If your electric toothbrush suffers a mechanical failure, it’s annoying. But what if you’re a diabetes patient and your injector pen jams in the middle of your insulin dose? Or a COPD patient and your inhaler lets you down? The consequences can be devastating.

That’s why a ‘quality by design’ (QbD) approach is crucial when it comes to drug delivery device development – and why the US Food and Drug Administration advocates the adoption of QbD practices in pharmaceutical development.

But what is QbD in the context of drug delivery device development? It is an approach to product development that is based on an in-depth understanding – understanding of both the design space and the manufacturing processes to make the product. Indeed, I would add that an understanding of the way the product will be used is also part of the philosophy.

What does this mean to engineers on the ground – and how can you ensure the principles are translated down into the mechanisms when a product is designed? Below are the 3 rules to follow.

Understand the design space of your product

  • Outline the product quality characteristics – From a pharmaceutical stand point, it is fairly clear how this applies to the drug product. For a medical device, this relates to setting out the key functional requirements that will ideally be achieved to ensure the desired product performance.
  • Define moving parts – As soon as you have a concept for a mechanical system, determine which parts need to move – and when – to ensure you understand the full scope of the mechanical requirements. A block diagram showing end stops and interactions between components is a good way to establish how parts move.
  • Understand the forces or pressures in the system and the interactions between parts - Are the highest forces in the system governed by internal stored energy or by input from the outside? Outside forces, usually from a user, are uncontrolled and require an extra safety margin on product robustness.
  • Develop sound mechanisms – Might be obvious but is often done badly. You must ensure all the critical parts are well guided and controlled, taking into account aspect ratios and clearances between moving parts. This often requires ingenuity to meet space, cost and functional requirements while ensuring designs remain easy to manufacture and fit for purpose.
  • Analyse the design Test prototypes, generate tolerance analyses and understand design sensitivities. Do your mathematical models reflect real life results? If not, why not? Record all analyses so that they can be updated as the design develops. Risk assessments based on the severity of harm to patients can help identify critical parts of the design which will require more in-depth analyses.

       Understand the manufacturing process

  • Identify critical processes and material attributes – Identify potentially high-risk processes and think how changes in parameters could affect outcomes. Which properties of materials are critical to function?
  • Carry out experiments – Use multivariate testing, and Design of Experiments techniques as necessary, to establish the acceptable operating range of each critical parameter.  Use statistical tools to identify main effects and measure process capabilities.
  • Construct a control strategy – Sources of variability should be managed. Decide the extent of incoming inspections, in-process controls and batch release testing. Try to push controls upstream in the process flow.

Understand how the product is used

  • Formative user studies – Understand what set of features and device forms suit the user population. What is it about each feature that they like?

QbD is not a revolutionary philosophy but with support from regulatory bodies, it is here to stay, so drug delivery device engineers must become familiar with the approach.  As shown here, if you break it down into sections it will seem less daunting.

Author
Dominic Reber
Senior Consultant

Dominic is a Senior Consultant with over 20 years' experience in the development of medical devices