Medical Device Link.

LifeScan was ordered to pay a criminal fine of $29.4 million and an additional $30.6 million in civil penalties, damages, attorneys' fees, and restitution to the U.S. government. In addition, LifeScan will be placed on probation for three years, during which time FDA, the U.S. Probation Office, independent regulatory auditors, and the Department of Health and Human Services will oversee a large portion of the company's activities.

Previously, Abbott Laboratories (Abbott Park, IL) was fined $168 million for noncompliance with QSR requirements, which included charges associated with actions mandated by FDA and a $100-million payment to the U.S. government. In addition to paying the fine, the company agreed to stop manufacturing and distributing certain diagnostic products until FDA ensured that its facilities were in conformity with QSR requirements. Failure to meet the timeline agreed upon for corrections could result in additional financial penalties.

By the sizes of the fines levied alone, either of the two instances would be noteworthy. But taken together, the two cases seem to suggest that FDA is making examples of IVD industry violators. While the Abbott case involved long-term corporate-culture issues, the LifeScan fine resulted in part from competitive pressures that affect all IVD companies. According to Alan Snitkof, chief technology officer of Hemadyne Research Inc. (Yonkers, NY), "The pressure to bring new products to market as quickly as possible is perhaps most acute in the IVD industry, where manufacturers need to provide innovative functionality for existing and new devices to recover development costs."

He continues, "As IVD manufacturers rush to design and build their latest generation of products, however, they may not realize that the development procedures that have worked faithfully for years are no longer compliant with FDA regulations. Unfortunately, the pressure to rush a product to market often wins over the need to implement a new design and development process, which can be time-consuming and expensive."

According to LifeScan's plea agreement, the SureStep product, manufactured and distributed by the company between May 1996 and August 1997, had two defects that resulted in problematic readings. The first, a software defect, caused the meter to display an "error" message instead of a "high" warning at blood glucose levels above 500 mg/dl, which is dangerously high. The second defect concerned test strips manufactured before March 1998, which, if not completely inserted into the meter, could yield false results up to 90% lower than the patient's actual blood glucose level, creating a significant medical risk.

The error-message issue affected the SureStep Consumer Meter, and the strip-insertion problem affected both the SureStep Consumer Meter and the SureStep Pro, a system used in hospitals. No other LifeScan products were affected. The company corrected the problems in 1997 and early 1998, and in June 1998, at the insistence of FDA, instituted a Class I recall of all SureStep meters manufactured prior to July 1997.

In its settlement with the government, LifeScan acknowledged "introducing an adulterated and misbranded medical device, failing to provide appropriate notifications and information to FDA, and submitting false and misleading reports to FDA." According to court documents, between 1996 and 1998 LifeScan received more than 2000 SureStep customer complaints of inaccurate low readings, some of which were attributable to incomplete strip insertion, and more than 700 complaints regarding error messages, some of which were attributable to high blood glucose levels. At least 61 of the error complaints were associated with illness or injury, including some hospitalizations. LifeScan estimates that 290,000 defective units were sold.

A Lesson Learned The FastTake glucose meter by LifeScan may display a y-shaped, nonnumeric character in the ones position. Apparently, quality problems aren't over for LifeScan glucose-monitor users. In November 2000, LifeScan issued a recall of its FastTake meters, which are also marketed under the brand names SmartScan, EuroFlash, and PocketScan, due to a possible display error. The meter is designed to display test results in either of two unit settings, mg/dl or mmol/L. When used in the mmol/L setting, a number of the meters may display test results that show a y-shaped, nonnumeric character in the ones position (see figure). This time around, however, unlike the way the company previously handled defects with its SureStep meters, LifeScan is actively promoting customer awareness of the FastTake defect and making the information available to the general public. The company is in the process of launching a comprehensive worldwide communication program to alert FastTake meter users to the issue. In addition to mailing letters to registered meter owners and healthcare professionals, notifications are being placed in FastTake system kits and test-strip boxes. Owner's booklets and procedure guides are also being supplemented with new information about the possible error. According to a company press release, "LifeScan is working to correct the problem as quickly as possible."

In pleading guilty, LifeScan admitted that it failed to advise customers of the two defects and to file MDRs with FDA on the serious injuries reported to the company by consumers. The reports the company did file with FDA contained false, incomplete, or misleading information in that they failed to disclose the existence of either the error defect or the incomplete-strip-insertion problem. Product submission documents were also false and misleading.

According to LifeScan, the basis for the plea was that no one at the company "engaged in intentional wrongdoing or intentionally sought to mislead consumers or the government." However, LifeScan admitted that labeling of the SureStep product was deficient, that the company did not properly notify the government of those deficiencies, and that it was slow to remedy them completely. Additionally, it should be noted that this case was initiated by company whistle-blowers, who documented the unreported serious health threats to the relevant government agencies after their management failed to act.

"Mistakes and misjudgments were made," said Ralph S. Larsen, chairman and CEO of Johnson & Johnson. "We fully acknowledge those errors and sincerely apologize for them." He added that the company is "committed to learning from this experience."

In announcing the guilty plea, a spokesperson from the U.S. Attorney's Office noted, "Consumers are entitled to know—and the law demands—that all companies honestly disclose problems and defects in medical devices. Corporations in the healthcare sector must be held to a high standard in regard to informing patients and FDA about the dangers of their products."

Some industry experts are taken aback by what happened at LifeScan. David Carville, president of Causeway Scientific (Mishawaka, IN), says, "In my opinion, if design controls were in place and clinical trials were performed, LifeScan should have detected both defects."

The question, really, is how could such a mistake have happened in a major company like Johnson & Johnson? According to industry experts, the answer may in part relate to the decentralized nature of the Johnson & Johnson companies. In other words, corporate compliance reviews of the company's glucose monitor product line, long known to have a high risk potential, were not effective.

Another potential answer has to do with design control issues—and in this case, specifically with software validation and verification. As Hemadyne's Snitkof explains, "Software validation and verification procedures have become increasingly critical, as medical device designs have grown substantially more complex in recent years. The consequence of such complexity has been the vast increase in difficulty and a corresponding multiplication of the effort necessary to achieve complete and accurate validation and verification of new medical devices.

"If the technologies required for comprehensive validation and verification are not built into the design flow from the very beginning of development, failures will be inevitable, with potentially serious consequences for both the company and the end-user. Devices intended for use by the general public exacerbate the problem. When products depend on the end-user to perform procedures such as inserting a reagent strip into a blood glucose meter, the potential for erroneous results grows geometrically."

Even so, note the experts, getting products such as glucose monitors into consumers' hands is critical for their long-term care. Such products are designed for consumer use, they note, and defects in design should in no way reduce the importance of effective home-use devices.

To be effective, Snitkof continues, manufacturers' overall product design and development systems must also include procedures to seamlessly integrate data from both customer complaint tracking and MDRs. "Doing as much is no small task, however, and many device companies don't handle it properly," he says. "Data from complaint tracking and MDRs are essential to quickly resolving device problems and finding flaws in the product's validation and verification processes. As newer devices become more complex, the requirement for such integration becomes more urgent."

As Snitkof concludes, "The propensity of IVD manufacturers to rush products to market may mean increased FDA enforcement activity and probably even more fines. Whether FDA will use fines against the IVD industry to set an example for the entire medical device marketplace remains to be seen, but the enormous recent fines seem to suggest increased vigilance by FDA and, in many cases, rightly so."

—Flora Nguyen