Street Smart

Originally Published January/February 2001

Thomas J. Gunderson

Today's smart dollar is chasing medical technology companies. Medical technology companies are showing greater economic returns than the average company in Standard & Poor's 500. The average cash return on capital invested in one of the 18 companies included in the U.S. Bancorp Piper Jaffray medical technology group, for instance, has been far above and beyond the cost of that capital. How are medtech companies achieving these superior results?

One way is by investing wisely in internal operations. Internal investment is always a challenging task for companies. Company executives face an array of appealing possibilities, any of which could be equally capable of producing either substantial benefits or disastrous consequences. Should a company buy back shares? Build new manufacturing facilities in the United States or overseas? Add to its sales and marketing force? Increase the number of projects in development?

Establishing Substantial Equivalence of Reprocessed Single-Use Devices

Originally Published January 2001

SINGLE-USE DEVICES

David L. West, Timmie Topoleskie, and William MacFarland

FDA has announced an intention to extend its enforcement of the premarket notification requirements of the Federal Food, Drug, & Cosmetic Act (FD&C Act) to reprocessors of single-use medical devices (SUDs). This is a major reversal of a policy established just two years ago.

Under the new policy, published in Guidance for Industry and for FDA Staff: Enforcement Priorities for Single-Use Devices Reprocessed by Third Parties and Hospitals (August 2, 2000), a reprocessor will be required to submit data to FDA for each type of device it reprocesses. These data must be of sufficient quality and quantity for FDA to find that the device is safe and effective in reuse, or that it is substantially equivalent to another legally marketed device, such as the original disposable device. Any reprocessed device unable to meet this standard presumably will be denied approval or clearance for sale and thus will be removed from the market.

While FDA has said it will require premarket submissions for reprocessed devices, it has not elaborated on the substance of what must be included in them. The agency has not yet provided formal guidance to the reprocessing industry, or to its own reviewers, regarding specific data that will be required to clear or approve a reprocessed device. Reprocessing a device that was designed for only one use introduces many new technological characteristics into the device and raises significant questions not considered in previous device reviews. This article addresses some of those issues and proposes questions that should be asked in reviews of premarket submissions for all reprocessed SUDs. Through a discussion of design considerations and of data on reprocessed devices, it explores the effects of reprocessing on key areas of product integrity, sterilization, biocompatibility, shelf life and packaging, and labeling, and suggests the kinds of submission data needed to address those effects.

The purpose of this article is to suggest regulatory and scientific requirements for the marketing of used and subsequently reprocessed SUDs to ensure that each device is as safe and as effective as its new counterpart. It is to be hoped that this discussion will open a dialogue in the scientific and regulatory community that will result in effective FDA reviews of premarket submissions for these products—reviews that could prevent unsafe or ineffective devices from being used on patients.

EMERGENCE OF THE REPROCESSING ISSUE

Medical devices are articles defined by section 201(h) of the FD&C Act and are regulated under the authority of FDA (see insert below). Historically, disposable, so-called single-use medical devices have been understood to be devices conceived, designed, and manufactured for use in delivering care to one patient and then disposed of afterward.

Recent economic and social factors, however, exerting pressure to contain or reduce healthcare costs, have led to the common practice of reprocessing disposable medical devices for reuse on one or more additional patients. In some circumstances the reprocessing is performed by the user facility. But reprocessing of disposable devices has become so widespread that an industry of commercial reprocessors has emerged to collect used devices from user facilities and reprocess and resell them on a large scale. As a result, disposable medical devices are often reprocessed several times and used on multiple patients.

Despite its authority to regulate SUD reprocessing strictly, FDA has for years exercised regulatory discretion in ignoring reprocessors' failure to comply with certain elements of the FD&C Act. Reprocessed SUDs have not been subject to FDA clearance or approval for use in patients.

FDA premarket review is intended to investigate and uncover patient-safety issues through an examination of the device and its intended use. Only after successfully completing the premarket review process are complex medical devices permitted to be sold in interstate commerce.

In justifying its past decision to ignore reprocessor noncompliance with the premarket requirements, FDA in 1998 issued a call for data demonstrating safety risks posed by reprocessed disposables.1 Those data are now beginning to be revealed and their implications understood.

In light of growing concerns raised by the emerging data regarding the safety of reprocessing, FDA made its decision to increase regulation of reprocessed disposable medical devices through enforcement of all aspects of the FD&C Act, including submission of marketing applications to the agency for review. This involves requiring premarket notifications (510(k)s) or premarket approval (PMA) applications for some, but not all, reprocessed devices.

Because most medical devices are cleared through the 510(k) process, and because the vast majority of devices that are both disposable and economic candidates for reprocessing are not subject to PMA requirements, the body of this article will refer only to the 510(k) regulatory path. The discussion encompasses devices that traditionally have been regulated under the premarket notification process and also those that are, by regulation, exempt from premarket notification. However, the safety and effectiveness issues considered below in the context of devices regulated under section 510(k) of the FD&C Act would also apply to devices subject to PMA requirements.

PREMARKET NOTIFICATION AND REPROCESSED SUDS

In determining substantial equivalence (see insert), FDA examines whether the device in question is at least as safe and effective as the device to which it is being compared (the "predicate device"). FDA has established and disseminated many policies to ensure that these determinations of substantial equivalence serve the agency's public health mission, are scientifically sound, and collectively provide a predictable, orderly, and equitable regulatory process.

The most notable policy was issued in 1986 and established the 510(k) decision tree and rationale.2 The 510(k) decision tree involves determining substantial equivalence through a series of questions that probe, with increasing focus, the device's intended use and its technological characteristics (Figure 1). Requiring data from submitters of 510(k)s is the only way that FDA can determine, in a rigorous and systematic manner, whether the subject device is comparable to the predicate device. For legal and practical considerations to be satisfied, the subject device must be at least as safe and effective as the predicate device to be found substantially equivalent.

A 510(k) submission typically includes, in addition to various summaries and administrative information, the following elements:

  • Device classification information.
  • Labels and labeling, covering product identity, intended use, indications for use, and directions for use.
  • A description of the device, its technology, and its mode of operation.
  • Device design and performance specifications.
  • A comparison of the device's indications for use and technological characteristics to those of a predicate device.
  • Performance data, sometimes including clinical data.
  • Manufacturing information.
  • A 510(k) summary or statement.

To date, reprocessed devices have not been involved in the classification or 510(k) processes. Current device classifications (see insert) are based on the collective clinical experience of OEM devices. They were not intended to cover reprocessing or reprocessed devices. Because the reprocessing of disposable medical devices is a relatively recent phenomenon, and because the practice has not been satisfactorily described, reprocessed devices cannot be assumed to have contributed significantly to the collective clinical experience supporting FDA's classification of a specific device.

Moreover, the collective clinical experience supporting classifications of OEM devices cannot be assumed to attest to the safety or effectiveness of reprocessed devices. Reprocessed devices should not be deemed equivalent to their OEM counterparts without rigorous challenge in the context of a 510(k) review process designed to examine the technological characteristics that distinguish reprocessed devices from OEM devices.

New Technological Characteristics. A reprocessed product differs from the OEM version in having technological characteristics unique to reprocessing. These new technological characteristics arise because the device was designed by the OEM to be used only one time and is now being considered for use more than once.

In accordance with FDA's 510(k) guidance, the new characteristics must be taken into account in a 510(k) review. It is the agency's policy that a medical device may have new characteristics relative to the predicate device, but that accepted scientific methods must exist for assessing the effects of those characteristics on the device's performance, and that performance data must be available.

For FDA to apply its policies consistently and to ensure scientific integrity in the review of 510(k)s, it must make certain that the new technological characteristics are described in reprocessed-product 510(k)s, and that performance data assessing relevant safety and effectiveness issues are included. As with any 510(k), the submitter (here, the reprocessor) bears the burden of identifying validated methods for assessing the new technological characteristics and the safety and effectiveness issues associated with them.

To appreciate how reprocessing introduces new technological characteristics, consider the unavoidable differences between any new device and its reprocessed counterpart. The incoming "starting material" used by the reprocessor to manufacture the reprocessed device (that is, the used device) is of unknown quality, in contrast with the starting materials specified by the OEM.

Original-device manufacturers typically perform quality tests on starting materials. For example, a manufacturer of surgical staplers, upon receiving a lot of polycarbonate to be used in manufacturing the device handles, will randomly sample the polymer pellets for quality testing. Such testing, in order to be meaningful, is necessarily destructive. If the samples pass the quality test, polymer pellets from that lot are then used to manufacture the stapler handles. The OEM can use random samples to characterize an entire lot of material because that material is made using validated processes that result in a homogeneous product.

Reprocessors, however, do not obtain a homogeneous lot of raw material and thus cannot perform traditional material testing. Testing performed by the reprocessor is limited to that which will not alter or destroy the device. Such testing is naturally incomplete because it cannot uncover latent defects that could lead to device failure. Even testing every single device in this way will not provide the assurance of material integrity possible with random destructive material testing.

Moreover, the reprocessor's incoming material has a use history that may not be known with certainty and will be different for each device. Yet the history of each device is central to its quality as a reprocessed product.

The new technological characteristics of the reprocessed device raise important questions in the following areas, each of which must be addressed by proper performance data.

  • Product physical integrity.
  • Sterilization and cleaning.
  • Biocompatibility.
  • Shelf life and package integrity.
  • Labeling.

The answers are critical to a finding that the reprocessed device is substantially equivalent to—that is, as safe and effective as—the predicate device. For original devices, these questions are typically addressed by either design verification or validation as required by FDA's quality system regulation.

In view of the substantial changes in an SUD brought about by reprocessing, and of the existing evidence of reprocessed-device failures, reprocessed devices cannot be presumed equivalent to their OEM counterparts. The reprocessor must address this issue prior to patient exposure, in a premarket submission. The existence of substantial data showing serious product defects exhibited by reused devices found on hospital shelves suggests the inadequacy of the FDA inspection authority to control these safety issues effectively.

