FDA posts hundreds of warning letters on its Web site, yet there are very few responses posted. To those outside industry, this gives the impression that FDA is almost always right, and that the companies are usually in the wrong.

James G. Dickinson

March 1, 2007

11 Min Read
FDA Warning Letter Web Site Convicts Companies Unfairly



An old saying has it that justice must not only be done, but it must be seen to be done. By this standard, FDA's warning letters Web page would seem to fail miserably. Only a small fraction of the letters posted there are accompanied by the target companies' side of the story in the form of their written responses, or in any form. It's likely that staff from healthcare procurement and reimbursement agencies visit this page most often. Visitors like these might be excused for assuming that companies do not often contest such letters and that the charges made by FDA are almost always true.

For example, for all posted letters to companies whose names begin with E (approximately 260 in all), only one response is posted. For all posted letters to companies whose name begins with P (more than 450), only six responses are posted. Under the heading “Search Most Recently Posted Responses,” only one letter is displayed. There are no instructions for searching for any other responses. I suspect that FDA has never told regulated entities how to get their responses to warning letters into the court of public opinion via its Web site.

I asked associate commissioner for public affairs Julie Zawisza what the agency's policy is on posting company responses along with warning letters. She said, “The responding firm must request posting and provide [the response] in the proper electronic format for posting. FDA then redacts any nondisclosable material (i.e., trade secret or confidential commercial) and posts it. FDA reserves the right to not post certain responses if, for example, posting would mislead the public about the safety or efficacy of the regulated product(s).”

Despite this, Colorado-based TMJ Implants (TMJI) in December began a struggle with FDA over its postings. TMJI wants the agency to remove a warning letter that it contends was based on a misunderstanding about statements on its Web site. Alternatively, it would like FDA to post its corrective written response alongside the offending letter. (For more on this letter, see “CDRH Targets TMJ Implants Web Site,” page 44.) TMJI says its effort has included writing letters to agency staff, including the designated CDRH compliance officer, Ronald Swan. In addition, it has sent letters to compliance director Timothy Ulatowski, CDRH director Daniel Schultz, and FDA commissioner Andrew von Eschenbach.

By mid-January, the only acknowledgment that TMJI received from FDA indicating it might act was a phone call on January 16 from Ulatowski. In the call, he said the agency was “studying” TMJI's response to the warning letter and would be “letting [the company] know.” Company president Robert Christensen commented that the conversation left him mystified as to what FDA would let him know.

A related problem concerns how to get FDA to remove a commercially damaging document that has been devalued or otherwise overtaken by subsequent events. Utah Medical Products conducted a lengthy battle with the agency to remove FDA-483s that had been factually repudiated by a federal judge. Only after the intervention of Utah senator Orrin Hatch did the agency respond. But rather than removing the contentious documents, it posted the judge's opinion along with them. FDA has said that it has a policy of never removing documents it has posted.

Utah Medical's president and CEO Kevin Cornwell told me that if FDA were motivated to protect the public health, “it would demonstrate a greater devotion to the truth.” Instead, he said, it uses “bureaucratic excuses to ignore responses to its cavalier and premeditated defamation of companies. A balanced and fair disclosure of the substance of issues is the last thing they care about.” The purpose of FDA's postings, he said, “is to carry out an initiative of creating maximum commercial harm.”

CDRH Focuses on TMJ Implants Web Site

FDA continues to apply the heat to TMJI. This time, it's a warning letter over alleged unapproved device promotions found on the company's Web site. TMJI has been embroiled in an ongoing dispute over whether the company should have filed MDRs. That dispute led to a subsequent and still-unresolved $630,000 civil monetary penalty case. TMJI now finds itself in what president Robert Christensen describes as the agency's “misunderstanding” of the components contained in its premarket-approved implant. The December 20 warning letter cited a Web site discussion about how the firm “can design and deliver hemi and full mandibles to meet…patient needs.” According to Christensen, the mandibles are components of the company's temporomandibular joint (TMJ) prosthesis systems. The parts are not marketed or distributed individually. In a response to FDA, Christensen acknowledged that the discussion should have made clear that the mandibles are used in the approved TMJ replacement devices. He also pointed out that the discussion was promptly removed from the site upon receipt of CDRH's letter.

Seven years ago, FDA forced TMJI to shut down production in the midst of a contentious 2000–2001 review of its two TMJ prostheses. Bernard Statland, then director of CDRH's Office of Device Evaluation, was able to quickly approve them over staff objections. The current MDR dispute involves 17 underlying events that occurred between October 2002 and July 2003. TMJI argues that the events are not reportable because its qualified experts determined the devices did not cause them.

TMJI is arguing that 21 CFR 803.20(c)(2) allows companies, rather than FDA, to decide when an adverse event is reportable. This provision says that a user facility, importer, or manufacturer does not have to report an adverse event if there is information to reasonably conclude that a device did not cause or contribute to a death or serious injury. Further, it must be concluded that a malfunction of the device would also not be likely to cause or contribute to a death or serious injury if the adverse event were to recur. Such conclusions must be drawn by a person who is qualified to make a medical judgment. Such persons include physicians, nurses, risk managers, and biomedical engineers. Companies must keep in their MDR event files (described in 21 CFR 803.18) the information that the qualified person used to determine whether a device-related event was reportable.

GE Radiology Units Shuttered by FDA

GE OEC Medical Systems Inc., GE Healthcare, and two of the companies' senior executives have signed a permanent injunction consent decree with FDA. The decree relates to manufacturing defects in GE OEC's x-ray surgical imaging systems. It prohibits the manufacturing and distribution of certain GE OEC x-ray surgical imaging systems at facilities in Salt Lake City and Lawrence, MA. It will be in effect until the devices and facilities have been shown to be in compliance with FDA's quality system regulation (QSR) requirements. The decree was filed January 12, 2007, in federal court in Utah.

