BB&T Washington Editor, and Staff Reports
A change at the commissioner's office at FDA can spook or encourage markets, and the latest change is much more likely to do the former than the latter. Margaret Hamburg, MD, the latest FDA commissioner, offered an unambiguous message in her address to the Food and Drug Law Institute (Washington) in August, letting it be known that her FDA will more strongly resemble the aggressive FDA of David Kessler than the relatively laissez-faire FDA of Andrew von Eschenbach.
One of the remarks Hamburg made was that she would like FDA to be in a better position to act unilaterally when dealing with products the agency perceives to be a threat to public health. "It is the case that FDA's arms are tied in ways that we'd like to liberate just a bit," she said in reference to tainted foods. While Hamburg did not explicitly state that the idea applies also to drugs and devices, she commented that when the agency comes upon information that a faulty product presents "a pressing public health concern," she would like the agency to be able to avail itself of "the ability to access certain kinds of records," and conduct "a more thorough trace-back" of a product to its origin than FDA is currently statutorily empowered to conduct.
On the subject of warning letters, Hamburg said that mandatory legal review of all warning letters will come to an end. "I have approved a new policy ... to limit warning letter review to significant legal issues," allowing warnings "to go through a streamlined process" unless legal review is indicated, she said. The move reverses a policy applied in the first year of the administration of President George W. Bush, which led to a substantial drop in the numbers of warning letters.
Hamburg said that the GC review created "a cumbersome process without a lot of demonstrated benefit," adding that GC reviews will be restricted to instances in which there is "a complex legal issue."
As has been widely expected since the election of 2008, inspections will become more frequent. However, Hamburg indicated that companies that get a warning letter will now be able to win a seal of approval from the agency upon successful completion of corrections. She described a "formal warning letter close-out process" whereby if a firm has fully corrected violations, "we will provide a close-out letter" stating that the issues have been addressed.
"Not every type of warning letter will be eligible for a close-out letter," Hamburg cautioned, adding that the purpose of the close-out process is "to communicate to the public that the problems have been corrected."
Among the changes Hamburg reported is that when FDA an investigator issues a 483, "we expect a prompt response to our findings," noting that the expectation is now that companies will respond within 15 days.
"The agency must place greater emphasis on significant risks of violations," and "must be able to respond rapidly to egregious violations," Hamburg remarked. The agency will also "prioritize enforcement follow-up," she said, and "will do more follow-up inspections."
Hamburg warned industry that FDA "will be prepared to act swiftly and aggressively to protect the public" from products deemed a threat to public health and that FDA will tolerate no more multiple warnings. "We will consider immediate action before we issue a warning letter" in the case of companies with a rocky compliance history, she said.
Schultz out at CDRH; Shuren is interim director
Dan Schultz, MD, director of the Center for Devices and Radiological Health at FDA turned in his resignation "by mutual agreement" with the new leadership at FDA in August.
According to a breaking story in the online edition of the Wall Street Journal, Schultz announced the move in a letter to CDRH employees in which he stated that his decision was "based on discussions with Commissioner [Margaret] Hamburg." The WSJ story also indicated that the departure "had nothing to do with any specific issue related to a device's approval process," although the intensity of the recent flap over the approval of the Menaflex 510(k) application by ReGen Biologics (Franklin Lakes, New Jersey) makes the claim seem questionable.
There has also been a more general controversy over the 510(k) program, which hit the nation's media thanks to letters from disgruntled employees to congressional leaders and the Obama administration. One of those letters also named the director of the Office of Device Evaluation, Donna-Bea Tillman, PhD, in allegations that she and Schultz placed relations with industry over safety considerations. According to a May letter from the renegade reviewers to Joshua Sharfstein, MD, at the time the acting commissioner at FDA, Schultz and Tillman seemed "far more concerned about ensuring their current positions and protecting and promoting their own careers and those of their cronies than they are about ensuring the safety and effectiveness of medical devices."
Schultz is said to have approved the Menaflex 510(k) while Tillman is said to have opposed the clearance. Among those whose role in the Menaflex clearance was seen as pivotal is Rep. Frank Pallone (D-New Jersey), chairman of the health subcommittee for the House Energy and Commerce Committee, which has spearheaded an effort to put the brakes on the 510(k) program.
