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Something Rotten in the State of FDA?

Article-Something Rotten in the State of FDA?

FDA continues to prosecute small companies for what it insists are violations. Why?


An objective reporter is supposed to keep his mind open and to tell both sides of the story. But after more than a decade of striving to do so in the case of CDRH enforcement, a tortuous trail of “no comments” and unanswered e-mails leaves me paraphrasing Hamlet: Something's rotten in the state of FDA.

I confess that I have failed to figure out what that something is. I know the symptoms but not the cause.

In case after case, the symptoms are the same. CDRH selects a small company for tough enforcement action on the basis of deficiencies in its documentation. There is no evidence of product defects or risk to public health, but CDRH demands so-called remedial action that would affect sales. The company, because it has no other revenue stream or because it feels outraged, pushes back. It wants to discuss the merits of FDA's position. Something about the company's demeanor or tone of voice angers someone at FDA. In response, CDRH causes prejudicial publicity that damages the company's sales. CDRH resolves to teach the company a lesson by sticking to its guns, refusing to further explain or discuss the case. It issues more damaging publicity and becomes unresponsive to all substantive questions, whether from the company, its lawyers, or the media. Appeals to progressively higher levels in FDA only solidify CDRH's original position.

This consistent enforcement behavior is only directed at small companies marketing FDA-approved specialty products. Things get p+ersonal quickly because the company's survival is jeopardized by the agency's demands. This behavior has produced a growing list of victims but has never, when brought before a federal judge, produced a single victory for FDA. Nevertheless, FDA recycles the same tactics year after year, as if unable to learn from its failures.

Companies that have bested FDA over the years include Bioclinical Systems (1988), Laerdal (1994), Myo-Tronics (1994), Andersen Products (1997), and Utah Medical Products (2004). Bioclinical Systems, though victorious, no longer exists. Laerdal closed its U.S. operation and moved overseas. Although Myo-Tronics is flourishing, Andersen was driven to the point of bankruptcy and will no longer talk about the case for fear of upsetting FDA. Utah Medical Products is waiting without much hope for FDA's parent HHS to compensate it for the agency's expensive errors.

All this is topical because the same CDRH enforcement strategy is currently playing against TMJ Implants (TMJI) and, until recently, was doing so against Shelhigh.

In the TMJI case, FDA has escalated to a civil money penalties claim for $630,000 before its administrative law judge. The company complains that the agency has refused to explain the medical basis for why TMJI needs to file MDRs for 17 patient events that the company says it has medically determined were not causally related to its devices. If filed, those MDRs would be posted on FDA's Web site to be used against the company in the marketplace. As in other cases, FDA claims its reasonableness by telling the court about 18 communications with the company, as though actual dialogue between the parties had occurred. However, TMJI says FDA's letters were only reiterations of FDA's unchanging original position.

That position relies on FDA's interpretation of the law and regulations, to which it says the courts should defer. In this case, FDA's core position is that unless the device can be conclusively ruled out to be the cause of an event with 100% certainty, the event must be filed as an MDR. FDA's position does not take into account the medical expertise of the reporter, the medical judgment of the firm, or the competitive harm that the firm might suffer. FDA's two outside TMJ disease experts, both of whom admitted they had no experience with the company's devices, concurred with FDA's interpretation in each of the 17 events at issue. FDA complains repeatedly about the company's “stubborn refusal” to file. However, it never addresses the company's complaints about its own refusal to discuss the medical merits.

As TMJI's final brief in the case said in June, it all boils down to a difference of opinion. But in such a disagreement, it is always FDA that is packing heat.

The Shelhigh case ended unexpectedly with the company's capitulation in July. In that case, the tissue-based device maker had been subjected to mass media publicity over FDA's concerns that its products may not be sterile. Shelhigh denied this, refused to conduct a recall, and complained that FDA would not discuss the scientific basis of its concerns. Nevertheless, in May the publicity caused Integra LifeSciences Corp. to recall all its Shelhigh-made EnDura No-React Dural Substitute products. Integra said it was notified by FDA that the agency classified its recall as Class 1.

Shelhigh also complained that FDA even refused to provide the company, or reporters, with a copy of the Health Hazard Evaluation the agency must fill out before ordering a product recall. According to Shelhigh, FDA said it should file a Freedom of Information Act request, whereupon the agency would likely still refuse to provide the evaluation on the grounds that it is part of an open investigatory file.

