Originally Published MDDI January 2005
Originally Published MDDI January 2005
Daniel Troy leaves FDA giving no public explanation; his stint as chief counsel was one of the most controversial in agency history.
James G. Dickinson
InSightec's MRI Device Approved for Fibroid Ablation | 11 Device Reprocessors Must Remove Products from Market | FDA Rethinks, OKs Cordis Cypher Stent | Lifecore Cited Over FDA Complaint Reporting | TherMatrx Promotional Literature Brings FDA Trouble | Tecan U.S. Cited for Quality Problems | Guidance on Spinal Augmentation Devices
Daniel E. Troy is probably the most controversial chief counsel in FDA history. The conservative Bush appointee resigned his post on November 16, the day after Secretary of State Colin Powell and three other cabinet members resigned theirs. Except for a possible theory that publicity about other high-level departures might help Troy's resignation go unnoticed by mainstream media, there was no connection in the timing. Troy avoided media attention, and often was not kindly treated by reporters.
Troy has been variously described by his legal peers as superb, arrogant, loyal, pedantic, exemplary, and offensive. He made no public explanation for his decision, but took with him his special assistant, Coleen Klasmeier, fueling speculation that he was returning to private practice. His silence also might be out of respect for ethical considerations in not seeming to solicit business for his next practice setting while still on the government payroll.
FDA commissioner Lester Crawford issued an all-hands internal e-mail memorandum on the two departures. In his e-mail, he expressed that his "regret at losing these two unparalleled talents is equaled only by the certainty that, wherever they land, they will continue to distinguish themselves as principled, hard-working, and brilliant attorneys."
After Crawford's announcement, speculation erupted on who would succeed Troy. Many assume that it will be Gerald Masoudi, a Washington private-practice trial attorney with Kirkland & Ellis. FDA had named Masoudi as deputy chief counsel only a week before Troy's resignation announcement.
Troy joined FDA one month before the September 11, 2001, terrorist attacks and two months before the anthrax attacks. These events shifted the agency's focus toward bioterrorism and counterterrorism efforts. Crawford's e-mail praised Troy's "tireless dedication" in addressing the "myriad public health dimensions" these attacks brought the agency.
His arrival at the agency immediately stirred interest and suspicion that he did nothing to allay. Troy had represented powerful brand-name drug companies in his private practice at Wiley, Rein and Fielding (Washington, DC). Many critics felt Troy brought to the agency an agenda that benefited drug and device companies. His refusal to create memoranda of his meetings with regulated companies or to acknowledge that such meetings had occurred on FDA's public calendar worried many.
Troy caused FDA to intervene on behalf of regulated companies in state personal injury cases on a number of occasions. His solicitation of lawsuit referrals where FDA could intervene was criticized as an unseemly service to the defendant companies. However, such criticism was balanced by support from several former FDA chief counsels who defended his actions. "There is a greater need for FDA intervention now because plaintiffs and courts are intruding more heavily on FDA's primary jurisdiction than ever before," said Peter Barton Hutt. Hutt is a partner at Covington & Burling and a former FDA chief counsel.
Crawford also defended Troy's interventions in such litigation. In his e-mail, he stated that the chief counsel put his "personal reputation on the line" in doing so. Nevertheless, he said, "the policy is the correct one for the public health."
Crawford's e-mail recognized Troy for his "principal legacy in having instilled in the agency a deep and abiding respect for the rule of law, and for the limitations imposed on FDA by the Constitution, especially the First Amendment, and by our own enabling statutes." One of his most notable accomplishments, Crawford continued, was a major package of reforms to the Hatch-Waxman amendments. The amendments were added to last year's Medicare overhaul and "are estimated to save drug consumers $35 billion over 10 years."
Other attorneys and former FDA employees felt that Troy's management style upset staff attorneys. Some think it caused former deputy chief counsel Michael M. Landa to take a position in FDA's Center for Food Safety and Applied Nutrition. Landa did not respond to a request for comment.
McKenna, Long & Aldridge partner Larry Pilot, a former FDA deputy director of medical device compliance, said it was "unfortunate that [Troy] wasn't there long enough to make a substantive difference to FDA's application of the law."
Pilot, however, was critical of Troy's delegated role in reforming FDA warning letters. This, he said, "hasn't helped the situation at all. There's still a lot of garbage going out. There are fewer warning letters, but as far as I'm concerned, not enough fewer." Pilot had coached Troy on the issues with warning letters three months before HHS deputy secretary Claude Allen issued a directive in 2001 that addressed the issue. The directive stated that all warning letters must be vetted for legal sufficiency by Troy's office.
