CIMIT: January 2008 Regulatory Affairs Newsletter

January 2008 Regulatory Affairs NewsletterPrint this page

• CMS Considers National Coverage Policy for Thermal Disc Therapies
• New Portal for FDA Dockets
• Approval Required for Most Labeling Changes
• Priorities for 2008 Shaped by FDA User Fee Commitments
• FDA and NIH Partner to Centralize Adverse Event Reporting
• FDA Publishes Guidance Documents on PMA Manufacturing Audits and Clinical Trial Inspections
• FDA to Establish Staff Positions Globally
• CMS to Expand DMEPOS Competitive Bidding
• New Initiatives Create Market for Novel Device Interventions for Preventing Hospital - Acquired Infections
• Medicare Device Provisions Still on the Table for 2008
• For-Cause Inspections Reveal 10-Year High in Clinical Trial Violation Rate
• New Process to Help Device Firms Meet Regulatory Requirements
• ClinicalTrials.gov Certification to Accompany Premarket Submissions
• FDA Petitioned to Require Additional Information on DTC Device Ads
• Growing Orthopedic Implant Market in India
• FDA Releases New Guidance Document: Interactive Review for Medical Device Submissions: 501(k)s,
Original PMAs, PMA Supplements, Original BLAs, and BLA Supplements
• Representatives Concerned About Medicare Cuts
• Voluven Receives FDA Approval
• Device Firms Advertise Directly to Consumers
• Barriers to Adoption Prevent Innovative Technologies From Coming to Market
• FDA Expert: User Fees are Destructive
• FDA Risk Committee to Assess Publication of Product Safety Information
• Supreme Court Likely to Find in Favor of PMA Preemption
• Ad Hoc Panel Finds FDA Scientific Expertise Inadequate to Handle New Device Technology
• FDA-Duke Clinical Trial Initiative Focuses on IRB Reform
• New FDA Guidance Document: Consensus Standards
• Proposed eMDR Rule Due in February

CMS Considers National Coverage Policy for Thermal Disc Therapies
The Centers for Medicare and Medicare Services (CMS) is considering the adoption of a national coverage policy for procedures that apply heat directly to spinal discs to treat pain in the lower back. Procedures such as Intradiscal electrothermal annuloplasty (IDET), in which a catheter and flexible electrode are used to apply heat directly to the
spinal discs causing lower back pain, are to be considered in this internally generated review. CMS’s decision could affect devices such as Valleylab’s discTrode, Baylis Medical’s TransDiscal, and Smith & Nephew’s SpineCath.
Although CMS has not articulated the reasons behind its decision to review coverage of these devices, some have suggested that the agency is responding to concerns about the evidence supporting thermal disc therapies. Public comments are due to the agency by February 14, 2008; CMS will propose a decision by July 15, 2008. Additional information is available at www.thegraysheet.com (paid subscription service).

New Portal for FDA Dockets
Public comments can no longer be submitted to the U.S. Food and Drug Administration through the agency’s
website. Effective January 15, 2008, those wishing to submit public comments to FDA must do so through the
Federal eRulemaking Portal at www.Rgulations.gov. All dockets that were previously managed by FDA’s system
will be moved to the federal system in the coming months. Additional information available at www.thegraysheet.com
(paid subscription service).

Approval Required for Most Labeling Changes
FDA published a new proposed rule on labeling changes for drugs, biologics, and medical devices in the January 16, 2008, Federal Register. The draft rule reiterates the agency’s position that manufacturers may only amend labeling for
a drug or device if they have "newly acquired" safety information about the product. The rule would clarify that even the strengthening of a contraindication or warning is permitted without prior FDA approval only when there is sufficient evidence of a casual association with the [product]. This draft rule seeks to codify the agency’s longstanding position
on when a labeling change may be made prior to FDA approval. The draft rule strengthens the PMA preemption
defense that many drug and device manufacturers assert in products’ liability tort actions. Additional information is available at www.thegraysheet.com (paid subscription service).

Priorities for 2008 Shaped by FDA User Fee Commitments
In response to the FDA Amendments Act of 2007 (FDAAA), and to the many commitment letters issued by the agency, FDA will pay special attention to in vitro diagnostics (IVD), which make up the device group that is the target of the greatest number of commitments. FDA has pledged to issue or revise guidance documents for six specific IVD topics and to assess numerous reforms to the process of granting waivers for tests under the 1988 Clinical Laboratory Improvement Amendments (CLIA). The agency will consider whether certain low-risk IVDs can be made exempt
from 510(k) requirements and whether its pre-investigational device exemption (pre-IDE) meeting process can be improved for these devices. In addition, the agency will look into streamlining and combining the 510(k)-review and
CLIA-waiver review process for IVDs. Additional information is available at www.thegraysheet.com (paid subscription service).