“The first questions to be answered in a Health Hazard Evaluation include a description of a defect, malfunction, or error in use of the device in question,” said Shelhigh marketing director Douglas Goldman before the company had settled. “Since there are no reported defects, malfunctions, or errors with Shelhigh devices of which I am aware, FDA doesn't have facts to support its request for a recall,” he said. “FDA is acting irresponsibly and abusing its authority by continuing to claim that Shelhigh products present a health risk without presenting evidence.”

There are three common threads in all of these cases that are troubling. First, FDA uses publicity-generating tools to punish companies in the marketplace when they dare to push back. In the case of a small specialty company, negative publicity often endangers its continued existence. Second, FDA refuses to discuss the scientific and medical substance of its concerns with the targeted company or with anyone else before the matter reaches court. Finally, FDA produces no evidence to the target company or anyone else of product defects that might be a risk to public health.

If these tactics had resulted in an occasional victory for FDA in federal court, my mind might still be as open as it should be. Most puzzling is that, from my experience, none of the other centers within FDA behave in this way. The others seem to know that free and open discussion of the agency's concerns among peers is the best way to promote healthy cooperation and to stay out of court.

United States, Canada Form Pact for Inspections

Under an agreement between FDA and Health Canada, qualified auditing organizations (AOs) may perform third-party audits and inspections of medical device manufacturers' quality systems. The results of these audits and inspections will meet both U.S. and Canadian regulatory requirements. A pilot multipurpose audit program (PMAP) opened last September. Officials from the two agencies said the pilot is a vehicle for further regulatory cooperation between the countries. They also expressed hope that the collaboration would lead to a reduction in the regulatory burden on the device industry.

Manufacturers participating in the PMAP gain an opportunity to be assessed by a single AO to both U.S. and Canadian regulatory quality management system requirements. “It is anticipated that this will reduce audit- and inspection-related interruptions in the workplace,” a CDRH program question-and-answer document said, “and result in resource savings for manufacturers.”

Because multipurpose audits and inspections are intended to satisfy different quality management system requirements, key indicators of PMAP success may include the level of manufacturer and AO participation. They may also include the ability of AOs to demonstrate that their preaudit inspection planning, documentation review, on-site assessment, and audit and inspection reporting still conform to the appropriate program requirements of both countries.

To be eligible to participate in the PMAP, manufacturers must

  • Meet FDA and Health Canada definitions of a device manufacturer.
  • Currently sell a Class II or III device in the United States that meets the U.S. definition of a medical device.
  • Currently have at least one valid medical device license to sell a Class II, III, or IV device in Canada.
  • Currently use the services of an AO that is both a Health Canada Recognized Registrar and an FDA Accredited Person.

Facilities an AO would visit during a multipurpose audit and inspection would include sites in North America and overseas where overall organization management takes place. In addition, sites where products are designed, where assembly takes place, or where products are packaged and stored would be eligible. Finally, sites where contract sterilization takes place, where outsourced processes related to the device are performed by suppliers to the manufacturer, and where device-related complaints and problems are received and reported on and device-related regulatory affairs are performed would be included.

Larry Kessler said at the Medical Device Manufacturers Association annual meeting in May that the basis for granting reciprocity to Canadian inspections lies in the fact that their inspectional criteria are based on the ISO 13485 standard, which is compatible with most FDA requirements. Kessler is CDRH science and engineering laboratories director. He also chairs FDA's Global Harmonization Task Force.

Greater harmonization of inspectional criteria can result in reducing duplicative inspections, which has obvious advantages to both FDA and manufacturers. However, Kessler admitted the concept nevertheless presents a “double-edged sword.” For example, if problems were found with a product or manufacturing facility in one region, say Japan, it might result in interruption of marketing in the United States and Europe until the problem was resolved. He expressed confidence, however, that “leveraging the information and experience of foreign regulators” is a worthy effort, and that practical means may be found to overcome any associated downsides to this concept.

FDA OKs Cordis Stents

FDA has told Cordis Corp. that it has resolved all outstanding quality issues related to stent manufacturing at six manufacturing facilities. In 2004, FDA sent the firm a scathing eight-page warning letter after six Cordis facilities that manufacture its Cypher stent were inspected during a preapproval audit for a carotid stent. That same year, Cordis's quality troubles followed it into a Circulatory System Devices Panel of the Medical Devices Advisory Committee meeting that was reviewing the PMA application.