InSightec's MRI Device Approved for Fibroid Ablation
FDA has approved an InSightec premarket approval (PMA) application for the ExAblate 2000 system. The ExAblate uses magnetic resonance image (MRI)–guided focused ultrasound to target and destroy uterine fibroids. According to an agency talk paper, the device is intended for women who have completed childbearing or do not intend to become pregnant.
The system uses an MRI machine to map the volume of fibroid tissue to be treated and monitor the uterine tissue temperature after heating. A focused ultrasound beam then heats and destroys the tissue with high-frequency, high-energy sound waves. FDA says the treatment can last up to three hours, during which the patient lies inside the MRI machine and the fibroid tissue is repeatedly targeted and heated.
To view FDA's talk paper, visit the agency's Web site at www.fda.gov/bbs/topics/answers/2004/ans01319.html.
11 Device Reprocessors Must Remove Products from Market
FDA has released a full listing of single-use devices that can no longer be reprocessed and legally marketed. The devices listed are based on a supplemental validation data review mandated by the Medical Device User Fee and Modernization Act of 2002.
The agency said 11 medical device reprocessors will need to remove their reprocessed devices from the market. An agency review of the reprocessors' supplemental validation data found the devices "not substantially equivalent" to a predicate device.
FDA said those device reprocessors can seek FDA clearance to market them by submitting a new 510(k) application. FDA is also "scheduling follow-up inspections of these firms to ensure compliance with these determinations and will initiate enforcement actions as required."
To view FDA's notice, visit the agency's Web site at www.fda.gov/cdrh/reuse/svs/.
FDA Rethinks, OKs Cordis Cypher Stent
FDA says Cordis Corp.'s Cypher stent is not associated with excessive subacute thromboses when implanted according to approved indications for use. An agency public health Web notification says FDA based its conclusion on information from a 30-day follow-up of 2063 patients. These patients were enrolled in Cordis' postapproval registry and agency review of bare-metal stent data.
A year ago, FDA had issued Web notifications concerning the possibility of higher subacute thromboses and hypersensitivity reactions in patients in whom the Cypher stent was implanted. Those notifications were based on reports received through the medical device report (MDR) system, FDA says.
"Based on our review of data from the registry as well as the MDR system, it appears that the reported rate of subacute thromboses is not greater now than it was during the premarket clinical trials, and is within the expected rate for any stent," the new notification says.
"We are also continuing to monitor reports of hypersensitivity reactions. In most cases reported to FDA, hypersensitivity seen with implantation of the Cypher stent was minor (e.g., skin rashes and itching that cleared up within a few days of onset). There were, however, rare severe reactions, including anaphylaxis. Although some of the reactions we have observed so far remain unexplained, most of the reactions seem to be related to periprocedural concomitant medications. Similar reactions to medications used in association with stenting have been well documented. Many of the reactions reported in association with the Cypher stent resolved spontaneously with discontinuation of the periprocedural medication(s)."
The Cypher stent, the agency stated, "remains a safe and effective product when used according to the labeling, particularly with regard to patient selection and appropriate periprocedural medications."
Lifecore Cited Over FDA Complaint Reporting
A CDRH warning letter to Lifecore Biomedical Inc. (Chaska, MN) said that its Gynecare Intergel Adhesion Prevention Solution was misbranded. The October 18 letter said the company failed to submit required MDRs for complaints involving serious injury or death or device malfunctions.
According to the letter, the company failed to submit MDRs for 11 separate events. The events involved information that the device may have caused or contributed to a death or serious injury. Also mentioned were two instances of information suggesting that the device malfunctioned and would be likely to cause or contribute to death or serious injury if the malfunction were to recur.
In a response to FDA-483s issued after an April inspection, the company said the complaints it had received did not involve a serious injury as defined in the MDR regulations. In some cases, the company said, qualified medical professionals had determined that the product did not cause or contribute to serious injury.
FDA's warning letter said CDRH carefully reviewed the complaints cited in the inspection report. The center determined that five of seven complaints should have been reported as serious injuries, and one of two malfunction complaints should have been reported.
CDRH said the company should take prompt action to correct the problems cited in the inspection report.
TherMatrx Promotional Literature Brings FDA Trouble
CDRH has sent a warning letter to TherMatrx Inc. (Northbrook, IL) over promotional literature for the company's TMx-2000 BPH Thermography System. The literature contains statements promoting the device for indications not approved by FDA. In addition, some statements suggest the system is safe and effective in circumstances for which FDA has not reviewed safety or effectiveness data.
