Human factors and combination products: the need for therapy

Presentations at the recent IBC conference on Human Factors for Drug-Device Combination Products (May 19-20, Philadelphia) were just what I had expected – generally very well prepared and delivered, with some questioning and debate. Break times, however, were more like therapy sessions, with attendees discussing their latest confusions, frustrations and uncertainties concerning FDA review and approval.

As Human Factors (HF) specialists, we were delighted to see the FDA draft guidance of 2011: Applying Human Factors and Usability Engineering to Optimize Medical Device Design. It felt like the analytical and empirical approach we had been encouraging clients and colleagues to adopt had been validated, and that optimising the usability of devices and instructions would become the norm – with a transparent, well-understood path to regulatory approval.

So what happened?

In hindsight, the ensuing confusion and inconsistencies aren’t surprising. The guidance, written by highly experienced HF practitioners in CDRH*, was issued at a time of enormous growth in the development of combination products – particularly biologic drugs to be self-administered via injection – which are more likely to be reviewed elsewhere in the Agency. Some reviewers in CDER, CBER et al, with no background in HF theory or practice, have subsequently given apparently unreasonable or at times contradictory feedback on test protocols and submissions. There are now just two HF specialists in CDRH, and the task of internal education and communication around best practice in HF is enormous.

Anyone involved with US regulatory approval for combination products knows that these are ‘interesting times’. I went to the HF conference hoping to learn something that might help us to help our clients – and despite the general air of frustration and concern, some of the discussions were insightful and positive.

  • Understand the drivers: CDRH have a process for device optimisation, testing and approval; it’s founded in the HF discipline and they’ll review your arguments accordingly. Other departments, such DMEPA (part of CDER), have the ‘baggage’ of their experience. They’ve seen what goes wrong, and they want to use that information to improve your instructions for use (IFU) and other labelling. So let’s have really strong empirical evidence that shows how our IFU has been tested, iterated and optimised, and be really well prepared for any debate. Most importantly – a point stressed by several former FDA employees – let’s have the debate, and not just accede to all requests for change.As Lee Leichter (P/L Biomedical and chairman of the conference) said: “Sometimes companies have too little respect for the HF process. It’s OK to argue with the FDA!” It’s also worth starting the debate early – send the IFU to DMEPA before finalisation and seek their feedback. As more combination product IFUs reach the market, more post-market information on use error will be available and DMEPA will be bringing that to the table. Considering and testing their input early will be much easier than seeing it first time at submission.
  • Work as an industry: the challenges of being in this industry are forging bonds between competitors. This was the second IBC conference on HF for combination products, and HF is being debated within industry groups. The Combination Products Coalition is actively lobbying for clarification and consistency from the Agency, as former FDA staff acknowledge that understanding of HF in the FDA is extremely limited. We should work together wherever possible to establish best practice, and develop a consistent, evidence-based ‘HF narrative’ for our submissions.

We’re pleased to hear that the Office of Combination Products is working with CDRH, CDER and CBER to produce a new guidance document on HF for combination products. We’re hoping that industry input will help shape this to prioritise sound analytical and empirical HF assessment and a realistic approach to residual risk. There’s no publication date for this new guidance, though – and it’s likely to be a challenging project. In the meantime, we plan to continue to develop good HF arguments and stand by them. Anyone up for a support group?


*If you’re reading this you probably don’t need the glossary, but just in case:

CDRH: Center for Devices and Radiological Health
CDER: Center for Drug Evaluation and Research
CBER: Center for Biologics Evaluation and Research
DMEPA: Division of Medication Error Prevention and Analysis (an office of CDER)

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