Originally Published MDDI June 2005

WASHINGTON WRAP-UP

On the eve of Crawford's nomination as FDA commissioner, an anonymous letter's allegations raise questions about his conduct at FDA.

James G. Dickinson

Enforcing Condition-of-Approval Device Studies| FDA Expert Agreed with Us, Utah Medical Says |FDA Rejects One Silicone Breast Implant, OKs Another |CDRH Office Takes Reins on Device Review Guidances

Just as the Senate committee overseeing FDA was about to vote to send acting commissioner Lester Crawford's nomination to the floor in April, an allegation of an affair and improper use of government funds stopped it in its tracks. The anonymous written allegation purportedly involves Crawford's special assistant, Susan Bond. Committee chairman Mike Enzi (R-WY) told reporters about the letter he received on the eve of the vote. The letter was poorly spelled, smudged, and badly written, and Enzi said he had dismissed its charges, which he declined to describe.

However, he also said he had forwarded the letter to FDA's Office of Internal Affairs for investigation. This office, which has a long history of ineptitude and bullying, reports to Crawford. Apparently, that did not sit well with HHS secretary Mike Leavitt, who then ordered his Office of Inspector General to take over the investigation. As he did so, his assistant secretary for public affairs, Kevin Keane, told reporters the charges in the anonymous letter were “completely false.” White House press secretary Scott McClellan added that Crawford retained President Bush's confidence. “The president believes Dr. Crawford is someone who brings great experience to the position,” McClellan said.

No official sources would disclose the nature of the allegations. However, several well-placed officials said in confidence that the letter to Enzi came from an FDA employee and alleged that Crawford and Bond had been having an affair. It also alleged that Crawford had abused government procedures by improperly promoting her and taking her on long-distance trips where her presence was not required, wasting government money.

Those who did comment, insisted that regardless of the other allegations, there simply was no affair between Crawford and Bond. Neither Bond nor Crawford responded to verbal and e-mail requests for comment.

“They are good friends and like to travel together, but there is no affair,” a confidant of Crawford said. Another FDA employee who knows Bond told an associate, “Susan's been at FDA for many years. She worked in the Office of Consumer Affairs and the Office of Science. She's a nice gal and has a cute little baby girl and a very supportive husband.”

Before this development, Crawford's confirmation was already in question. A group of Democratic senators, including Hillary Rodham Clinton (D-NY) and Patty Murray (D-WA), said they intended to put it on indefinite hold. They were waiting on FDA's decision on whether to allow an over-the-counter version of the prescription drug Plan B, an emergency “morning-after” contraceptive, to go on the market.

Enforcing Condition-of-Approval Device Studies

FDA's lack of follow-up on postmarket studies is hurting industry, said Edward Basile, senior partner at the Washington, DC, law firm King & Spalding LLP. This happens, he said, when FDA advisory committees demand postmarket studies as conditions of approval (COA).

Basile pointed to CDRH's failure to insist on receiving postmarket studies. He said that committee members might be more cautious in recommending approvals for products about which they remain skeptical. Even if they might otherwise recommend approval, members might not if their skepticism involves safety or other issues. “Panel members are asking, ‘If we can't be sure studies will be done, how can we give our approval?'” Basile said. He made these comments at the annual conference of the Food & Drug Law Institute (FDLI) in April.

CDRH director Daniel Schultz cited lack of agency resources to follow up or to monitor manufacturers' compliance with COA agreements. However, he pledged greater attention to this problem in the future.

The issue came up at the end of Schultz's presentation on current and future issues confronting CDRH. He said device industry trends call for scrutiny of smaller, more-complex devices. This category includes combination devices, some of which combine diagnostic features and therapeutic action. This, in turn, increases the regulatory burden on the agency.

Schultz cited a recently approved single device for diabetics that measures blood sugar levels and features an insulin pump. He pointed out that such products often comprise patented products or ideas from two or more manufacturers. He stressed that review applications should be coordinated between these firms. For at least one such application, Schultz said, CDRH was placed in the difficult position of having to provide this coordination.

CDRH surveillance and biometric director Susan Gardner spoke at another FDLI session. Gardner said the center is committed to adding an epidemiologist to each PMA review team to focus on postmarket monitoring plans. The center also plans to revamp COA study design and tracking after an internal report uncovered program weaknesses. Adding epidemiologists is probably the “biggest change” the center will put into effect as it does so, said Gardner. The report found that more than half of the studies the center required manufacturers to do were never conducted. In addition, CDRH lacked any formal tracking mechanism to monitor requested studies.

Another industry trend, and regulatory challenge faced by CDRH, is the growing number of sophisticated products intended for use by nonprofessionals at home. Patients and consumers use these products without close medical supervision. Examples of such products, said Schultz, include home defibrillators and home testing kits for HIV. Schultz also pointed to the impending “genomics/proteomics revolution” and its promise of individualized medicine. It will undoubtedly pose important new challenges to the agency, he said, for which ever more specialized review staff will be required.

FDA Expert Agreed with Us, Utah Medical Says

Utah Medical Products (Midvale, UT) says that FDA medical device national expert Monica Wilkins cannot fault the company's compliance with certain regulatory requirements. An April 7 statement from Utah Medical says its lawyers obtained that admission from Wilkins under deposition. The questions involved a five-week inspection she and two other FDA device experts conducted at Utah Medical last year. Utah Medical is defending an FDA federal court complaint for permanent injunction over alleged quality system regulation (QSR) and GMP violations.

