Bridging Issues of Route

  • Amy L. Mihalchik-BurhansEmail author
  • Dexter W. SullivanJr.


Current regulatory guidelines call for the identification and quantification of chemical compounds which may migrate out of a medical device, combination product, or a drug container closure system, and into an individual. Compounds that migrate from these devices often have little available toxicity data resulting in a major challenge in performing an adequate assessment of biological or toxicological risks and thus potentially compromising patient safety. These limited toxicity data may exist by alternative routes. Therefore, route-to-route extrapolation of the available data may be considered for use in these instances. Here we discuss the factors to consider when performing route-to-route extrapolations for L&E compounds beginning with historic and regulatory approaches. This will be followed by a review of pharmacokinetic and pharmacodynamic considerations regarding the applicability of route-to-route extrapolation. Finally, we will discuss route-specific considerations and the derivation of safe exposure limits.


Route-to-route Extrapolation Leachables Extractables L&E Risk assessment TTC 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Amy L. Mihalchik-Burhans
    • 1
    Email author
  • Dexter W. SullivanJr.
    • 1
  1. 1.Gad Consulting ServicesRaleighUSA

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