To perform comprehensive Design Verification Testing (DVT), under cGxP controls, for a breath-actuated inhaler focusing on the mechanical function, performance, and reliability of the product, in line with the latest standards and regulations.
We performed functional analysis of numerous inhaler samples throughout their 120 dose use life. We tested up to 8 key functional requirements on each actuation per inhaler sample. To achieve this we developed and validated over 30 test methods and commissioned and qualified 2 complex semi-automated test instruments which were used in-house exclusively throughout this programme.
We tested more than 1,000 inhaler samples through more than 120,000 actuations. The evidence we gathered and reported for this DVT programme supported the launch of the product in Europe in September 2018, which is now available as an asthma treatment for adults and adolescents.
At a glance
Inhalation drug delivery
Team staff on project
Design verification testing for an inhaler
Mundipharma partnered with Team Consulting for the industrialisation, scale-up and DVT of their novel breath-actuated pMDI. The product submission had already been filed so one of the biggest challenges was to work within full cGxP controls, which meant that scope for change was extremely constrained.
In addition to the DVT programme, we also carried out tolerance analysis and mathematical models to build a picture of how well the device was performing. We also carried out testing programmes to de-risk the design and optimise performance.
As the data was to be used to support a product launch, the DVT programme had to produce detailed high integrity documents to provide a sound rationale for the product’s specifications, DVT approach and analysis strategy, all in line with current EU regulations, ISO standards and industry Best Practices.
A unique testing challenge
With up to 8 functions requiring measurement on each actuation and throughout each device’s 120 dose use life, the relative complexity of this inhaler presented a testing challenge.
We had to meet specific statistical sampling requirements, resulting in the need to test 1000s of samples ‘through life’ according to the requirements specified in ISO 20072.
To overcome this challenge we designed, commissioned and validated bespoke semi-automated test instruments which became the ‘work horses’ of DVT, outputting comprehensive data for detailed analysis.
All testing work was performed in Team’s laboratory facilities capable of maintaining the closely controlled ISO 20072 ‘standard atmosphere’ test environment needed for all inhaler testing.
The amount of information we needed to gather and analyse during DVT was daunting and would not have been possible with traditional, manual testing.
Through this approach, we were able to gather large volumes of detailed information. This, coupled with the insights from our team of technicians and analysts, allowed us to understand and analyse key inhaler functions with a high level of confidence.
Jamie Greenwood, Head of Device Testing
Environment, health and safety matters
Due to the potent nature of the drug and the numerous doses needed to be fired for testing, we had to implement containment measures to avoid exposure. This included containment measures and monitoring, to ensure the health and wellbeing of our staff throughout testing.
A cross discipline involvment
The testing work required great flexibility so we emphasised co-location of teams and cross-discipline involvement. Our experienced device testing technicians witnessed the function of many 10s of devices a day during high-volume testing.
Their knowledge and insights from being ‘at the coal-face’ were critical to identify performance issues early-on, which was pivotal for test methodology refinements.
The familiarity of the device characteristics by the analysts brought to the front the more subjective observations, the sounds and the feel of the device, which helped target specific solutions to optimise manufacturing parameters at the component level, thus ensuring capable moulding and assembly processes leading to a robust product.
Nick Salt, Device technical lead
Automated dose counter assessment
The product includes an integrated mechanical dose counter, indicating the number of puffs remaining. This information needs to be presented clearly and correctly to end users, so we also had to test the reliability of the dose counter.
The challenge was to develop a method which allowed for the dose counter to be assessed in an objective way and remain compliant to current data integrity requirements. To achieve this, the dose counter display had to be captured by pictography after every actuation.
To save time, we automated this process. The result was a validated methodology, built on our detailed understanding of the inhaler functions, which produced comprehensive and robust data.