BB&T Washington Editor

The FDA last month filed its report on the operations of the Office of Combination Products (OCP) for FY06, and while the number of applications decreased slightly from the previous year, the agency had to work harder to get the applications classified. The suggestion is that combination products are becoming more complex and will continue to will stretch the agency's resources for years to come.

In a cover letter of the report, FDA commissioner Andrew von Eschenbach, MD, said that despite the decrease in filings the agency "is receiving significantly more combination products for review as technological advances continue to merge product types and blur the historical lines of separation" between devices and other types of therapeutic products. The FDA chief said that OCP "has made significant progress in enhancing the regulatory transparency and predictability of the combination product lead center assignment and review process."

The cover letter said also that "one large industry trade association" wrote to FDA to state that OCP "has done an excellent job in meeting the goals outlined in MDUFMA in spirit and in practice," but did not name that association.

In the document's executive summary, FDA said that OCP had "issued 26 combination product RFD [requests for designation] in the last fiscal year" and that the agency had satisfied all those requests within the required 60-day period.

The number of RFDs tailed off slightly in FY06 from FY07, dropping from 273 to 231, but that 15% decrease was offset by an increase in inter-center consultations from 275 to 335, a reflection of the complexity of the applications that OCP had to adjudicate. FDA approved five new combination products in FY06 and so far in the current fiscal year, only two.

FDA published a final rule in November 2005 outlining how OCP assigns jurisdiction over a combination product. A combination product is assigned to one of the centers based on the product's primary mode of action, defined as the mode that "provides the most important therapeutic action." Should an analysis of the primary mode of action prove indecisive, the product is assigned to the center with the most familiarity with products that raise similar safety/efficacy questions.

According to an appendix attached to the report, the most common type of application in FY05 by characteristic of intended use was for devices coated or impregnated with a drug, which accounted for 78 applications. Tied for second were pre-filled drug delivery/device systems and a category described as "possible combination based on mutually conforming labeling of separate products." Other categories rounding out the 273 products that OCP handled in FY05 included devices coated/impregnated with biologics at 18, and convenience kits at 12 applications.

More than half the applications, or 156, ended up at the Center for Drug Evaluation and Review as investigational new drug applications, and another 78 were sent to the Center for Devices and Radiological Health (CDRH) as "original" 510(k) applications. CDRH also reviewed 26 applications from OCP as investigational devices.

OCP currently has seven full-time, dedicated staff members and anticipated the number will rise to 11 "when financial resources to support" the increase are available.

Failure of preventive health services in the U.S. costing lives

U.S. healthcare has long espoused the need for preventive healthcare, but it has not translated to actual practice, according to a recent report by the non-profit health policy group, Partnership for Prevention (Washington). The report says that the use of just five preventive services would save more than 100,000 lives each year in the U.S.

"One of the reasons we did the study is to bring attention back to the preventative services that mean the most . . . prevention pays and we can get a really good value for a relatively modest investment," Ashley Coffield, a senior fellow with Partnership for Prevention, told Biomedical Business & Technology. "We could pay now [for preventive services], or we can pay a lot more later [for treatment]."

The report, titled "Preventive Care: A National Profile on Use, Disparities, and Health Benefits," calls for renewed efforts to help smokers quit, more colorectal cancer and breast cancer screening and annual flu shots for people over 50. Among its main findings:

• Of the five prevention tips, the U.S. would see the biggest impact if adults took a low dose of aspirin every day to prevent heart disease, a step that could save 45,000 lives a year.
• Increasing the number of smokers who receive such services to 90% would save an additional 42,000 live each year. Only 28% of smokers who are advised by a health professional to quit are offered medication or other assistance.
• Up to 14,000 lives would be saved each year if the portion of adults over 50 who are up-to-date with any recommended screening for colorectal cancer was increased to 90%. Fewer than 50% of adults are up-to-date with such screening, the report says.
• If 90% of adults over 50 received annual flu shots — instead of just 37% — 12,000 lives would be saved each year
• Nearly 4,000 lives would be saved each year if 90% of women over 40 were screened for breast cancer in the past two years, compared to 67%. The report also calls for more screening for chlamydial infection among sexually active young women, noting that 30,000 cases of pelvic inflammatory disease would be prevented each year if 90%, compared to 40%, of young women were screened annually.

Adding to these gloomy findings, Coffield said Partnership for Prevention does not expect improved use of preventative services to happen quickly or easily. "We often take for granted that most children get vaccinated, but this didn't happen overnight," Coffield told BB&T, noting that it took a significant amount of time and attention by public policy makers and government bodies to ensure that most children get vaccinated regularly. "If we gave the same kind of attention to preventative services we could save so many lives and we could prevent so much disease."

"A lot of Americans are not getting [life-saving] preventive services, particularly racial and ethnic minorities," said Eduardo Sanchez, MD, chair of the National Commission on Prevention Priorities, a blue-ribbon panel convened by Partnership for Prevention to guide the study. "As a result, too many people are dying prematurely or living with diseases that could have been prevented. We could get much better value for our healthcare dollar by focusing upstream on prevention."

