Generics, chemisimilars and biosimilars: is clinical testing fit for purpose?

British Journal of Clinical Pharmacology
John B Warren

Abstract

The effectiveness and safety of generic drugs are backed by sound physicochemical control and regulatory bioequivalence acceptance criteria. Statistical testing of bioequivalence, comparing the pharmacokinetic profiles of the test and reference products, was made possible by modern drug assays. When the pharmacokinetic profile correlates with the dose, such comparisons show assay sensitivity and readily detect differences in dose. For large biological molecules, different manufactured batches cannot be validated using pharmacokinetic data alone. For these biosimilars, there is a three-stage assessment of pharmaceutical quality, laboratory testing and clinical data. This approach has also been applied to certain chemical products, termed 'chemisimilars', which have variable or complex synthesis of the active substance, or complex formulation, or a complex delivery device. Although there may be no detectable difference between the test and reference on clinical testing, many of the outcome measures are insensitive to even large differences in dose. For testing to be fit for purpose it should distinguish important dose differences, but many clinical tests of chemisimilars and biosimilars do not. As pharmacokinetic and pharmacodyna...Continue Reading

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Citations

Apr 14, 2015·British Journal of Clinical Pharmacology·Fernando de Mora
Sep 1, 2016·British Journal of Clinical Pharmacology·Johanna MielkeByron Jones
Jul 24, 2013·Rheumatology·Morton A Scheinberg, Valderilio F Azevedo
Mar 27, 2018·British Journal of Clinical Pharmacology·Johanna MielkeFranz Koenig
Jul 19, 2019·The British Journal of Ophthalmology·Ashish SharmaAnat Loewenstein
Sep 6, 2019·British Journal of Clinical Pharmacology·Fernando de MoraRafael Martínez
Jun 7, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Daohong Chen, Eric Yining Qi

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