Transforming FDA

FDA Issues HPV Test Guidance

mddi — Thu, 08 Oct 2009 17:08:46 +0000

FDA has published a draft guidance titled Establishing the Performance Characteristics of In Vitro Diagnostic Devices for the Detection or Detection and Differentiation of Human Papillomaviruses. It contains recommendations for studies to establish the analytical and clinical performance of in vitro diagnostic devices intended for detection or detection and differentiation of human papillomaviruses (HPV).
The guidance says that the devices are used in conjunction with cervical cytology to aid in screening for cervical cancer. They include devices that detect a group of HPV genotypes, particularly high-risk viruses, and devices that detect more than one genotype of HPV and further differentiate among them to indicate which HPV genotypes are present.
FDA says that the guidance provides detailed information on the types of studies that the agency recommends to support premarket approval for these devices. It is limited to studies intended to establish the devices’ performance characteristics and does not address HPV devices that are intended to be used independent of a cervical cytology result. It specifically addresses devices that qualitatively detect HPV nucleic acid from cervical specimens, although many of the recommendations are also applicable to devices that detect HPV proteins. The guidance may be accessed at www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm181509.htm.

—James G. Dickinson [Washington Wrap-Up, November]

LDTs Still Face Pressure from FDA

mddi — Thu, 08 Oct 2009 17:05:31 +0000

There is no timeline yet for doing it, but FDA still intends to regulate laboratory-developed tests (LDTs) under FDA “enforcement discretion,” CDRH acting director of chemistry and toxicology devices Courtney Harper told the RAPS annual meeting audience in September. LDTs are presently marketed under the Clinical Laboratory Improvement Amendments (CLIA) without agency premarket approval.
LDTs “present risks to patients,” she said. Harper defined them as tests that have been fully developed in a single laboratory for use only in that laboratory, and that have no premarket review, no independent research basis, and no requirement for clinical validity.
“A company announces it is setting itself up as a lab to develop a new test as a biomarker,” she told RAPS, “and the next week we’ll see a news release that it is starting clinical tests for that soon. To us, that means that they actually don’t have enough information about the parameters of that test, if they’re still doing clinical studies on it.” That tells FDA, she said, that the labs still don’t understand the tests’ clinical performance and that the labs are marketing them for what is an investigational use without giving patients their right to informed consent.
“CLIA doesn’t require any type of clinical validity,” Harper said. “It doesn’t preclude the labs from doing that type of research. All it requires is that the test be analytically valid. It does not require that you actually have knowledge of the link between the test result and the clinical diagnosis.”
Due to the wide variability in lab quality, she added, “it’s very difficult for a doctor or a patient to predict what they’re getting when they order a lab-developed test.”
Harper noted that FDA is actively considering a 10-month-old Genentech petition that says the bifurcated FDA/CLIA practice of regulating by business model “doesn’t make any sense.” She said that until FDA’s policy on LDTs is changed, “we’re evaluating tests by risk. We really need to make some significant public health and policy decisions.” She promised that the decisions would be made transparently and with stakeholder input. The best way for stakeholders to participate now is to comment on the Genentech petition.
Harper also said that FDA regards tests that are distributed between different sites within a single corporation as not qualifying as LDTs, but as different laboratories; such tests require FDA premarket clearance or approval.
She warned that companies selling LDTs have more responsibility for the potential uses of their products than many realize. Although a company may have labeled a product for research use only, it may know through agreements or conversations with customers that the test is being used for clinical purposes. So “they have a responsibility under [21 CFR 801.4] to correctly label that product. That means the company would not be able to look the other way and say ‘that’s their problem.’ A disclaimer doesn’t protect the company as much as some people think that it does.”

—James G. Dickinson [Washington Wrap-Up, November]

FDA Asked to Reconsider Dental Amalgam Rule

mddi — Thu, 08 Oct 2009 17:01:21 +0000

While FDA’s new leadership touts the importance of exemplary science at the agency, a 47-page petition seeking the reconsideration of the agency’s August 4 final rule on mercury-containing dental amalgam trashes the science FDA used in it. The petition also alleges a selective literature search and says that the agency’s clear priority was to “defend at all costs the continued use of mercury in dentistry.”
The petition was filed on September 3 by Tulsa, OK, lawyer James M. Love for 17 others, including the Washington group Moms Against Mercury and celebrity osteopath and Internet natural products marketer Joseph Mercola. It seeks a formal ban on encapsulated mercury amalgam fillings or, alternatively, their reclassification into Class III instead of the final rule’s Class II.
The petition says a “defensible” amalgam risk assessment would require a detailed and quantitative analysis of the exposure to mercury vapor in the general population, but FDA’s analysis “only alludes to average or typical exposure levels, citing dated (predating 1993) reviews which they themselves only cite other yet older reviews.” Further, it says, FDA’s assessment omits measure of those maximally exposed to mercury vapors—patients with up to 25 mercury-filled teeth. FDA stops at 10, it says.
Further, the petition says, FDA’s risk assessment did not assess mercury vapor exposure from fillings in infants as young as 3, notwithstanding evidence that fillings are made in such teeth and notwithstanding EPA’s stipulation in 1998 that such exposures are especially pronounced. In sharp contrast to FDA, the petition says, Health Canada did consider all such extreme exposures when recommending against the use of mercury amalgams in 1995.
On the agency’s previously much-criticized literature search to support its position, the petition says the agency failed to utilize “a methodological ‘weight of evidence’ of the toxicological literature.”
The petition says that although FDA has the resources and expertise to properly assess amalgam’s risks, its “clear priority is to defend at all costs the continued use of mercury in dentistry—even at the expense of the public health. It is not surprising, therefore, that FDA declined to validly and defensibly compare its estimate of the average or typical mercury vapor exposure to the very reference exposure levels it represents to be safe for the general population.”

