Presentation
Exploring Methods for Assessing Design Differences Between Generic Drug-Device Combination Products and Reference Listed Drugs
DescriptionThere is a need to enhance understanding of factors related to design differences between generic drug-device combination products (g-DDCP) and reference listed drugs (RLD) to support development of and increase generic drug access to Americans. As stated in the 2017 draft guidance for industry “Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA," g-DDCP can be expected to produce the same clinical effect and safety profile as the RLD. This guidance recommends prospective ANDA applicants conduct comparative analyses to assess user interface differences between a proposed generic and RLD and if “other” design differences are identified, additional information may be requested to support the generic does not introduce a risk that impacts the clinical or safety profile as compared to the RLD.
Alternative methods to conducting comparative use human factors (cuHF) studies to assess “other” design differences remain relatively unexplored. The objective of this presentation is to discuss research that investigated and explored potential alternative methods to evaluate design and user interface differences of generic drug-device combination products (g-DDCP) in comparison to the reference listed drug (RLD) and provide recommendations based on findings. This presentation reports outcomes from a multi-year FDA/CDER funded research project granted to Battelle Memorial Institute.
Our method development consisted of in-depth comparative analyses between a proposed g-DDCP and its RLD. This analysis encompassed a range of assessments including comparative task analysis (cTA), comparative physical device assessment (cPDA), comparative use error analysis (cUEA), comparative labeling assessment (cLA), and comparative risk assessment (cRA) through a comparative uFMEA/URRA (cuFMEA/cURRA). When differences between a proposed generic and RLD device user interface impact critical tasks, further evaluation of those differences on risk for user error currently relies heavily on comparative use human factors studies (cuHF), which can be burdensome and costly. Much of our research focused on recommendations on alternative methodologies. Battelle’s proposed changes and recommended alternative methodological approaches include:
-Recommendations on alternative methodology to evaluate “other design differences” beyond the use of a cuHF study. We propose the use of the cURRA/cuFMEA to take the outcomes of thresholds analyses and relate them together in a unified document to identify critical task identification, controls, and validation requirements.
-A recommendation to reduce the testing burden by leveraging early engineering testing and formative human factors comparisons as bridging studies to demonstrate that the rationale for why a specific g-DDCP–RLD design difference was determined when product differences are required due to patents, reliability, or manufacturability. Leveraging early comparative testing may reduce the time to market and cost for generic manufacturers by reducing the scope of testing later in product development, which would be required only if completing a cuHF study.
-A recommendation to improve the g-DDCP ANDA development and review processes by reducing the burden of using a cuHF study through a proposed alternative methodology to the cuHF study. We recommend the use of a traditional human factors validation study, using 15 RLD-naïve and 15 RLD-experienced users of each user group, along with a bridging study as an appropriate alternative path to demonstrate the safety and effectiveness of a g-DDCP with regard to critical tasks, which would continue to demonstrate the acceptability of the design differences.
This research was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) through a grant U01FD007359 totaling $ 499,311 with 100 percent funded by FDA/HHS. The presentation contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.
Alternative methods to conducting comparative use human factors (cuHF) studies to assess “other” design differences remain relatively unexplored. The objective of this presentation is to discuss research that investigated and explored potential alternative methods to evaluate design and user interface differences of generic drug-device combination products (g-DDCP) in comparison to the reference listed drug (RLD) and provide recommendations based on findings. This presentation reports outcomes from a multi-year FDA/CDER funded research project granted to Battelle Memorial Institute.
Our method development consisted of in-depth comparative analyses between a proposed g-DDCP and its RLD. This analysis encompassed a range of assessments including comparative task analysis (cTA), comparative physical device assessment (cPDA), comparative use error analysis (cUEA), comparative labeling assessment (cLA), and comparative risk assessment (cRA) through a comparative uFMEA/URRA (cuFMEA/cURRA). When differences between a proposed generic and RLD device user interface impact critical tasks, further evaluation of those differences on risk for user error currently relies heavily on comparative use human factors studies (cuHF), which can be burdensome and costly. Much of our research focused on recommendations on alternative methodologies. Battelle’s proposed changes and recommended alternative methodological approaches include:
-Recommendations on alternative methodology to evaluate “other design differences” beyond the use of a cuHF study. We propose the use of the cURRA/cuFMEA to take the outcomes of thresholds analyses and relate them together in a unified document to identify critical task identification, controls, and validation requirements.
-A recommendation to reduce the testing burden by leveraging early engineering testing and formative human factors comparisons as bridging studies to demonstrate that the rationale for why a specific g-DDCP–RLD design difference was determined when product differences are required due to patents, reliability, or manufacturability. Leveraging early comparative testing may reduce the time to market and cost for generic manufacturers by reducing the scope of testing later in product development, which would be required only if completing a cuHF study.
-A recommendation to improve the g-DDCP ANDA development and review processes by reducing the burden of using a cuHF study through a proposed alternative methodology to the cuHF study. We recommend the use of a traditional human factors validation study, using 15 RLD-naïve and 15 RLD-experienced users of each user group, along with a bridging study as an appropriate alternative path to demonstrate the safety and effectiveness of a g-DDCP with regard to critical tasks, which would continue to demonstrate the acceptability of the design differences.
This research was supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) through a grant U01FD007359 totaling $ 499,311 with 100 percent funded by FDA/HHS. The presentation contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.
Event Type
Oral Presentations
TimeTuesday, March 2611:30am - 12:00pm CDT
LocationContinental Ballroom, Lobby Level
Medical and Drug Delivery Devices