There are a variety of valuable human factors (HF) updates that fall outside of what the packaging and medical device communities think of as the “regulated space,” according to Tiffany McIntire, principal human factors engineer at Roche Pharmaceuticals.
In her years of experience, McIntire—also a psychologist—has worked on over 10 submissions with the FDA and has transitioned from working on combination products to looking at the wider portfolio at Roche.
At Pharmapack Europe, she discussed how she and her team identify human factors projects, including several questions to ask as you evaluate conventional use and packaging.
Knowing when to bring human factors into a project
McIntire highlighted a checklist she uses in packaging projects to determine if human factors should be involved. “The motivation behind this was when I first came into Roche, I was given a project where we had a bottle configuration for the U.S. and then a bottle with oral syringes and a press-in bottle adapter in Europe. The thinking was that in the U.S., we don't have to co-package because all this is going to be available in the pharmacy. We're going to make it look like another product that we had on the market,” she said. “But when I started looking at the project more closely, there was a short in-use period so they would have to do several different steps: mix with water at home, put in the press-in bottle adapter, and extract the dose that they need. For me, that was immediately a red flag. It fell outside of what I would call conventional use. That’s one of the things we benefit from—having a cross-functional team full of people from different nationalities in Switzerland,” to understand use cases in various countries.
Questions on the checklist include whether the product is intended for pediatrics or elderly patients, if an over/under/missed dose requires medical intervention, and if it has a complex dosing regimen. These can greatly affect what McIntire calls PCA: perception, cognition, and action attributes, and their related impairments.
- Perception is the way we receive information (considerations include visual or hearing impairments)
- Cognition is the way we process information (considerations include cognitive fog from pain, chemotherapy; overstimulation; or processing issues from age or disease)
- Action or physical characteristics are the parts of the body we use to accomplish a task (considerations include hand dexterity issues or limited mobility)
In the small molecule space, products tend to be developed first for adults as oral tablets, then they are transitioned for use in pediatrics. “We have to make a decision for the pediatric patient, how is that going to get into their body? From zero to six months, you're probably only consuming liquids. And then after that, you could be having whole foods,” she noted. “How easy is it to get a liquid into the child's mouth versus having potentially mini tablets and sachets? [Consider] the constitution steps that can happen at home. These are a lot of the conversations that we're having upfront with small molecule development now. But really, it came from a trend of getting projects or getting assigned to projects later on in development.”
McIntire credits colleagues on the packaging team that began bringing her into the process, which is where the questionnaire was born. “This is given to every packaging engineer when they get a project, and it essentially tells them whether or not they need to bring me in,” she explained. “Right now we're working to get involved a little bit earlier in the process with the technical development teams, the CMC teams, small molecule formulation, large molecule formulation, to give them similar questionnaires, to get them to think about the complexity of the products that they're putting out into the market, and how people are actually going to use them and whether that's going to be acceptable.”
She highlighted a few other key questions:
- What physical issues might the patients typically have, including comorbidities, sensory, or cognitive issues? “Rheumatoid arthritis is something that usually comes to mind, if you have a patient who has diabetes, they could have neuropathy, hearing issues, visual issues, even age can be related to these. So that comes into play with the assessment quite a bit,” she said.
- Is the process and delivery of medication acceptable? McIntire offered a recent example in which a colleague asked if it’s acceptable for the patient or caregiver to have to mix something for 10 minutes. “The answer is that it depends. Do they have to shake the bottle for 10 minutes? Do they have to do this every day? How many other medications are they managing? What's the therapeutic benefit of the product?” she said. “Anyone that works in medical devices or pharma in general knows we talk about risk-benefit all the time. The risk is probably non-compliance. Then the benefit—they could be motivated into compliance, even if it's inconvenient, because the therapeutic benefit is there. For example, if you don't have to have an intrathecal (spinal) injection, and you have to just shake a bottle for 10 minutes once a week, people may be motivated to do that. So it's never really straightforward or clear cut. But at least in my opinion from this checklist, if you can check yes on one of them, then I start to look at the problem and hash out those details.”
Some of the questions in the checklist might be difficult for a packaging engineer to answer, such as specific dosing regimen or comorbidities. Another tool they use is a pipeline assessment, where McIntire has added columns looking at factors like the route of administration, the disease state, and whether the dose is being administered at home or in the hospital. (There are, of course, many combined use cases where things are being used in both contexts.)
McIntire focuses more on home use because patients and caregivers tend to have less education and experience. From the user's perspective, she looks at if there are perceptual, cognitive, or physical issues that could occur. Again, there could be comorbidities—one example is Ulcerative Colitis and Crohn's disease, where patients might also tend to have rheumatoid arthritis. It's good to consider what percentage of comorbidity exists for the given disease state and feed that information into the process.
Learn and apply
When McIntire begins a project treating a new disease state she hasn’t worked on before, her first step is to look at the drugs currently on the market and what patients currently have experience with. “Could they be using that drug at the same time as mine? You can start to get an idea of what the patient workload looks like, but also personal factors and how they could affect use,” she said. “Is the patient going to be independent in their care? Is the caregiver going to be helping them significantly?"
Another prevalent example is Alzheimer's disease, where she said there can be unexpected use cases. For an elderly person who's experiencing dementia, their caregiver might be their spouse, who is likely also elderly. At times in human factors, people may check a box for caregiver and an age range. But McIntire explained that you have to make sure that caregiver is actually representative of your context.
“I've worked at some companies where if you start going above and beyond what FDA asks [people worry] that you're going to raise the bar and you're going to have to keep performing there. And my response to that would be ‘God forbid we have usable products.’”