According to Utah Medical, Wilkins said she found no procedures required by FDA that did not exist at the company. She found no proof of Utah Medical failing to follow its own procedures or of a correction plan not being opened when it should have been. She also found no instance of a fully pursued and completed corrective action being undertaken improperly. Wilkins also agreed that a number of her comments differed from those of a previous FDA investigator.

In the statement, Utah Medical's CEO, Kevin Cornwell, said he regretted the method FDA chose to discuss their disagreement. Utah Medical has said that FDA's investigators and reviewers who stated the observations and opinions do not have the training, responsibility, or experience in manufacturing medical devices. Cornwall stated, “Our efforts to exercise our option to ‘disagree with any agency decision, action, or operation without fear of retaliation' as expressed in a required attachment to the FDA-482 announcement of inspection were rejected and ignored. Our repeated requests for feedback regarding [Utah Medical's] detailed written responses to FDA-483 observations were ignored. Our multiple appeals to supervisory personnel were ignored. Our request to mediate prior to filing of the lawsuit was ignored. This was not the reception we expected when we sought to exercise our option to disagree in the year 2001.”

Meanwhile, FDA has answered a Utah Medical abuse-of-process counter-claim in the same court. The agency says the Federal Tort Claims Act (FTCA) protects FDA against the charges.

Utah Medical had complained that certain FDA actions amounted to an abuse of process. It claimed FDA personnel distorted the investigational process such that it did not ensure objectivity and fairness. Utah Medical alleged that CDRH QSR expert Kimberly A. Trautman arranged an inspection and FDA-483 write-up to set FDA's case against the firm's compliance status.

FDA disagrees. It says that telling investigators what information Trautman would need to pursue potential violations is not the same as telling them to misrepresent facts. FDA says helping investigators describe their findings in language that would withstand scrutiny is sound, agency-approved practice. It is not, FDA asserts, tantamount to creating observations that had not already been made.

Also, FDA argues, the Supreme Court supports the agency. “The Supreme Court has flatly stated that ‘actions taken in furtherance of' a regulatory program are ‘protected, even if those actions were negligent,'” FDA says. It notes that the high court devised a two-part test to decide whether certain acts are protected from suit under FTCA.

The first part of the plan includes an analysis of whether the challenged conduct involves choice or judgment. The second involves whether the actions involve public policy. “Deciding how to focus an investigation, how to evaluate the observations, which observations to include in a report, and how to convey those observations linguistically are decisions that require the exercise of judgment and the making of choices,” FDA says. “If that judgment and those choices are—or, when viewed in the abstract, could be said to be—grounded in considerations of public policy, then the challenged acts and omissions are beyond the purview of the FTCA.”

In addition, FDA says, Utah Medical's counterclaim should be dismissed. The company failed to submit its claims to FDA first for “administrative consideration,” the agency asserts. Also, FTCA excludes abuse-of-process claims unless the abuse is committed by “investigative or law enforcement officers.” That description does not include FDA officials.

FDA Rejects One Silicone Breast Implant, OKs Another

Twenty-four hours after rejecting an Inamed Corp. premarket approval (PMA) application for its silicone breast implant, an FDA panel recommended that the agency approve Mentor Corp.'s rival implant. FDA's General and Plastic Surgery Device Panel voted on April 13 and urged strict conditions, including the following:

• Patient informed consent to the risk of potential breakage, which would require removal or replacement.
• Sales limited to board-certified plastic surgeons who complete special training on how to insert the implants in a way that minimizes breakage risk.
• Establishment by the company of a patient registry to track long-term patient experience.
• Postmarket studies of 10-year rupture rates conducted by the company.

Panel members were impressed by Mentor's clinical studies, which involved 400 patients. The results showed that only about 1% of implants ruptured in the first three years after insertion. Data also suggested the devices may last as long as 10 years without rupturing.

Members also recommended that the labeling advise patients to get an MRI scan five years after implantation and every two years thereafter.

The day before, the same panel said Inamed had not provided enough evidence about its implants. The data did not show how long the implants would last, or what would happen if they were to rupture. Inamed had argued that its new technology products are less likely to rupture and leak than earlier versions marketed before FDA banned them 13 years ago.

The panel, with a few different members, had narrowly recommended allowing Inamed's implants back on the market 18 months ago. FDA rejected that decision because of the durability concerns. “Obviously we're disappointed,” said Inamed vice president Dan Cohen. He said the company would work with FDA to get the additional evidence as soon as possible.

CDRH Office Takes Reins on Device Review Guidances

CDRH Office of Science and Engineering Laboratories director Larry Kessler says his office is taking the lead in education and guidance development for guidance on device reviews. Specifically, it focuses on those dealing with risk management to reduce variability in requirements, potentially reduce information required, and apply the total product life cycle concept within industry and CDRH.

Fitness for safe use will be a guiding principle as guidance is developed, Kessler says. It is no longer enough to manage individual risks, he adds, but it is necessary to ensure that the overall risk also is acceptable.

Manufacturers will be able to choose how best to ensure that each important harm has been managed and mitigated where possible.

In risk-management and premarket review, Kessler says sponsors must consider all adverse outcomes and other harms. They must also take a forward-and-backward approach as an evaluation of hazards, seek causes for hazards, and document the basis for concluding that mitigation is adequate.

Copyright ©2005 Medical Device & Diagnostic Industry