What are the FDA software design validation requirements for software as a medical device (SaMD) and software in a medical device (SiMD).
If your product has software, then the investigator is instructed by the FDA QSIT Inspection Manual to consider reviewing software validation. Since inadequate software validation causes many quality problems with devices, you should be shocked if an investigator doesn’t review the software validation of a device containing software. Software-containing devices are also the only devices that manufacturers are required to submit a risk analysis for when submitting premarket notifications (i.e., 510k submissions).
Software Design Validation
Validation confirms that a device meets the user needs. Software validation is no different. Unfortunately, “software design validation” is also the term that we use to mean software design and development–which includes software verification activities and software validation activities. The software verification activities consist of unit testing, integration testing, and system testing. In software verification, we are verifying that each requirement of the software design specification (SDS) meets the requirements of the software requirements specification (SRS). In contrast, software validation involves simulated use or actual use testing of the software to confirm that it meets the user needs of the software. The “device” is the final complete software program in the operating environment in which it is intended to be used (i.e., operating system and hardware), and the “user needs” may be defined as system-level requirements in the SRS or as the intended purpose of the software in the software description.
To facilitate the validation of software, a traceability matrix is typically used to facilitate the construction of validation protocols. The traceability matrix will identify each requirement in the left-hand column of the matrix. The columns to the right of the requirements should include the following:
- hazard identification
- the potential severity of harm
- P1 – the probability of occurrence
- P2 – the probability of occurrence resulting in harm
- risk controls
- design outputs or references to the code modules that are responsible for each requirement
- references to verification and validation testing for each risk control
- estimation of residual risks
- risk/benefit analysis of each risk and overall risk
- traceability to information disclosed to users and patients or residual risks
Since the failure of each module can easily result in multiple failure modes, the above approach to documenting design requirements and risk analysis is generally more effective than using an FMEA. This approach also has the benefit of lending itself to assessing risk each time new complaints, service reports, and other post-market surveillance information is gathered.
The use of a traceability matrix also lends itself to the early stages of debugging software modules and unit validation. Each software design requirement will typically have a section of code (i.e., a software module) that is associated with it. That module will be validated initially as a standalone unit operation to verify that it performs the intended function. In addition to verifying the correct function, the software validation protocol should also verify that the embedded risk controls catch incorrect inputs to the module for that module. The correct error code should be generated, and applicable alarms should be triggered.
Finally, after each requirement has been verified, the entire software program must be validated as well. When changes are made, the module and program as a whole must be re-validated. Inspectors and auditors will specifically review changes made in recent versions to verify that revalidation of the entire program was performed–not just unit testing. You must also comply with IEC 62304, medical device software – software lifecycle processes. This is required for CE Marking as a harmonized standard and recognized by the US FDA. One of the implications of applying IEC 62304 is that you must consider the risk of using software of unknown pedigree or provenance (SOUP).
Software Risk Analysis
Each requirement of the software design validation requirements document will typically have a risk associated with it if the software fails to perform that requirement. These risks are quantified concerning the severity of harm and the probability of occurrence of harm. The likelihood of occurrence of harm has two factors: P1 and P2, as defined in Annex E of ISO 14971:2007 (see our updated risk management training).
P1 is the probability of occurrence, and for software, we have two factors. First, the situation must occur that will trigger a failure of the software. Second, does the software have a design risk control that prevents harm or provides a warning of the potential for harm? P2 is the probability that occurrence will result in harm; P2 has one factor. P2 is determined by evaluating the likelihood that failure will result in harm if the risk control is not 100% effective.
An investigator reviewing the risk assessment should verify that risk has been estimated for each software design requirement. There should be harm identified for each software design requirement, or the traceability matrix should indicate that no harm can result from failure to meet the software design requirement. Next, the risk assessment should indicate what the risk controls are for each requirement identified with the potential for harm. In accordance with ISO 14971, design risk controls should be implemented first to eliminate the possibility of harm. Wherever it is impossible to eliminate the possibility of harm, a protective measure (i.e., an alarm) should be used.
Each risk control must be verified for effectiveness as part of the software validation. Also, the residual risk for each potential harm is subject to a risk/benefit analysis in accordance with EN ISO 14971:2012, Annex ZA Deviation #4. The international version, ISO 14971:2007 (which is recognized by the US FDA and Health Canada), allows companies to limit a risk/benefit analysis to only unacceptable risks. Therefore, the European requirement (i.e., EN ISO 14971:2012) is more stringent. Companies that intend to CE Mark medical devices should comply with the EN version of the risk management standard instead of the international version for risk management.