FDA and NIH Partner to Centralize Adverse Event Reporting
The U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH) are partnering to develop a centralized internet based adverse event reporting system. The aim of the collaboration is to lower costs, improve
report quality, and reduce delivery time. A recent memorandum of understanding between FDA and NIH combines the efforts of the two. Until now, FDA has been working toward a single, agency-wide portal, called MedWatch Plus. Meanwhile, the NIH has implemented the Federal Adverse Event Task Force to develop a similar portal. The
combination of these efforts is expected to create a portal that will allow any user to submit adverse event information electronically to a centralized database. Additional information is available at www.thegraysheet.com
(paid subscription service).

FDA Publishes Guidance Documents on PMA Manufacturing Audits and Clinical Trial Inspections
On January 8, 2008, FDA's Center for Devices and Radiological Health’s (CDRH) published two new final guidance documents. The first, entitled, The Review and Inspection of Premarket Approval Application Manufacturing Information and Operations, available at http://www.fda.gov/cdrh/comp/guidance/1566.pdf,
describes facility inspection policies for premarket approval (PMA) applications and outlines FDA’s timeline commitments for such inspections, which the agency must meet in order to comply with user fee performance goal deadlines. The second, entitled, The Review and Inspection of Premarket Approval Applications under the Bioresearch Monitoring Program, sets forth the timetables that medical device firms can expect when premarket approval applications and supplements are under review by CDRH’s bioresearch monitoring division. This document is
available at http://www.fda.gov/cdrh/comp/guidance/1602.pdf.
Additional information is available at www.thegraysheet.com (paid subscription service).

FDA to Establish Staff Positions Globally
The FDA is hoping to establish staff positions in a number of foreign countries. The focus of these staff would be to perform overseas inspections and to foster relationships with foreign governments and industry. FDA is concerned
that its current approach is no longer adequate to perform its domestic duties and cites increasing concerns about the international implications of the agency’s work as a major driving factor. Agency officials note that the products
regulated by FDA are increasingly global products. Although the agency hopes to establish a number of overseas
posts, China will likely be the site of the first — negotiations to this effect are currently underway with the Chinese government. Additional information is available at www.thegraysheet.com (paid subscription service).

CMS to Expand DMEPOS Competitive Bidding
On January 8, 2008, the Centers for Medicare and Medicaid Services (CMS) announced that it will expand competitive bidding for durable medical equipment, prosthetics, orthotics, and supplies (DMEPOS). New York, Chicago, and Los Angeles are among the 70 additional metropolitan areas for which competitive bidding will determine payments for
eight product types: oxygen equipment and supplies; standard and rehabilitative power wheelchairs; enteral nutrition
supplies; respiratory assist devices and continuous positive airway devices; hospital beds; negative pressure wound therapy pumps; and walkers. The bidding process is expected to begin this summer despite pressure to postpone
any expansion until the current program’s impact can be evaluated. Additional information is available at www.thegraysheet.com (paid subscription service).

New Initiatives Create Market for Novel Device Interventions for Preventing Hospital - Acquired Infections
As state and federal legislatures and the public pressure hospitals to reduce infection risks, a stream of new medical devices aimed at preventing hospital-acquired infections is hitting the market. According to the Centers for Disease Control and Prevention, approximately 1.7 million Americans experience hospital-acquired infections each year; in
2002, 99,000 of these patients died as a result. In response, many state legislatures have passed laws requiring hospitals to publicly report rates of certain hospital-acquired infections. On the federal level, the Deficit Reduction Act
of 2005 requires the Centers for Medicare and Medicaid (CMS) to deny payment for the added costs associated with certain, preventable hospital-acquired conditions. As a result, the device industry is faced with a unique opportunity to develop products that help hospitals increase their screening and testing of patients. Several such products such as rapid molecular assays and antimicrobial-coated devices, are already available and many others are expected to hit
the market in 2008 and 2009. Additional information is available at www.thegraysheet.com (paid subscription service).