Performance Data. In reviewing performance data, FDA reviewers should keep in mind that the new technological characteristics involve both product design issues and process issues. This means that performance data for reprocessed-device 510(k)s will normally include both design verification testing and process design verification testing.

Design verification and process design verification questions that should be asked in reviewing reprocessed-SUD performance data to address new technological characteristics introduce each of the following discussions on the areas of concern identified above. Each discussion considers some of the performance problems that have been reported, as well as other problems that could arise.

PRODUCT PHYSICAL INTEGRITY

New technological characteristics introduced by reprocessing raise questions about product physical integrity such as the following:

  • Have performance specifications been established that translate into adequate clinical performance? How will the device be tested for conformity to those specifications?
  • How are nonobvious OEM design changes detected and accounted for?
  • What is the extent of material and mechanical degradation following use, cleaning, and sterilization?
  • How has reliability for each subsequent reuse been addressed?
  • What are the potential failure modes of the reprocessed device?
  • How is the test procedure designed to measure failure?
  • How will the number of reuses of a product be tracked?

Regarding the last question, FDA has made clear its intent to approve reprocessed SUDs for just one additional use despite multiple-use practices already firmly established by reprocessors. Failing to require data to support the maximum allowable number of reuses is inconsistent with FDA's regulation of other multiple-use devices.

Device Use History. Whereas an OEM product has no use history, a reprocessed product may have been used once or many times, and the nonhomogeneity of that use history must be taken into consideration. The unique use history of a reprocessed device could have a significant impact on future performance. In fact, reuse of individual units of the same model of a device, all reprocessed in the same way, could lead to completely different outcomes determined by conditions of prior use, such as the anatomy of the patient on whom the device was first used.

For instance, a surgical needle previously used in scar tissue may exhibit a markedly different failure profile than a needle that has merely passed through normal tissue. Future performance and possibility of failure of these two seemingly identical needles is likely to be different. A 510(k) for such a reprocessed device would need to include performance data that assess the effects of this new technological characteristic (varying failure profile) and demonstrate equivalence to the OEM device.

Similarly, the atherosclerotic plaque that blocks the coronary arteries of angioplasty patients may differ in hardness and pliability from patient to patient. The same type of percutaneous transluminal coronary angioplasty (PTCA) catheter may thus be subjected to very different inflation pressures, material interactions, and other conditions in different patients. Such differences will affect the future distensibility of the balloon components of PTCA catheters employed to reestablish normal flow in the artery. Such balloons are designed to inflate to preset diameters. This performance feature degrades as the balloon is repeatedly stressed with reuse, and may be compromised to an unknown degree by aspects of the anatomy of patients on which it was previously used.

OEM product performance testing is concerned with initial failure. By contrast, performance testing for reprocessed products must take device exhaustion, or wear-out, into consideration. This means that, in addition to assuring that the reprocessed product meets functional specifications, the reprocessed-device 510(k) must characterize time to failure or number of uses to failure.

Because its use history is unknown and destructive device testing is not feasible, it may be impossible to inspect or test a product to determine whether it is at or near the wear-out stage of use. The 510(k) for such devices must identify alternative methods for detecting and, more importantly, predicting such wear-out. Otherwise, such failures will only be detected in use, possibly resulting in patient injury or medical error.

Material Effects of Reprocessing. In addition to prior use, reprocessing itself may alter key material and mechanical properties of the device. For example, cleaning and sterilization may introduce new failure modes to the device or accelerate the wear rate of a reprocessed product.

Some stainless steels, including mar-tensitic alloys of the 400 series, designed for maximum hardness, are used in the manufacture of disposable scalpel blades and knives. The material mechanisms that impart high hardness to these stainless steels render them especially susceptible to corrosion. Small scratches left from grinding, sharpening, or scrubbing may be readily attacked by certain cleaning and sterilization chemicals, including peracetic acid, which can lead to corrosion. Such corrosion can in turn lead to catastrophic failure of the instrument on subsequent use.

For reprocessed stainless-steel devices, then, it is imperative that the 510(k) characterize these new technological characteristics. In addition to identifying the type of stainless steel used to manufacture the device, the reprocessor would need to characterize the likely failure points on the device and the average number of cleaning and sterilization cycles the device could undergo prior to such failure.

Many studies focusing on reprocessed SUDs have reported malfunctioning or out-of-specification devices. These studies are useful in identifying changes introduced by reprocessing that must be accounted for in the 510(k).

In an FDA study of the effects of cleaning and reuse on device materials, both used and new, purposely contaminated PTCA balloon catheters were cleaned, packaged, and EtO sterilized before being analyzed. Results demonstrated that the guidewire tubes of a number of reprocessed balloons were curled up inside the balloon as a result of overinflation, while other balloons shrank due to reprocessing and EtO sterilization. Analysis of the unused balloons subjected to cleaning revealed changes in balloon diameter as much as 10% outside of the manufacturer's specification. Results also showed that reprocessed balloons were stickier than new balloons.3

One study demonstrated functional failures specific to balloon catheters. These included poor trackability, probably due to the unfolded condition of the balloon as it was removed from the package; inability of balloons to be prepared in accordance with instructions for use; curved inner bodies and S-shaped inner bodies in the balloon upon inflation for testing; and failure to withstand an average burst pressure of 21 atm.4

In that same study, functional failures involving diagnostic and guiding catheters included failure of reprocessed diagnostic catheters to perform as well as new catheters in two types of torque testing and signs of material degradation in the guiding catheters following tensile overload tests. All of the guiding catheters and two-thirds of the diagnostic catheters displayed out-of-tolerance shape conformance. One-third of the diagnostic catheters had outside-diameter measurements above their preestablished specifications and top inner diameters that were below preestablished specifications. Failure to withstand five injections to the pressure rating indicated on their hubs characterized one-fifth of the diagnostic catheters.

A corporate study subjected 27 reprocessed cardiac catheters to functional testing. All balloon catheters failed to perform adequately in trackability and balloon preparation tests. In addition, 9% of diagnostic and guiding catheters failed tests for shape conformance, and up to 56% of all catheters did not pass some aspect of the visual inspection, exhibiting such faults as flaking of the exit marker, kinks, bends, a sliced outer body and strain relief, or an open fuse.5

Clearly, resterilization and the use history of reprocessed catheters contribute many new technological characteristics to these devices, which must be defined and evaluated in 510(k)s as part of the bid for a conclusion of substantial equivalence. While much of the available data on reprocessed SUDs concerns cardiac catheters, several other device types have also been studied, including orthopedic devices.

In one study, investigators collected reprocessed devices from area hospitals to assess whether they still conformed to the specifications of a new device.6 Devices studied included cutting accessories, which are precision instruments designed to rotate at up to 100,000 rpm while delivering clean cuts. Results of the investigation demonstrated that attempts to resharpen a used device removed essential material, which depleted and destabilized the device, making it unreliable. The resharpening of such devices has produced misdimensioned cutting accessories and flawed instruments that could result in longer surgeries and poor surgical outcomes. Of the 213 devices analyzed, 81 (38%) had flaws in their integrity. Of these 81 devices, 23 had worn, damaged flutes.

In this case, a lack of design understanding on the part of the reprocessor seems to have led to inappropriate reprocessing. A 510(k) for such a reprocessed device would need to include data that characterize the resharpened surface and evaluate the device's ability to operate as intended. Such data would be necessary to support the claim of substantial equivalence.

A similar report revealed that an ultrasonic device blade had not been uniformly sharpened on reprocessing. Ultrasonic cutters must vibrate at a particular frequency in order to achieve their dual cutting and coagulation effect. Imperfect shaping, scratching, or other surface damage to the blade of such a device will cause it to vibrate improperly. As a result, the device may not activate in midprocedure; or it may cut but not coagulate, resulting in internal bleeding; or the blade may fracture during use, possibly depositing fragments in the patient. So that such negative outcomes may be avoided, the reprocessed-device 510(k) must demonstrate the reprocessor's clear understanding of the device's key design features and functionality.

This example demonstrates the importance of having FDA reviewers who are fully conversant with the safety trade-offs inherent in reprocessed devices. How FDA will actually decide which trade-offs are acceptable, in light of its requirement that all 510(k) devices must be at least as safe as their predicate devices, has not been addressed in the reuse guidance document.

In addition to design considerations, a reprocessed-device 510(k) must identify all the materials used in the device and account for the effects of reprocessing on each one. Reprocessing can significantly affect the integrity of a device. Postprocess testing must ensure that processing steps, including sterilization, do not adversely affect a device's material or mechanical properties. Final testing conducted before sterilization is insufficient to provide such assurance.

Damage to metals, polymers, and adhesives found in devices taken from hospital shelves demonstrates the ineffectiveness of reprocessed-device testing prior to sterilization as a control for these types of safety issues. This is not surprising from a regulatory perspective. It confirms the longstanding FDA policy that product quality and reliability cannot be achieved through device testing. These attributes must be designed into medical devices, and devices must be manufactured with validated processes to ensure reproducibility.

For instance, aluminum used to manufacture disposable intubation stylets may develop subcritical damage that leads to an undetectable flaw and then device failure. A serious injury to a surgical patient was reportedly brought about by the use of a reprocessed aluminum intubation stylet.7 During a difficult intubation, a 10-cm section of the disposable stylet broke off in the patient's esophagus. It was not detected until several weeks later when the patient reported acute stomach pains, which were traced to the stylet fragment having perforated the duodenum.

This incident underscores the need to have the performance characteristics of a device designed in. It also reinforces the importance of understanding how many times a device can be reused before it will fail, and of the need to provide an adequate safety margin for patients.