—James G. Dickinson [Washington Wrap-Up, November]

Can FDA’s New Plan Better Communicate Risk to Patients?

mddi — Fri, 02 Oct 2009 16:44:34 +0000

FDA has issued a Strategic Plan for Risk Communication, outlining the agency’s efforts to release more meaningful public health information. The plan lays out a framework for FDA to provide information about products to healthcare professionals, patients, and consumers. It also outlines how the agency oversees industry communications.

The agenda involves 70 specific actions for the FDA to take over the next five years, 14 of which the agency commits to accomplishing over the next year. Some of these immediate items relevant to medical devices include the following:

* Designing a series of surveys to assess the public’s understanding of, and satisfaction with, FDA communications about medical products.
* Producing a research agenda for public dissemination.
* Creating and maintaining a useful, easily accessible internal database of FDA and other relevant risk communication research.
* Posting pictures of FDA- regulated products affected by Class I or high-priority Class II recalls as part of recall notices/information.
* Developing detailed action plans at the agency and center levels for implementing and achieving the proposed action steps, including timelines, responsibilities, and resource needs.

According to the press release, the plan reflects FDA’s belief that risk communications must be adapted to the needs of different audiences and should be evaluated to ensure effectiveness.

Schultz on His Resignation

mddi — Thu, 20 Aug 2009 17:00:07 +0000

Former CDRH director Dan Schultz had this to say when reflecting on his tenure at the center’s helm:

â€œWhen I look back over the last five years, I see many CDRH accomplishments to reflect on and many unfinished tasks still ahead. The implementation of device user fees with its influx of resources and people has led to a more efficient and consistent premarket review process. Scorecards, project management plans, and extensive IT innovations have allowed us to track, measure, and adjust our programs while adding increased accountability. Science prioritization has both strengthened our research enterprise and ensured that science and regulation are firmly integrated in all of our many activities. And the postmarket transformation process has provided an opportunity to fundamentally rethink the way that risk/benefit information is collected, analyzed, and acted upon using all available resources within the center and utilizing available data and opportunities for collaboration outside the center as well. The matrix as both a construct and a concept is identifying and implementing new paths to a more effective CDRH and better risk management for the products we regulate.

â€œThere is always more to be done. Developing methodologies for quantitative decision making across the product life cycle will not only allow us to make better decisions but will enhance our ability to explain and replicate those decisions. Working within the center and with other agency colleagues to prioritize and streamline the processes for regulation, policy, and guidance development will provide greater clarity both internally and externally as to the responsibilities that each of us has in maximizing the safety and effectiveness of the products that we regulate. Linking internal performance goals to public health outcomes and budget allocations in a way that can be measured and communicated will enhance the centerâ€™s fiscal strength and our ability to advance public health through access to better and safer medical devices and radiological products.â€

â€”Jim Dickinson (Washington Wrap-Up, MD&DI October)

[Read more about Schultz's resignation in Jim Dickinson's Washington Wrap-Up column in the October issue of MD&DI]

CDRH Chief Resigns

mddi — Tue, 11 Aug 2009 21:54:20 +0000

The Associated Press has reported that Daniel Schultz, head of CDRH, is resigning his post. In a letter to agency staffers, Schultz said that he and FDA Commissioner Margaret Hamburg agreed that his resignation â€œwould be in the best interest of the center and the agency,â€ according to the Associated Press.

Earlier this year, nine scientists wrote a letter to Obamaâ€™s transition team that alleged that the device approval process was corrupted. The letter, coupled with growing complaints about the 510(k) process, have led to increased scrutiny of CDRH methods. This monthâ€™s Washington Wrap-Up column takes a closer look at Schultzâ€™s role in the process.

