FY 2003 ODE/OIVD Annual Report - Part 5 - Other Program Activities

 ODE Implementation of the Medical Device User Fee and Modernization Act of 2002 (MDUFMA)

During FY 2003, ODE invested considerable effort to ensure a smooth implementation of MDUFMA. MDUFMA provides essential additional resources to the device evaluation program and, in turn, establishes a comprehensive set of very challenging device review performance goals for fiscal years 2003 through 2007. The past year’s efforts have focused on laying the groundwork to ensure we will be able to meet these performance goals. During FY 2003, we drafted guidance for FDA staff and industry, developed new data systems to track performance, worked with stakeholders to develop agreement on the basic direction of the program, and began to hire additional medical, technical, and scientific staff. We will build on these efforts in FY 2004 and the future.

Additional information concerning our implementation of MDUFMA is available in CDRH’s FY 2003 annual report, and at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ Overview/MedicalDeviceUserFeeandModernizationActMDUFMA/default.htm. The MDUFMA Internet site provides the full text of the new law, useful reference materials, all of our MDUFMA guidance documents, and links to FDA’s FY 2003 report to Congress on our progress towards meeting MDUFMA’s performance goals.

 Guidance for Industry and Reviewers

In FY 03, ODE/OIVD published 25 final guidance documents and published 6 draft guidance documents for comment. See INDUSTRY INFORMATION for a complete listing of all ODE guidance documents published in FY 03.

 Public Health Response

OraQuick® Rapid HIV-1 Antibody Test: In November 2002, the FDA/CBER Approved OraQuick® Rapid HIV-1 Antibody Test manufactured by OraSure Technologies, Inc., of Bethlehem, Pa. The test is the first rapid HIV point-of-care (i.e., testing and results are available in one visit) test approved by the FDA. It is also the first test for HIV that OIVD has waived under the Clinical Laboratory Improvement Amendments (CLIA). Following the CLIA waiver by OIVD the HHS Secretary Tommy G. Thompson announced that HHS has extended the availability of the OraQuick Rapid HIV-1 Antibody Test from 38,000 laboratories to more than 100,000 sites, including physician offices and HIV counseling centers. The Secretary added "Ensuring the widespread availability of a rapid HIV test to outreach services in communities where people are at high risk of HIV is vital to the public health, without today's action (CLIA Waiver), this test would be limited to use in laboratory settings where many high-risk people do not go for testing."

Widespread availability of the rapid HIV test is likely to increase overall HIV testing and decrease the number of people -- an estimated 225,000 Americans -- who are unaware they are infected with the HIV virus. Early testing enables infected individuals to obtain medical care earlier in the course of their infection, potentially saving lives and limiting the spread of this deadly virus.

SEVERE ACUTE RESPIRATORY SYNDROME (SARS): An IDE for a SARS Coronavirus, submitted by HHS, Centers for Disease Control and Prevention (CDC), was approved. This allowed CDC to make available to about 100 public health laboratories nationwide, a new experimental laboratory test for patients suspected of being infected with the SARS virus. The experimental diagnostic test was rapidly developed by CDC over the past few months in an urgent effort to address this pressing public health need. HHS, Food and Drug Administration (FDA) worked closely with CDC to develop appropriate information for patients and health professionals in order to make the test available on an investigational basis. Because information about the test's performance is still being collected, patients will be asked for written consent before the test is used.

 OIVD Compliance Activities

Class I Recalls

8/11/03 (Recall number Z-1094-03), Becton Dickinson Diagnostic Systems, BD ProbeTec? ET Instrument. The incorrect installment of fiber optic bundles, exposed patients screened by this device to a risk of life threatening consequences due to inaccurate test results.

9/10/03 (Recall number Z-1209-03), bioMerieux, Inc., VIDAS? Chlamydia Assay. The raw material (bovine serum albumin (BSA)) caused an accelerated degradation of the product’s performance leading to false negative results, exposing patients screened by this device to a risk of potentially life threatening consequences due to inaccurate test results.

Warning Letters

10/10/02, Eagle Diagnostics, Inc., in vitro diagnostic devices. The warning letter references adulterated devices, misbranded devices, catalog listings of unapproved devices, and registration issues.

3/28/03, Applied Imaging Corporation, ariol SL-50 automated image analysis system (ariol SL-50). The warning letter references adulterated, unapproved and misbranded device issues.

 Bioterrorism Preparedness

ODE and OIVD continue to be involved in several resource-intense initiatives related to national bioterrorism preparedness and response. ODE and OIVD established liaisons and continue collaborate with other government agencies and the military to prepare for and assume regulatory responsibilities applicable to in vitro diagnostic products and other medical devices that are critical to bioterrorism preparedness efforts. ODE and OIVD are currently developing guidance and procedures for timely premarket review and approval of these devices.

