Presentation
MDD10 - Development of a New ANDA Comparative Use HF Method for Comparing Products with Consideration of Potential Harm Resulting from Use Errors
SessionPoster Session 2
DescriptionApproval of a proposed generic drug-device combination product (DDCP) through FDA’s abbreviated new drug application (ANDA) pathway requires data demonstrating both equivalence of the drug product as well as interchangeability of the corresponding device administering the drug. The 2017 FDA draft guidance entitled, “Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA” provided a foundation for conducting a human factors comparison of user interface (UI) design features of a proposed generic DDCP to that of its reference listed drug (RLD) for review by FDA.
Prior FDA funded research conducted by our team (1) surveyed industry stakeholders experienced in ANDA submissions and identified key challenges inhibiting industry adoption of the CUHF process, and (2) created a user interface (UI) design taxonomy creating a classification system for identifying UI design attributes and linking them to specific user tasks when using a DDCP.
Building upon this prior research, this presentation will summarize our modified proposed process for ANDA submissions, including steps to determine whether a CUHF study, alternative study, existing data, or no data is required for FDA review of a proposed generic product. In this presentation the process will be demonstrated using a case study comparing an FDA approved generic inhaler (Wixela Inhub) to its RLD counterpart (Advair Diskus). FDA stakeholders from CDER (including OGD and DMEPA) provided input to help develop this novel process.
Development of a new comparative use HF process centered around incorporating HF best practices and addressing challenges previously identified in stakeholder interviews as well as the team’s own experiences conducting CUHF studies. The following components are incorporated in the proposed new process:
• Instructions for calculating sample sizes and study outcome metrics
• Templates for outcome data presentation
• Inclusion of close calls and/or difficulties in addition to incidence of use errors
• Meaningful outcome metrics considering the potential severity of harm associated with use events
• Use-related risk analysis that includes root cause analysis
• Framework for drawing conclusions from outcome data
Additionally, the proposed process aimed to address the Agency’s desire to provide alternative pathways for justifying device UI design changes, including alternative studies to CUHF and/or data in situations where a full CUHF study may not be required.
Our new proposed process for HF information in ANDA submissions requires up to 5 steps of analysis prior to submission, outlined below:
1: Product Overview. The product overview provides side-by-side detailed descriptions of the RLD and proposed generic, including Indications for Use, User Characteristics, Context of Use, Dosage Strength, Physical Device Description and FDA Application Number for the RLD.
2: Product Comparison by Task. This step requires creation of detailed task analyses, one for the RLD and one for the proposed generic. Using the task analyses, a side-by-side, task-by-task comparison of the UI designs, product labeling, and potential use errors provides a framework for directly linking UI design features directly to potential use errors at the task level. This helps FDA and sponsors determine minor and other design differences between the two product designs.
3: Comparative Analysis Determination. The comparative analysis determination requires systematic assessment of all comparisons completed in steps 1 and 2. The output is a ‘Determination Report’ with a conclusion stating whether additional data is needed for the HF assessment. The Determination Report includes a Summary/Justification, Product Background, and Justification of UI/Labeling Design Differences. From this report, sponsors can determine whether a full CUHF study, alternative HF study, existing alternative data, or no additional data is required for consideration of the proposed generic DDCP by the FDA. At this stage, the HF team also considers if UI design differences between the two products qualify as “minor” or “other” differences. The best practice is to submit the comparative analysis Determination Report as a Pre-ANDA submission to obtain agency feedback through a controlled correspondence. If no additional data is required for the HF analysis, FDA feedback should be taken into consideration before submitting the final ANDA. If further data or studies are deemed necessary, the HF team should first submit to the FDA a draft protocol for whatever study the sponsor believes is needed, and then conduct the study following the protocol agreed upon by the FDA prior to submitting the ANDA.
4: Comparative Use Human Factors (CUHF) Study (if required). If a CUHF Study is determined to be required, the analysis should be built off a detailed task analysis to ensure appropriate information is submitted to the FDA. Our new proposed CUHF study will include comparison of observational test data (occurrence of use errors, close calls, difficulties and correct use), the potential severity of harm associated with each use error, and a root cause analysis based on post-task interview data. From this data we propose a new metric, “Task Risk Level” for comparison between the proposed generic and its RLD.
