Post-market Surveillance for Prequalified In Vitro Diagnostics

Manufacturers of WHO-prequalified in vitro diagnostics (IVDs) must follow WHO guidelines for post-marketing surveillance as part of their on-going commitment to WHO prequalification. In order to be able to do this they must be familiar with relevant international standards, including ISO 9001:2015 Quality management systems Requirements, ISO 13485:2016 Medical devices Quality management systems Requirements for regulatory purposes and ISO 14971:2019 Medical devices Application of risk management.

Key responsibilities

Manufacturers of WHO-prequalified products must carry out the following post-market surveillance obligations: These consist of:

  • Encouraging users/customers to report any feedback including all adverse events and/or product problems experienced during use of a prequalified product, as soon as they become aware of these using a standardized form such as the WHO customer feedback form included in WHO's guidance document for post-market surveillance of IVDs. 

Adverse events may include:

  • death of the patient, end-user or any other person
  • serious deterioration in the health of the patient or end-user
  • a false negative result
  • a false positive result
  • non-reproducible results
  • high or low readings
  • high or low test results.

Product problems may relate to:

  • packaging: damaged, defective or tampering suspected
  • labelling: instructions for use inadequate or illegible
  • sampling: device doesn’t collect/transfer specimen
  • liquid: leak, splash
  • data: capture, display or storage affecting product functionality
  • software: network, programme, algorithm or security affect product functionality

or be:

  • mechanical: misalignment, jam
  • electrical: unable to charge, power loss or fluctuation
  • environmental: noise, temperature, humidity/ moisture, fungal/bacterial growth or dust, affecting product functionality

or the device may:

  • fail to calibrate
  • generate an increased rate of invalid or unreturnable test results
  • generate obviously incorrect, inadequate or imprecise results or readings
  • be unable to obtain a reading.
  • Ensuring their economic operators are aware of their post-market surveillance obligations and timelines.
  • Notifying the relevant regulators of specific complaints as defined in national guidelines.
  • Notifying WHO of specific complaints relating to a WHO-prequalified product that have affected (or could have affected) the performance of the assay, the quality of the assay, the safety of the individual being tested/of users of the assay/of any person associated with the assay. Specifically:
  • Manufacturers should report events/observations that represent a serious public health threat immediately and not later than 48 hours to WHO (e-mail: rapidalert@who.int).
  • Other serious events/observations including death, or serious deterioration in health that has occurred for the patient, end-user or other individual, should be reported as soon as possible but no later than 10 days by manufacturers to WHO (e-mail: rapidalert@who.int).
  • Other serious events/observations including death, or serious deterioration in health that might have occurred for the patient, end-user or other individual, should be reported as soon as possible but not later than 30 days by manufacturers to WHO (e-mail: rapidalert@who.int).
  • Any complaints that require a field safety correction action, such as withdrawal of the relevant IVD from sale or distribution, physical return of the IVD to the manufacturer, IVD exchange, destruction of the IVD, IVD modification/s or additional advice provision to customers to ensure that the IVD continues to function as intended should be reported as soon as possible.
  • All feedback (including serious, moderate and mild complaints, as well as technical service calls, etc.) should be reported to WHO annually, including the effectiveness of Field Safety Corrective Action Reports (FCSAs), as a periodic summary report.

Manufacturers' investigation reports should be submitted to WHO (and to national regulators) using the WHO manufacturer investigation report form included in WHO's guidance document on post-market surveillance for IVDs. Adverse Event Terminology and Coding set down by International Medical Device Regulators Forum must be used to standardize documentary evidence.

Complaint handling and vigilance

Manufacturers are obliged to review all customer feedback using risk management principles and determine action to be taken. The following documentation should be retained by the manufacturer:

  • initial/follow-up/final manufacturer investigation reports
  • root cause analysis reports
  • corrective action/prevention action plans
  • FSCAs and Field Safety Notices
  • annual post-market surveillance summary reports.

Vigilance information exchange with NRAs should be managed according to national regulations. The NRA of the country in which the complaint is made may have its own reporting templates and specific deadlines. These should be adopted, where appropriate. If no guidance is available from the relevant NRA(s), annexes in WHO's guidance for post-market surveillance of in vitro diagnostics should be used.

Disclaimer

The act of reporting a complaint is not an admission of manufacturer, user or patient liability for the event or its consequences. Submission of an adverse event manufacturer investigation report does not, in itself, represent a conclusion by the manufacturer that the content of this report is complete or confirmed, that the IVD(s) listed failed in any manner. It is also not a conclusion that the device caused or contributed to the adverse event. It is recommended that reports carry a disclaimer to this effect.