The medical and public health preparedness and response to bioterrorism threats include the identification of threat agents by using in vitro diagnostic devices. Most laboratory reagents and test kits used for the identification of threat agents are not routinely used in the clinical laboratory and have not been cleared or approved by FDA. Some have not been classified. OIVD is developing notices of proposed rule making (NPRM) describing the proposed classification of B. anthracis and Y. pestis, and guidance containing the types of information needed to assess premarket submissions of the devices FDA is proposing to classify. OIVD is also working on the NPRM that proposes an amendment to the exception from general requirements for informed consent to apply in certain circumstances when investigational IVDs are used to identify agents potentially associated with terrorism threats.

In addition, OIVD continues interacting with manufacturers involved in the development and data gathering on devices for the identification of bioterrorism threat agents. This year OIVD has met or communicated by phone with several companies to clarify the premarket review requirements and routes available to obtain clearance or approval for medical uses, including investigational uses. Our scientists have participated in discussions with industry, the CDC and the military in determining options for making new in vitro diagnostic devices available and in clarifying requirements for testing during the investigational phase of the products.

 Least Burdensome

The two sections of the Food, Drug, and Cosmetic Act (the act) commonly referred to as the “least burdensome provisions” were enacted by Congress in 1997 to ensure the timely availability of safe and effective new products that will benefit the public and ensure that our Nation continues to lead the world in new product innovation and development. During the last few years, CDRH has been working with its stakeholders to develop an interpretation of the least burdensome provisions. In the May 3, 2001, Federal Register, the draft guidance document entitled, “The Least Burdensome Provision of the FDA Modernization Act of 1997: Concept and Principles” was released for comment. While the agency received very few comments on the draft, almost all of them strongly supported the guidance and encouraged full implementation of it as soon as possible. Several comments recommended that FDA develop a training program for its staff as well as ways to assess both the Agency’s success in implementing the principles and the stakeholders’ satisfaction with FDA’s incorporation of them into its daily activities. The agency agreed with these recommendations and has incorporated them into the final guidance. The final document was released on the internet on September 30, 2002 and in the October 4, 2002 Federal Register (67 FR62252). The guidance may be found on the Center’s website.

 Study Determination Inquiries

Every year, the Office of Device Evaluation (ODE) receives numerous inquiries regarding the need to submit an IDE application for research involving medical devices. These inquiries are received through a variety of means - in meetings, by telephone, e-mail, fax or letter. Such inquiries are initiated by a wide variety of entities, including device manufacturers, clinical investigators, and IRB members. In order to respond to these inquiries, we may refer to the IDE regulation (21 CFR 812), particularly sections 812.1 (Scope), 812.2 (Applicability), and 812.3 (Definitions), and the FDA Information Sheet entitled, "Significant Risk and Nonsignificant Risk Medical Device Studies" (hereafter referred to as SR/NSR guidance).

Often, the inquiries we receive can be easily answered by referring to the sources identified above. Occasionally, inquiries will present new situations not clearly identified in the regulation or the SR/NSR guidance. A few inquiries involve the scope of the IDE regulation and/or jurisdictional issues that may require consultation with the other FDA centers. An IDE Memorandum (#D01-1) dated, October 26, 2001 was issued to establish written procedures for handling inquiries regarding the need for an IDE application for research involving medical device.

When responding to these inquiries, there are three possible responses: the research is exempt from the IDE regulation; the abbreviated IDE requirements must be met (nonsignificant risk [NSR] study); or the full requirements of the IDE regulation must be met, that is, an IDE application must be submitted to FDA (significant risk [SR] study). In FY 03 ODE received 49 inquires. Of the 49 inquires, there were 13 SR determinations, 13 NSR determinations, 22 exempt determinations, and 6 inquires still under review.

 Significant Jurisdictional Issues

Title 21 of the Code of Federal Regulations Part 3 PRODUCT JURISDICTION describes the procedure the agency uses to assign Center jurisdiction over medical products whose jurisdiction is not clear or is in dispute. Requests for Designations (RFDs) over such products are made in writing to the Office of Combination Products which took this role over from the Office the Chief Mediator and Ombudsman in mid-FY 03. These formal submissions contain the material describing the requester's product and/or products, a proposal regarding which Center should be given lead designation over their product, and whose authorities (Biological, Device or Drug) should apply.

In FY 03 CDRH participated in the review of 26 out of 34 RFD's received by the FDA's Ombudsman's Office, in addition to completing the reviews of 5 RFDs received in FY 02. The reviews of the new requests were assigned to the ODE Divisions as follows: DGRND was assigned 11 (eleven); DRARD was assigned 9 (nine); DAGID and DCD were each assigned 2 (two); and POS was assigned 1 (one) to review. The remaining RFD was assigned to OIVD to review.

Of the 31 RFD’s [26 assigned in 2003 and the 5 carry over from 2002] which CDRH completed reviews of in FY 03 by both ODE and OIVD:

- CDRH was assigned the lead center in 14 of those requests
- CDER was assigned lead center in 8
- CBER was designated lead in 6 RFDs
- One was ruled by the Office of Combination Products as not an FDA regulated product and
- 2 were not due for completion until FY2004.

