Originally Published MDDI May 2005

WASHINGTON WRAP-UP

Using the pediatric drug legislation as a model, a new FDA office will address the lag in developing medical device technology that is appropriate for children.

James G. Dickinson

PMA Speed Continues to Improve | Budget Boost Requested for FDA User-Fee Goals |FDA Warns Tyco over Mexican GMPs|Problems with MDUFMA Implementation| Policy Staff Changes at FDA| Hydro-Med Cited for GMP Violations| AdvaMed Loses CEO| Third-Party Inspections Coming to FDA

FDA will establish an office this fiscal year that will introduce pediatric medical device standards. The standards will be similar to those the agency is implementing under statutory mandate for drugs, said Lester M. Crawford.

Crawford made these comments at his confirmation hearing for FDA commissioner on March 17, 2005. He was answering a question from Sen. Mike DeWine (R–OH) about devices that are not sized for children's special needs. According to pediatricians, DeWine said, the development of devices suitable for children's bodies can lag up to 10 years behind those for adults. “That's really not acceptable,” he said.

In response, Crawford referred to legislation for pediatric drugs that he implemented at FDA in 2002. “The same people that have spearheaded this effort with drugs will do it also with devices,” he told DeWine. “They'd have essentially the same kind of scheme, the same authorities in order to get it done. You have my assurance that I'm fully committed to that project. I'll make the resources available for it, and I expect the same kind of results. And we'll hold them to that expectation. Timing is within this fiscal year.”

The pediatric drugs model focused on special labeling for pediatric uses and market exclusivity in exchange for clinical studies in children. The hearing did not address whether Crawford felt legislation would be needed for pediatric devices. However, his answer to DeWine clearly suggested there is much FDA can do immediately, without legislation.

His hearing was for the most part congenial and collegial. The little static that occurred was on drug safety controversies and the agency's delay in approving the Plan B birth-control pill.

Addressing some favorite industry complaints about FDA, Crawford in his prepared remarks tried to reassure the senators. “We're transforming our culture to one of transparency, collaboration, and cutting-edge thinking. We're going to tap into new technologies and new ways of thinking, and build upon collaborations with a broad network of partners—public and private, U.S. and international.

“By adopting a quality systems approach in all our operations, we will increase productivity and promote better health outcomes. In particular, I'm committed to addressing existing concerns.”

PMA Speed Continues to Improve

CDRH's Office of Device Evaluation (ODE) increased its premarket approval (PMA) application review speed by 25% last year over 2003. The office's annual report says reviews for these devices averaged 157 days, compared with 210 in FY 2003 and 256 in FY 2002. Industry's performance in these reviews improved even more than FDA's, according to the data, averaging 26 days, compared with 67 the year before and 133 in FY 2002.

But the office made no headway in improving 510(k) review speed, according to tables provided in the report. It showed almost no progress from year to year, for FDA and industry alike. The average review time last year was 100 days, with 74 being FDA's share and 26 non-FDA. Comparable figures for FY 2003 were 76 and 20, and for FY 2002, 79 and 21, respectively.

ODE received 255 third-party-reviewed 510(k)s last year, the report says. “This was a 34% increase over the 190 submissions received last fiscal year, and more than twice the 127 submissions received in FY 2002.” The report speculates that this increase may be attributed to the implementation of the Medical Device User Fee and Modernization Act's [MDUFMA] user-fee provisions. They require applicants to pay a fee when submitting 510(k)s without a third-party review. The report provides no comparison of review times for third-party versus ODE-reviewed 510(k)s.

To access the report, visit www.fda.gov/cdrh/annual/fy2004/ode/toc.html.

Budget Boost Requested for FDA User-Fee Goals

FDA's FY 2006 budget request seeks a $5.9 million increase. The request, now under review on Capitol Hill, allocates the new funds to meeting the agency's MDUFMA obligations.

Included in the request is the $220.8 million anticipated by MDUFMA for FY 2006. It also covers the $138,000 that the agency needs to make up for the rescission from the FY 2005 appropriation.

In FY 2006, FDA expects the device-review program to raise $40.3 million in user fees, an increase of almost $6.4 million over FY 2005. The additional funds will be used to hire more staff and develop better review systems.

