Drugs

Law Firm Seeks Lower Bioequivalence Standards for Xarelto

The Hyman, Phelps and McNamara (HPM) law firm says FDA’s bioequivalence recommendations for generic copies of Janssen Pharmaceuticals’ Xarelto (rivaroxaban) should be re-evaluated and revised. In just-posted comments submitted on behalf of an unnamed generic drug company client, HPM says revisions to a recent draft guidance should be made to lower bioequivalence standards based on the “known mechanism of action, the documented wide therapeutic range, well-established safety margins, moderate intra-subject variability in pharmacokinetics, and differences in food effect from lower to higher strengths of rivaroxaban.”

The current recommendation, according to HPM, calls for “fully replicated bioequivalence (BE) studies on the 20 mg strength under fasting and fed conditions with BE evaluation using average bioequivalence approach with limits of 80-125%, without any scope of utilizing reference scaled average BE approach in the view of a steep exposure-response relationship of rivaroxaban for both efficacy and safety. Moreover, the draft guidance also recommends a statistical comparison of the within-subject variability of test and reference products with resultant upper limit of the 90% confidence interval for the test-to reference ratio of the within-subject variability ≤ 2.5, as referred in the guidance on warfarin sodium — a typical narrow therapeutic index drug.”

Instead of the guidance’s BE recommendations, HPM urges FDA to revise these with the following study requirements:

A single-dose, 2-way, cross-over in vivo study under fed conditions for the 10 mg tabletA single-dose, 2-way, cross-over in vivo study under fasting conditions for the 10 mg tabletA single-dose, 2-way, cross-over in vivo study under fed conditions for the 20 mg tablet

Overall, HPM argues that rivaroxaban does not fit in the typical definition of a narrow therapeutic index drug. Therefore, it says, if a potential generic product is bioequivalent with the innovator in a two-way cross over design, the two of them can be considered “switchable” in the view of their comparable rate and extent of absorption.

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome