst protocols.

Effects of Mechanical Stimulation on Chondrocyte Phenotype and Adhesion for the Production of Tissue Engineered Medical Products

  • Conducted preliminary experiments exposing chondrocytes to dynamic compression  to identify the effects of mechanical stimulation on model chondrocytes TEMPs systems. 
  • Submitted for publication to Cells, Tissues and Organs: Phenotype Shift and Adhesion of Bovine Chondrocyte Monolayer Cultures Grown on a Polystyrene Surface.”
Ultrasonics(Division of Solid and Fluid Mechanics)

Medical ultrasound spans a wide array of diagnostic, therapeutic, and surgical applications.  An important part of establishing the safety and effectiveness of these devices is acquiring accurate and meaningful performance information.  Therefore, to support the pre- and post-market regulatory review of these products, the Ultrasonics Laboratory maintains a research program devoted to exposure measurement, performance analysis, and regulatory guidance and consensus standards development.

Accomplishments

Thermal safety of medical ultrasound devices

  • Developed experimental and computational means for characterizing high intensity focused ultrasound (HIFU) surgery devices.
  • Developed and evaluated a technique based on acoustic streaming for free-field characterization of HIFU transducers (presentation and paper at 8th International Symposium on Therapeutic Ultrasound, 9/2008).
  • Developed and characterized a blood mimicking fluid for HIFU (presentation and paper at 8th International Symposium on Therapeutic Ultrasound, 9/2008; paper published in Journal of the Acoustical Society of America, 9/2008).
  • Measured temperature rise and cavitation threshold during HIFU exposures in ex-vivo porcine muscle to evaluate pre-clinical testing procedures for HIFU devices (abstract and presentation at 155th Meeting of Acoustical Society of America, 6/2008).
  • Measured temperature rise and cavitation threshold during HIFU exposure in lab-developed tissue-mimicking material to evaluate pre-clinical testing procedures for HIFU devices (presentation and paper at 8th International Symposium on Therapeutic Ultrasound, 9/2008).
  • Developed and made available for general distribution a user-friendly software package for simulation of pressure field, temperature rise, and thermal dose distributions for HIFU transducers (presentation and paper at 8th International Symposium on Therapeutic Ultrasound, 9/2008).
Standards – Risk Management (Division of Electrical and Software Engineering)

A DESE staff researcher, along with other joint working group members of ISO TC 210 JWG1 received the 2008 AAMI Technical Committee Award. Each year, up to two technical committees or working groups may receive this award. The honor came in recognition of the working group efforts to produce ISO 14971:2007, the second edition of the medical device risk management standard. The AAMI Standards Board selects those to be honored based upon the importance of the contributions, benefits, and effects that resulted or will result from a standard, or a group of standards (e.g., contribution to patient safety, international trade, etc). The basis for this award is as follows:

To date, all documents published under the aegis of JWG1 (and the U.S. sub-TAG) have had unanimous approval in ISO and IEC. The risk management standard has become adopted by regulatory agencies worldwide as evidence of achieving the risk management requirements of their regulations (U.S., Japan, EU, Canada, etc.). ISO 14971 has been referenced by more than 100 other medical device standards and forms the basis for achieving state-of-the-art in the general IEC safety standard, IEC 60601-1:2005. The risk management standard is forming the basis for the on-going effort to revise ISO Guide 63:1999, Guide to the development and inclusion of safety aspects in International Standards for medical devices. The standard forms the basis for achieving ever-improving safety and effectiveness of devices worldwide. ISO 14971 also forms the basis of IEC 80002, Medical device software - Guidance on the application of ISO 14971 to medical device software.

In 2002, the joint working group began conducting workshops with the regulated industry to learn of any problems they encountered with understanding and meeting the complex requirements of the standard. OSEL staff had a central role in these meetings, providing technical positions on a wide range of system safety issues. In 2003, the working group began developing the second edition of the standard with the intent of revising certain key requirements and adding informative annexes to explain the intent of the requirements. DESE’s representative both authored and co-authored three of the annexes on risk concepts applied to medical devices and was the central driving force for four major changes to the standard: 1) establish the basis for determining how safe is safe enough, i.e., risk acceptability; 2) establish manufacturers' responsibilities for both developing policy for determining acceptable risk and accepting overall system safety results; 3) require that all device hazardous situations be managed before overall system safety results can be accepted; and 4) prevent use of alternative methods for determining risk acceptability (a common problem in the device industry).

CDRH Standards Management Program

The Standards Management Program remains an integral part of the mission of both the Center and of the Agency.

The current status of the CDRH Standards program includes the following:

  • 771 recognized voluntary consensus standards;
  • 261 FDA staff served as liaison representatives; and
  • 535 standards committees involved FDA/CDRH participation revising or developing new medical device relevant standards. 

Fifteen of the designated CDRH liaison representatives hail from other Centers within the Agency including the Center for Biologics Evaluation and Research (CBER), Center for Drugs and Evaluation Research (CDER), and the Office of Regulatory Affairs (ORA).

The CDRH Standards Program databases were used as templates for two Agency-wide databases. The first database is a Standards Activity Database which identifies all standards committees with FDA staff participation and the Agency liaison representatives to those committees. The database can be searched by Center, by committee work, or by the FDA representative name. This provides a greater accounting of the effort that goes into voluntary consensus standards for CDRH, the other Centers, and FDA. The second database is one that allows all FDA staff to have access to published consensus standards that have relevance to the mission. CDRH has consistently managed licenses to outside databases of published standards for internal CDRH use only. Once the Agency determined the value in having the same access, all FDA Centers came together to collaborate on the access and license fees for that access. Now anyone in FDA can view and download consensus standards relevant to their regulatory responsibilities. These are huge steps forward for the Agency and they help all of the Centers collaborate more effectively on the use of and participation in voluntary consensus standards.