An FDA news release said the systems subject to the decree are radiological image processing and image-intensified fluoroscopic x-ray systems. The products are used during diagnostic, surgical, and interventional procedures.

A month-long FDA inspection last summer at the company's Salt Lake City facility found multiple deficiencies. Among them was failure to establish and maintain adequate design validation procedures and failure to establish and maintain adequate procedures for implementing corrective and preventive actions. An earlier inspection at that facility resulted in a March 31, 2005, warning letter. FDA said it took the latest enforcement action when the 2006 inspection showed inadequate responses to problems cited in that warning letter.

Under the terms of the consent decree, the companies will take necessary measures to ensure compliance. The firms also must comply with CGMP requirements and FDA regulations for reporting adverse events and malfunctions and device corrections and removals. The decree also requires the companies to hire an independent expert to inspect the Utah and Massachusetts facilities. The expert must certify to FDA that corrections have been made. Manufacturing and distribution can resume at the two facilities once FDA is satisfied that they are in compliance.

The companies may continue to provide routine service maintenance, replacement parts, and accessories for imaging systems that are already in U.S. healthcare facilities.

FDA Issues Nucleic Acid Assay Guidance

FDA has issued a guidance for industry and FDA staff called “Class II Special Controls Guidance Document: Quality Control Material for Cystic Fibrosis Nucleic Acid Assays.” It supports classification of quality control material for cystic fibrosis nucleic acid assays into Class II. The guidance says the material is a device intended to help monitor the reliability of a test system. It detects analytical deviations such as those that may arise from reagent or instrument variation in genetic testing. This includes recombinant, synthetic, and cell line–based DNA controls.

To access the new guidance, visit www.fda.gov/OHRMS/DOCKETS/98fr/06d-0515-gdl0001.pdf.

HemoSense Cited over QSR Problems


The problems FDA cited in a warning letter to HemoSense related to the firm's in vitro diagnostic system, the INRatio INR.

An FDA inspection last summer at HemoSense Inc. (San Jose) found QSR problems in the firm's manufacturing facility. The problems relate to its INRatio INR system, an in vitro diagnostic system that provides a quantitative prothrombin time value with the use of fresh capillary whole blood.

Violations cited in a recently released warning letter from FDA's San Francisco district office included failure to ensure that QSR requirements are established and maintained and also failure to investigate the cause of nonconformities. In addition, the firm failed to investigate complaints involving possible failure of a device, labeling, or packaging to meet any of its specifications. Finally, failure to promptly review, evaluate, and investigate complaints and failure to ensure that all personnel are trained to adequately perform their assigned responsibilities were cited.

The inspection also found that HemoSense has failed to follow MDR requirements. It had not reported within 30 days information suggesting a device may have caused or contributed to a death or serious injury, or has malfunctioned and could cause or contribute to a death or serious injury. The warning letter said the company's responses were inadequate. They did not provide sufficient details and documentation of the firm's root-cause analysis. FDA uses those details to determine whether a firm's preventive actions are adequate to prevent recurrence of the problems.

The company was told to take prompt action to correct the violations and notify the district office within 15 days of specific corrective actions taken or to be taken.

GAO: Third-Party FDA Inspections Unpopular

FDA has made strenuous efforts to persuade medical device companies to agree to third-party facility inspections in lieu of FDA inspections. However, only two agreed during a 19-month period studied by the Government Accountability Office (GAO). GAO released a 27-page report on January 5. The two inspections by FDA-accredited third-party organizations were conducted at one U.S. facility and one foreign facility. In the same period, March 11, 2004, through October 31, 2006, accredited organizations participated with FDA in one foreign and 36 domestic inspections.

GAO said that it found the willingness of device manufacturers to pay for inspections by accredited organizations instead of by FDA is influenced by three factors.

First, they are attracted by potential incentives (e.g., reductions in the number of inspections). They are also concerned about possible disincentives (e.g., cost and uncertainty about potential consequences). Finally, they are influenced by any reasons to defer participation (e.g., existing contracts with inspection firms accredited by other countries that FDA has not yet cleared).

GAO offered no recommendations for improving the participation rates in this program. To view the report online, visit www.fdaweb.com/source/GAODeviceInspections010507.pdf.

CDRH's Kessler Leads Global Task Force

Larry Kessler has been named chairman of the Global Harmonization Task Force (GHTF) for the next 18 months. Kessler is currently director of CDRH's Office of Science and Engineering Laboratories. Founded in 1992, GHTF comprises regulatory authorities from the United States, Canada, Japan, and Australia, as well as medical device–related trade associations. Its mission is to help harmonize medical device regulatory practices and drive further technological progress in the industry. The group has released about 40 harmonized guidances that are followed by many countries, including the United States.

Previously, Kessler chaired a GHTF study group that developed programs for medical device postmarket surveillance. “This study group also set a standard for a unified, worldwide system of reporting adverse events associated with medical devices,” an FDA release says. It produced major documents on what defines an adverse event, and what, when, and how to report it, the release continues.

Kessler joined CDRH in 1995 as Office of Surveillance and Biometrics director. Previously, he served for nine years as the chief of the National Institutes of Health Applied Research Branch. His accomplishments while at CDRH include implementing the MDR regulation. He also developed a program for reducing the burden of repetitive reporting and introduced the center's sentinel system on adverse-event reporting by user facilities.

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