"Validation" is one of those terms that can be confusing for people new to medical device development.
This word, "validation", is used in (at least) three different contexts that are not necessarily related.
Let's take a look at each one of these in turn.
The regulatory lingo (in this example from FDA 21 CFR 820.3) for "Design Validation" declares that it is about “establishing by objective evidence that device specifications conform with user needs and intended use(s).”
It is a mandatory step in the medical device development process and if you are developing a medical device you will have to perform it at some point.
Design Validation is about proving that we have "built the right thing". This is often contrasted with Design Verification which is meant to prove that we "built the thing right".
The difference lies in that the latter checks that the device was designed/built according to specifications (which is very important), whereas the former checks that the device works as it is intended to work for the end-user, where the intention is documented in the User Needs and to some extent in the intended use.
As you can see, their regulations have foreseen that there might be a discrepancy between the intention and the specifications derived from the intention when developing the device.
It might be the case that the designers have not solved the user needs in a way that makes the device usable.
"Anecdata" provides endless examples of devices that are built "correctly" according to specs but turns out to be unusable/dangerous when used by the end-users in a real environment e.g. a glucose monitor alarm is not loud enough to be heard when traveling on a noisy bus.
Does this all sound like "usability" and "human factor analysis" activities to you? Then you are exactly right. Design Validation bears many similarities with usability activities. However, Design Validation also includes clinical tests in order to establish that clinical results correspond to expected levels are under intended use.
How do you know what to validate? Simply put, your User Needs. Therefore, it is important to define the User Needs in a manner that makes them possible to validate in a practical way.
Hence, the next time you write down your User Need, think hard about how you plan to validate them.
Design Validation is usually performed at the end of the design process, often after the Design Verification has been completed but before the medical device is transferred to production.
The instances of your medical device used in the validation should ideally exist in a production-equivalent state.
The Design Validation tests are generally performed by real users (doctors, nurses, patients, etc.), preferably in the actual intended environment (in the hospital, in the lab, in the ambulance, at home, etc.). The idea is to get as close as possible to "real use by real users".
Engaging this type of personnel can be both complicated and costly. It is therefore important to plan ahead and secure necessary resources (location, personnel, etc.) well in advance.
If the validation reveals serious flaws in the device, which requires re-design, severe consequences on development timelines and costs are at stake.
It is therefore important to involve real users throughout the design process and not only at the end.
Like all other Design Control stages, the Design Validation needs to be planned, which is documented in a Design Validation Plan, and then executed, which is often documented in validation test cases and results. The summary and outcome are documented in the Design Validation Report.
Traceability, consistency, and completion are of course important steps at this stage. Therefore, Aligned Elements is a great tool to use for these activities.
Process Validation most often means validation of your manufacturing process or parts thereof (although many other processes can be subject to this validation as well).
Or in FDA lingo, "process validation means establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications."
So why is this important? FDA requires (21 CFR 820.75) the "results of the process" ("results" = your medical device, "process" = your manufacturing process) to be "fully verified by subsequent inspection and test".
This is a way to say that each unit of your produced medical device must undergo "full" final testing and inspection and thereby we ensure that this particular instance of the medical device is safe for the user to use.
Now, there are cases when it is not possible to verify a safety-relevant characteristic of the device using testing and inspections, with the typical example of sterile devices as prime contender.
To verify a device being sterile, one would need to break the sterilization barrier (open the packaging) which would of course make the device non-sterile and therefore unusable/unsellable.
So when it is not possible to "fully" inspect and test the device, you can resort to process validation.
Thus, you employ process validation to check that the production process gives your medical device that particular, safety-relevant characteristic every time for every device.
Although ISO 13485 and FDA QSR 820:75 both list process validation as something very important, they are both a bit elusive on exactly which parts to validate. Basically, all the characteristics that cannot be fully covered in the final inspection are eligible to process validation.
For more information, the go-to document for Process Validation, although published in 2004, is the GHTF SG 3 NB 99:10:2004.
Generally, process validation is a pre-production activity, meaning that the production line is fully operational but you have not yet started production "for real".
Just like for Computer Software Validation, the legal manufacturer is the responsible party. However, it is not uncommon to outsource parts of the work 3rd party supplier or OEM manufacturers.
The "GHTF SG 3 NB 99:10:2004" goes a long way in describing the recommended documents. Very broadly speaking, there ought to be a Process Validation Plan, sections describing IQ, OQ, and PQ activities, and finally a Process Validation Report.
FDA explicitly requires the following from the validation, which ought to be properly documented:
This type of validation, often shortened as "CSV", concerns "data processing systems are used as part of production or the quality system" (from FDA QSR 820.70) or, as freely interpreted from ISO 13485:2016, all computerized systems being used in any of the processes regulated by the QM system.
Thus, it does not concern the software in your device. Rather it refers to computer systems used to design and produce your medical device. Aligned Elements is an example of such a system. Other examples include Excel Spreadsheets, e-QMS systems, measuring equipment in production, and so forth.
A multitude of regulations (FDA 820, FDA CFR 20 Part 11, ISO 13485, GAMP5) recognizes that patients/users are potentially exposed to safety risks if the computer systems employed in the design and production process of the device does not behave as intended.
Computer Software Validation is the suggested remedy to this perceived risk.
The input for the CSV is the User Requirements that should, as one might think, specify what the software under test can do, but rather what the organization plans/intends/want to do with it.
If you plan to use Excel for calculating a tolerance, then you the User Requirement should state exactly that.
It is recommended to take a risk-based approach to the testing and focus on the User Requirements that render the most severe risk impact if not adequately fulfilled.
So what about the validation of the software used in your device? Since you are then validating the design of your device, go check the Design Validation section.
CSV should be performed on the target computer system before it is put in use.
The responsible party getting the CSV activities planned and executed is clearly the organization that uses the computer system. However, the actual leg work is sometimes outsourced to 3rd party suppliers. Note that it is not mandatory for end-users to be involved in the actual testing.
How the organization performs CSV shall be defined in a company SOP. The SOP shall define which computer system types fall under CSV, how to plan and execute the CSV activities, and under which criteria a re-validation is applicable.
In its most basic form, a CSV plan should state the User Requirements which captures the intended use of the systems. The User Requirements are then tested in IQ, OQ, and PQs, and the results of these tests and, if applicable, deviations are summarized in the Validation Report.
As we can see, although these three types of Validation do not have a lot to do with each other, they are very important to Medical Device manufacturers.
A common trait for all activity groups is that they need to be properly documented, often following the same type of scheme, starting out with a plan document stipulating the "things to check for" (requirements), a number of test protocols to be executed, collection of objective evidence, traceability and report generation.
Aligned Elements is a perfect tool to structure and manage these types of validation activities and manufacturers can therefore benefit from Aligned Elements in all three areas.
For a free trial of Aligned Elements, start here.