The letter said the device's PMA, approved in July 2001, described it as a nonsurgical device for treating specific cases of symptomatic benign prostatic hyperplasia. The device is approved for use in men who have a minimum prostatic urethra length of 30 mm and a total prostate volume between 30 and 100 cm3. FDA has designated it a restricted device whose advertising may not be false or misleading in any particular.
Promotional material FDA reviewed at a professional meeting, CDRH wrote, claimed that the TMx-2000 "treats enlarged median lobe." The PMA submission did not contain clinical data to support such a use. The literature also says physicians can "see other patients during treatment." That statement conflicts with precautions in the approved labeling that say attention by a qualified physician is required during system use.
The warning letter also listed three unsubstantiated promotional claims for proven five-year durability, permanent tissue necrosis, and superior peak-flow-rate improvement.
The company was told to stop using violative promotional materials. It is to submit a plan for discontinuing their use and a plan for disseminating truthful, nonmisleading, and complete information to audiences that received the violative materials.
Tecan U.S. Cited for Quality Problems
An October warning letter from FDA's Atlanta district office says a May inspection at a Tecan U.S. facility in Durham, NC, found several quality control regulation violations. The violations were found in the Tecan clinical workstation used to perform in-vitro diagnostic tests on patient samples.
An FDA-483 was issued after the inspection. The agency said it found the following significant quality system observations:
- Failure to have complete validation of the software program.
- Failure to both establish and maintain procedures for implementing corrective and preventive actions.
- Failure to establish and maintain control of device design procedures to ensure that specified design requirements are met.
- Failure of management to review the quality system suitability and effectiveness at defined intervals and with sufficient frequency to ensure quality system requirements are met.
- Failure to establish procedures for quality audits, to conduct audits to ensure the quality system's compliance with the established requirements, and to determine quality system effectiveness.
- Failure to evaluate complaints to determine whether they represent an event that is required to be reported to FDA.
- Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit.
The warning letter says FDA also reviewed marketing literature collected during the inspection. The agency found the literature indicated that the device can identify hepatitis A, C, E, and G, as well as HIV and HTLV. Such identifications are beyond the scope of the device's current Class 1 510(k) exemption status. To make such claims, the company would have to submit another 510(k).
District director Mary Woleske, who signed the letter, asked for a response within 15 days outlining steps already taken and to be taken to resolve the problems. She acknowledged that she had received a number of letters this year responding to the FDA-483. Those letters were being reviewed and would be addressed separately, she said.
On May 3 and May 5, Roche recalled the Tecan workstation because of software problems. FDA said the recall was identified as a Class I recall because software errors could assign sample results to the wrong patient. Furthermore, the errors enabled the workstation to do so without notifying the equipment operator of a problem, resulting in false-positive and false-negative results. Such notices, FDA said, could lead to mistreatment and unneeded exposure to antibiotics.
In an earlier warning letter, FDA said Roche's addition of the workstation to already marketed 510(k) products should have required another 510(k) submission because it is considered a "significant modification." That warning letter followed an inspection of the firm's Indianapolis manufacturing facility. The inspection was conducted after FDA received an MDR concerning the potential for mismatching patient identification with sample results in analysis for Chlamydia trachomatis and Neisseria gonorrhoeae infective agents.
Guidance on Spinal Augmentation Devices
CDRH has published a guidance with information on clinical studies for devices used in spinal vertebral body augmentation. The devices treat insufficiency fractures of the spinal vertebral body due to minor trauma, osteoporosis, or other lytic conditions. The guidance is called Clinical Trial Considerations: Vertebral Augmentation Devices to Treat Spinal Insufficiency Fractures. It notes that devices used in spinal vertebral body augmentation include polymethylmethacrylate-based bone cements, which are classified Class 2, as special controls. The guidance says that, in some instances, FDA recommends clinical studies to support a new material or a change in an existing formulation.
"Whether FDA recommends that you conduct a clinical study depends on how significantly different your material or formulation is from those of devices we have cleared for the same intended use," the guidance says. "It is likely in the future that different materials such as resorbable and permanent polymers and other types of materials may be injected into the vertebral body for the purpose of stabilizing the fractured spinal vertebral body in spinal augmentation procedures. The purpose of this guidance is to provide information related to clinical studies FDA may recommend to support premarket notification submissions (510(k)s) for these devices."
The guidance covers clinical indications, surgical procedures, a clinical investigational plan, study monitoring, and conclusions.
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