5: Final Report for ANDA Submission. The Final Report for a proposed generic product submitted through an ANDA should carefully consider the FDA’s expectations for CUHF study results submitted in an ANDA per the “Contents of a Complete Submission for Threshold Analyses and Human Factors Submissions to Drug and Biologic Applications” guidance, CDER/CBER, 2018.
Prior FDA funded research conducted by our team (1) surveyed industry stakeholders experienced in ANDA submissions and identified key challenges inhibiting industry adoption of the CUHF process, and (2) created a user interface (UI) design taxonomy creating a classification system for identifying UI design attributes and linking them to specific user tasks when using a DDCP.
Building upon this prior research, this presentation will summarize our modified proposed process for ANDA submissions, including steps to determine whether a CUHF study, alternative study, existing data, or no data is required for FDA review of a proposed generic product. In this presentation the process will be demonstrated using a case study comparing an FDA approved generic inhaler (Wixela Inhub) to its RLD counterpart (Advair Diskus). FDA stakeholders from CDER (including OGD and DMEPA) provided input to help develop this novel process.
Development of a new comparative use HF process centered around incorporating HF best practices and addressing challenges previously identified in stakeholder interviews as well as the team’s own experiences conducting CUHF studies. The following components are incorporated in the proposed new process:
• Instructions for calculating sample sizes and study outcome metrics
• Templates for outcome data presentation
• Inclusion of close calls and/or difficulties in addition to incidence of use errors
• Meaningful outcome metrics considering the potential severity of harm associated with use events
• Use-related risk analysis that includes root cause analysis
• Framework for drawing conclusions from outcome data
Additionally, the proposed process aimed to address the Agency’s desire to provide alternative pathways for justifying device UI design changes, including alternative studies to CUHF and/or data in situations where a full CUHF study may not be required.
Our new proposed process for HF information in ANDA submissions requires up to 5 steps of analysis prior to submission, outlined below:
1: Product Overview. The product overview provides side-by-side detailed descriptions of the RLD and proposed generic, including Indications for Use, User Characteristics, Context of Use, Dosage Strength, Physical Device Description and FDA Application Number for the RLD.
2: Product Comparison by Task. This step requires creation of detailed task analyses, one for the RLD and one for the proposed generic. Using the task analyses, a side-by-side, task-by-task comparison of the UI designs, product labeling, and potential use errors provides a framework for directly linking UI design features directly to potential use errors at the task level. This helps FDA and sponsors determine minor and other design differences between the two product designs.
3: Comparative Analysis Determination. The comparative analysis determination requires systematic assessment of all comparisons completed in steps 1 and 2. The output is a ‘Determination Report’ with a conclusion stating whether additional data is needed for the HF assessment. The Determination Report includes a Summary/Justification, Product Background, and Justification of UI/Labeling Design Differences. From this report, sponsors can determine whether a full CUHF study, alternative HF study, existing alternative data, or no additional data is required for consideration of the proposed generic DDCP by the FDA. At this stage, the HF team also considers if UI design differences between the two products qualify as “minor” or “other” differences. The best practice is to submit the comparative analysis Determination Report as a Pre-ANDA submission to obtain agency feedback through a controlled correspondence. If no additional data is required for the HF analysis, FDA feedback should be taken into consideration before submitting the final ANDA. If further data or studies are deemed necessary, the HF team should first submit to the FDA a draft protocol for whatever study the sponsor believes is needed, and then conduct the study following the protocol agreed upon by the FDA prior to submitting the ANDA.
4: Comparative Use Human Factors (CUHF) Study (if required). If a CUHF Study is determined to be required, the analysis should be built off a detailed task analysis to ensure appropriate information is submitted to the FDA. Our new proposed CUHF study will include comparison of observational test data (occurrence of use errors, close calls, difficulties and correct use), the potential severity of harm associated with each use error, and a root cause analysis based on post-task interview data. From this data we propose a new metric, “Task Risk Level” for comparison between the proposed generic and its RLD.
5: Final Report for ANDA Submission. The Final Report for a proposed generic product submitted through an ANDA should carefully consider the FDA’s expectations for CUHF study results submitted in an ANDA per the “Contents of a Complete Submission for Threshold Analyses and Human Factors Submissions to Drug and Biologic Applications” guidance, CDER/CBER, 2018.
Event Type
Poster Presentation
TimeTuesday, April 14:45pm - 6:15pm EDT
LocationFrontenac Foyer