Testing a device before release merely demonstrates that it functioned when tested. It does not provide assurance that the device will work the next time it is used on a patient.

In the case of devices manufactured from polymeric materials, the 510(k) for a reprocessed SUD must identify the various polymers used in the construction just as the 510(k) for the OEM device must. Further, to address the new technological characteristics of these reused devices, the reprocessor needs to characterize the susceptibility of each polymer to various reprocessing changes along with the effect of such changes on both material integrity and device mechanics. Absorption of cleaning fluids, for instance, can have a plasticizing effect on some polymers and alter their mechanical properties.

In one in-house study, a reprocessed single-use trocar developed both a complex crack in the housing near the stopcock and a chip in the leading beveled edge of the trocar sleeve after reprocessing. The disinfecting solutions used in reprocessing weakened the plastic and caused it to crack at stress points.8 Cracks at stress points can cause a trocar to break during reuse, resulting in plastic shards in the patient.

Many single-use devices incorporate long, narrow, polymer tube components. Such components can easily bend and kink and thereby produce crazing, an alignment of polymer molecules that changes the fundamental mechanical properties of the polymer and increases the likelihood of device failure. Crazing causes the distinct white line that often forms at the point where plastic products are bent. This line signals a change in the polymeric properties and marks the most likely site of failure.

Model-by-model process design verification is essential in 510(k) review of reprocessed devices in order to ensure that devices at or near the point of critical failure are identified. In fact, FDA's Office of Science and Technology (OST) has stated, in response to results of testing in agency laboratories, that only model-by-model evaluations of reprocessed SUDs would be acceptable.9 The way that different polymeric materials used to manufacture similar devices may demonstrate markedly different degradation profiles over time is charted in Figure 2. Mechanical degradation can be related to fatigue, wear, loss of tensile strength, crazing, or another precursor of failure.

Figure 2. Possible polymer failure profiles, showing why it is essential to identify materials of construction in reprocessed-device 510(k)s.

The effect of multiple uses is not addressed in the 510(k) for a new single-use device. Therefore, the reprocessed-device 510(k) must identify the types of polymers used in its manufacture, along with their degradation profiles, in order to appropriately identify predictors of failure. Devices made from polymers A or C in the figure may fail catastrophically with little warning, the polymer-A device perhaps after first use. The polymer-C device may be reprocessible, but it will likely fail without warning. Devices made of polymer B may act more predictably. For devices in which signs of wear or degradation are not evident, accurate tracking of use history is essential in order to minimize the possibility of patient injury.

Most single-use medical devices are made up of several different polymers or metals. The abutment of different materials generates additional reprocessing questions. Adhesives used to join materials can

A New Standards Policy: A New Era?

Originally Published January/February 2001

Cliff Henke

We've heard this one before: the United States says that it is really, truly serious about creating a coherent standards-development policy that puts the nation in the strongest possible position vis-à-vis international bodies, but then it doesn't happen. Now a new standards policy has been announced. Will this time be any different?

Standards development is decidedly not a sexy subject. It is like the bill-paying aspect of marriage—not the best part, but a necessary part without which the rest might not survive. Though standards development may seem as plain as bread and butter, it is undeniably an important matter.

Agenda for the Century: Henney Pledges Good Science, Openness at FDA

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

Originally Published January 2001

Editor's Page

Addressing the National Press Club on a politically historic day, FDA Commissioner Jane Henney outlines the agency's fundamental operating principles for the years ahead.

Approximately one month before you'll be reading this, FDA Commissioner Jane Henney delivered a major summary address that resembled the proverbial tree falling in the midst of an uninhabited forest. In other words, unless you're in the habit of checking in at the Web site of the National Press Club, it's unlikely that you heard about it. You see, Commissioner Henney's appearance at an NPC luncheon in Washington took place on December 12, when the attention of every citizen—let alone every reporter—was riveted on the impending Supreme Court decision that would finally decide the presidential election that same evening. On a day that there was only one story, it was ironic that Henney would open her talk on "FDA: Preparing for the 21st Century" by touting the agency's high public profile and the fact that "it seems we're always in the news." But if the Commissioner was decidedly overshadowed on this occasion, she nevertheless delivered a number of intriguing indications regarding FDA's future that deserve to be brought into the light.

Citing a recent survey conducted by the Pew Research Center and Princeton Research Associates, Henney maintained that FDA receives unusually positive marks from the public it serves. Although only 26% of consumers, health professionals, and industry officials said that they "trusted the federal government to do what is right," from 72 to 85% of those same respondents stated that they "trusted FDA to make the right decision." To retain this confidence in an era of unprecedented change, said Henney, the agency must follow what the Commissioner referred to as "four fundamental principles."

The first of these principles is that FDA must continue to "ground decisions in science." The Pew survey found that 75% of respondents believed that FDA bases its decisions on "good science." Henney admitted that sustaining this capability in the face of revolutionary developments in genomics, proteomics, nanotechnology, robotics, and artificial intelligence—that is, having the expertise to evaluate devices that will incorporate these technologies—represents a major challenge for FDA. "If we are not scientifically strong," she said, "our decision-making will become risk averse, or, what is worse, simply wrong."

FDA's second guiding principle, according to Henney, is "increased openness and transparency." Critics of the agency might be surprised at the Commissioner's claim that FDA "enjoys a worldwide reputation" for promoting such open policies as public-advisory committee meetings, consumer-affairs offices, and notice-and-comment rule making. Henney emphasized that the agency's Web site—which contains some 110,000 documents and receives more than 60,000 visits per day—is now posting specific advance information on upcoming advisory committees, transcripts of advisory-committee meetings, more-extensive information following product-approval decisions, and details regarding enforcement actions such as warning letters.

Augmenting FDA's effectiveness through "leveraging" is Henney's third principle, one that "allows FDA to bring a wider range of scientific thinking to bear on public health issues." Examples cited by Henney include work with private and state accreditation bodies to implement the Mammography Quality Standards Act.

The fourth and final principle entails taking the agency on the road to "expand the traditional mission of FDA beyond that of domestic consumer protection." Pointing out that FDA has historically fostered an international presence, Henney noted the imperative of economic globalization and the nation's aggressive trade policy in driving FDA's involvement in various regulatory harmonization efforts. Whether the agency is setting standards, organizing compliance programs, or resolving disputes, Henney envisions an FDA with "enormous potential for improving the public health worldwide."

Jon Katz
jon.katz@cancom.com


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Copyright ©2001 Medical Device & Diagnostic Industry

Healthcare E-Business: Dot-Com or Dot-Gone?

Originally Published January/February 2001

Cliff Henke

With all the news of dot-coms crashing daily, some observers may wonder what these companies and their investors were thinking. Among the 30-plus Internet firms in the healthcare sector, none has yet turned a profit. In one indicator of the dot-com economy, several reports have noted that Internet advertising fell precipitously in the first half of 2000 when compared with the same period in 1999. And even the most profitable segment of Internet companies, pornography Web sites, is beginning to show signs of market saturation.

Do these statistics mean that all the hype was phony? Not a chance, say analysts—especially when it comes to the healthcare sector. The savings potential for medical technology companies with the right e-business strategies is enormous, and market reports continue to forecast a very large prize indeed for the right solutions.

The Mighty Have Fallen

Human Factors Roundtable Part I: The Regulatory Imperative

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

Originally Published January 2001

Human factors can be defined as knowledge regarding the characteristics and capabilities of human beings that is applicable to the design of systems and devices of all types. In the medical industry, there is increasing awareness of the importance of good human factors practices in the design of safe, effective, and commercially successful products— especially in the wake of FDA's adoption of the quality system regulation. In the special roundtable discussion that follows, MD&DI has brought together a varied group of human factors specialists—regulators, consultants, device industry experts, clinicians—to explore how companies can promote better product design and excel in the new product development environment.

The roundtable was organized with the assistance of MD&DI contributing editor Michael E. Wiklund, vice president and director of the American Institutes for Research (Concord, MA). Like the other participants, Wiklund has played a prominent role as a member of the Human Engineering Committee of the Association for the Advancement of Medical Instrumentation (AAMI), which has prepared a standard for medical device design that is expected to be approved in the summer of 2001. Joining Wiklund in the roundtable were Peter B. Carstensen, a systems engineer who is the human factors team leader at FDA's Center for Devices and Radiological Health (CDRH); Rodney A. Hasler, senior technical field response manager at Alaris Medical Systems (San Diego); Dick Sawyer, a human factors scientist at CDRH; and Matthew B. Weinger, MD, professor of anesthesiology at the University of California, San Diego and staff physician at the San Diego VA Medical Center, who is also co-chair of the AAMI committee.

This first part of the roundtable focuses on human factors and FDA regulations. The second part, on standards development and human factors implementation issues, will appear in MD&DI's February 2001 issue.

MD&DI: The first question is directed to our participants from FDA. Current GMPs make good human factors practice a regulatory imperative. Can you give a short history lesson on how we got to this stage?

Carstensen
Carstensen: I think it really had its beginnings back in 1974–75. I joined the agency in 1974, as the agency was anticipating the Medical Device Amendments of 1976, and got involved right out of the gate with an ancillary committee that had been working on a standard for anesthesia gas machines for a number of years. At that point the standard had specified about 80% of the requirements and was beginning to deal with what were essentially human factors issues, and I introduced the committee to MIL STD 1472, which is the military version of an AAMI guideline. That gave rise to the organizing of the AAMI human factors committee. I managed to convince the future chairman of that committee—designated Z79—to approach AAMI and get a human factors committee set up and write general standards for guidance for human factors in medical equipment.

And then around 1984 we had a major anesthesia incident, and the subsequent congressional oversight hearings revealed the significant extent to which human error contributed to such incidents. Jeff Cooper up at Harvard had done a study on critical anesthesia incidents, a 1984 study, in which he had talked about as many as 20,000 avoidable anesthesia deaths every year, with 90% or more of those caused by or related to human error. That got FDA's attention, and we organized a human factors group—the agency's first identifiable human factors group—in 1993. The group comprised Dick Sawyer, myself, and a couple of other people, and the whole human factors program at FDA really grew out of that.