AdvaMed released the following statement after Schultz’s departure:

“Dan Schultz served the nation for more than 30 years promoting and protecting the public health as a member of the U.S. Public Health Service.Â Dan supervised FDAâ€™s device center at time of unprecedented scientific advancement and helped continue U.S. leadership in the development of safe and effective medical treatments. As CDRH director, Dan was instrumental in crafting the historic agreement in 2007 reauthorizing medical device user fees, which has provided FDAâ€™s device program with a stable source of funding to help meet its regulatory responsibilities.Â In addition, he launched CDRHâ€™s Postmarket Transformation Initiative, which is designed to improve the collection, analysis and utility of the agencyâ€™s multiple sources of postmarket medical device data.Â Dan also has been a leader in efforts to strengthen and harmonize global medical device regulatory requirements and has supported FDAâ€™s work on the Global Harmonization Task Force. We wish Dan all the best in his future endeavors and look forward to working with Acting CDRH Director Jeff Shuren as the search for a permanent director of the device center proceeds.â€

[from DeviceTalk]

FDA Flip-Flops on Mercury in Dental Fillings

mddi — Wed, 05 Aug 2009 15:38:38 +0000

FDA has concluded that dental amalgam fillings are not a health hazard. The agency reached this conclusion after a six-year review of hundreds of studies on the fillings. What makes FDA’s position a little puzzling is the fact that just last year, CDRH issued a new policy statement that recognized health problems posed by mercury amalgam. The risks were notably higher for children (fetuses included), pregnant women, and others with mercury immuno-sensitivity or high mercury body burdens. The page containing CDRH’s previous statement statement has been taken down.

Susan Runner, who leads CDRH’s Dental Devices Branch, had this to say: “The best available scientific evidence supports the conclusion that patients with dental amalgam fillings are not at risk for mercury-associated adverse health effects.”

How to Reach CDRH During Its Move

mddi — Tue, 21 Jul 2009 16:53:03 +0000

Construction of CDRH’s new facility was recently completed, and now the entire staff is ready to move in. The address of FDA’s White Oak campus in Silver Spring is below:

10903 New Hampshire Ave., Silver Spring, MD 20993

CDRH began the move two months ago, and all staff should be located at the new campus by August 3, 2009. The center recommends that people reach staff members via e-mail because all office addresses, as well as phone and fax numbers, will change. If you can’t reach someone and you have questions, contact the center’s industry assistance staff:

E-mail: Â DSMICA@fda.hhs.gov
Phone:Â 800/638-2041
International: Â 301/796-7100
Fax: Â 301/847-8149

CDRH’s Brand Spanking New Facility

mddi — Wed, 08 Jul 2009 17:26:09 +0000

Construction on CDRH’s new facility in Silver Spring, MD, has been completed three months early. It marks the third building completed at FDA’s Silver Spring campus in the past five years (the other two: the $89.2 million, 573,261-sq-ft CDER building and the $42 million, 123,000-sq-ft central shared use facility).

The $93.7 million, 393,000-sq-ft, six-story CDRH facility has an exterior made of brick, cast stone, and curtain wall. Employees can use steel pedestrian bridges on the second and third floors for access to the adjacent laboratory facilities. A six-story atrium than stretches the length of the building is the new facility’s centerpiece. The new digs also include high-density storage space and a 150-person conference center.

510(k): The Mindless Rubber Stamp?

mddi — Tue, 07 Jul 2009 19:24:21 +0000

CDRH’s Daniel Schultz told attendees at the Medical Device Manufacturers Association annual meeting that FDA and industry have not done a very good job of communicating to the public that the 510(k) process is not the â€œmindless rubberstamp that some people are making it out to be.â€ You can read more about his comments in Jim Dickinson’s Washington Wrap-Up column in the August issue of MD&DI. But below are some excerpts that may not make it into the print issue.

During the question and answer period at the meeting, Schultz was asked to comment on sponsorsâ€™ perception that the advisory committee process isnâ€™t always as predictable as planned because of panel members asking questions outside the scope of the meetingâ€™s agenda. â€œWe try to be selective on what we take to panel,â€ he responded. â€œWe try to take devices where we have specific questions that we want [OEMs] to address as opposed to taking every PMA to panel and no 510(k)s for instance.â€ That approach may change. Schultz said that the focus should be on what the question is and on the type of expertise necessary to make the best decision. â€œSo I think maybe weâ€™ll see a more risk-based approach to making those decisions.â€

In terms of predictability, Schultz said one of the issues CDRH needs to focus on is making sure the right expertise is represented on the panels. Conflict-of-interest issues make that challenging, he added, because a particular discipline may be very narrow. There may be only a few experts and they may all be conflicted, resulting in â€œhaving people [on the panel] who really donâ€™t understand the particular issue or technology, giving you a variety of opinions that may not be exactly on point.â€ Schultz said that in terms of transparency, there will be more panel meetings, and the advisory panels have a valuable role to play there. He added, â€œthen it becomes a matter of figuring out how to use the system as well as we can possibly use it.

â€œWe canâ€™t tell the panel members what to say, so obviously they have the right to ask the questions that they see fit,â€ Schultz said. â€œWe can provide training for them to understand the regulatory questions we are seeking answers to, and we can focus the questions” in such a way that the panelists will help get FDA the answers it needs.