Lester M. Crawford spoke to the House Appropriations Subcommittee on Agriculture, Rural Development, FDA and Related Agencies. “MDUFMA requires FDA to pursue a complex and comprehensive set of review goals,” he said. “Each year brings additional goals, and the goals become more aggressive. We must report on performance relative to the specified goals at the end of each year.

“We have also committed to two ambitious long-term goals for reducing average total approval time for medical device premarket applications. We have already achieved one of these goals, even though it was targeted for fiscal years 2005–2007.” That goal calls for a 30-day reduction in average approval time for premarket applications given expedited approval. The goal is similar to priority approval for drugs and biologics. “We have already achieved that goal—a 33-day reduction in average approval time compared with the baseline of fiscal years 1999–2001,” Crawford told the subcommittee.

FDA Warns Tyco over Mexican GMPs

CDRH has sent warning letters to Tyco Healthcare Group over CGMP violations at company facilities in Tijuana and Juarez, Mexico. CDRH says it may hold products without physical assessment upon entry into the United States until the problems are fixed.

In a February 25 warning letter, CDRH referenced an inspection last November at a plant in Tijuana. The inspectors found that production of the CapnoProbe SLS-1 sublingual sensor failed to meet GMP requirements of the quality system regulation (QSR). Problems cited included the following:

• Failure to monitor and control process parameters and component and device characteristics during production.
• Failure to establish procedures for purchasing control data that clearly describe or reference specified requirements for purchased or
otherwise received products and services.
• Failure to review and evaluate a manufacturing process and perform revalidation, where appropriate, when changes or process deviations occur.

CDRH acknowledged receiving a response from the company's vice president for regulatory affairs. However, the response was inadequate because it failed to include corrective actions, evidence of implementation of corrections, and other information. The center requested a detailed letter with specific steps taken to control the violations. This includes an explanation of how the company plans to prevent these or similar violations from occurring again.

Likewise, another February 25 warning letter addressed an October inspection at Tyco's Juarez facility. It covered GMP violations in production of Shiley tracheostomy products; Mon-a-therm, Warmtouch, and Warmflo temperature-management products; and Mallinckrodt tracheal tubes. Problems cited included the following:

• Failure to establish and maintain procedures to adequately control environmental conditions.
• Failure to review and evaluate process changes and perform revalidation where appropriate.
• Failure to establish and maintain procedures to investigate the cause of nonconformities relating to product, processes, and the quality system.
• Failure to verify or validate corrective and preventive actions to ensure that such actions are effective and do not adversely affect the finished device.

FDA again said it might take regulatory action if the company fails to take prompt corrective action. This action includes holding products without physical assessment upon entry into the United States. FDA acknowledged responses received in November and December, and the agency listed several reasons for the responses' inadequacy. It also asked for specific information and verification of steps taken.

Problems with MDUFMA Implementation

A CDRH first-quarter MDUFMA report says that the center is making progress in implementing the user-fee law. However, some problems persist, including

• Cycle goals not being met.
• Difficulty reducing preapproval GMP inspection times.
• Information technology support for device review just beginning.
• Additional costs associated with modular PMAs and third-party 510(k)s.
• Development of MDUFMA standards and guidance competing with meeting review goals.
• New requirements from third-party inspections.
• Lack of experience in handling complex applications.
• Competing internal training
priorities.
• Device firm totals growing 7% annually, with 20% turnover.

Companies can expect the speediest response when applications are complete and of high quality, the review team is trained and ready, and the guidance is up-to-date. Responses are also expedited when IMAGE processing occurs within one week and everyone knows what to expect with cycle and decision times. There will be delays, the report says, if applications are low in quality, the review team is not trained in the technology, and the guidance is out-of-date. Slowness also occurs when IMAGE processing takes two weeks, expectations are clarified as the review proceeds, and unexpected cycles occur.

Major delays are likely if an application is incomplete and low in quality, the review team is not ready, and the guidance is not prepared. Other delays can happen if information technology support is delayed, no one knows what to expect, and the review bogs down in many cycles.