Medicare Device Provisions Still on the Table for 2008
Although Medicare was a hot topic for Congress in 2007, by year’s end, few policy changes were effected, leaving many issues up for debate in 2008. Despite heated debate on the topic, Congress passed a scaled back Medicare bill, which excludes many provisions that device firms lobbied for, as well as many they lobbied against. This means that many of the same issues addressed in 2007—such as, imaging cuts and comparative effectiveness legislation—will be addressed again in 2008. Top priorities for the medical device industry this year include: reimbursement for remote monitoring of devices and molecular diagnostics; charge compression; monitoring of CMS’ charge-with-evidence-development policy; competitive bidding for durable medical equipment; and gainsharing arrangements. Additional information is available at www.thegraysheet.com (paid subscription service).

For-Cause Inspections Reveal 10-Year High in Clinical Trial Violation Rate
The violation rate for sponsors of clinical trials reached a 10-year high in fiscal year 2007. Many of the violations were uncovered as a result of inspections triggered by complaints from industry competitors, clinical trial subjects, clinical investigators, and firm employees, to name a few. Insufficient monitoring of clinical sites was identified as the most frequent problem for trial sponsors in 2007. Other notable problems included failure to submit progress reports or
obtain investigator compliance; hiring unqualified study monitors; and failing to receive appropriate Institutional
Review Board (IRB) or Food and Drug Administration (FDA) approval before beginning a trial. Janice Hogan, a partner
in the at the Washington, D.C., law firm Hogan & Hartson who represents medical device companies, attributes the increase in violations to higher expectations from FDA. According to the agency, a key factor for firms to consider when choosing clinical sites to work with is whether the site has well structured training programs or quality systems
standard operating procedures. The agency believes that such programs will help reduce sponsor violations in the future. Additional information is available at www.thegraysheet.com (paid subscription service).

New Process to Help Device Firms Meet Regulatory Requirements
Asymtec and YESTech have developed a process by which medical device firms can more easily meet regulatory requirements imposed by the U.S. Food and Drug Administration (FDA) for traceability and validation in the
manufacture of certain medical products. Specifically, the process combines the dispensing capabilities of Asymteck with the automated optical inspection technology of YESTech to validate that fluid droplets are accurately dispensed
and correctly placed on medical devices, such as Lab-on-a-Chip devices, lateral flow test strips, and sensors, among
others. Additional information is available at
www.asymtek.com/applications/medical_device/default.htm.

ClinicalTrials.gov Certification to Accompany Premarket Submissions
The Food and Drug Administration Amendments Act of 2007 (FDAAA) requires that additional information be
submitted to the clinical trials data bank, www.ClinicalTrials.gov, including information about and results of qualifying clinical trials. One new provision requires that applicants filing human drug, biological, and device product
submissions certify compliance with all applicable requirements of section 402(j) of the Public Health Service Act
(PHS Act). FDAAA requires that certifications be submitted to the U.S. Food and Drug Administration (FDA or the
agency) beginning no later than December 26, 2007. For the Center for Devices and Radiological Health (CDRH), certifications must accompany premarket approval (PMA) applications, humanitarian device exemption (HDE) applications, and premarket notifications (510(k)). The certification form can be viewed at
www.fda.gov/opacom/morechoices/fdaforms/FDA-3674.pdf.
Additional information is available at www.fda.gov/cdrh/news/121307.html.

FDA Petitioned to Require Additional Information on DTC Device Ads
Consumers Union, a consumer advocacy group, recently sent a petition to FDA requesting that the agency require all direct-to-consumer (DTC) advertisements for implantable medical devices to warn consumers of possible failures or infections that may occur once the devices are implanted. This petition comes in response to a recent spike in advertisements for implantable devices, most of which lack basic information about the possibility of severe or fatal
side effects. FDA was recently granted increased authority to pre-review such advertisements and require specific disclosures by the Food and Drug Administration Amendments Act of 2007 (FDAAA).
Additional information is available at www.fdanews.com.

Growing Orthopedic Implant Market in India
India is positioned to become the largest market for knee and hip implants over the upcoming five years; the Indian market is growing at a rate of over 30% annually. The total number of joint replacements in India is currently estimated
to be around 40,000–50,000 and is doubling every year. In particular, knee replacement surgeries are growing faster than any other category, due in part to the availability of gender-specific devices developed specifically for the Asian population. It is estimated that two out of every ten people in India over 65 years of age currently have osteoarthritic knees. Additional information is available at http://www.devicelink.com/newsedge.