Although the panel voted 6–5 to recommend approval, FDA officials cautioned that before issuing the approval, the agency would have to evaluate the required corporate corrective and preventive action plan. That plan, FDA said, should address quality issues related to its Cypher stent. The stent was finally approved last year after FDA reinspected the company's manufacturing facilities and determined that no significant quality problems remained.

Ortho-Clinical Reagent in Class 1 Recall

FDA has classified a recall involving two lots of Vitros Immunodiagnostic Products Troponin I Reagent Packs as Class 1. The packs are made by Ortho-Clinical Diagnostics. FDA says some clinical laboratories that analyzed the tests reported inconsistent results, including false-negative results. “A false-negative test result would show no evidence of a heart attack or damage to the heart muscle in a person who did have a heart attack,” it says. FDA recommends that patients who have been tested since January contact their doctor to discuss their results. Doctors use the test in diagnosing damage to the heart or to detect a heart attack in people who have had chest pain.

To read the FDA notice online, visit

FDA Supports Reclassification of Intervertebral Devices

CDRH has issued a guidance for industry and FDA called Class II Special Controls Guidance Document: Intervertebral Body Fusion Device. The guidance supports reclassification of intervertebral body fusion devices that control bone-grafting material into Class II (special controls). It says that an intervertebral body fusion device is an implanted single- or multiple-component spinal device made from a variety of materials, including titanium and polymers. The device is inserted into the intervertebral body space of the cervical or lumbosacral spine, and it is intended for body fusion. The guidance does not apply to intervertebral body fusion devices used in conjunction with bone morphogenic proteins or scaffolds.

Risks to health identified with the devices are infection, adverse tissue reaction, pain and loss of function, and soft-tissue injury. Other risks include vertebral end-plate injury, reoperation, and pseudoarthrosis. Recommended mitigation strategies for each risk also are included in the guidance.

The guidance covers device description, risks to health, material characterization, mechanical testing, animal testing, clinical testing, sterility, biocompatibility, and labeling.

To access the guidance, visit

Guidance on Quality Control Material

CDRH has published a guidance for industry and FDA staff called Assayed and Unassayed Quality Control Material. It includes recommendations for manufacturers regarding preparation of premarket notifications and labeling for quality control (QC) materials. QC materials are intended to monitor a test system's reliability and help minimize reporting of incorrect test results. The guidance says the materials are often a laboratory's best source of ongoing feedback regarding whether results reported to physicians are sufficiently reliable.

Both assayed and unassayed QC materials are discussed in the guidance. Although both types are subject to the quality system regulation, most types of unassayed QC materials are exempt from premarket notification. However, some aspects of the guidance, such as labeling, stability, and matrix effects, are still relevant for those materials.

The guidance covers classification and identification of QC materials, assayed and unassayed QC materials for qualitative and quantitative assays, and labeling.

To access the guidance, visit

FDA: Keratitis Cases on the Rise

FDA has issued a preliminary public health notification on a recent increase in reported cases of Acanthamoeba keratitis in soft contact lens wearers. The notification says CDC found a potential association between the cases and the Complete MoisturePlus Multipurpose contact lens solution by Advanced Medical Optics. The company announced a voluntary recall of the product in May.

FDA's notice includes recommendations for contact lens users and providers and information on the CDC investigation. It also provides background on Acanthamoeba keratitis and directions for reporting adverse events and obtaining additional information.

An FDA news release said it is estimated that Acanthamoeba keratitis infections occur in two out of every million contact lens users in the United States each year. But a CDC multistate investigation found that the risk of developing the infection was at least seven times greater for consumers using the Complete MoisturePlus solution.

Last year, Bausch & Lomb permanently removed its ReNu with MoistureLoc solution from the market worldwide due to a concern that a unique characteristic in its formulation could increase risk of Fusarium keratitis infection.

To read FDA's news release, visit

Alcon Refractive Horizons Lasers in Class 1 Recall

Alcon Refractive Horizons has recalled 102 Ladar6000 excimer lasers because they were linked to “corneal abnormalities.” An FDA notice says the use of the laser's CustomCornea algorithm caused “central islands” and in some cases decreased visual sharpness. The algorithm had been used to treat myopia with astigmatism and myopia without astigmatism. FDA warns that the abnormalities may not be corrected by further laser treatment or with glasses or contact lenses. Under the Class 1 recall, Alcon has deactivated each device's ability to perform the questionable CustomCornea procedures.

Copyright ©2007 Medical Device & Diagnostic Industry
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