There will be no appeal of the federal court decision dismissing all three of FDA's long-running GMP complaints against Utah Medical Products. In effect, Judge Bruce S. Jenkins ruled that FDA is not the sole arbiter of what quality system regulation (QSR) compliance requires. Saying “many roads lead to Rome,” he stated in his opinion that it “makes no sense” for FDA to order Utah Medical to comply with QSR requirements; it's already doing so, albeit by means different from those demanded by FDA.
Apparently FDA could not sway the Justice Department, which notified the company on December 15 that it would not appeal. The decision caught many FDA watchers off guard. Just the week before, FDA deputy chief counsel Eric Blumberg had told an FDLI conference that the defeat did not mean FDA would stop pursuing firms with alleged quality control problems, even if there were no safety-related issues. He said a product is considered adulterated if it is not made according to GMPs. Furthermore, he said, the agency does not need to prove safety problems exist to bring an action.
An attorney present at the FDLI conference said Blumberg's statements didn't surprise him. Rather, he said, “I believe that he just doesn't get it.”
Retired FDA Denver district director John Scharmann, in whose former district Utah Medical is located, reviewed many of the documents underpinning the case. He noted that if FDA were to be faulted for the defeat, “it should be for failing to do an adequate job of evaluating the case.”
Scharmann, now a consulting editor for Dickinson's FDA Webview, said there were not enough QSR deviations to support FDA's case against the firm. “This was not recognized by FDA's legal staff when it took in good faith the evidence reported by the investigators and supporting FDA experts,” he said. “This is the area that FDA should concentrate on if it wishes to avoid a repeat of this fiasco.”
Scharmann noted that when developing a case, FDA's legal counsel must be confident in the guidance of its experts. “For some reason, the experts in this case provided faulty support,” he said. “FDA's legal counsel may have been remiss in not investigating these experts and, as a result, based the case on this faulty evidence. While trust is an admirable quality, it may not be an attorney's best friend.”
Finally, he said, he suspects that strong personalities allowed the case to become a personal matter. “The facts in the case were ignored and replaced with an ‘I'll show you' attitude, which is not a good basis for a federal court action.”
Guidant Confident about FDA Follow-Up
Guidant Corp., which was acquired in January by Boston Scientific Corp., has said it can fully address all quality system issues raised by FDA. The firm received a warning letter on December 22, 2005, and a second letter two weeks later. Both letters addressed observations made during an inspection at Guidant's St. Paul, MN, cardiac rhythm management facility last August. The letters also addressed FDA's request for corrections and a timetable update.
“Management anticipates that all company actions will be completed on or before their target dates and that the company will be ready for FDA's follow-up inspection in mid-2006,” a Guidant statement said.
The warning letter said FDA's inspection had found CGMP violations related to the manufacture, packing, storage, or installation of implantable cardioverter-defibrillators and pacemakers.
The warning letter acknowledged a September 22, 2005, letter Guidant had sent to physicians about failures within Insignia and Nexus pacemakers. It also acknowledged receipt of several Guidant letters to FDA describing actions taken to respond to the postinspection FDA-483. However, it said Guidant had failed to address all of the violations listed.
The Guidant statement said the company has taken a “broad, thorough, and systematic review of its quality system.” It also said that the firm has made substantial steps toward addressing all of the FDA-483 observations.
Guidant's Warning Letter
FDA cited Guidant's facility for the following violations:
• Failing to ensure that when results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedure.
• Failing to establish and maintain procedures for when changes or process deviations occur, to ensure the review and evaluation of the process and to ensure that revalidation is performed where appropriate, and to document all these activities.
• Failing to establish and maintain procedures to identify the actions needed to correct and prevent recurrence of quality problems.
• Failing to analyze sources of quality data to identify existing and potential causes of quality problems.
• Failing to establish and maintain procedures for changes in a specification, method, process, or procedure, where such changes shall be verified or validated before implementation and these activities shall be documented and approved.
• Failing to establish and maintain procedures for process controls necessary to ensure conformance to specifications.
• Failing to document rework and reevaluation activities in the device history record.
• Failing to maintain device history records that include acceptance records that demonstrate a device is manufactured in accordance with the device master record.
Mentor Breast Implant Leakage Investigation
A whistleblower's charges about leaking silicone breast implants has prompted FDA to interview Mentor Corp. employees. According to a source, FDA's Office of Criminal Investigations (OCI) began the interviews in January.
In December, a Washington Post story reported that a former Mentor Corp. senior engineer turned whistleblower had made allegations against the firm. He claimed Mentor had doctors show models of silicone gel breast implants to prospective patients that were not the same as those actually implanted.
The engineer gave the Post a copy of a letter he sent to FDA. In it, he said he and others at Mentor had been asked to prevent a silicone oil leak. The oil leaked from the prostheses through a hole created by the manufacturing process. He said they devised a patch that was put on demonstration samples but not on implants shipped to doctors.
“I am very concerned about the safety of women using these breast implants if they were to become widely available as an FDA-approved product,” the engineer wrote. He said he thought it was misleading to show patients modified devices but then implant the original ones.
At the time, CDRH director Daniel Schultz said FDA had received the letter and was taking the charges seriously. At press time, Mentor officials had not returned a call for comment.
Mentor has a history of FDA trouble. In 1998, FDA and Mentor entered into a consent decree over deficiencies in the firm's breast implant manufacturing. FDA signed the decree to bring Mentor into compliance with the QSR requirements. At the time, FDA said that the deficiencies had not been shown to result in an increased risk to women who have the breast implants. However, FDA said, “FDA inspections of Mentor's manufacturing facility found deficiencies in the plant's quality assurance system that could potentially affect the safety and quality of the breast implants.” Such deficiencies included Mentor's failure to validate its manufacturing process and to correct and prevent quality problems. The decree was vacated in 2003 after FDA found the firm to be in substantial compliance.
In 2002, the House Energy and Commerce oversight and investigations subcommittee requested details about a four-year OCI probe that had been closed without any further enforcement action by FDA. The existence of the investigation was confirmed in committee documents disclosed in April 2000. The documents indicated it was “based on allegations of serious irregularities in breast implant studies.” At the time, Mentor denied such an investigation was ongoing. Instead, it said, FDA's probe focused on manufacturing issues.
Class I Recalls by Boston Scientific, Ortho-Clinical
FDA says Boston Scientific initiated a Class I recall in December. The recall applies to stainless-steel Greenfield vena cava filters with 12 Fr femoral introducer systems manufactured before March 10, 2004. The company says there have been reports of detachment at the bond between the carrier capsule and the outer sheath of the filter's delivery system during the implant procedure. The detachment puts patients at risk of cardiac and pulmonary embolization. Potential adverse events include serious patient injury or death. Class I is FDA's most stringent recall; it applies when a device failure may have life-threatening or irreversible health consequences.
Also in December, Ortho-Clinical Diagnostics (Rochester, NY) issued a Class I recall. It applies to its Vitros Immunodiagnostic HBsAg Confirmatory Kit. The diagnostic device is used for testing blood and serum samples for hepatitis B. “An unknown component in the diluting solution used to test blood and serum samples may produce Not Confirmed results for samples found to be positive with the initial test,” an FDA notice said. That result can cause some results to be classified as false negatives. It says false-negative results may prevent some patients infected with or carrying the hepatitis B virus from receiving necessary treatment. The agency is particularly concerned with false negatives in pregnant women, whose babies will not be properly treated. Untreated infants have a 90% chance of progressing to chronic hepatitis B virus infection. Such an infection can lead to the need for a liver transplant or early death, it says.