Medical Device Validation: What You Need to Know and Why It is Important

 

The word Validation is most used in Pharmaceutical and Medical Device industry. It is such an important requirement that if not done, or not properly done, invite warning letter from US FDA while various punitive measure may emerge from other regulatory bodies involved in Pharmaceutical and medical device Industry.

Most of the warning letters are issued by US FDA is on validation aspect and it also becomes difficult to manage. Validation is operational activity where various process activities are done and data evaluated while regulatory people who are direct link with regulatory body knows the importance of validation but do no know much about this. Operational people though perform the validation but rarely challenged about the process followed and later gets challenged by regulatory bodies.

It is thus particularly important to know what validation is. There are several definitions so rather than going through definition of CFR 21,820 which is broad, let us understand the approach to be taken for validation.

Validation starts from process design stage to continuous commercial production which establishes that process is capable of delivering medical device in continuous manner with required quality and safety. Process validation involves series of activities taking place over lifecycle of product and process.

Though design and process validation are part of validation process both are different with different objective. We have seen above what process validation seeks similarly design validation means establishing by objective evidence that device specification conforms with user needs and its intended use or uses. Customer or user will just go by specification and user needs with intended uses. It is not role of user to verify whether validation activities are performed adequately. They are mostly reviewed by external body during audit or and complaint or adverse event occurs while using this device.

Validation and verification are also associated terms in validation activities but they are different. Verification means it meets each and every element involved in making of medical device meets their specification and standards thus the manufacturer must conduct intensive work of selecting vendor its qualification and inhouse testing before release for use. Validation requires that verification be complete before validation is taken up.

As good manufacturing company, system needs to be established in the organisation that validation protocol and report both are reviewed by team where R&D and regulatory people are also part of team. They should also undergo validation training though they may not have exclusive role of conducting validation which is usually done by production and quality. For many, validation can still be confusing because it has its own language and must be understood thoroughly. It is also recommended that protocols are not just reviewed by above team but debated and risk assessment approach is taken to ensure that nothing is missed out while finalising protocol.

Regulatory people are now stressing lot on risk involved and expect that manufacturer make thorough use of it while designing process and declaring intended uses. Sometime there are some unmet needs, this must be evaluated through risk analysis. FDA inspector also always looks at how the organisation has developed the risk management process and uses it towards many processes like validation.

There is new challenge in the industry with advancement of use of software in medical device. Software validation is thus new challenge. There are also internet connected devices which has risk of hacking. Here special knowledge is needed by software engineer to carryout software validation. Recent problems and experiences are emerging from software validation and each one needs to be looked in to toto and problem or risk if found must be resolved.

Similarly cyber security is also new concern and regulators are also looking at it very seriously. Though it may be difficult to understand but one can hack into pacemaker and negate the properties used to control such lifesaving drugs.

There are also challenges for validation of critical devices where its functioning are linked with life and death of user. Recent incidence of use of ERCP duodenoscope a type of endoscope, which resulted into spread of deadly bacterial infection resulted into death of people. This device was made more effective but in that design process they overlooked the cleaning effectivity (it become more difficult to clean).

Another technological development is 3 D printing, where end product may not be possible to be inspected or tested, high reliability remains on validation. The methods used in the validation must also be validated. Unlike pharma dosages where sterilised product is also tested, medical device after sterilisation cannot be tested and hence the sterilisation process validation must be made such a thorough for internal satisfaction but also to convince and explain how you have arrived at that conclusion.

Validation is complex exercise and should not be taken lightly. Just to site one example of warning letters of medical device company considering 2020 as review, “Failure to ensure that processes are adequately validated” repeat observation of 2013. “Failure to establish and maintain procedure for monitoring and control of process parameters for validated process” repeat observation of 2018. “Changes impacting device design are not verified or validated prior to implementation” new 2020 observation.

Some professional guidelines are available and firm may avail the special services from expert professionals rather than simply depend on internal resources.