Adverse Event and Malfunction Reporting

Safety reporting is the mechanism by which the regulatory system learns anything after approval. Premarket studies enroll a limited number of subjects under controlled conditions; the market enrolls everyone. The duties that follow are allocated by role, and the same event generates different obligations for the hospital that observed it, the importer that supplied the product and the manufacturer that made it.

Drug reporting and the two words that control it

Postmarket drug reporting turns on two defined terms. An adverse drug experience is serious where the outcome is death, a life-threatening experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability or incapacity, or a congenital anomaly, or where medical or surgical intervention is required to prevent one of those outcomes.

An experience is unexpected where it is not listed in the current labeling. This is a documentary test rather than a clinical judgment. A reaction well known to physicians is unexpected if the labeling does not list it, and a reaction that surprises everyone is expected if the labeling does. Where an experience is both serious and unexpected, an expedited report is required; the remainder are captured in periodic reports.

Applicants must also promptly investigate reports they receive, whatever their source, and must maintain records of them. Reports arriving from foreign markets, from published literature and from postmarketing studies all count. What the agency assembles from these reports is often the origin of a change of the kind described in labeling content and how it is changed.

Device reporting and the malfunction trigger

Device reporting adds a category with no drug analogue. A manufacturer must report where it becomes aware of information from any source that reasonably suggests a device it markets may have caused or contributed to a death or serious injury. It must also report where a device has malfunctioned and the device or a similar device would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.

Serious injury has its own definition and it is broader than the word suggests. It covers an injury or illness that is life-threatening, that results in permanent impairment of a body function or permanent damage to a body structure, or that necessitates medical or surgical intervention to preclude permanent impairment or damage. The last branch captures a great many events that resolved well precisely because someone intervened, and firms that report only outcomes rather than interventions miss them.

That second branch is prospective. No one need be harmed. The question is whether recurrence of the observed malfunction would be likely to produce a serious outcome, which requires an analysis rather than an incident. Firms that report only when someone was hurt are systematically under-reporting, and this is among the most common reporting findings on inspection.

Who reports what, and to whom

The device rules distribute the duty across three roles. A device user facility, meaning a hospital, ambulatory surgical facility, nursing home or outpatient treatment facility, reports a device-related death to the agency and to the manufacturer, and a device-related serious injury to the manufacturer, or to the agency where the manufacturer is unknown. Facilities also submit an annual summary of the reports they made.

Splitting the duty this way has a purpose. The user facility sees the patient and the circumstances but does not know the device's history across the market. The manufacturer sees every report about that device but not the clinical context of any one of them. Requiring the facility to report to both the agency and the manufacturer means the manufacturer learns of events its own complaint line would never have received, and the agency learns of events a manufacturer might not have forwarded.

An importer reports deaths and serious injuries to the agency and to the manufacturer, and reports malfunctions to the manufacturer. A manufacturer reports deaths, serious injuries and reportable malfunctions to the agency. Each report must contain the information the regulation specifies, and supplemental reports follow when significant new information is obtained.

How reporting connects to everything else

Reporting is not a standalone function. It begins in complaint handling, where each communication alleging a deficiency must be reviewed and evaluated to determine whether it describes a reportable event, and that evaluation is part of the system examined in quality systems and inspections. A firm whose complaint procedure does not address reportability produces two findings from one gap.

Reporting also runs into field action. Where the event indicates a problem with distributed product, the manufacturer is likely to be simultaneously deciding whether to remove or correct it, an obligation with its own reporting duty described in recalls, corrections and removals. The five work day report exists precisely for the case where remedial action is needed to prevent unreasonable risk of substantial harm.

During development the same information travels a different route. Serious and unexpected suspected adverse reactions are reported to the agency and to participating investigators on the expedited schedule set out in the investigational regulations, with the shortest deadline reserved for reactions that are fatal or life-threatening, a duty described alongside the rest of the investigational obligations in the investigational application and the clinical hold. Accumulated safety information from either period is what supports, or undermines, the claims made in the application and its review cycle.