The 21 CFR 803 is the section of the Code of federal Regulations which regulates the medical device reporting (MDR) according to FDA regulation. We have been trough the requirements related to vigilance reporting according to EU MDR 2017/745; in this article we will go through Complaint management, that is one of the key activities of the Quality Management System, based on 21 CFR 820 as it has a direct impact on the safety of the device on the market.
FDA can receive reports related to medical device adverse events from the following entities:
- Manufacturer of medical devices
- Importers
- Device User Facilities
When an organization communicates an adverse event to the FDA, it has to be kept in mind that a report does not constitute an admission that the device, reporting entity, or the entity’s employee caused or contributed to the reportable event.
When an event is considered reportable to FDA based on 21 CFR 803 requirements?
According to the requirements mentioned in Code of Federal Regulation 21 CFR 803, an event is considered reportable when:
- a device may have caused or contributed to a patient death or serious injury
- a malfunction of the device did occur and it would be likely to cause or contribute to a death or serious injury if the malfunction were to recur
It is very important to clarify specific wording which is used in the test above.
Caused or Contributed: 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 or serious injury, including events occurring as a result of: (1) Failure; (2) Malfunction; (3) Improper or inadequate design; (4) Manufacture; (5) Labeling; or (6) Use Error.
Serious Injury: it is an injure that: 1) Is life-threatening; 2) Results in permanent impairment of a body function or permanent damage to a body structure; 3) Necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.
Malfunction : The failure of a device to meet its performance specifications or otherwise perform as intended. 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 the device is labeled or marketed.
What are the repeatability requirements according to 21 CFR 803?
Different timelines shall be respected by the manufacturer when reporting adverse events to the agency. Specifically, there are mainly two scenario:
- Individual adverse event shall be reported no later than 30 calendar days after the day the manufacturer becomes aware of a reportable death, serious injury, or malfunction.
- Individual adverse event reports no later than 5 work days after the day that the manufacturer become aware of:
- (i) A reportable event that requires remedial action to prevent an unreasonable risk of substantial harm to the public health, or
- (ii) A reportable event for which FDA made a written request.
Few words shall be spent on the so-called “Reportable Malfunction”. This is the case where a malfunction did occur to a device and this malfunction would likely to cause death or serious injury if it were to recur. The interpretation of this point is not straightforward, as it is not simple to define if a specific malfunction is likely to lead to DSI (Death/Serious Injury). Of course, risk analysis could definitely help but it does not answer all the questions. For medical devices which are well established on the market and for which extensive post-market surveillance data are available, a statistical approach based on PMS data could be used to define if a malfunction is likely to cause to DSI or not. For example, one could argue that if in the last 3 years, considering the number of sold devices, the specific malfunction did not cause any serious consequence to patient, user or any other person, this malfunction is not likely to cause death or serious injury. This is of course just one of the approach that could be used to support repeatability devision of specific events involving medical device.
Requirements for the Electronic Submission of Medical Device Reporting
If in the past it was somehow possible to send paper version of Medical Device Reporting to the FDA, currently, since 2015, eMDR (Electronic Medical Device Reporting) is mandatory for manufacturers and importers.
FDA published a specific guideline on Medical Device Reporting process to clarify all the aspects related to the submission of MDR files to the agency.
The submission of electronic medical device reporting is performed through a system called Electronic Submission Gateway (ESG). The FDA ESG is the central transmission point for sending information electronically to the FDA. ESG then relays the product specific report to the appropriate FDA center. All the submitters must have a digital certificate associated to their ESG account.
To further help manufacturers and importers in the preparation of eMDR, the e-submitter tool has been developed. Basically this software generates an electronic version of Form 3500A in zip file format that is sent via ESG.
Complaint Files and Medical Device Reporting according to 21 CFR 803
The MDR events is obviously link to complaint management. In general all the reportable events are associated to a specific complaint which needs to be documented, investigated and analysed from risk management standpoint. There are specific requirements related to record keeping changes associated to the Medical Device Reporting Process: specifically, the section 21 CFR 803.18 requires keeping copies of all reports submitted to FDA, whether paper or electronic. Moreover, the same section 21 CFR 803.18 requires the retention of all acknowledgments that FDA sends to the manufacturer or importer.
What the Agency does with the MDR Files received
All the reportable events submitted as per 21 CFR 803 are reviewed by the agency which might ask for further information or clarifications. Moreover, all the events are inserted in a specific public database called MAUDE (Manufacturer and User Facility Device Experience). It is always possible to have an overview of the adverse events or reportable malfunction which are associated to a specific medical device.