So it was in the wake of those congressional hearings that FDA first talked about adding design control to the good manufacturing practices regulation. A further impetus was the Lucian Leape study of human error in hospitals in New York state, which I believe came out in 1991. Leape later published an article in JAMA, called "Error in Medicine," in which he extrapolated the New York data across the country and talked about anywhere from 44,000 to 98,000 avoidable deaths every year in the United States. By the way, many people actually think those are very conservative numbers, as staggering as they are.

In 1995, we held an AAMI/FDA conference on human factors in which we really laid out our strategy and our new human factors program. Two years later, the National Patient Safety Foundation was created. And then this dynamite report came out from the National Academy of Sciences—the Institute of Medicine (IOM) report, "To Err Is Human"—which was really based on the earlier Leape study. So these were the crucial events driving our program.

Sawyer
Sawyer: In conjunction with what Pete's talking about, you may remember the recall study FDA carried out in the late 1980s—I believe it was completed in 1990—indicating that about 44% of manufactured recalls were due to design problems. A case-by-case examination of those recalls indicated the prevalence of design-in errors, or errors induced by bad design. So this really gave us the leverage to introduce design issues into the Safe Medical Devices Act of 1990. I think the center had to fight very hard to get the word design into that document—which then served as a basis for getting design into our GMP regulation as part of the design controls.

MD&DI: Did we really need new design controls in the GMP regulations, as opposed to allowing industry or the marketplace to provide the impetus for better human factors?

Wiklund
Wiklund: I think the gist of this question goes to political views regarding whether regulation is the way to effect change in an industry as opposed to letting change be driven by the marketplace.

Carstensen: I think you could make a case that it could be marketplace driven to some extent. There certainly are companies that do human factors for marketing reasons—perhaps in addition to liability concerns. Clearly, there are companies I know that invest a lot of resources to get a marketing advantage. But yes, I think that in our judgment a regulation was needed, if for no other reason than to get the attention of the industry and give companies the good news that it is in their self-interest to have a strong human factors program.

Sawyer: In most other critical industrial arenas—the military, air-traffic control, transportation, and so forth—there has been a need for some regulation to get things off the ground so that companies really start paying attention to human factors issues. There are clearly precedents in other sectors for regulation.

Carstensen: I would add one other thing. I think we still see plenty of evidence that companies aren't doing as good a job as they should. But we are convinced that it's more a result of ignorance than of any effort to evade their responsibilities. Getting the attention of companies through the regulation enables us to provide the education and guidance that can help them do what really is in their self-interest.

MD&DI: For readers unfamiliar with the discipline, would someone define human factors? How does the application of good human factors practice make medical devices better?

Wiklund: Today, more and more people are probably familiar with the term human factors because of the impact that good human factors practice is having in making things like consumer software applications or electronic devices more usable. Many companies in the commercial sector are promoting good human factors as equivalent to good design or good-quality consumer experiences. As far as defining the discipline, I consider human factors to be the application of what we know about human characteristics to the design of products and systems, including, of course, medical devices. Human factors considers people's mental and physical capabilities as well as their perceived needs or preferences, and tries to accommodate these in the development of good designs that will be safe, usable, efficient, and satisfying. Obviously, when you're talking about medical devices—which serve a life-critical function—there is an inherent justification for a very strong focus on human factors to help achieve important design objectives, especially safety.

Given the proper attention to human factors, one would expect that a medical device could be improved in myriad ways. For example, it would be more ergonomic, which means that it's better suited to the physical interactions of those exposed to it. If it's something you pick up, the handle will be properly shaped so it's comfortable, so that you don't accidently drop it. When you design a display according to good human factors principles, the display is readable from the intended viewing distance and the information is organized in a fashion that is complementary to the task at hand. Controls will be laid out, shaped, and labeled in a manner that is as intuitive as possible, so that the threshold for learning how to use the device is lower and long-term usability is assured.

Hasler
Hasler: I would agree with the definition we just heard. I also think it reflects the dichotomy of human factors. There are two distinctive components to human factors. The first is ergonomics, which applies human physical capabilities to the device. The second is the cognitive component, which applies the human thought process to the device design.

Weinger: The second part of the question asked how using good human factors processes makes devices better. Mike described the outcomes and how they can be improved through good design, but I think another key element is that a good process involves users—via testing and other techniques—throughout both the initial and iterative design stages. One could very well assemble a good human factors team in terms of knowledge or data and put them together with a bunch of talented engineers and they could design a device that from a theoretical standpoint should have good usability, but until you actually get users in there to use it, you don't know that your solutions are correct. I think that's a key element that needs to be part of that description.

Wiklund: That's a good point. Some of the work that the AAMI committee on human factors is doing hinges on trying to get companies to adopt a human factors process that includes early and continual involvement of the end-users, whether they be physicians, nurses, or patients using medical devices in their own homes. The objective is to get users involved in the process of coming up with good designs that meet their needs and preferences.

Weinger
Weinger: You can get users involved, but if you simply do focus groups you may end up with a less-than-optimal outcome. And so another element of a successful human factors design process is applying not only the knowledge, but also the tools that will actually describe or verify usability and efficacy in all these critical elements—in other words, usability testing.

MD&DI: Do the people who use medical devices on a daily basis think that there's a usability problem? Do they recognize good human factors design from bad?

Weinger: At present, there is much greater recognition of human factors design than there was 5 or 10 years ago by clinicians across the board. However, those clinicians that have been interacting with medical devices in high-stress, rapid-tempo types of environments like the operating room or the emergency room have recognized problems for quite a few years, and in fact have played a key role in moving both the standards-making and regulatory processes forward. More generally, when clinicians use a device, they may not know about human factors, but most of us know how to cuss at a product when it doesn't make our job easier but rather makes it more difficult, or makes us more error-prone, or prevents us from doing what we want to do, or slows us down. As soon as you tell someone what human factors and usability are they say, "Oh that's the problem with this or that device!" So they may not know the word, but they certainly know what the problems are.

MD&DI: How would you gauge the magnitude of the problem? You spoke about cussing at devices, and those of us not in the clinical environment every day don't have a real good sense of whether this is an unusual or a very frequent event.

Weinger: The answer to that is rather interesting, in that towards the latter part of the 1980s things were actually somewhat better, and then in the last 10 years they've gotten worse again—and the reason for that is computers. Basically, mechanical devices like the old anesthesia machines had gone through 40 years of iterative design to make them more usable. And it's only been in the last 10 or 15 years that we've progressively introduced microprocessor-based devices throughout healthcare, and the human-computer interface has now become a real problem and it's not just in medicine. I'm frequently aggravated with my desktop computer when it crashes suddenly and I lose my work. And from a practical standpoint, there's actually been more time to develop usability of consumer devices. In the operating room, you could imagine that if you're trying to take care of a patient and your monitor suddenly freezes up, that would be a very bad thing. In fact, I've personally seen it happen.

MD&DI: Is there a particular class of devices that are hard to use and vulnerable to user error?

Weinger: Although all types of devices pose a risk, the more complex the device, and the more microprocessor-based technology it includes, the greater the risk. The criticality of the device is also paramount. A device whose failure means that a patient could die—for example, a cardiopulmonary bypass machine—obviously carries tremendous risk. Generally, devices that incorporate both control and display pose a greater risk than ones that are simply used for displays, but it also depends on the condition of the patient. For example, intravenous infusion pumps have received a lot of negative press recently. I think that's partly because they're so widely used and because they have both control and display components and are employed in high-acuity situations. They are probably the one device that comes most readily to mind, but I don't think that pumps are an isolated phenomenon, by any means.

MD&DI: In terms of FDA's overarching view of all the medical device reports and so forth, which categories of devices does the agency point to as more generally problematic?

Sawyer: There's such a huge range of devices that it's hard to characterize. The problems that we commonly see are with devices such as infusion pumps, ventilators, and other intensively interactive kinds of devices. The more a user manipulates or responds to a device in addition to merely reading it, the more there is to go wrong and the more obvious any error. Conversely, if somebody misreads a monitor that is not interactive, FDA will probably never know about it, since it's unlikely to be reported.

Weinger: It's a more widespread problem than what FDA sees, because things that get reported to FDA are generally safety related. But, as Mike pointed out earlier, human factors encompasses more than just safety—it has to do with efficacy and efficiency and satisfaction. When you're sitting in your office working on your computer and the thing crashes, there's no safety issue involved, but your efficiency, efficacy, and satisfaction are all reduced. And many times in the medical environment, devices make our jobs more difficult rather than easier. This isn't going to get reported to FDA, but it probably adds to overall healthcare costs, both directly and indirectly.

Wiklund: Let me ask you a follow-up question, Matt. Let's assume that clinicians recognize that they are well served by devices in which there's a substantial investment in good human factors. Do manufacturers expect that, if they invest heavily in human factors, they'll actually see a tangible benefit in terms of the popularity of their device in the marketplace—how well it sells relative to a device that did not benefit from a comparable attention to human factors? In other words, do you think clinicians have a strong enough voice in getting their institutions to buy products that reflect good human factors design?

Weinger: A year or two ago, I would have been more hesitant to say yes. As everyone knows, the economic pressures in the healthcare marketplace are extremely powerful. A very well-designed device that has good usability but is more expensive than a competitive product might be more difficult to purchase, even if the clinicians want it. But the IOM report and the increased emphasis on safety have begun, I think, to turn the tide in favor of devices supported by the kind of clinician input that says, "This device is easier to use and, we believe, is going to be safer." Such consensus carries much more weight now than it might have even two years ago.

Hasler: I absolutely agree. As Matt mentioned, there are mitigating problems and institution-specific issues—which can include group purchasing contracts and things like that—but, given a level playing field, when you're talking about sales opportunities, a product that is well designed has a powerful advantage with human factors.

MD&DI: Matt, how would you respond to the statement that the ultimate responsibility for the proper use of medical devices—for avoiding user error—rests with the caregivers?

Weinger: The succinct response would be "yes, but," so let's talk about the "but." If a patient is injured during device use, the manufacturer is likely to be as liable as the clinician from a medical, legal, and regulatory standpoint—particularly if the clinician points out that the device contributed to the adverse event. Because there are many other impediments to safe practice besides the device, the clinician doesn't always have the opportunity or time to deal with a device that is poorly designed. The goal for both device manufacturers and clinicians is patient safety and good outcomes, and they should work together to those ends. It's not productive either to point a finger at manufacturers and say it's entirely their responsibility to produce the best possible device, or to target clinicians and insist that they bear the sole responsibility to make sure the device is used correctly. There needs to be a collaboration.

MD&DI: Does FDA find that medical device manufacturers are aware of the new regulations? Are manufacturers responding to FDA's satisfaction?

Carstensen: Well, they're probably not aware to the extent that we'd like. I think we've come to that conclusion, but it's difficult to measure the industry as a whole. We do see some encouraging signs showing that many companies are putting more effort into human factors. But we also see key indications that there are a lot of companies out there that still don't understand what's needed.

MD&DI: What are those encouraging signs?

Carstensen: We get to look at a limited number of the premarket applications, and I'm really basing my comment on that: what we've experienced in terms of looking at the device descriptions that come in as part of the premarket approval program.

Sawyer: People like Mike and other consultants or designers also have told us that they're seeing more and more business, getting more and more opportunities. In the year following the design control development requirements going into effect, FDA did a sampling study by field investigators that indicated that somewhat more than half of the companies out there were doing human factors. How well we don't know, but there were early indications that companies were actively looking at human factors issues. Again, how completely and how well is going to vary tremendously, no question about that.

MD&DI: Awareness among manufacturers is important. Could you point to a few of the things FDA has done to this point to maximize awareness? For companies that are just now discovering there's a human factors imperative, where can they turn to get up to speed quickly?

Sawyer: FDA is doing a number of things. Of course, we put out guidance documents, which were disseminated some years ago, on design controls. Another guidance, on device use safety, just came out recently. We have teleconferences on human factors; there's one coming up in the near future. We're putting out a video for field investigators that tries to get them to understand the linkage between design and errors, to have a feel for when human factors input is necessary in the design process. We do presentations at industry trade events such as MD&M or the ASQC meetings. More and more, we're actually getting involved in giving talks to practitioners or those in industry—to doctors, nurses, biomedical engineers. And of course we monitor the results of human factors practices in regulatory efforts such as premarket review.

Carstensen: For promoting human factors, the premarket review activities contribute in a very limited way. We reach many more people through conferences and articles or through the FDA Web site. We have a pretty robust human factors section up on our site. It includes a great deal of information for manufacturers, and we find that most manufacturers are well aware of the FDA site and and have taken time to explore it. And also you could say that the AAMI human factors standard itself is an educational tool that FDA plans to promote. Once that standard is published under our standard-recognition program it will be granted official FDA recognition, which I think will make manufacturers more inclined to pay attention to it. Most of what we've done that has been effective has really been educational in nature.

MD&DI: Moving beyond education, what is FDA's stance on enforcement and what are the consequences of noncompliance with the regulations?

Sawyer: That's a difficult one. Companies are obviously at risk if they don't comply with the design control requirements. FDA can act with regard to premarket approval if a company hasn't followed the design practices, produces an overtly bad design, and is unwilling to respond. What we really try to accomplish is to educate not only people in industry, but those at FDA, at CDRH—through presentations, device evaluations, and similar means. In terms of enforcement, however, it's a slow, progressive effort. We do find that most companies, when they know there's a real safety problem with a device, will try to do something. There are always exceptions, but most companies are responsive.

Carstensen: The odds of a company getting cited for failing to comply are difficult to quantify. You have to recognize that the field is understaffed and the premarket reviewers are not all up to speed on human factors issues. So there's probably not a high risk for a noncompliant company of being discovered and getting nailed, but that's going to change over time. As we educate more and more of the reviewers and get the field more up to speed, I think companies that ignore human factors will be putting themselves at increased risk.

Weinger: What is FDA's mechanism for responding to a situation in which a human factors or usability problem with a device manifests itself in the marketplace, through comments by users or in the literature?

Carstensen: It depends on the severity of the problem and on how much information is available.

Sawyer: We do get involved, and it's a very difficult area. First of all, most devices that get in trouble, so to speak, were designed prior to design controls. So very often it's hard in an inspection, for example, to follow up on a given postmarket problem—it's difficult to find a procedural violation of, say, design controls. Although we may get a lot of reports on a device, there's tremendous underreporting: we may hear that there's been one death, when in fact there may have been 10. We don't really know how much underreporting there is. In addition, the depth of the reports we receive is highly variable. Often, a report doesn't really isolate the problem for us, doesn't tell us precisely what the design problem is or specify the linkage of that problem to the error and the linkage of the error to the injury or death.

Nonetheless, we do pursue postmarket problems when there are injuries, or potential injuries. Often, we'll get together with manufacturers; if the manufacturer recognizes that there's a safety problem, it's likely that they will try to do something about it. I don't know if "gentle persuasion" is the right term to use, but especially with older devices for which design controls were not involved in the original design or modifications, it's kind of an iterative process trying to persuade the company to correct a problem.

Carstensen: Postmarket enforcement is probably the least effective way for FDA to encourage the industry to address human factors. Once you get into a postmarket action, the stakes are so high for the company and the difficulty so significant for FDA that huge amounts of resources are consumed on both sides just dealing with the situation. It's really an object lesson for everybody, I think, that one needs to prevent these kinds of incidents that are so devastating to a company and so resource-intensive to deal with for FDA. It's just not worth it, so we need to be putting the right stuff in at the front end, getting the job done correctly the first time. Companies need to have good design controls and validation before they start marketing a device.



To the MDDI January 2001 table of contents | To the MDDI home page

Copyright ©2001 Medical Device & Diagnostic Industry

Marketing to the Brave New Healthcare World

Originally Published January/February 2001

Donna Krupa

The impact that the mapping of the human genome will have on health and medicine has been likened in significance to Neil Armstrong's l969 walk on the moon and mankind's subsequent understanding of the universe and space. To be sure, the secrets to be revealed from understanding human DNA and the interaction between genes and disease will bring about radical new scientific realities and drive significant changes in medical and professional practices.

But such discoveries will also have an equal, if not greater, effect on the commercial principles of the healthcare industry and the infrastructures—manufacturing, marketing, sales, etc.—that support the industry. Medical device and diagnostic manufacturers and the healthcare industry are today where rocket ships and the space program were some 30 years ago. Then, as now, things will never be the same.

The Admissibility of Medical Device Reports in Civil Litigation

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

Originally Published January 2001

MEDICAL DEVICE REPORTS

Anthony G. Brazil, Matthew L. Marshall, and Michele L. Abracen

In the normal course of business, medical device manufacturers routinely submit medical device reports (MDRs) to FDA whenever they become aware of the probability that their devices may have caused or contributed to a patient death or serious injury or illness. The forms used by many companies contain language similar to the following: "Submission of this report does not constitute an admission that medical personnel, the user facility, the distributor, the manufacturer, or the product caused or contributed to the event described herein." Some manufacturers also include a statement indicating that MDRs must be submitted before complete information has been obtained by the company and, therefore, do not constitute an admission of fault. For example, one medical device manufacturer includes the following preliminary statement:

This report may be required by medical device reporting regulations contained in 21 CFR section 803. These regulations are vague in a number of respects and subject to different interpretations. Moreover, these regulations require us to make a decision on reporting before having complete information, including our own analysis of returned products. Thus, our decision to file this report does not reflect, nor may it be used to support, a conclusion that the report constitutes an admission that the device, or its components, caused or contributed to the reportable event.

While such statements may appear to limit the use of MDRs in potential product liability lawsuits, these disclaimers often provide little more than a false sense of security. Several courts across the country have already allowed adverse reports to be presented in civil actions, and, as the Internet renders such reports instantly accessible, plaintiffs' attorneys will undoubtedly continue campaigning for their admissibility at the time of trial. (The Manufacturer and User Facility Device Experience—or MAUDE—Web site, enables all interested parties to search for adverse reports pertaining to medical devices by typing in key words, the name of a manufacturer, or the name of a device. All searches are free of charge.)

Given these trends, manufacturers need to stay well-informed regarding their product liability exposure. This article addresses several key issues, including the reasons certain courts have deemed adverse reports admissible, the confidentiality of information contained in MDRs, the possible grounds for courts to exclude MDRs from civil litigation, and the ability of plaintiffs' attorneys to use other documents as evidence of adverse reactions to medical devices. Finally—and perhaps of most importance to manufacturers—methods for limiting liability in lawsuits based upon adverse reports are suggested.

COURT RATIONALES FOR ADMITTING ADVERSE REPORTS

In an effort to sway a jury and obtain a verdict against a medical device company, plaintiffs' attorneys may try to present MDRs submitted by the manufacturer— or other reporters such as user facilities, distributors, etc.— to FDA as evidence in civil litigation. Despite the disclaimers and additional statements often included on MDR forms, some courts have ruled adverse reports are admissible for certain specific purposes: (1) to establish that the company knew its product was associated with a particular risk but failed to provide consumers with a warning of that risk, (2) to assist a jury in assessing punitive damages, and (3) to explain the basis for an expert's opinion presented at the trial.

At this time, there are few existing court rulings on this topic; however, the majority of the published decisions appear to support the admissibility rather than the exclusion of adverse reports. While the case law cited below may not apply in any given jurisdiction, the reasoning contained therein will probably be used by plaintiffs' attorneys to argue for the admissibility of such reports in many future product liability cases.

Reports Admitted to Show Knowledge and a Duty to Warn. In most cases where a court has allowed plaintiffs' counsel to introduce evidence of adverse experience reports, it has done so not because the reports constituted definitive evidence of liability on the part of the manufacturer, but rather because they might show that the company knew there was a particular risk associated with its product but failed to provide a consumer warning. The following examples are illustrative of lawsuits that involved this failure-to-warn theory.

In the case of Worsham v. A.H. Robins Company, Inc. (734 F.2d 676, 1984), the plaintiff, Margaret Worsham, had been wearing a Dalkon Shield intrauterine device (IUD) for five years when she went to an emergency room and was diagnosed with pelvic inflammatory disease. Shortly thereafter, her condition worsened and she had to undergo a complete hysterectomy. Worsham subsequently filed a product liability action in Florida against A.H. Robins, the manufacturer of the IUD.

The contraceptive device featured an exposed string that facilitated its removal and allowed the wearer to verify that it was in place. This string was alleged to have a "wicking tendency" that allowed bodily fluids and bacteria to travel to the wearer's uterus, where they could cause an infection.

The plaintiff's attorney sought to have 10 adverse reports filed by Robins introduced at trial on the grounds that they addressed the issue of whether the manufacturer knew there were problems associated with its product and therefore should have taken action to notify consumers of those risks. In this case, the trial court allowed such evidence to be introduced for this limited purpose. Based in part on the 10 reports, the jury found for the plaintiff and awarded her $2.5 million in compensatory damages and $1 million in punitive damages. Although these monetary amounts were eventually reduced, Worsham was able to obtain a $1 million judgment.

Golod v. Hoffman La Roche (964 F. Supp. 841, 1997), decided in New York state, deemed adverse reports submitted to FDA by a pharmaceutical manufacturer admissible for the purpose of establishing knowledge and a duty to warn. In this case, the plaintiff took a drug called Tegison from 1984 to 1990 to treat her severe psoriasis. Although the package insert began warning of "adverse ocular effects" in 1986, the plaintiff filed suit against Hoffman after she developed permanent blindness in her right eye.

The defendant filed a motion for summary judgment arguing, in part, that it had not breached its duty to warn of known or knowable risks since it had not known of the serious, irreversible, ophthalmic effects associated with Tegison when the plaintiff began taking it. In opposing the motion, the plaintiff's attorney submitted adverse experience reports and an FDA printout summarizing reports of adverse reactions. The reports and the FDA printout were deemed admissible evidence for purposes of opposing the motion for summary judgment. In its ruling, the court explained that although such documents could not be used to establish that the drug actually caused the plaintiff's blindness, the reports were pertinent to establishing that the defendant knew during the relevant time frame that there were serious ophthalmic risks associated with the use of its product and thus should have provided a warning. Although this case concentrated on the admissibility of adverse drug reports for purposes of opposing a motion for summary judgment, it is nevertheless significant because it may be used to argue that comparable evidence should also be admitted during trial and in cases involving devices.

In Palmer v. A.H. Robins Company, Inc. (684 P.2d 187, 1984), the plaintiff filed a lawsuit in Colorado against the manufacturer of the Dalkon Shield IUD after she had experienced a septic abortion. During the trial, Palmer's attorney sought to introduce adverse reaction reports as evidence of the manufacturer's knowledge of adverse consequences associated with the use of its device. A significant component of the plaintiff's claim was that, by failing to eliminate known dangers or to give warnings of them, the manufacturer had prevented the plaintiff and her physician from making an informed decision on the use of the IUD. Even though the MDRs in question involved injuries other than septic abortion, such as pelvic inflammatory disease, the court held that they were admissible because they constituted legally relevant evidence on the issue of the manufacturer's knowledge of the potentially dangerous character of the device. The jury subsequently awarded Palmer $600,000 in compensatory damages and $6.2 million in punitive damages.

Reports Admitted for Purposes of Punitive Damages Assessment. Some courts, while generally unwilling to admit adverse reports as evidence of manufacturer liability, will allow MDRs to be considered for the purpose of determining an appropriate punitive damages award after liability is established. For example, Hern v. Intermedics (U.S. App. Lexis 1630, 2000), a California product liability case, was bifurcated into liability and damages phases. During the liability phase, the plaintiff was prohibited from introducing MDRs to show that the defendant had made submissions to FDA pertaining to its device's susceptibility to failed batteries. The court indicated in that ruling that if liability was established, however, it would entertain a request for admission of the MDRs to assess the amount of punitive damages warranted. Although the plaintiff in this case did not renew the request for admission of the reports during the trial's damages phase, the ruling is important because it establishes the possibility of the admission of adverse reports if liability can be established.

In another case, a court ruling in New York noted, with respect to prescription drugs, that if a manufacturer learns of a danger associated with its product after putting it on the market but does nothing to remedy the situation and "deliberately closes its eyes," punitive damages may be warranted (Roginsky v. Richardson–Merrill Inc. [378 F.2d 832, 1967]). Therefore, plaintiffs' attorneys can be expected to increase their arguments for the admissibility of adverse experience reports once liability is established in order to show that a defendant took insufficient steps to remedy or warn of a risk associated with its product.

Reports Admitted via Expert Testimony. Some courts also have allowed adverse reports to be admitted at trial during expert testimony. Generally, expert witnesses may base their opinions on any and all matters they deem significant, even if such evidence would ordinarily be inadmissible. Thus, even if a court prevents a plaintiff from presenting actual MDRs as evidence, it may allow an expert to testify that his or her opinion is based upon reviewing FDA submissions involving the device in question. For example, in Benedi v. McNeil (66 F.3d 1378, 1995), a Virginia case in which the plaintiff claimed liver damage, an expert testified that he believed the manufacturer of Tylenol should have warned of the danger of mixing its product and alcohol based upon his review of 60 adverse drug reports.

Although these and other cases reveal that some courts will permit adverse event reports to be introduced at trial, medical device manufacturers must not be tempted to respond to these rulings by submitting fewer MDRs to FDA. In addition to regulatory sanctions, underreporting of adverse events can lead to serious obstacles during the course of product liability litigation. For example, in a case where a plaintiff with an alleged device-related injury raises a failure-to-warn claim, one of the strongest defenses the device manufacturer has is that it did not have a duty to warn of the particular risk cited because that risk was unknown. To that end, defense counsel may rely upon the fact that the company had filed no MDRs involving the claimed injury. If it can be shown that the company had been notified of such injuries and did not report them, however, then it will be difficult to argue that it had no duty to warn of the risk associated with its device.

MAINTAINING THE CONFIDENTIALITY OF MDR DATA

Despite the fact that MDRs have become admissible in some civil actions, most courts will protect the confidentiality of some information in the reports, including the names of the reporters, patients, doctors, and hospitals. Motions for protective orders are commonly granted, allowing MDRs to be produced with such information redacted. Relevant cases include York v. American Medical Systems Inc. (U.S. App. Lexis 30105, 1998), Eli Lilly v. The Honorable John Marshall (850 S.W.2d 164, 36 Tex.Sup.J. 683, 1993), and In Re Eli Lilly & Company (142 F.R.D. 454, 1992).

The pertinent Lilly v. Marshall ruling came in a case filed in Texas against Lilly by the family of Michael Biffle, who had committed suicide six days after he began taking Prozac. In pretrial discovery, the plaintiff's counsel sought production of, among other things, various documents that had been submitted to FDA, including adverse reaction and drug experience reports that had been initiated by physicians and other healthcare providers. The trial court ordered Lilly to produce the reports with only the patients' names redacted; however, in Lilly v. Marshall, the Texas Supreme Court reversed that order and required that the names of the reporters also be redacted. Under the Federal Food, Drug, and Cosmetic Act at 21 CFR 314.430 (e)(4)(ii), FDA must keep confidential the identities of the patients who were harmed and of the person or institution that reported an adverse reaction. Thus the state supreme court found that the trial court should have required the plaintiff to show a particular relevance of and need for the reporter data that outweighed the important congressional objective in keeping such information confidential. In so doing, the court referenced cases in several other jurisdictions (Tennessee, Louisiana, New York, Indiana, Kentucky, and Texas) that had required reporters' identities to be redacted, but it also concluded that upon a sufficient showing by plaintiffs, such information might be discoverable.

GROUNDS TO EXCLUDE ADVERSE REPORTS

Although certain courts have permitted plaintiffs to introduce adverse reports in product liability cases, medical device manufacturers have strong grounds to argue that such evidence should be deemed inadmissible at trial based on the adverse event reporting statute. Device manufacturers also can seek to thwart the admission of adverse reports during trial based upon a plaintiff's failure to retain an expert, among other arguments.

Inadmissibility Based on Statutory Language. A viable argument can be made for the exclusion of adverse reports given that the language of the MDR regulation generally prohibits the use of such documents in civil actions. Specifically, 21 USC 360(i)(b)(3) states that:

No report made under paragraph (1) by (A) a device user facility, (B) an individual who is employed by or otherwise formally affiliated with such a facility, or (C) a physician who is not required to make such a report, shall be admissible into evidence or otherwise used in any civil action involving private parties unless the facility, individual, or physician who made the report had knowledge of the falsity of the information contained in the report.

In other words, MDRs initiated by user facilities or physicians may not be used in any civil action, including product liability suits, unless it can be shown that the reporter knowingly incorporated false information in the report. The citation of this statutory language has been significant in at least two cases, In Re Medtronic (184 F.3d 807, 1999) and Adcox v. Medtronic (U.S. Dist. Lexis 20277, 1999).

In In Re Medtronic, filed in Arkansas, the plaintiff, who claimed harm from a Medtronic pacemaker, sought the discovery prior to trial of the names of patients, physicians, and facilities involved with other allegedly defective pacemakers made by the manufacturer, and specifically requested the names of physicians who had reported adverse incidents similar to that of the plaintiff. In ruling on that request, the trial court ordered the manufacturer to send letters to 4000 patients whose experiences led to the filing of MDRs to give them the opportunity to waive their attorney-client privilege. Medtronic appealed the ruling, arguing that the proposed letters, which had been drafted by the plaintiff's counsel, were designed to identify potential plaintiffs in violation of 21 CFR 20.63(f), which protects the names of patients and adverse event reporters.

The government, which had been invited to submit a brief on this issue by the court, then introduced the question of the applicability of 21 USC 360(i)(b)(3). The government brief explained that this section generally prohibits the use of adverse reports in civil actions, and on that basis argued that the defendant could not be compelled to write letters to the subjects of the MDRs. Ultimately, the appellate court indicated it "agree[d] with the government's analysis of this legislation" and vacated the trial court's discovery orders.

A similar result was achieved in Adcox v. Medtronic, a product liability suit in which the plaintiff alleged that the design of her pacemaker was defective. The plaintiff's counsel moved for discovery of information contained in adverse reports filed voluntarily by patients and their legal representatives and in voluntary and mandatory MDRs filed by doctors and device user facilities. The court granted the motion only as it related to complaints filed by patients or their legal representatives and stipulated that any information that would have identified these reporters had to be redacted. In denying the other part of the plaintiff's request, the court held that discovery of voluntary reports from doctors and user facilities is explicitly prohibited under 21 CFR 20.63(f), while discovery of mandatory reports is prohibited under 21 USC 360(i)(b)(3). In so ruling, the court explained that section 360(i)(b)(3) explicitly states that mandatory reports "shall not be admissible into evidence or otherwise used in any civil action involving the parties." The court interpreted "used in any civil action" to preclude pretrial discovery of mandatory reports.

Inadmissibility Based on Failure to Retain an Expert. McDaniel v. Merck (367 Pa.Super. 600, 1987) provides another basis to seek the exclusion of adverse reports. This product liability action was filed against Merck after Carol Lee, who had been taking Mefoxin, developed severe anemia and died. Her estate claimed, among other things, that the decedent's anemia was related to her use of Mefoxin. At trial, the plaintiff's counsel attempted to introduce adverse drug reports relating to Mefoxin. The court, excluded such evidence, however, and as a result the case was dismissed via nonsuit before the matter reached the jury. For various reasons, the appellate court ordered a new trial. In its ruling, the appellate court found that the trial court had acted properly in excluding the adverse drug reports because they were "sufficiently technical, [and] complex," but it also stated that should the plaintiff retain an expert to explain the adverse drug reports to the jury at the retrial, the reports should be "deemed admissible." Under this opinion, therefore, defendant companies can seek to exclude evidence of adverse reports at trial if the plaintiff fails to retain an expert to interpret the reports for the jury's benefit.

Other Arguments to Exclude Reports. Another potential basis for a defendant's argument against disclosure of adverse reports is the concept known as the self-critical analysis privilege. This privilege, which is recognized in some states, encourages individuals and businesses to candidly assess their compliance with regulatory and legal requirements without creating evidence that might be used against them by their opponents in future litigation. Thus, manufacturers may claim that MDRs are part of the analysis process and as such are not admissible at trial or subject to discovery.

Another argument in favor of exclusion is the fact that the admission of adverse reports may be more prejudicial to the defendant than the reports are probative to the plaintiff. That is, the existence of a large number of reports may imply that there is a defect in the product even when the reports offer no proof that a defect exists. Finally, because reports submitted by parties other than the manufacturer may be highly unreliable, companies may be able to argue for the exclusion of such reports on the basis that there is no proof establishing the truth of the information contained therein and thus the reports lack the requisite foundation necessary to be admitted into evidence.

The use of MDRs in civil litigation can be quite influential in the subsequent determination of whether a device was a contributing factor to the plaintiff's claimed injuries. Therefore, whenever such reports are sought in pretrial discovery or introduced at trial, the defendant should carefully review the particular circumstances of the case and put forth as many credible arguments as possible to encourage the court to exclude the reports. The circumstances of a given case may give rise to other viable arguments supporting exclusion in addition to those described above.

PLAINTIFFS' ABILITY TO OBTAIN INFORMATION FROM OTHER DOCUMENTS

In some litigation involving medical products, plaintiffs have been able to discover information about potential adverse reactions from documents other than adverse experience reports. For example, in Waelde v. Merck, Sharp, & Dohme (94 F.R.D. 27, 1981), a product liability suit filed in Michigan, the plaintiff specifically requested that the defendant produce its new drug application (NDA) for Clinoril; documents concerning postmarketing adverse reactions, premarketing studies, and animal tests that showed the effects of the drug on blood-forming organs of the body; and correspondence that discussed effects of the drug on persons receiving it with a particular focus on the blistering disease known as Stevens-Johnson syndrome. The defendant objected to the notice to produce, claiming that the contents of NDA files are trade secrets and are so treated by FDA.

In its response, the court held that trade secrets and confidential information in the possession of FDA, whether contained in NDA files or otherwise, are not available for public disclosure based on 21 CFR 20.60, 20.61, 20.100(17), and 314.14, but that not all the data contained in an NDA file are necessarily trade secrets or confidential commercial information. The ruling went on to state that certain categories of information may be disclosed after a drug application has been approved or if the information had been disclosed to the public previously. For example, safety and effectiveness data, which include "all studies and tests of a drug on animal and human subjects and all studies and tests of the drug for identity, stability, purity, potency, and bioavailability," may be released if they had been publicly disclosed previously or if certain other conditions are met. It should be noted that because this case involved a drug, not a device, 21 USC 360(i)(b)(3) was not asserted, leaving device manufacturers to wonder whether the court would have ruled differently had that statutory language been applicable.

METHODS TO LIMIT LIABILITY

Armed with the knowledge that adverse reports may ultimately need to be produced during the pretrial discovery process in civil litigation—or may even be admitted into evidence at trial— device manufacturers must prepare all submissions made to FDA with extreme care. The following suggestions are offered with the aim of limiting a company's liability in subsequent lawsuits.

In preparing MDRs, select the words used and the information contained in the report carefully. Avoid using words that describe the product in a negative manner, and be sure to include any available information that may establish a cause for the patient's problem other than a device-related adverse event. Remember that plaintiffs' attorneys may often cite phrases or sentences from a report out of context.

If additional steps need to be taken to establish the cause of a patient's problem, such as a review of medical records or product retrieval and testing, such steps should be set forth in the MDR so that anyone reviewing the report later will understand that the company had incomplete information at the time the report was filed. Any and all reliable information pertaining to the patient's history and the occurrences leading up to the reportable event should also be included in the report. In addition, if a report is based upon allegations in a consumer complaint or statements made by a plaintiff's attorney, be sure to note the source of the information being reported and make it clear to potential readers whether certain statements are admitted facts or mere claims or allegations.

Once an MDR has been submitted to FDA, make sure to perform the follow-up steps outlined in the report. Follow-up is essential for several reasons. Most importantly, it may reveal that the product was not involved in, or was not the cause of, the patient's problem. In such cases, the company should immediately file a supplemental report with FDA indicating this finding. If a supplemental report is not filed, the company may face the difficult task of explaining away the original report to a jury. Conducting follow-up also may be crucial to avoiding or limiting punitive damages awards. If a plaintiff's attorney is able to show that a company has submitted MDRs for problems associated with a product but has failed to undertake appropriate follow-up, he or she may be able to convince a jury that such conduct amounts to reckless indifference or willful and wanton conduct, which could result in the imposition of substantial punitive damages.

CONCLUSION

With the growth of the Internet, adverse event reports associated with medical devices have become easily accessible. With a few keyboard strikes, potential plaintiffs in product liability cases and their attorneys can access the FDA MAUDE database and find a profusion of reports pertaining to the product of interest or similar devices made by other manufacturers. At trial, plaintiffs will undoubtedly attempt to introduce such reports in order to influence the jury's perception of the defendant company and convey the not-so-subtle message that the mere existence of adverse reports shows that there must have been something wrong with the device. While grounds exist for defendants to argue that MDRs should be excluded from evidence, it is critical for manufacturers to understand that a growing number of courts are allowing such documents to be presented. Thus, it has become increasingly important to prepare submissions to FDA carefully. MDRs should include any information that may provide an alternative explanation for the adverse event and should outline any necessary follow-up steps. It is also essential that companies perform the follow-up measures needed to determine the cause of the reported problem. By taking these steps, they will be better prepared to face any civil lawsuit that may be filed later.

Anthony G. Brazil, Matthew L. Marshall, and Michele L. Abracen are attorneys with Morris, Polich, and Purdy LLP (Los Angeles).

Illustration by Janusz Kapusta/SIS



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Copyright ©2001 Medical Device & Diagnostic Industry

Recruiting Technological Talent

Originally Published MX January/February 2001

In a market filled with new and emerging technologies, medical device companies face continual challenges in sourcing, attracting, and retaining skilled personnel.

Joseph Mullings

In the United States, the national unemployment rate is currently at a record low of 3.9%—the lowest it's been, in fact, since the mid-1970s. Couple this with the strength of today's economy, the stock market rising to record levels, higher per-capita income, and a higher GDP than in years past, and employers find themselves having to offer more than just a competitive wage to attract and retain employees.

Such challenges are especially problematic for medical device companies, where access to specialized skills is increasingly important if a company is to keep pace with constantly changing and continually emerging new technologies. The demand for software developers, for example, has created a highly competitive market. In this area, medical device companies are facing real difficulties in gaining access to software engineers who have not made the jump to a dot-com.

FDA Guidance on Review Procedures Made Available

Medical Device & Diagnostic Industry Magazine
MDDI Article Index

Originally Published January 2001

FDA explains methods for identifying and responding to deficiencies.

Also:

  • Is FDA Biased against EU Devices?
  • SUD Reprocessing Enforcement
  • New Vascular Graft 510(k) Guidance

According to a November 10 guidance document, CDRH reviewers should use a four-part approach when identifying deficiencies during the course of a premarket approval (PMA) or 510(k) review. The guidance, Suggested Format for Developing and Responding to Deficiencies in Accordance with the Least Burdensome Provisions of FDAMA, says the reviewer should do the following:

  • Clearly identify the specific issue.
  • Acknowledge the information submitted and explain why that information did not adequately address the issue.
  • Establish the relevance of the deficiency to a PMA determination of "reasonable assurance of safety and effectiveness" or a 510(k) determination of "substantial equivalence."
  • Request the necessary additional information needed to adequately address the issue and, when possible, suggest alternate ways of satisfying the issue.

The guidance also provides models for reviewers to use. The following, excerpted from the guidance, should be used for a PMA deficiency related to determining reasonable assurance of safety and effectiveness.

(1) According to your Investigational Plan, your device is intended to fuse a bone fracture by the 24-month follow-up assessment.
(2) You reported that 55% of the study subjects had been followed for 24 months. We are concerned that a meaningful statistical analysis cannot be conducted on this study cohort.
(3) To thoroughly evaluate the effectiveness of your investigational device, the data set should be complete enough to have sufficient statistical power when compared to the control group.
(4) Please continue to follow your study subjects until you have sufficient statistical power at the 24-month follow-up point.

The document outlines a 510(k) deficiency in the following way:

(1) In your submission, you proposed to use your suture anchor for repairs of the rotator cuff and ankle ligament.
(2) You have submitted all of the appropriate testing with the exception of "pull-out" testing for the anchor. We believe that this testing is needed in order to fully characterize the performance of the device.
(3) "Pull-out" testing will help to ensure that the device can adequately handle the physiological loading experienced by the rotator cuff and ankle joints.
(4) Please provide a complete test report for this testing or justify why it is not necessary.

In addition, the guidance provides recommendations and a format for sponsors to follow when responding to deficiency letters. "In developing a response to a deficiency, industry should first provide an exact copy of the agency's question to remind the reviewer of the information that had been requested," the document says. If the deficiency is a follow-up question to an earlier deficiency, manufacturers should include both the original and follow-up question. Extensive responses should be organized for easy access with a table of contents, list of figures, and list of tables. "A description or justification of how the information adequately addresses the agency issue is advisable, unless obvious," the guidance adds. When referencing a standard in lieu of data, identification of the standard, its revision date, applicable sections, and any deviations from the standard should be included.

If a sponsor disputes a more-information request as not relevant to the regulatory decision, then the sponsor should articulate this position in the response, the guidance says. Alternatives can be provided by the sponsor "to optimize the time, effort, and cost of reaching resolution of the issue within the law and regulations. This could include alternative types of bench testing, proposing nonclinical testing in lieu of clinical testing, the use of standards, etc." The following is an example of a sponsor response to the above PMA deficiency example:

FDA requested that additional study subjects be evaluated at 24 months to ensure a meaningful statistical analysis at the 24-month follow-up point. To date, 30 additional study subjects have reached the 24-month follow-up assessment, bringing to 75% the percentage of study subjects that have been evaluated at 24 months. Please find on the following pages: a) an analysis of the 24-month data representing 75% of the study subjects, and b) a rationale supporting 75% as an adequate percentage of the study cohort to allow meaningful analysis.

The new guidance may be accessed at http://www.fda.gov/cdrh/modact/guidance/1195.html.


Is FDA Biased against EU Devices?

An analysis of 10 years of FDA warning letters with product detentions issued to medical device manufacturers in Europe—when compared with similar actions against U.S. firms—"demonstrates a remarkable bias against European device manufacturers," according to Washington, DC, attorney Larry R. Pilot (McKenna & Cuneo). Pilot says he made the analysis for a presentation he gave in October to the annual general assembly of Eucomed, the European medical device industry association, in Berlin.

In the 1991–2000 period, Pilot says, about 238 warning letters were received by 200 European manufacturers, of whom about 120 were notified that their products may be detained upon entry to the United States. This contrasted with the equivalent experience of U.S. manufacturers, Pilot says. In the 1991–96 period, they received 2995 warning letters but only 141 seizures and 32 injunctions. Unless there are multiple seizures or a contrary court order, Pilot says, a U.S. manufacturer whose devices are seized may continue to ship them.

Pilot contends that the heavy hand CDRH applies to European manufacturers is not shared by its drugs counterpart, CDER. Since 1991, FDA's drug center sent 18 warning letters to firms in Italy, Germany, France, and England, but only four of those contained an explicit reference to CDRH-type detentions, he told Eucomed. "If the FDA detentions represent a barrier to trade for which there is no justification that is reasonably related to safety or effectiveness, the EU and member states need to express their views."

CDRH director David W. Feigal told this writer that Pilot's assumption that device manufacturing is of equal quality throughout the world was "dubious." He said the fundamental issue was that while the agency does GMP inspections every three to four years in the United States, it only performs them every 10 to 12 years at foreign sites. "A much higher proportion of these are for-cause when we have such infrequent inspections," he said. "So the violation proportion would be expected to be higher. I think you could argue that the lower inspection rate abroad discriminates against U.S. firms."

Feigal also noted that Pilot's Eucomed presentation "was a mixture of time frames. He presented 10-year European data and five-year U.S. data. The 10-year data capture the Kessler years when the proportion of inspections overall with warning letters was 20 to 25%. Over the last five years the rate has been half that, so the way he showed the data was almost sure to show a lower rate. He also didn't have any denominators."

A critique of Pilot's charges prepared at Feigal's request by CDRH's Office of Compliance called them "misleading because of what he is comparing. He compares 120 import detentions over 10 years to 12 domestic detentions over an almost 10-year period." The critique went on to say:

Domestic detentions are not the same thing as foreign detentions. Foreign detentions are put into place and remain in place until the firm corrects the problems. They can be in place for years. On the other hand, the domestic detention is used very sparingly and typically only to gain control over product that we have reason to believe will be intentionally shipped by the affected firm or others. This action is usually taken when there are other compelling circumstances such as when the device represents a public health risk. In the last 25 years, we have taken probably no more than 50–60 such actions. Administrative detention also places a significant due process burden on FDA. For example, once we detain, the firm can appeal and within five working days of the appeal, FDA has to hold an administrative hearing (usually presided over by a regional director) and present our case. We've had a few hearings and it has been a significant challenge to meet these deadlines.

The office said automatic detentions are the only viable action the agency can take after issuing a warning letter to a foreign firm. "We consider that action to be a comparable enforcement tool to an injunction more so than a product seizure on the domestic side," the office said. An injunction, like a detention, immediately stops the firm from shipping product in U.S. commerce. "A seizure only captures specific goods that we identify are violative but does not specifically prohibit the shipment of new product (although we can and have amended seizures to injunctions when shipment continued after a seizure). When considering a detention, we should always ask ourselves whether the deficiencies would warrant injunction domestically." The statement said the office is doing this "fairly consistently."

On Pilot's additional charge that CDRH is more severe in its foreign warning letters than FDA's drug center is in similar situations, the CDRH Office of Compliance said it has asked the FDA Office of Regulatory Affairs for comparative data on this. It also noted that direct objective evaluation of Pilot's data was made difficult by missing data and old records in FDA's system that have not been computerized.


SUD Reprocessing Enforcement

CDRH's PMA enforcement deadlines for hospitals that reprocess single-use devices (SUDs) were provided in a recent agency letter. In it, CDRH listed its enforcement dates for premarket submission requirements: February 14, 2001, for all Class III devices; August 14, 2001, for all nonexempt Class II devices; and February 14, 2002, for all nonexempt Class I devices.

CDRH added that it intends to enforce the nonpremarket requirements (i.e., registration and listing; the quality system regulation; medical device reporting; labeling and tracking; and corrections and removals) by August 14, 2001. CDRH also stressed that hospitals should pay particular attention at this time to the regulatory requirements for GMPs: "Any hospital that intends to continue reusing and reprocessing SUDs will need to understand these requirements, which include process validation, corrective and preventive action, quality system inspection, and controls used for packaging, labeling, storage, installation, and servicing of all reprocessed SUDs."

Shortly after issuing the letter, CDRH posted to its Web site a list of SUDs (designated appendix A) known to be reprocessed, which was taken from the August 14, 2000, Guidance for Industry and for FDA Staff: Enforcement Priorities for Single-Use Devices Reprocessed by Third Parties and Hospitals.

The guidance can be found at http://www.fda.gov/cdrh/reuse/1168.html, and the appendix at http://www.fda.gov/cdrh/reuse/1168a.html.


New Vascular Graft 510(k) Guidance

FDA's latest views on special controls for vascular graft prosthesis 510(k)s can be found in a new agency guidance document. The guidance was "developed to support the reclassification from Class III to Class II for vascular graft prostheses of less than 6 millimeters in diameter . . . and also applies to vascular graft prostheses of 6 millimeters and greater diameter."

It reminds all manufacturers that they must comply with the quality system regulation and identifies a host of significant overall controls they should be aware of, from design controls to test equipment.

Key steps in process validation are also noted, including acceptance activities and preventative action, as well as certain risk factors—thrombosis embolic events, occlusion stenosis, and more. Their appropriate controls are also included.

The guidance may be accessed at http://www.fda.gov/cdrh/ode/guidance/1357.pdf

.

James G. Dickinson is a veteran reporter on regulatory affairs in the medical device industry.



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Copyright ©2001 Medical Device & Diagnostic Industry