CDRH says companies should meet early with FDA and organize an application clearly. It is important to understand the likely timing of cycle and final FDA decisions, and communicate during the review.

Policy Staff Changes at FDA

FDA associate commissioner for policy and planning William Hubbard announced his retirement in February. He will be replaced by Office of Planning chief economist Randall Lutter.

Hubbard joined HHS in 1973 and has held his current position for 14 years. His accomplishments include playing a leading role in FDA's efforts in support of passage of MDUFMA and participating in the development of the nutrition label requirements. He was also involved in negotiating the Prescription Drug User Fee Act and redesigning labels for over-the-counter drugs.

Lutter joined FDA in 2002. He has “broad experience in determining the economic and policy aspects of FDA's work,” according to a news release. In his new role, he will serve as a senior advisor to Lester M. Crawford on all major agency matters.

A prolific writer on the economics of government regulation, prior to joining the agency, Lutter was a resident scholar at the American Enterprise Institute (AEI). He was also a fellow with the AEI-Brookings Joint Center for Regulatory Studies. Lutter may be more critical of FDA than of its adversaries in formulating policy. In 2003 testimony before the House Transportation and Infrastructure Committee reprinted by AEI, Lutter said that “regulatory agencies generally are motivated to make their own initiatives look good.” Before he joined AEI, he served as a staff economist with the Office of Management and Budget (1991–1997) and as a senior economist on the President's Council of Economic Advisors (1997–1998).

Hydro-Med Cited for GMP Violations

FDA's Dallas district office conducted an inspection late last year at Hydro-Med Products (Dallas). The company is a division of Spectrum Laboratories and manufactures sterile devices. The investigators found that the facility was failing to meet CGMP requirements and the company had failed to submit required reports on recalled devices. Products affected are surgical drapes; sterile Esmarch bandages; and sterile equipment drapes for ultrasound, arthroscopic, camera, and endoscopic accessories.

A February warning letter says the inspection identified eight different types of QSR violations. It also says that on September 28, 2000, the firm recalled 350 sterile ultrasound-probe drapes from the market, but did not report its action to FDA. The recall was due to defective packaging that created the potential for a breach in product sterility.

The company's response to the inspection report outlining a general corrective action plan was acknowledged. However, FDA said it was incomplete unless and until the firm provided update reports, which must document specific corrective action activities the firm has taken and verify the effectiveness of the corrective actions. These actions must address the specific FDA-483 observations and issues identified in the warning letter.

FDA also suggested that Hydro-Med retain independent third-party regulatory and technical consultants. The suggestion was motivated by the seriousness of the observations and the lack of executive management controls at the facility.

AdvaMed Loses CEO

Pamela G. Bailey, president and CEO of AdvaMed since 1999, has resigned to become president and CEO of the Cosmetic, Toiletry, and Fragrance Association. There, she will succeed Ed Kavanaugh, who is retiring after 22 years in that post.

Bailey was a former deputy director of public affairs in the Reagan White House. She came to AdvaMed in 1999 from an 11-year stint as CEO of the Healthcare Leadership Council. Adva-Med's board has formed an executive search committee and reportedly already has several prospects.

Third-Party Inspections Coming to FDA

To reduce its labor costs in the field, FDA is intending to contract out to third-party organizations some of its plant inspections. Deputy commissioner for policy Amit Sachdev spoke of the agency's intention to the AEI-Brookings Institute in February. Until now, discussion of third-party inspections has been restricted to a little-used option for qualified manufacturers of Class II and Class III devices. Under that option, manufacturers can choose the third-party inspectors at their own expense. If FDA goes ahead with its own use of such contractors, it will be paying the bill.

FDA's idea, said Sachdev, stems from a desire to bring its field organization's Office of Regional Operations (ORO) into line with the rest of FDA's labor costs. ORO's labor cost consumes 80% of its budget. The rest of FDA uses only 60% of its budget for labor cost, according to Sachdev.

Use of external inspectors will theoretically save money. FDA won't be paying for contractor employees' fringe benefits, as it does for its own. However, FDA's most recent experience with contracting out is in the area of information technology. There, the cost of contracts has reportedly exceeded the cost of what FDA had been paying for its IT
employees.

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