BB&T obtained an all-hands e-mail posted at FDA by Hamburg in which she thanked Schultz "for his long service to the agency and to the public." Hamburg added that Schultz "has worked tirelessly to advance the public's health through the approval and monitoring of innovative and safe medical devices."
The new commissioner said that under Schultz's leadership, "CDRH enhanced our understanding of the risks and benefits of using medical devices in pediatric populations, increased the agency's safety efforts by expanding MedSun, and led the agency in the Postmarket Transformation process, which has provided an opportunity to fundamentally rethink the way risk/benefit information is collected, analyzed, and executed." She said the physician "has left a tremendous legacy, and we wish him well in all his future endeavors."
Hamburg also reported that Jeffrey Shuren, the agency's associate commissioner for policy and planning, will serve as the interim director of CDRH. Hamburg said Shuren "has a deep understanding of medical device law and policy" and that the agency will commence with "a national search for the position of director of CDRH."
Mark Leahey, executive director of the Medical Device Manufacturers Association (MDMA; Washington) told BB&T in an e-mail; "MDMA has appreciated working with Dr. Schultz over the years to provide patients with timely access to safe and effective products and wish him the best."
Steve Ubl, President/CEO of the Advanced Medical Technology Association (AdvaMed; Washington), said in a statement that Schultz "served the nation for more than 30 years" and that he "supervised FDA's device center at time of unprecedented scientific advancement and helped continue U.S. leadership in the development of safe and effective medical treatments."
Ubl remarked that Schultz "was instrumental in crafting the historic agreement in 2007 reauthorizing medical device user fees" and "launched CDRH's Postmarket Transformation Initiative." The statement also notes Schultz's leadership "in efforts to strengthen and harmonize global medical device regulatory requirements."
Not all the reactions were positive. Diana Zuckerman, PhD, President of the National Research Center for Women and Families (Washington) told BB&T in an e-mail that she sees it as "essential that the FDA's new leadership expands beyond the FDA Commissioner and Deputy Commissioner, and Dr. Schultz' resignation is a crystal clear sign that the process of reinvigorating a more public-health oriented FDA has begun." Zuckerman added that the change "is especially important to baby boomers, who increasingly rely on implants such as artificial knees and heart valves, as well as cosmetic injections such as wrinkle fillers, many of which have been allowed to be sold without adequate safety testing."
Fast release of data led to rapid changes in DES
E-mail, search engines, smart phones and other new technologies that disseminate new medical information quickly led to an almost immediate change in clinical practice for drug-eluting stents (DES), according to a study reported in Circulation: Cardiovascular Quality and Outcomes. Matthew Roe, MD, lead author of a study on the subject and associate professor of medicine at Duke University Medical Center (Durham North Carolina), told BB&T, "we were interested in whether practice patterns changed after the presentation of these studies," he said. "That's indeed what we showed."
Researchers examined data from two large patient registries that showed from January 2006 through September 2006 (before the data were released), about 90% of patients with non-ST-elevation myocardial infarction who underwent coronary stent implantation received drug-eluting stents.
In September 2006, a number of studies were presented at the European Society of Cardiology scientific sessions suggesting that drug-coated stents were associated with a higher risk of late stent thrombosis compared with bare-metal stents. By the end of March 2007, DES use fell to 67% and continued to drop to 58% by the beginning of 2008, Roe said.
Report says Midwest startups down
Midwest healthcare startups reported $402 million in total investments across 81 companies in the first half of 2009, according to the BioEnterprise (Cleveland) Midwest Health Care Venture Investment Report. The numbers are down 9% compared to the levels of investment seen in the first half of 2008 and significantly lower than 2007's record-setting pace. According to recent data from the National Venture Capital Association, venture investments nationally are down by more than 50% compared to 2008 and are at levels not seen since 1996.
"While Midwest healthcare venture investment is down from 2008, the region's companies are currently faring better than their national peers," said Baiju Shah, president/CEO of BioEnterprise. "However, the venture funding environment remains very challenging for Midwest healthcare start-ups."
