Edward M. Basile and Elizabeth A. Schmidtlein
While the new regulations require manufacturers to file MDR reports for the same categories of device-related events as before, there are changes to the definitions of terms and to the standard for when device-related events are reportable. Summaries of the requirements are listed in Table I.
Table I. Summary of MDR reporting requirements. (FDA has stayed the denominator data requirement until completion of a pilot program, which is estimated to take 12 to 18 months; the annual certification requirement has been stayed indefinitely.)
|Reporter||Report What?||To Whom?||When?||Changes from 11/26/91 Proposal|
|Manufacturer||Annual certification.||FDA||Coincides with firm's annual registration date. (Requirement stayed.)||Form FDA 3381 developed for reporting.|
|Manufacturer||Baseline report to identify and provide basic data on each device that is the subject of an MDR report.||FDA||With 30-calendar-day report when device is reported for first time. (Denominator data requirement stayed).||Eliminated listing of remedial actions, and frequency and severity statement.|
|Manufacturer||Five-day report on events that require immediate remedial action to prevent an unreasonable risk of substantial harm to the public health and on other types of events designated by FDA.||FDA||Within five work days.||Replaced proposed 72-hour report of imminent hazard.|
|Manufacturer||Thirty-day reports of deaths, serious injuries, and malfunctions.||FDA||Thirty calendar days from becoming aware.||Eliminated monthly report and all associated requirements; replaced with 30-day report of each individual event; serious injury definition no longer necessitates "immediate" intervention, just medical or surgical intervention.|
Who Is a Manufacturer? The new regulations amend the definition of a manufacturer for the purpose of MDR reporting. Under the old regulations, manufacturers were defined as persons required to register under 21 CFR 807.20, including manufacturers of finished devices, repackagers/relabelers, device specification developers, and manufacturers of components and accessories to medical devices that are ready to be used and are labeled for commercial distribution.9 The new definition includes these same types of companies, with the exception of distributors, and adds U.S.-designated agents. Additionally, because the definition is no longer linked to FDA's registration requirements, FDA has stated that foreign manufacturers now meet the definition of manufacturer and therefore are subject to the MDR regulations.10
If a person or company is not considered to be a manufacturer under the new regulations, they may still be required to report adverse device events as a distributor under 21 CFR 804. (Because FDA's new regulations do not address distributor reporting requirements, those requirements are not addressed in this article.)
Standard for Reporting. The new regulations require manufacturers to file MDR reports for the same categories of events required under the old regulations: deaths, serious injuries, and certain malfunctions. However, changes in definitions of these terms and in the standard for reporting these categories of events necessitate changes in the analysis used by manufacturers to determine whether an MDR report is required.
The general standard for determining the reportability of adverse events is as follows:
An MDR report is required when a manufacturer receives or otherwise becomes aware of information, from any source, that reasonably suggests that a device marketed by the manufacturer: (1) may have caused or contributed to a death or serious injury; or (2) has malfunctioned and such device or similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur.11
As an initial matter, manufacturers should be aware of several important definitions and considerations. First, FDA has defined the term become aware to mean "that an employee of the entity required to report" has acquired certain information.12 This definition presents a problem, particularly for manufacturers with multiple divisions or operating units, because FDA has not defined an entity. For example, has the entity become aware of a reportable event when an employee of the manufacturer's catheter division learns of an adverse event involving a device from the dental instrument division? Particularly in multidivision companies or large corporations, it would make more sense to define an entity as a division or operating unit rather than as a company or entire corporation.
For the majority of MDR reports required under the new regulations, a manufacturer is required to file such a report when any employee of the firm becomes aware of information about an adverse event that is required to be reported under the regulations. FDA has stated that even independent service personnel contracted by manufacturers to service their medical devices are considered employees for this purpose.13 The agency expects manufacturers to train employees to recognize when they have received information on an adverse event that may be reportable and to know that this information must be forwarded to appropriate company personnel responsible for MDR reporting.14
The agency also defines the phrase information that reasonably suggests that a reportable event occurred. Under the new regulations, this phrase includes "any information, such as professional, scientific, or medical facts and observations or opinions, that would reasonably suggest that a device has caused or may have caused or contributed to a reportable event."15 Thus, the regulations provide a threshold to the quality of the information received that would trigger the need to report an event. The regulation further provides that
entities required to report under this part do not have to report adverse events for which there is information that would cause a person who is qualified to make a medical judgment (e.g., a physician, nurse, risk manager, or biomedical engineer) to reach a reasonable conclusion that a device did not cause or contribute to a death or serious injury, or that a malfunction would not be likely to cause or contribute to a death or serious injury if it were to recur. Information which leads the qualified person to determine that a device-related event is or is not reportable must be contained in the MDR event files.15
Thus, if a person qualified to make a medical judgment can rule out a device as a possible cause or contributing factor to an adverse event within the time frame for reporting, an MDR report need not be filed.
FDA also appears to be imposing a duty on manufacturers to obtain the requisite quantity of information to determine whether an event is reportable when information is received regarding an adverse device event. According to the agency, a manufacturer must evaluate each reportable or potentially reportable event in accordance with the good manufacturing practices (GMP) regulations that require manufacturers to conduct both failure investigations and complaint investigations.16 FDA contends that the failure to do so is considered a failure to comply with the GMP and MDR requirements for manufacturers.16 While FDA's connection here may be tenuous, this suggests that the agency expects manufacturers to conduct further investigations when they receive information about a potentially reportable event but lack adequate information to determine whether it is in fact reportable.
The regulations contain two other exceptions to the reporting requirements: an MDR report is not required, first, when the manufacturer determines that the information received is erroneous (in that a device-related adverse event did not actually occur), and, second, if the manufacturer determines that the device involved was manufactured by another manufacturer.17 In the latter case, however, the regulations require the manufacturer to forward the information about the event to FDA with a letter explaining that information regarding the event was sent to the firm in error and that the device in question was not manufactured by it.
As under the old regulations, there is no exception for serious injuries or deaths attributable in whole or in part to user error. In such situations, a manufacturer must submit an MDR report and should explain that the event was caused by user error. According to FDA, such reports may indicate that the device is misbranded in that it fails to bear adequate directions for use or adequate warnings, and may alert FDA to the need for improved labeling to prevent future injuries.18
Another consideration is that unlimited sources of information can trigger an MDR report. Thus, a manufacturer's employees must act on information received by telephone, fax, letter, oral statements to sales or service representatives, scientific articles, newspaper reports, lawsuits, or internal trend analyses. Information may come from device users, patients, attorneys, user facilities, distributors, or FDA. Consequently, manufacturers should train employees regarding the breadth of adverse event information sources.
A final consideration is that a manufacturer's obligation to report adverse events for devices it manufactured continues as long as it remains in business.19 Thus, even if a manufacturer discontinues making a device, it is still required to file MDR reports when it becomes aware of reportable adverse events involving a device it manufactured.
The MDR Decision Tree. When information about an adverse event has been received, MDR analysis is most easily handled by asking a series of questions.
Has a Death Occurred? The first question to ask is whether a death involving a device marketed or formerly marketed by your company has occurred. If the answer is yes, the next step is to determine whether the device may have "caused or contributed" to the death. This step contains two elements: "may have" and "caused or contributed." Keep in mind that a report may be required even if a manufacturer is not absolutely sure its device played a role in the death. According to FDA, the question to ask is whether there is a reasonable possibility that the device caused or contributed to the death.20 On this point, FDA cautions that manufacturers "should not assume unreasonable or unrealistic cause/effect relationships between devices and events. If the chance that a device may have caused or contributed to an event is very remote or unlikely, the event should not be reported."20
FDA has defined caused or contributed to mean
that a death or serious injury was or may have been attributed to a medical device, or that a medical device was or may have been a factor in a death . . . including events occurring as a result of: (1) failure; (2) malfunction; (3) improper or inadequate design; (4) manufacture; (5) labeling; or (6) user error.21
Thus, the manufacturer may ask a series of questions regarding each of these areas (e.g., Is there a reasonable possibility that a device failure was a direct or indirect factor in the death? Is there a reasonable possibility that a device design defect was a direct or indirect factor in the death? Is there a reasonable possibility that the device labeling was a direct or indirect factor in the death?). If the answer to any such questions is yes, an MDR report is required unless one of the exceptions previously discussed applies. FDA indicated in the preamble to the final rule that an adverse event is reportable even when a device indirectly causes an event, and rejected a suggestion that MDR reports be required only if the device is a significant factor in causing an adverse event.22
Has a Serious Injury Occurred? If a death involving a marketed device has not occurred, the manufacturer should ask whether an injury involving a marketed device or previously marketed device has occurred. This includes injury to a patient, health professional, or other person coming in contact with the device. If the answer is yes, the manufacturer must determine whether the injury meets the definition of serious injury. The new regulations have redefined the term to mirror the statutory definition at section 519(a)(2) of the FD&C Act. Under the new definition, which is narrower than the old one, serious injury means any injury or illness that is (1) life threatening; (2) results in permanent impairment of a body function or permanent damage to body structure; or (3) necessitates medical or surgical intervention to preclude such permanent impairment or damage.23Permanent is defined as irreversible impairment or damage to a body structure or function that is not trivial.