 CLIA Activities

Congress passed the Clinical Laboratory Improvement Amendments in 1988, establishing quality standards for all laboratory testing to ensure the accuracy, reliability and timeliness of patient test results regardless of where the test was performed. The categorization of commercially marketed in vitro diagnostic tests under CLIA has been the responsibility of the FDA since January 31, 2000. OIVD performs the CLIA complexity categorization that includes the assignment of these test systems to one of three CLIA regulatory categories (high, moderate and waived) based on their potential risk to public health. During FY 03 OIVD performed categorizations on a total of 2170 tests including 215 High, 1661 Moderate, and 194 Waived tests. FDA, CMS, and CDC are working together to publish a final rule on CLIA waiver. More information on the CLIA program can be found at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ IVDRegulatoryAssistance/ucm124105.htm.

 TSE (Transmissible Spongiform Encephalopathy)

ODE has been an active participant in both agency and CDRH TSE activities. As a member of the CDRH Transmissible Spongiform Encephalopathy (TSE) Working Group, ODE helped develop a TSE risk document to address medical device TSE risk issues.

ODE joined the other CDRH offices and CDER, CBER, and CFSAN in the Center for Biologics July 17-18, 2003 FDA CBER TSE Advisory Committee (TSEAC) meeting. ODE was responsible for planning the medical device portion of the meeting, including recruiting speakers, developing the agenda and making presentations regarding decontamination of medical devices that have been exposed to TSE. At the TSEAC meeting, ODE was evidence of the CDRH TSE WG FDA wide collaboration. In addition to ODE, all other offices in CDRH participated along with other centers in FDA - CBER,

CDER and CFSAN all developed sessions and shared information. At the TSEAC meeting, ODE and OST initiated a 2 hour session with the panel experts where medical device questions related to decontamination of medical devices and equipment used in manufacturing were presented to the expert CBER panel that included an ODE panel expert on infection control. This participation by ODE and the comments from the panel provided the opportunity to initiate discussion on TSE decontamination of medical devices at this public meeting with HHS, industry and international attendance. The TSEAC panel recommended a workshop to further assess the current state of knowledge of decontamination/inactivation of TSE for medical devices, facilities, and other medical applications of animal derived products. ODE is presently taking the lead in the CDRH TSE Working Group efforts to investigate the potential benefits of an international workshop on medical device decontamination.

 Advisory Panel Activities

The Center’s Medical Devices Advisory Committee (MDAC) with its 18 panels provide clinical and scientific advice to FDA in several areas of activity fundamental to the regulation of medical devices. The most significant of these areas of activity are: (1) classification and reclassification of medical devices into one of three classes based on risk, (2) review and make recommendations on premarket submissions such as Premarket Approval Applications (PMAs), Product Development Protocols (PDPs), and Premarket Notification submissions (510ks), (3) provide advice on guidance documents which convey to industry and the agency staff FDA’s expectations for studies and data for premarket review, and (4) provide input on issues or problems concerning the safety and effectiveness of medical devices.

In FY03, ODE held thirteen panel meetings. The panels reviewed and made recommendations on: twelve PMAs, one 510(k), two reclassification petitions, and three general issues. In FY03, there were 12 training sessions for members and consultants. The panels reviewed PMAs for significant medical device breakthrough technologies such as a drug-coated coronary artery stent and a stair climbing wheel chair.

A new draft guidance document, “Pediatric Expertise for Advisory Panels” issued for comment on June 3, 2003. This guidance document describes the process that CDRH intends to follow to ensure that an advisory panel review of a PMA or 510(k) includes pediatric specialists on the panel, when appropriate. The website for this draft guidance document is: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ GuidanceDocuments/ucm082185.htm. This year, the Center has recruited more than twenty pediatric specialists to serve as a member or consultant on an advisory panel for any premarket submission that may be indicated for use in a pediatric subpopulation.

CDRH continuously recruits highly qualified experts to serve as members and consultants on our panels. Potential candidates are asked to provide detailed information concerning financial holdings, employment, and research grants and contracts to identify any potential conflict of interest. Interested individuals should send their curriculum vitae to njp@cdrh.fda.gov.
The MDAC advisory panels are key to ensuring that the agency has access to the nation’s most esteemed medical experts and to making the FDA medical device review process transparent to stakeholders. The Office of Device Evaluation greatly appreciates the significant contributions that the advisory panel members and consultants make to the medical device review program.

 ODE Integrity Program

During this fiscal year, ODE/OIVD considered about 41 cases concerning the integrity of data submitted to the agency in premarket applications. Under the Application Integrity Program (AIP), one firm was placed on the AIP list and AIP restrictions applied against this firm, while AIP restrictions were removed from two firms. An Integrity Hold was placed on two firms’ applications during FY 03.

ODE handled 29 instances related to questions arising under the standards of conduct for employees. During FY 03, as in years past, the ODE/OIVD staff received several unsolicited gifts from the regulated industry. Both the offering of gifts and their acceptance in general, are prohibited under applicable laws and regulations. The regulated industry, their agents and representatives should not send gifts to staff members. See Standards of Ethical Conduct for Employees of the Executive Branch on the internet at
http://www.usoge.gov/ethics_docs/publications/reference_publications/rfsoc_02.pdf.