Pharmacology
FDA to Discuss Levothyroxine Products' Bioequivalence Standards
By FDA advisory committe
Apr 21, 2005, 13:50

FDA is reopening discussion of the regulatory standards for determining the therapeutic equivalence between levothyroxine sodium products nearly one year after approving a number of equivalence claims.

The agency will hold a public meeting May 23 in Washington, D.C. and will accept written comments on the therapeutic equivalence of levothyroxine sodium drug products until July 23.

The workshop will include FDA staff and representatives of three medical societies, the American Thyroid Association, the Endocrine Society and the American Association of Clinical Endocrinologists, which have questioned the agency's regulatory standards for determining therapeutic equivalence within the class, FDA's 1meeting announcement states.

"The public meeting is intended to review FDA's regulatory and scientific approach to levothyroxine sodium products, including manufacturing standards, in vitro dissolution studies and bioavailability/bioequivalence methods," the agency noted.

The workshop also will address "clinical, scientific and methodological issues relevant to the possible use of serum thyrotropin concentration as a pharmacodynamic measure of levothyroxine sodium bioequivalence."

The announcement of the public meeting suggests FDA is re-evaluating its position on the interchangeability of levothyroxine sodium products.

The agency has approved seven NDAs for levothyroxine sodium products since declaring them subject to new drug regulation in 1997: Alara's Levo-T, Vintage's Levolet, King's Levoxyl, Genpharm's Novothyrox, Abbott's Synthroid, Lloyd's Thyro-Tabs and Jerome Stevens' Unithroid.

None were originally rated as interchangeable with any other, but last year FDA cleared supplemental NDAs from some sponsors demonstrating therapeutic equivalence, as well as an ANDA from Mylan for a generic version of Synthroid.

The flurry of approvals last June suggested FDA considered levothyroxine sodium products to be interchangeable.

The approvals followed the rejection of a 2003 citizen petition from Abbott urging FDA not to approve bioequivalence claims without studies in athyreotic patients. Abbott claimed the agency's bioequivalence standards could allow doses of generic levothyroxine sodium to be off as much as 12.5% and still be considered bioequivalent.

FDA responded, however, that it used a similar bioequivalence methodology for approving generic levothyroxine sodium as it did for Abbott's Synthroid NDA.

More recently, a federal court of appeals reinstated lawsuit claims by Jerome Stevens relating to FDA's approval of levothyroxine sodium products, particularly to confidentiality of Unithroid data.

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