An analysis of DMEPA human factors and labels and labeling reviews from 2016-2020

DMEPA Analysis

An analysis of DMEPA human factors and labels and labeling reviews from 2016-2020

Medication error and the resulting medical consequences can be deadly, costly, and are unfortunately common. The good news is that many medication errors are also preventable. Every drug product on the market has been carefully developed by the companies that engineered them and gone through a rigorous process of regulatory approval, and for good reason. Since the issuance of the final human factors guidance documents by the FDA in 2016 and subsequent draft guidance documents, medical devices and combination products reviewed by the FDA have been expected to incorporate human factors evaluations into their product development when appropriate. With improved product user interfaces, promotion of a culture of safety within organizations, and prioritizing a proactive approach to identification of preventable medication errors we can increase the safe and effective use of drug products.

Here at Agilis Consulting, we often ask “What does the data say?” and we decided to apply that question to the FDA Novel Drug Approvals list from 2016-2020. From this list a review was conducted of the available DMEPA human factors reviews. In this analysis, we looked at patterns in risk mitigation, interaction timespan, and trends in labeling recommendations to develop an understanding of what the data says, and how to apply this information to client needs moving forward.

Background on HF review

The Division of Medication Error Prevention and Analysis (DMEPA) is located in the Center for Drug Evaluation and Research’s (CDER) Office of Surveillance and Epidemiology (OSE). Human factors reviews under CDER’s jurisdiction are conducted by DMEPA and further information on review of combination products is established in the FDA staff manual on inter-center consults for review of HF information[1].

Medication Error

Medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer. The causes of medication error may be attributed to communication, name confusion, labeling, human factors, packaging/design, etc. To get an idea of the variety of medication errors, the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) taxonomy of medication error types[2] are listed in Table 1 below.

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Human Factors and Medication Error Prevention

Adverse events associated with medication error are, unfortunately, often incorrectly attributed to the user; however, identification of true root causes can result in mitigations and actional updates to reduce or prevent these events. Approaches for the prevention of medication error may involve a proactive or reactive approach. Preventable design flaws may be identified and addressed proactively (i.e., pre-market) or reactively remedied (i.e., post-market) to avoid adverse events from occurring. These design flaws may lie in the device itself, the labeling and packaging, or the associated instructional materials (paper instructions, instructional videos, and associated training). Relying on training or the instructional materials is often seen as a solution, but the best update to a design flaw is a product revision to prevent the adverse event from happening in the first place. Preventable errors may include quality defects, medication errors, or issues of non-compliance, whereas unpreventable events could be due to an unknown allergic reaction to a medication or unavoidable side effects of some medications.

Human Factors and Medication Error Analysis

Evaluating products for potential avenues of medication error includes human factors and instructional design (labels and labeling) as well as other factors which can contribute to medication error such as product naming.

What does the data say?

This investigation focused on Human Factors and Labels/Labeling and Packaging. The FDA Novel Drug Approval database (inclusive of years 2016-2020) was used to search for products which required human factors validation. Of the 228 products approved, there were 14 in which a DMEPA human factors review was published and 2 of these discussed the review of a validation protocol. Product type included 9 combination products (mostly injection devices) and 5 single ingredient products, with an even split between NDA (New Drug Application) and BLA (Biologic License Application).

Human Factors

Our initial analysis looked specifically at the years 2019-2020 and found the timespan for engagement around the Human Factors work discussed range from 4 to 11 months, with an average of 7 months. Identified factors in longer interaction times include additional labeling submitted on part of the applicant that was not included in the original submission, container labeling feedback provided by FDA prior to full response, and user groups not adequately identified/recruited/tested for the human factors evaluation.

Many reviews contained a redacted account of the applicant’s root cause analysis (RCA), the applicant’s discussion of mitigation strategies, and DMEPA’s analysis and recommendations. Based on these recommendations, the following patterns emerged:

  • Root cause:

    • Subjective feedback was typically reviewed to determine if the Applicant’s root cause determination supported their conclusion.

  • Negative transfer root cause typically did not result in incurred revisions, as long as:

    • There was clear and accurate instruction for the task, and

    • The task itself was not unique to the product.

  • User subjective feedback used as rationale:

    • To increase prominence of task instruction in training or for labels and labeling,

    • To clarify instructions such as injection site location or expiration date location.

  • Several reviews cited risk acceptability of use errors/difficulties around IFU tasks that are not unique to the product and are present with other products of the same type, such as hand washing, using alcohol swabs, etc.

Labels/Labeling/Packing/Product Design

Trends observed in the instructional design (labels, labeling, packaging) space were revisions to common occurrences in labels and packaging of medical products. The following list includes simple but important aspects of the products labels and labeling to consider and adhere to:

  • Eliminating trailing zeros (1.0 versus 1),

    • To reduce 10-fold dose misinterpretation medication errors

  • Expiration date format allowed as follows:

    • YYYY-MM-DD

    • YYYY-MMM-DD (if alphabetical month)

  • Expiration date & Lot format allowed (if your product includes a lot number):

    • EXP:

    • LOT:

  • Commonly confused symbols to avoid (< and >)

  • Add unit of measure after each numeric (“2 to 3 mL” to “2 mL to 3 mL”)

  • Linear barcode specifications,

    • Barcodes often become unscannable; therefore, it is important to not rely solely on barcodes to convey pertinent information

  • Consistent spacing between numbers and units of measure (5mL versus 5 mL)

  • Make sure to keep figures consistent throughout user interface

  • Avoid clutter near “Avoid” or “Warning” statements

These are just a few of the items flagged by DMEPA for revisions, many of which can easily be avoided by using the associated FDA guidance documents during product development.

Conclusion

Each DMEPA review presents valuable and interesting data relevant to the medical and pharmaceutical industry. Therefore, this compilation sought to determine patterns in risk mitigation tactics and their associated labeling to better understand regulatory discretion and how it has evolved since the 2016 HF guidance issuance. This research encompassed over 200 novel drug approvals from 2016 through 2020. While there were valuable lessons learned, there is absolutely room for digging deeper for additional analysis and review. If you have questions related to this article, please don’t hesitate to reach out. If something interests you, then it interests us here at Agilis.

 
 

About the Author:
Lauren Jensen, PhD

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Dr. Lauren Jensen, PhD, is a Biomedical Engineer and Human Factors Consultant with Agilis Consulting Group, LLC. Lauren is experienced in applying human factors principles to the design, evaluation and validation of medical devices and products. Prior to joining Agilis Consulting Group, Lauren worked in the startup space in Austin, TX engineering wearable medical products, and competed as a top ten finalist for the NASA iTech Cycle III for innovative technologies. During her PhD at Tulane University School of Medicine, Lauren developed and validated a therapeutic wearable to reduce surgeon tremor and fatigue in the OR.

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Lauren Jensen, PhD