Human Factors Studies for Generic Combo Products: FDA Offers Draft Guidance

Posted 13 January 2017 | By Zachary Brennan 

Human Factors Studies for Generic Combo Products: FDA Offers Draft Guidance

The US Food and Drug Administration (FDA) on Friday continued its flurry of draft guidance for generic drug companies (releasing its third in the last two days), this one for potential applicants planning to develop and submit an abbreviated new drug application (ANDA) to seek approval of a generic combination product that includes both a drug and a delivery device.

The draft comes as the controversy over Mylan’s EpiPen has simmered down, though the only current generic version of the product is an authorized generic from Mylan. Other competitors have had issues with the device components of their EpiPen knockoffs.


The draft’s recommendations focus on the analysis of the proposed user interface (components that the user interacts with) for the generic combo product when compared to the reference listed drug (RLD), including the delivery device and any associated controls and displays, as well as product labeling and packaging.

In terms of minimizing the differences between the generic and RLD, FDA further explains general principles, including how to conduct three types of threshold analyses for the identification and assessment of the differences to ensure the same clinical effect and safety profile as the RLD under the conditions specified in the labeling:

  • Labeling comparison: “FDA recommends a side-by-side, line-by-line comparison of the full prescribing information, instructions for use, and descriptions of the delivery device constituent parts of the generic combination product and its RLD.”
  • Comparative task analysis: FDA recommends that potential applicants “systematically dissect the use process for each product, i.e., both the proposed generic product and the RLD, and analyze and compare the sequential and simultaneous manual and intellectual activities for end-users interacting with both the products. FDA recommends that sponsors analyze the differences with the goal to characterize the potential for use error.”
  • Physical comparison of the delivery device constituent part: “FDA recommends that the potential applicant of the proposed generic combination product acquire the RLD to examine (e.g., visual and tactile examination) the physical features of the RLD and compare them to those of the delivery device constituent part for the proposed generic combination product.”

If the threshold analyses determine that a user face’s design difference may not be minor, potential applicants should first consider modifying the design, FDA says, noting it may also request data “to support that the user interface design difference(s) will not preclude approval of the generic combination product in an ANDA. Such data may be gathered in a comparative use human factors study that evaluates user performance of the critical tasks related to the external critical design attributes that are found to be different.”

In terms of labeling issues, FDA notes: “There has been some confusion regarding whether FDA expects for ANDA approval that a generic combination product be used in accordance with the labeling for the RLD. FDA does not necessarily expect for approval that a generic combination product can be used according to the RLD labeling per se, but rather it is critical that the generic combination product can be substituted for the RLD without additional physician intervention and/or retraining prior to use. To this end, a comparative use human factors study as described in this guidance could be designed to account for how a particular proposed generic combination product might be used when substituted for the RLD.”

Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA

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