Literature reviews are both easy and low-cost and can provide lots of great information if you’re good at them, she noted. Specifications may emerge from the literature reviews. If someone has neuropathy issues, the product need something that they can actually feel such as added textures. If they're elderly, and a device has an audible component, the product may need to be at a certain hertz level for them to hear it. “Then with the questions that we can't answer, we start getting into some of other tactics—contextual inquiry. If I can't find this information readily, I may have to go into the hospital or the patient's home, start understanding that context,” she said.
Other key learnings:
- Though they weren’t getting complaints, her team knew that some bottles were difficult to open, and they started doing usability testing on them anyway. McIntire explained that while people were struggling to open the bottle, some expressed that the medication packaging isn’t what they wanted to be using.
- It can be difficult to balance product protection with usability, but also consider real-world applications. “There's a long list of requirements that we're trying to get through. In those requirements, they're looking at designs that protect the drug product in a certain way from moisture sensitivity, etc. But if the patient can't open the bottle, or because they can't open the bottle, they leave it open, you've kind of just defeated the whole purpose of that requirement,” she said. Additionally, as has been brought up in industry, patients may remove and store the product or primary package away from instructions on a carton or leaflet.
- McIntire has encountered complicated constitution methods for pediatric patients, including difficulties with stick packs and mini tablets: “You have people that are in the hospital that may be on an NG- or G-tube. You still have to get the dose into a liquid somehow. Mini tablets are coated for taste masking, and if you have to break down that coating, it takes about 20 minutes. What are you going to do for these other use cases? Is it going to clog the NG- or G-tube, or be difficult for pediatric patients zero to six months when they require liquid administration?”
HF is a culture
It’s important not to look at human factors as simply testing to check a box for the FDA, or keep things specific to the U.S. While her talk focused on practices that do fall under regulations and guidance, McIntire emphasized that keeping strictly to regulations isn’t always what’s best for the patient.
“This is you making sure that you have a high-quality product that meets the needs of your patients, not just because the FDA told you. So human factors is a culture I'm trying to cultivate,” McIntire said. “I've worked at some companies where if you start going above and beyond what FDA asks [people worry] that you're going to raise the bar and you're going to have to keep performing there. And my response to that would be ‘God forbid we have usable products.’”
New developments—benefits of starting from scratch
A new development often kicks off with a workshop. Being early in the process allows for time to plan activities, design iterations, and contact design consultancies. “I will clarify, I don't do my own research and design, I do literature reviews, because then I can frame those things and what they're going to look like,” said McIntire. “But I like to hire experts that do this every day. I don't recommend doing design internally, because you will probably take two to three times as long as an external consultancy. They know how to write requirements, and they know how to find them.”
With a learn and apply philosophy, her team develops a user journey map, listing out all the different steps in which the user interacts with the product: opening, preparing a dose, administration, storage, and package disposal. “With stick packs, for example, they could be retrieving a few stick packs, then putting them back. Are they traveling with the stick packs? People do go on vacations, so how are they going to handle these different circumstances? We also go through the user journey map as different people,” McIntire noted.
Real-life scenarios should be considered. Another product she highlighted is intended for prophylaxis—used as prevention and treatment. “If you're in a household full of kids, and one of them gets sick, they're all probably going to get sick,” she said. “We went through that mindset, that if Mom and Dad are sick and the kids are sick… it's just going to be chaos. So if it's chaos while they're trying to use our products, they have that cognitive load while they're doing it. We try to keep that in mind with every product—that's going to be specific to each one.”
Bringing in the right people
In workshops, McIntire suggests bringing in a variety of stakeholders beyond human factors and designers. “I try to get people from the CMOs, from production, packaging engineers, project managers. If you're involved in deciding my budget, if you're involved in actualizing or realizing the things that we're coming up with, I really want you in that room and a part of the process. I want you to understand this is why we're doing this,” she said. “And I also want you to be able to raise your hand so that you can tell me something’s great, but the patient needs to have a quick reference guide, and I don't have space on the package to put it there. Or this is going to be a high-volume line, so I can't put that many pieces of literature inside of the box.”
It's good to have these discussions early on so the design choices are practical. There may be trade-offs that have to be made. Some design aspirations can’t be realized because of manufacturing constraints, but they’re good to keep in mind for the future.
Viable production is patient-centricity
While it may be possible to create a device or package that ticks a lot of boxes, its value lies in reaching patients. McIntire said they try to prioritize usability without creating complexity. “Recently, it's been flu season and there have been shortages of Tamiflu and Tamiflu generics. We want to make sure that we have a simplified manufacturing process so we don't create shortages for medications, as well. Sometimes you have to keep in mind, it's not just about usability. This is also still patient-centricity, but maybe not in that direct lens,” she explained. “Business viability is obviously something we have to keep in mind, like with high volume lines, making sure we don't have shortages. And ensuring technical feasibility—that those lines can actually produce what we want.”
She also cautioned that co-packaging [contract packaging] is not always as simple as it seems: “From having the medical device experience, I’m able to give an earlier consultation that if you co-package, you really have to be confident in that co-packaging, because you increase manufacturing complexity. And you add a whole lot of regulations.”
Sustainability also continues to evolve. For Roche, the packaging team performs sustainability assessments on every incoming project because they want to continue to understand their CO2 emissions and their impact on the environment. “That's also why I wasn't allowed to fly here today. We have a strict CO2 emission cap for the department,” she explained.
Check out Part 2: Human Factors Projects—Quick Wins and Practical Tips