The third prong of the new definition no longer includes the concept of unanticipated temporary impairment. Also note that the new definition requires reports for temporary injuries if they are life threatening under the first prong of the definition. If the manufacturer determines the injury to be a serious injuryas defined under the regulationsthe analysis outlined above should be followed to decide whether the device may have caused or contributed to the serious injury. If the answer is yes, an MDR report is required. In light of the narrowed definition, manufacturers should reexamine previously reported serious injury events to determine whether they will need to be reported under the new definition.
Has a Malfunction Occurred? If a serious injury has not occurred, a manufacturer should ask whether a device malfunction has occurred. FDA defines malfunction as the failure of a device to meet its performance specifications or otherwise perform as intended.24 Performance specifications include all claims made in the labeling for the device. The intended performance of a device refers to the intended use for which it is labeled or marketed, as defined in 21 CFR 801.4.
A malfunction is reportable if the device or a similar device marketed by the manufacturer "would be likely to cause or contribute to a death or serious injury if the malfunction were to recur."25 FDA has stated that manufacturers must assume that malfunctions will recur. Therefore, manufacturers are required to assess only the likelihood of the malfunction causing or contributing to a death or serious injury upon recurrence. A report is required even if such a malfunction can be corrected during routine service or device maintenance.26
In the preamble to the final rule, FDA appears to suggest that a malfunction would be reportable if any of the following is true:
- The chance of death or serious injury occurring as a result of the recurrence of the malfunction is not remote.
- The consequences of the malfunction affect the device in a catastrophic manner that may lead to a death or serious injury.
- The malfunction results in the failure of the device to perform its essential function and compromises the device's therapeutic, monitoring, and diagnostic effectiveness, which could cause or contribute to a death or serious injury.
- The malfunction involves a long-term implant or device that is considered to be life supporting or life sustaining and thus essential to maintaining human life.
- The manufacturer takes or would be required to take action under section 518 (notification; repair, replacement or refund; recalls) or section 519(f) (reports of removals and corrections) of the FD&C Act as a result of the malfunction of the device or similar devices.26
Given that these five situations will not always meet the standard for malfunction reportability under the regulations, this is an area where further clarification from FDA is needed.
In FDA's guidance document for MDR reporting, the agency further advises that a manufacturer should consider it likely that a malfunction will cause or contribute to a death or serious injury if the malfunction has actually done so in the past. Whether these interpretations of the malfunction reporting requirements are entirely consistent with the regulation's language may be questionable. Device manufacturers should nevertheless be aware of the agency's viewpoint, since it reflects how the regulations will be enforced by the agency.
Manufacturers of investigational devices with an investigational device exemption (IDE) under 21 CFR 812 or 813 are exempt from the MDR regulations and subject to reporting requirements under the IDE regulations. However, in the preamble to the final rule, FDA stated that it considers devices with IDEs that are approved for export to be in commercial distribution and, therefore, subject to MDR regulations. As noted by the Health Industry Manufacturers Association (HIMA) in its comments on the final rule, however, FDA is authorized under section 519(a) of the FD&C Act to require MDR reports only for events involving marketed devices, and investigational devices are not "marketed" in the United States; indeed, manufacturers are prohibited from marketing or commercially distributing investigational devices in the United States. If devices are not in commercial distribution in the United States, the agency does not have the statutory authority to require MDR reports for them. Manufacturers should be prepared, however, to argue this issue with FDA if such reports are not made.