FDA Sees “Extraordinary” Interest in Human Factors Guidance

Approaching the second anniversary of its issuance, and at least the third decade of its widely recognized importance, FDA’s draft guidance on Applying Human Factors and Usability Engineering to Optimize Medical Device Design has attracted an “extraordinary” number of comments. That’s the assessment CDRH combination products human factors specialist QuynhNhu Nguyen made to IBC Life Sciences’ Human Factors for Drug-Device Combination Products conference in May.

Some of the comments are similar to each other, and others are conflicting; some are easy to address and others will require discussion with management on policy, Nguyen said. She also mentioned that FDA staff is working to get the guidance out as soon as possible. In FDA parlance, especially in these post-sequestration times, this means nobody has any idea when it will see light of day as a final document.

In the meantime, Nguyen indicated there is much that sponsors need to understand about human factor evidence for combination products, including the fact that combination products (e.g., pre-filled syringes, pen injectors, autoinjectors, inhalers, and transdermal patches) are among the most complicated products FDA reviews, because they involve multiple Centers at the agency and present regulatory challenges, and also because they can cause different opinions in the review process.

For the pharmaceutical, Nguyen acknowledged, it’s a paradigm shift for companies to move from statistically and clinically-driven studies to human practice validation studies that are focused more on individual errors, their root causes, and context. “Of course we do see objective data… in the validation studies,” she said, “but one of the critical types of data that we look at…is the subjective data that you collect from your test participants….So, the comments and the subjective information, [that is, the participant] perspective is very important.”

Nguyen added that it’s also important to follow up with those test participants on how they committed the error, whether they were aware of it, and if the design or the instructions helped them realize the error.

Nguyen warned the audience that when a device component has a potential risk for medication errors or dosing errors, the Center will look at whether there is human factors information in that submission: “And if we determine from the risk analysis standpoint that the study is necessary, even though the manufacturer may say otherwise, we are going to be asking for that.”
She also said that for human factors studies, the focus is more on the use error observed, and CDRH doesn’t consider a 10% error rate as evidence of safety and effectiveness. “We are going to focus more on that 10% and focus more on the analysis that you provide for that 10%,” and on whether additional mitigation and a revaluation study are needed.

However, she noted that in general, “Depending on the type of errors that you observe and the risk associated with those, you might be able to justify that those errors are reasonably acceptable and that the benefit of having the device on the market outweighs the risk of that type of use error.”

For human factor tests on combination products, Nguyen said it’s most likely a sponsor will be looking at groups of patient users, of healthcare providers, and of family caregivers. “Special considerations should be given to pediatric and other types of populations with special needs or conditions associated with the disease states that need to be addressed,” she said.

The Center generally recommends that these studies be done on U.S. populations, she explained, because other populations may not be representative of the U.S. people in terms of labeling, typical conventions, units, language, and practice of medicine.

If a patient will get only minimal training for a product, such as a discussion in the doctor’s office, Nguyen said it might be helpful to justify the types of risk associated with that training. “We leave the responsibility to you to decide the type of training that your users will receive,” she told the audience.

Asked about prefilled syringes, she said her group only gets involved when those products are transitioned from clinical use or use by health care providers to home use. As a rule of thumb, when the product will be used in the home there are concerns with potential dosing and medication errors and the agency wants the sponsor to clearly describe how those will be mitigated, whether in a risk analysis or validation study or otherwise.

The agency’s expectations for generic combination products are the same as for others, Nguyen said: “It has to be demonstrated through a risk analysis and a validation study that the risks are effectively mitigated and the device can be used safely and effectively by the intended user.” If the product has been on the market for a while, the switch to a new product could result in some “negative training transfer” that should be considered in the design and development, she advised.

Nguyen noted CDRH believes simulated use testing is adequate to demonstrate safety and effectiveness unless there is an aspect related to product design, the injection process, or use environment that can’t be captured in simulation. Those instances may call for studies in a clinical or active use environment.

Nguyen indicated that if product modifications to a delivery device are independent and do not impact the overall product, “then you can perform a human factors study just focusing on the modifications and the tasks associated with those modifications.”

She also directed the audience to FDA’s Web site on device human factors and the site the Association for the Advancement of Medical Instrumentation collaborated on providing resources and consultants for human factors.