FDA Releases New Guidance Document: Interactive Review for Medical Device Submissions: 501(k)s,
Original PMAs, PMA Supplements, Original BLAs, and BLA Supplements
On December 28, 2007, the FDA released a new guidance document outlining the roles of both FDA and industry in a new interactive review process designed to help FDA meet new performance goals set in response to the Food and Drug Administration Amendments Act of 2007 ("FDAAA"). The interactive review process is intended to facilitate timely and efficient review of premarket submissions and contemplates increased informal interaction between FDA and applicants during the review process. Specifically, the interactive review process is designed to improve interaction between FDA and applicants, prevent unnecessary delays, ensure that FDA's concerns are clearly communicated
to the applicant, minimize the number of review cycles and questions, and to ensure timely responses from
applicants. The guidance document can be accessed at
http://www.fda.gov/cdrh/ode/guidance/1655.pdf.

Representatives Concerned About Medicare Cuts
A bipartisan group of 69 representatives has written to House Speaker Nancy Pelosi to express concerns regarding additional cuts to imaging services provided by Medicare. The cuts are being considered in the House version of the
Children's Health and Medicare Protection Act. The group also expressed support for the Access to Medicare Imaging
Act of 2007, which seeks to impose a two-year moratorium on the Deficit Reduction Act, which has cut medical
imaging by $13 billion this year. Additional information available at www.fdanews.com.

Voluven Receives FDA Approval
On December 27, 2007, the U.S. Food and Drug Administration approved Fresenius Kabi's Voluven for treating loss of blood volume, which can occur during surgery. Voluven, which contains a synthetic starch that does not dissolve in
water, is made by linking individual starch molecules together and combining them with a salt solution. The product expands the volume of blood plasma, thereby drawing fluid into the capillaries. Clinical trials demonstrate that Voluven
is as safe and effective as other blood volume expanders for adults, newborns, and infants. Additional information is available at www.fda.gov/bbs/topics/NEWS/2007/NEW01765.html.

Device Firms Advertise Directly to Consumers
Medical device manufacturers are increasingly advertising directly to consumers, rather than physicians, through television commercials for their products. But, some physicians are skeptical about the information presented in these ads. Specifically, physicians are concerned that the complex safety and adverse event information for these devices cannot adequately be conveyed to lay consumers in a short television commercial. Device manufacturers are
cautioned not to alienate physicians in the race to extend marketing to the consumer. If firms target consumers too
early in the marketing process, physicians may not be adequately informed or educated about the product to answer patient questions appropriately. And many physicians are concerned that patients who request a product on the basis
of short, television commercials do not always understand what they are asking for. Although television ads may serve as a vehicle for patient education when done properly, device firms should be sure not to imply that the product has no potential complications. The U.S. Food and Drug Administration (FDA) expects these advertisements to present a balanced view of the product’s risks and benefits, but notes that the requirements for risk statements in device ads are minimal when compared with those for drugs. Congress recently gave FDA the authority to fine drug companies based on their false or misleading ads—the agency is expected to tighten the enforcement of device ads as well. Meanwhile, industry has requested guidance on preparing short direct-to-consumer advertisements. Additional information is available at www.thegraysheet.com (paid subscription service).

Barriers to Adoption Prevent Innovative Technologies From Coming to Market
Although device firms have developed technology to monitor a patient’s physiological condition, as well as that of the device, from many locations, the market is generally limited due to a reluctance among companies to advance interoperability. Industry insiders believe that all-around barriers to adoption, rather than a lack of technology, is
holding back patient care. In particular, insiders are concerned that many manufacturers design products that will not communicate with complementary products by other manufacturers, limiting the value that each individual device to
the patient. One key issue appears to be the lack of incentive to device firms to push interoperability as quickly as
technology would allow; however, some are looking for a solution. For example, third-party software programs that act
as mediators between disparate devices, allowing them to communicate through a central server, have recently appeared on the market to address providers’ interconnectivity problems. Insiders agree that health care providers
have an important role to play in pushing for better interoperability of medical devices. Along those lines, device firms
can incorporate standard wireless network connections into their devices as a first step. Additional information is available at www.thegraysheet.com (paid subscription service).

FDA Expert: User Fees are Destructive
According to Peter Barton Hutt, a senior counsel at Covington & Burling in Washington, D.C., Food and Drug Administration (FDA) user fees are destructive to the agency’s mission and should be discontinued. Hutt recently presented a report to FDA that the agency is not positioned to meet its current or emerging regulatory responsibilities, calling for more funding and better trained staff. According to Hutt, because Congress is required to fund cost-of-living increases to premarket review functions to trigger FDA user fee collection, but no similar increase is required for non-review functions, Congress has neglected to provide sufficient funds to non-user fee activities. As such, the non-premarket review core functions of the FDA lost approximately $250 million in funding between 2002 and 2005. Hutt concludes that as a result of user fees, FDA’s core mission is systematically being dismantled.
Additional information is available at www.thegraysheet.com (paid subscription service).

