# \[e-drug\] Bio equivalence studies of endogenous substances **URL:** \ **Category:** e-drug\ **Created:** [September 26, 2017, 3:09pm UTC](https://talk.edrugplus.org/t/e-drug-bio-equivalence-studies-of-endogenous-substances/43913 "2017-09-26T15:09:58Z")\ **Posts on this page:** 1\ **Page:** 1
**Author:** ![Maryam\_Bigdeli](https://avatars.discourse-cdn.com/v4/letter/m/b77776/32.png) [@Maryam\_Bigdeli](https://talk.edrugplus.org/u/Maryam_Bigdeli)\ **Post date:** [September 26, 2017, 3:09pm UTC](https://talk.edrugplus.org/t/e-drug-bio-equivalence-studies-of-endogenous-substances/43913/1 "2017-09-26T15:09:58Z")
E-DRUG: Bio equivalence studies of endogenous substances --------------------------------------------------------------------------- Dear e-druggers Some of you may have followed the Levothyroxine crisis in France. To avoid overloading this discussion group, I will not relate the crisis itself and will keep my question very simple: How does your country manage approval of endogenous substance substitutes, based on bioequivalence studies ? Or in other terms what norms of bioequivalence does your country apply? Especially for Levothyroxine. A small background information: As you know, generic medicines can be approved based on bioequivalence studies. However, these bioequivalence studies are difficult to realise for substitutes of endogenous hormones such as thyroxine. Bioequivalence on healthy volunteers is problematic because these subjects have a natural production of T4 that will bias the results. FDA requirements are therefore to do bioequivalence studies with supra-therapeutic doses (600 mcg bolus dose) and measurement of plasmatic T4 levels corrected for baseline (the correction being negligible because of the large bolus dose) The American Endocrine Society disputes these norms because of the narrow therapeutic range of Levothyroxine and urges FDA to either change their requirements (and require switch studies of therapeutic doses on patients without a thyroid) or to NOT declare thyroxine substitutes as equivalent. Several publications also contend this approach to bioequivalence of Levothyroxine. However,the alternative option is to test new formulations on patients without a thyroid, and checking for TSH levels rather than T4: this alternative raises an ethical issue of subject recruitment and length of the study (several weeks, to allow TSH levels to stabilize). Hence my question: do you know what requirements your country applies? And can you share these with me? Many thanks in advance Maryam Bigdeli Health Systems Speciaist Maryam Bigdeli \