FDA Releases Q&A Guidance On Human Factors Engineering For Combination Products

By Tim Sandle, Ph.D.

Human factors engineering involves the design of objects and systems by accounting for human capabilities, limitations, and characteristics. Applied to pharmaceuticals, the goal would include designing products for safe, effective, and comfortable human use, and it answers questions like “how easily can a person use this medicine?”

When outlining the application of optimal design principles, human factors are often subdivided into physical, cognitive, social, cultural, and emotional factors. By working through these subfactors and appropriately validating combination products, human factors engineering aids personnel in analyzing patient safety events and in developing workable and effective countermeasures.

An important component of pharmaceutical products and medical device research and development is a focus on the users of the device. Developing an effective device or medication can be easily undone if it is not used correctly, and errors made by patients or clinicians are often a direct result of design limitations.¹ Weaknesses can be overcome by focusing on human factors, undertaken through a process of iterative design and testing and supported by measuring and analyzing the interactions between people and medicines.² One area where errors can occur is combination products. These are medicines that contain two or more separate products packaged together in a single package, or they are provided as a unit comprising a drug and a device, a device and a biological product, or biological and drug products. Examples of combination products are the emerging set of digital health products that include digital interfaces, and which are designed to collect data.

To support the co-packaged design process, the U.S. FDA has issued a new guidance document, in the form of a Q&A, titled Application of Human Factors Engineering Principles for Combination Products: Questions and Answers.³ In this article, I review some of the pertinent points from the guidance.

Emphasis On Quality Risk Management

As with most recent FDA guidances, the document emphasizes risk management. There are risks associated with the device, use-related risks associated with the medicine, and use-related risks associated with the combination product as a whole, beyond those that arise from using either the device or drug alone.⁴ The use-related risks are expanded upon in the FDA document, particularly regarding the user interface and the need for a human factors engineering assessment.

The user interface includes all points of interaction between the combination product and the user(s), including displays, controls, packaging, product labels, carton labeling, and instructions for use. In addition, this may need to include training for the patient or clinician, if applicable.⁵

The guidance discusses different levels of risk. The most serious of these is described as a “combination product critical task.” This is a task undertaken by the user which, if performed incorrectly or missed, could cause compromised medical care. For example, a freeze-dried product requires reconstituting using a liquid, and this must be completed within a certain time frame, with the objective of providing a homogenous solution. If the patient is unable to complete the task within the time frame due to the product design or a characteristic of the product (such as the product not dissolving fast enough), this would represent a product critical task.

The important points to consider in the human factors engineering risk assessment include:

• A sufficient knowledge about human behavior, abilities, and limitations, together with other characteristics relating to the intended the users of the products, must be built. This requires an understanding of the intended user population, including concomitant diseases and conditions.
• Limitations extending from specific health conditions that could impact the use of the combination product need to be accounted for.
• General health factors need to be considered. The FDA document provides an example relating to digital technology: If the intended patient is classed as geriatric, then the images and sounds need to be suitably clear and supported by intuitive technology. It may also be necessary to consider how a product might be used by a person undergoing cognitive decline.
• For other patient groups, varying literacy levels need to be understood.
• The location where the product is to be used will need to be assessed, including any limitations connected to two-way communication and data transmission. For example, products designed to transmit data may not perform where there is only limited internet access or disrupted cellular services.
• Consider how the design of the user interface affects interactions with the combination product and could potentially result in harm, including a medication error.

The FDA guidance expands the risk-based approach to consider some specific hazards, as noted below.

Injectable Products

One of the risk areas considered includes devices that inject a medication into the patient. The first human factors area addressed is pain. If pain is considerable, then this carries the potential for the user not to complete the injection task. This could lead to dose omission or at least an underdose.

A second factor with injectable medicines is the viscosity of the product. A high drug viscosity could increase the injection delivery time of the drug through the needle; in turn, this could increase the length of time the user needs to hold the injector in place to deliver the medicine. A prolonged hold time could also reduce the user’s ability to complete an injection task and again result in an underdose. This could arise, for example, if a needle needs to be fully depressed prior to injection, but the instruction to the patient that the needle needs to be fully depressed is not clear.

Direct Harm

Another risk area is a combination product with the potential to result in harm, such as causing physical injury, adverse events; events that need patient monitoring to confirm no harm occurred; or events that may lead to hospitalization. Each of these potential outcomes should be modeled and the associated risks reduced.

To avoid such harm, the concepts of a device being error-resistant and error-tolerant can be introduced.⁶ These terms are not explicitly used in the guidance, but they are useful to keep in mind. “Error-resistant” means that, as far as possible, the design should protect users from making errors. “Error-tolerant” infers the design should minimize the consequences of any human errors that are committed.

Site Of Administration

The design of the device and the instructions must be sufficiently clear so that the administration impact of the product is reduced. Problems that could arise include the patient targeting the wrong site of administration as well as improper preparation of the medicine prior to administration.

Route Of Administration

Instructions about the route of administration need to be clear. For instance, if a capsule is provided with an inhaler, it cannot be assumed that the patient knows to place the capsule in the inhaler and for the medication to be delivered by inhalation. If the patient was to simply swallow the capsule, the medication would be ineffective (and possibly dangerous) due to the incorrect route of administration being selected.

Time Delays

The design of some combination products may lead to time delays. For example, if a patient is required to administer one dose of a product followed by a dose of a second product within a short time frame, then something like the cap of a vial being difficult to remove presents a human factors problem since this could delay the patient getting the second dose ready within the required time frame. On the other hand, if the two doses are not time dependent, additional time to remove a cap will matter less.

Validation

The FDA guidance emphasizes the importance of including the use of the combination product within the validation exercise for assessing the pharmaceutical product. It is necessary to evaluate users’ interactions with the final finished combination product across different scenarios. To support any future changes, the reassessment of validation forms an important part of the change management process.

Root Cause Analysis

The human factors approach also can be applied to root cause analysis. This is not addressed in the FDA guidance, but it is a useful adjunct. Instead of thinking why the people involved are so “odd” as to “misuse” a product, the human factors approach should drive companies to understand why the patients’ decisions and actions make sense and to incorporate this insight into continuous improvement practices.

References

1. Dakken S. Field guide to human error investigations. Burlington, VT: Ashgate Publishing Co, 2002
2. Battles JB, Keyes MA. Technology and patient safety: A two-edged sword. Biomedical Instrumentation & Technology. 2002;36(2):84–88
3. FDA. Application of Human Factors Engineering Principles for Combination Products: Questions and Answers, Guidance for Industry and FDA Staff, Office of Combination Products: https://www.fda.gov/media/171855/download
4. Panagioti M, Khan K, Keers RN, et al. Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis. BMJ 2019; 366:l4185
5. Welch DL. Human error and human factors engineering in healthcare. Biomed Instrum Technol.,1997;31:627–31
6. Implementing Human Factors in Healthcare: How to guide (volume 2): http://www.institute.nhs.uk/images/documents/SaferCare/Human-Factors-How-to-Guide v1.2.pdf

About The Author:

Tim Sandle, Ph.D., is a pharmaceutical professional with wide experience in microbiology and quality assurance. He is the author of more than 30 books relating to pharmaceuticals, healthcare, and life sciences, as well as over 170 peer-reviewed papers and some 500 technical articles. Sandle has presented at over 200 events and he currently works at Bio Products Laboratory Ltd. (BPL), and he is a visiting professor at the University of Manchester and University College London, as well as a consultant to the pharmaceutical industry. Visit his microbiology website at https://www.pharmamicroresources.com.