If a drug delivery device fails a design verification test, the consequences can be far-reaching. If, for example, the volume of drug being delivered does not meet the specifications, it could put patients at risk as they would receive insufficient medication. Everything therefore has to be put on hold if the device does not work as intended and the root cause of the problem is unknown. If commercialization was imminent, that means lost revenue for the pharma company. And for patients it could mean delays in receiving a particular drug.
Immediate action can take the form of fish bone charts for root cause analysis (RCA), coupled with forensic analysis of the failed device samples. The suitability of the test methods needs to be verified, with the risk assessment revisited to check for potential known failure modes. Establishing how many test samples remain is crucial, as this may limit RCA activities. And manufacturing has to be put on hold until the root cause can be identified and fixed.
Next steps include evaluating which test methods to apply to new device samples to replicate and confirm the RCA. A complete test plan needs to be developed, covering everything from test methods and sample quantity to acceptance criteria.
Volume delivery could be affected by silicone and plunger performance, for example. This could involve characterizing silicone layer thickness and distribution as well as checking the break-loose and gliding forces as they may have changed due to aging or making last-minute process changes.
Even when prioritized internally, execution of the test plan may not be immediate. Project delays can be compounded by additional lead time to implement testing from the RCA. That’s where a full-service partner such as Stevanato Group comes into its own – with end-to-end experience of analytical and testing services ranging from design verification and device functionality testing services to customized product manufacturing. Our container closure testing capabilities span a variety of orthogonal approaches from break-loose force to particle analysis to glass delamination.
Working in conjunction with Stevanato Group Technology Excellence Center, the design, assembly process or settings can be changed, as required. The silicone recipe can be adjusted, for example, or the tip-cap assembly process optimized. New batches of devices can then be manufactured, based on the new settings – and the design verification tests repeated with the new devices.
But prevention is always better than cure – and a clear design verification testing plan at the start can avoid problems further down the line. Clear definition of the target product profile is vital, involving all device components – device, container, human factors, etc – as well as how they interact as a system. Robust and system-minded engineering and design verification tests need to be designed. These should include early feasibility and other phase-appropriate testing, and the tests should take into account the whole system and all stakeholders – internal and external.
Subject matter experts should be consulted for system components, and test plans should not be developed in isolation. Additional test samples should also be produced, in case the design verification testing has to be extended. Evaluating engineering tests early in the life-cycle management process is also important – looking at the transition from vial to syringe, for example, and screening tests when selecting container components.
Analytical services are all in a day’s work for the multidisciplinary team at Stevanato Group. So, help is at hand for every step along the way on the road to a successful commercial launch of a world-class drug delivery device.