The report underlines the tendency of Americans to focus on disease treatment, rather than prevention. "This report illustrates that the health benefits would be great if more people took preventive actions," said Julie Gerberding, director of the Centers for Disease Control and Prevention (CDC; Atlanta). "More illnesses would be avoided, fewer lives would be lost, and there would be more efficient use of our limited healthcare resources. It's important that all of us make a concerted attempt to focus our energies and efforts on preventing disease, not just treating it."

Gerberding's comment underlines the CDC's recent shift from focus on disaster response to everyday, chronic, preventable diseases.

The report also uncovers racial disparities in the use of preventive care.

For example, Hispanic smokers are 55% less likely to get help to quit smoking from a health professional than white smokers, and Asian Americans are less likely to take aspirin or get screened for breast, cervical and colorectal cancer.

"Those disparities have got to be eliminated," Coffield said.

Health Canada appears poised for roll-out of med-tech user fees

Health Canada (HC) is working to refine its regulation and surveillance of medical devices, and the department in August published a strategic plan titled "Building for the Future," which is geared to helping the government "get ahead of the issues before they impact us." Perhaps the most interesting passage in the report indicates that the agency is set to roll out a user fee program for makers of medical devices and other regulated healthcare products.

The cover letter for the report says that responsibility for medical device regulation is divided between three agencies at HC, and that the government "will review alternative governance and organizational structures that could be implemented over the longer term."

The passage in the report addressing user fees describes the program as a cost-recovery initiative, and "an up-to-date external charging framework that covers the regulation, licensing and post-market surveillance of health products, including medical devices." The system will "ensure charging covers all allowable aspects of the program." Canada's National Assembly passed the law allowing user fees in 2004.

The HC web site includes a page that lists some details on the proposed fees, including: fees for evaluations of submissions and applications; licensing fees (to offset the cost of inspections); certification fees for drug and device master files; and fees connected with authorization to sell devices, drugs and biologics. The fee schedule describes the percentage of the cost of these functions that industry will pay. According to the HC web site, industry will pay 75% of the total cost of the government's review of new drug and device submission, and half of the cost of authority-to-sell functions.

Industry will bear the entire cost of the other two functions: establishment licensing and master file certification. HC also noted that user fees are becoming commonplace in the developed world, with FDA purportedly recovering 60% of cost and Australia's Therapeutic Goods Administration recovering all such costs.

The report says that the action is at least partly motivated by the need to respond to a report by the Canadian government's Auditor General, which serves a function analogous to that of the U.S. Government Accountability Office. The cover letter, written by the directors general of HC, says that the bureau eliminated a backlog of pre-market applications "and achiev[ed] 81% of decisions within target for Class II, III and IV applications in 2006." The remaining class, Class I, is the category into which products such as toothbrushes fall.

CDRH ombudsman report indicates no increase in complaints

Les Weinstein, ombudsman for the FDA's Center for Devices and Radiological Health (CDRH), last month released his annual report for 2006, indicating no upward spike in the number of complaint calls that he handled for that year. (See tables.)

The Office of Device Evaluation (ODE) has consistently led the CDRH offices in total complaints, but the ODE's share of complaints is tailing off. Weinstein said that this "might have to do with user fees and the performance goals [CDRH staff members] have to meet," pointing out that a tally of the reasons for complaints shows that time of product review turnaround is a smaller problem of late.

Weinstein's report notes that on three occasions in 2006, companies applied to go before a dispute resolution panel, with two getting the go-ahead. That number is up from zero for each of the two previous years. One such request was filed in 2003, but the report for 2005 says that the hearing was postponed indefinitely. Weinstein said that the three dispute resolution requests in 2006 probably constituted "a statistical aberration."

He noted that a dispute panel sided with the company in a 2001 hearing and said, "I thought, at that point, I'd be getting a lot more" such requests. However, he said that such panels are "very expensive and resource-intensive" for companies, which takes some of the edge off industry's appetite for that avenue of appeal.

"The message that I've been giving is that [a dispute resolution meeting] should be a last resort," Weinstein said. He added that the most recent panel sided with the agency, a fact perhaps making companies less likely to request a panel. He said he has fielded no requests for a dispute panel meeting so far this year.

Asked if the issues between FDA and industry are getting tougher to resolve, Weinstein said that the most recent 81% rate of resolution "was much higher" than in the previous two or three years. "Maybe that's an indication that they're not so far apart" on most of the issues.

Weinstein said he receives "only two or three contacts a year" from foreign device makers. In this area, he said he does not see "an upward trend, and I thought I would," given the growth of the device industry in other nations. "It could be that they're not aware of" the ombudsman's office," he said, as one explanation for this.

"The thing that strikes me the most is how constant the number of complaints is from year to year," Weinstein said, adding that the total "seems to be around 120, plus or minus a few."