FDA Risk Committee to Assess Publication of Product Safety Information
A new risk communication advisory committee, scheduled to meet for the first time in early 2008, is tasked with helping the Food and Drug Administration (FDA) to systematically analyze how the public receives and interprets product
safety information. Although historically such information was released only after a time-consuming evaluation, today’s
patients and doctors want this information earlier than ever before. Thus, FDA is caught making safety judgments
based on incomplete information — the agency does not want to wait so long that patients are unnecessarily harmed
by an unsafe product, but does not want to remove a beneficial product from the market based on preliminary data. Experts caution that device safety information must be carefully scrutinized before informing the public; while a drug
can easily be removed from the market, implantable devices pose a more difficult question. Additional information is available at www.thegraysheet.com (paid subscription service).

Supreme Court Likely to Find in Favor of PMA Preemption
On December 4, 2007, the U.S. Supreme Court heard oral arguments in the case of Riegel v. Medtronic. At issue in
the case is whether section 360k(a) of the Federal Food, Drug, and Cosmetic Act ("FDC Act") supports preemption of
state-law claims seeking damages for injuries caused by medical devices that have received premarket approval ("PMA") from the U.S. Food and Drug Administration ("FDA"). Court observers note that a majority of Supreme Court justices appear to support some form of federal PMA preemption; however, it is likely that the decision will carve out some caveats in which certain types of claims are preempted and others are not. The case looks very good for Medtronic, who argued that premarket approval of a medical device and its labeling protects companies from liability
for patient injury in state court. Legal experts agree that the Court will likely find in Medtronic's favor; the question is
how broadly or narrowly the Court will define PMA preemption. Additional information is available at
www.thegraysheet.com (paid subscription service).

Ad Hoc Panel Finds FDA Scientific Expertise Inadequate to Handle New Device Technology
According to a November 29, 2007, report issued by the Subcommittee on Science and Technology, an ad hoc panel
of FDA's Science Board, the Center for Devices and Radiological Health ("CDRH") is ill equipped to understand the
science underlying many cutting-edge device technologies. Specifically, the report finds that CDRH needs more resources and personnel to improve its scientific understanding of nanotechnology, wireless devices, robotics, and other new technologies. Subcommittee members cite the accumulating unfunded statutory responsibilities placed on the agency, the rapid advance of scientific technologies, and the complexity of new products, among other issues, as contributing to the agency's precarious position. The report also prioritizes 15 areas of new technology in which
CDRH expertise is lagging, including artificial organs, genomics and proteomics, home- and self-care devices, and telemedicine. Without additional CDRH personnel to handle the scientific needs in the premarket review process of emerging technologies, the panel concluded that such technologies may be unable to reach their full potential. Additional information available at www.thegraysheet.com (paid subscription service).

FDA-Duke Clinical Trial Initiative Focuses on IRB Reform
The new public/private partnership between FDA and Duke University intended to modernize clinical trials has named institutional review board ("IRB") reform as one of its first goals. The partnership plans to streamline and standardize
the process of obtaining IRB approval for clinical research so that larger studies can be completed more quickly and less expensively. The partnership believes that under the current system, IRBs are expected to do too much, resulting
in unnecessary delays to clinical research for devices and drugs. The IRB regulations were written in the early 1970s,
at a time when most clinical trials were conducted at a single study site. The partnership intends to update these outdated regulations to better define the role of IRBs and devise ways to expedite the IRB approval process.
Additional information is available at www.thegraysheet.com (paid subscription service).

New FDA Guidance Document: Consensus Standards
The FDA recently published a new guidance document for medical device manufacturers that rely on recognized consensus standards in their premarket submissions. Conformity to consensus standards may reduce the amount
of documentation and time necessary to complete the premarket review process. A current list of FDA recognized standards can be found at
www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.
The new guidance document, "Recognition and Use of Consensus Standards; Guidance for Industry and FDA Staff,"
can be viewed at www.fda.gov/cdrh/osel/guidance/321.pdf.
Additional information is available at www.fdanews.com.

Proposed eMDR Rule Due in February
The FDA expects to release a new proposed rule in February 2008 to make electronic medical device reporting
("eMDR") mandatory. The proposed rule is expected to give companies one year from issuance of the final rule to
begin using eMDR. The agency does not expect medical device firms to experience difficulty making the transition to
an electronic reporting form. Additional information is available at www.fdanews.com.