Integrating Human Factors from Day One: Q&A on Successful Validation for Combination Drug Products and Medical Devices

By Anthony Andre, PhD, CPE, Director, Interface Analysis Associates LLC

When developing a combination drug product or medical device that falls under FDA regulatory review, sponsors often recognize the importance of benefit-risk analysis around the drug or medical procedure, but frequently overlook the risks associated with insufficient human factors (HF) approaches to prove safety and effectiveness.

At Interface Analysis Associates (IAA), we have seen numerous countless sponsors lose one or more years on their timeline–or risk the entire project failing to receive approval/clearance–by not engaging a human factors program at the start of the project.

Below is a synopsis of a typical call or email from a potential new client, many of whom are located from outside the United States.

“Hello. We have developed a new combination drug product (or medical device/system) and need to perform a human factors validation as quickly as possible. Are you available to perform this service and can you send us a quote?”

And when I ask about human factors activities prior to them contacting IAA, the answer is almost always, “We have conducted internal formative HF studies and feel the product is ready for validation.”

Perhaps not surprisingly, I don’t typically prepare a proposal for a human factors validation study in response to this type of request. Below, I will explain why through a series of key Q&As on avoiding pitfalls to a successful FDA validation program by engaging an insightful and successful HF journey.

Q: What is the main misconception regarding HF validation for FDA-regulated devices?

A: The industry understands that the FDA requires HF validation. However, the main pitfall for sponsors is placing HF activities at the end of the development timeline, rather than incorporating them throughout the process.

Too many sponsors view HF validation as a final, stand-alone activity; something they can check off a list. However, human factors are a vital part of the product development process. Sponsors not only need to conduct an HF validation study at the end of their program development, but they also need to succeed in it.

Simply stated, at the time of conducting an HF validation study, the human factors attributes of the product are set in stone. The application of human factors science always comes before the validation study, not during it. Human factors engineering can positively influence early decisions about a device, ensuring safe and effective product interaction with minimal residual risk to the user.

Q: Why is this misconception so pervasive?

A: The FDA offers guidance around HF and usability engineering to confirm that intended users can use the device safely and effectively. There is naturally a great deal of focus on submitting the final HF report to achieve FDA approval, so the emphasis for some predictably shifts to the endgame rather than the entire process or journey.

And to be honest, the FDA contributes to this problem by overemphasizing the HF validation study in their responses to sponsors. Remember, the real goal is not just to submit a validation study report to the FDA, but to demonstrate proper inclusion of HF throughout development in the context of use-related risk management.

I always encourage sponsors to incorporate HF from the start of the development journey, leading up to the final HF validation study and culminating in a successful FDA review. Invoking HF early saves time and money, and at the same time, increases the chances of success in the later HF validation study.

Q: Why should sponsors not just jump into a final HF validation study?

A: A stand-alone validation study at the end of development is missing the entire HF journey. The FDA will review the study report and see gaps where usability inputs are missing, such as:

• HF experts weren’t engaged to infuse the science of HF into the product interfaces
• No formative studies on use-related risk were conducted
• No assessment of known problems in similar products
• Absence of iterative design mitigations to enhance usability and user experience

Beyond these gaps, rest assured that without these HF activities being incorporated into the product design process, sponsors cannot expect a comprehensive validation study of the HF properties of their product offering to be successful.

Think about this example: A company based outside of the United States (OUS) has developed a new medical device. The interfaces include the device itself, with controls and displays, the instructions for use (IFU), the packaging, and device labeling. No professional human factors or usability engineer was involved in the product design process. No usability testing has been done with US citizens or by an HF consultancy in the US. Human factors science and principles were not used to drive the product design, interface design, IFU, or other elements of the product. Yet, this company believes it’s ready to pass a comprehensive HF validation study for which their approval will be largely based!

Simply stated, the HF validation study should not be the first time you learn how US users interact with your product under the lens of human factors. This is especially true of more complex products, and of products created outside of the United States. Instead, the validation study should be the culmination of iterative efforts to evaluate and optimize product use by intended users.

Q: What should sponsors know about the FDA’s HF guidance and requirements?

A: The FDA guidance offers only general building blocks for your user journey. On top of these are evolving interpretations and practical applications. Viewing dozens of FDA responses per year, we have access to the metadata on how the FDA interprets its own guidance from year to year, and how it applies this guidance to various product categories and specific products. We also see the individuality between reviewers.

A sponsor should rely on their HF expert’s expertise for relevant and timely insights that can smooth the regulatory takeoff, journey, and landing. Understanding these nuances will pay off in terms of developing effective strategies towards a successful HF review the first time. Infusing human factors early into your product development process, rather than late, will save headaches, time, and money as you position your product for marketplace launch.

Q: Does HF analysis have to be a long and expensive process?

A: Absolutely not! The timeline could be as short as three or four months, if you take advantage of efficiencies from the start. For example, when developing a drug to be delivered via an autoinjector, our vast expertise with this type of combination drug product allows us to streamline the process and rapidly move from evaluation to validation. If a novel device is considered, by integrating human factors into the design process from the start, much time and hassle can be saved.

Q: What should sponsors know to avoid surprises when applying HF to their product development programs?

A: First, understand that the FDA requires validation based on first-time use. If you think back to the first time you used a new smartphone or got into your new car, there likely was a learning curve. Human behavior experts can help address these learning curves and ensure devices are safe and effective from the start. HF services help clinical trials run more smoothly with better-designed devices, clearer instructions, and more effective patient training – leading to better outcomes.

Another aspect to consider is the need to evaluate every step of the user experience—from opening the package and reading the instructions, to using the device for the first time and storing it. There may be 10 different metrics for which HF experts must ask, “What could possibly go wrong?” Behavioral scientists can pinpoint each step, document every imaginable problem, and troubleshoot all factors to mitigate risk.

Additionally, be aware that the FDA requires documentation of close calls and difficulties that occur during first-time use. Your HF experts will understand the product and process to ensure best practices for success. You can and should optimize human factors for both safety and user satisfaction.

Conclusion

For combination drug products and medical devices alike, it is critical to build human factors inputs into the entire development process to ensure patient safety and effectiveness, and to prevent issues later when attempting to validate the product’s human factors qualities. This approach reduces risk, optimizes your timeline and investment, and positions your product for a successful validation and market launch. Planning for successful HF validation from the outset will help you tell a robust HF story in your report, leading to a successful FDA review. 

To learn more about how Interface Analysis Associates’ human factors services can help gain FDA approval or clearance for your combination drug product or medical device, please contact us.

Dr. Andre and his staff have been at the forefront of the combination drug product and medical device Human Factors movement, having managed and executed hundreds of HF programs for pharma, biotech, and medical device sponsors all over the world. IAA’s 32 years of healthcare human factors experience is incomparable. Dr. Andre has provided human factors training to the FDA reviewers, and for 10 years moderated an annual FDA-Industry human factors workshop.