Minnesota continued to lead the way, attracting $118 million across twelve healthcare ventures. Ohio and Michigan followed with $87 million and $65 million respectively.
AAOS creates independent joint replacement registry
The American Academy of Orthopaedic Surgeons (AAOS; Rosemont, Illinois) has incorporated the American Joint Replacement Registry (AJRR), a nonprofit organization dedicated to collecting and reporting on hip and knee joint replacement procedures.
AAOS plans to begin capturing data as early as 2010 with the hope of capturing data from at least 90% of all such procedures. In 2006, there were more than 1 million hip and knee replacements performed in the U.S. Of these, about 7.5% were revisions, accounting for 77,000 procedures at a cost of more than $32 billion.
A national joint registry will help doctors to more quickly match patients, procedures and devices to optimize outcomes. Therefore, the AJRR could help patients and payers save money and could limit the number of revision. Based on the projected procedures through 2030, the potential savings could exceed $13 billion over 20 years. The AJRR is estimated to cost $20 to $25 million to initiate.
Medtronic, Abbott settle stent patent fight
Medtronic (Minneapolis) and Abbott (Abbott Park, Illinois) reported the global resolution of outstanding intellectual property litigation between the two companies. Terms of the agreement stipulate that neither party will sue each other in the field of coronary stent and stent delivery systems for a period of at least 10 years, subject to certain conditions.
The agreement includes a $400 million settlement payment to be made to Abbott and also results in a $42 million success payment to evYsio (Vancouver, British Columbia) as part of a Medtronic sublicense to Abbott of evYsio's stent technology. Medtronic expects to report a special charge in its first quarter financial results as a result of the agreement.
Following the resolution of these disputes with Abbott, Medtronic said it has now resolved or settled "substantially all" intellectual property litigation affecting its stent design and stent delivery systems. Abbott said the one-time impact of this settlement will be treated as a specified item in 3Q09 earnings.
NIH to map 'wiring diagram' of brain
It comes as no surprise that "no two brains are wired up exactly the same," Michael Huerta, PhD, associate director of the National Institute of Mental Health (NIMH) told BB&T. But with the help of a new $30 million project, scientists will have an opportunity to learn more about how the brain is wired and how that wiring differs between brains.
Huerta is the lead NIH contact for the Human Connectome Project (HCP) being launched by the National Institutes of Health Blueprint for Neuroscience Research.
HCP will use "cutting-edge" brain imaging technologies to map the circuitry of the healthy adult human brain. By systematically collecting brain imaging data from hundreds of subjects, the HCP may yield insight into how brain connections underlie function and open up new lines of inquiry for neuroscience.
The connections between brain regions are important for shaping and coordinating the various functions, but scientists know little about how these different parts connect. "If we knew more about the connections within the brain – and especially their susceptibility to change – we would know more about brain dysfunction in aging, mental health disorders, addiction and neurological disease," said Story Landis, PhD, director of the National Institute of Neurological Disorders and Stroke (NINDS), also part of the NIH Blueprint.
In addition to brain imaging, the HCP will collect DNA samples, demographic information and behavioral data. These data could hint at how brain connectivity is influenced by genetics and the environment, and in turn, how differences in brain connectivity relate to behavior. Primarily, however, the data will serve as a baseline for future studies.
The brain may contain more than 100 billion neurons forming trillions of connections, and while neurons can connect across distant regions by extending long axons, the trajectories these axons take are almost entirely uncharted. In the HCP, researchers will optimize and combine brain-imaging technologies to probe axonal pathways and other connections.
Sophisticated versions of MRI have recently emerged that can look beyond gross anatomy to find functional connections. Functional MRI (fMRI), for example, uses changes in blood flow and oxygen consumption within the brain as markers for neuronal activity and can highlight the brain circuits that become active during different behaviors.
NIH also expressed an interest in three other imaging techniques for carrying out the HCP: high angular resolution diffusion imaging with magnetic resonance (HARDI), resting state fMRI (RfMRI), and electrophysiology and magnetoencephalography (MEG) combined with fMRI.
Since this is the first time that researchers will combine these technologies to systematically map the brain's connections, the HCP will support development of new data models, informatics and analytic tools to help researchers make the most of the data, NIH said.