For each complaint received about a prequalified in vitro diagnostic (IVD), the manufacturer should undertake a root cause analysis to determine whether complaints (including adverse events) can be verified and their root cause.

Root cause analysis is a structured process that can assist in identifying the factors or causes underlying a complaint. Understanding the contributing factors or causes of a system failure can help develop actions that sustain the correction

Depending on the findings, the risk management file should be updated. 

Following the investigation of a complaint, the manufacturer should consider whether to:

• take no action
• carry out immediate correction
• institute additional surveillance of the IVD in use
• undertake design modification, manufacturing process modification, etc.
• carry out field safety corrective action, e.g. recall or quarantine of existing stock, modify instructions for use or product labelling
• issue a field safety advisory notice, including urgent information to inform those responsible for the device or affected by the problem
• retraining of staff
• carry out other possible action, such as retesting of individuals and/or special monitoring of individuals previously tested using the affected IVD.

In certain circumstances, however, and in order to protect individual health and public health, corrective action may be need to be taken before the root cause has been definitively identified.

Corrective and preventive action

Corrective action/preventive action (CAPA) are improvements made to the manufacturing process as part of the overall quality management system to eliminate causes of nonconformities. Any process for CAPA should focus on the systematic investigation of discrepancies (failures and/or deviations) in an attempt to prevent their reoccurrence. The action taken should be dependent upon and related to the risk, size and nature of the problem and its effect(s) on product quality.

Corrective action should be handled according to ISO 13485:2016, Section 8.3 (Control of nonconforming product) and 8.5.2 (Corrective action), depending on whether a nonconforming IVD is involved or if action is taken to prevent recurrence of a nonconforming IVD.

Preventive action is a proactive process undertaken by the manufacturer to identify opportunities for improvement of the IVD in advance, before a problem is identified. Preventive action is taken when a potential nonconformity is identified as the result of lot testing, complaints from the field, and other relevant sources of information. Examples of preventive action include:

• reviews of contracts (with key suppliers), purchasing, processes, design
• software validation and verification for analysers
• supplier surveillance
• preventive maintenance and calibration controls for analysers
• management review of quality management system
• user training programmes, job aids
• trend analysis
• benchmarking.

Risk management file

The risk management file should be updated including with information about:

• risk analysis:
  • through identification of intended use and characteristics related to safety of IVD, identification of hazard and estimation of risk for the hazardous situation
• risk evaluation
• risk control
• risk control option analysis, implementation of risk control measures, residual risk evaluation, risk/benefit analysis, risks arising from risk control measures, completeness of risk control
• evaluation of overall residual risk acceptability
• risk management report
• production and post-production.