text: Bioequivalence In determining bioequivalence between two products such as a commercially available Branded product and a potential to-be-marketed Generic product, pharmacokinetic studies are conducted whereby each of the preparations are administered in a cross-over study to volunteer subjects, generally healthy individuals but occasionally in patients. Serum/plasma samples are obtained at regular intervals and assayed for parent drug (or occasionally metabolite) concentration. Occasionally, blood concentration levels are neither feasible or possible to compare the two products (e.g. inhaled corticosteroids), then pharmacodynamic endpoints rather than pharmacokinetic endpoints (see below) are used for comparison. For a pharmacokinetic comparison, the plasma concentration data are used to assess key pharmacokinetic parameters such as area under the curve (AUC), peak concentration (Cmax), time to peak concentration (tmax), and absorption lag time (tlag). Testing should be conducted at several different doses, especially when the drug displays non-linear pharmacokinetics.
  In addition to data from bioequivalence studies, other data may need to be submitted to meet regulatory requirements for bioequivalence. Such evidence may include:
  analytical method validation
  in vitro-in vivo correlation studies (IVIVC)
  Regulatory definition
  The World Health Organization
  The World Health Organization considers two formulation bioequivalent if the 90% confidence interval for the ratio multisource (generic) product/comparator lie within 80.00–125.00% acceptance range for AUC0–t and Cmax. For high variable finished pharmaceutical products, the applicable acceptance range for Cmax can be expanded (up to 69.84–143.19%).
  Australia
  In Australia, the Therapeutics Goods Administration (TGA) considers preparations to be bioequivalent if the 90% confidence intervals (90% CI) of the rate ratios, between the two preparations, of Cmax and AUC lie in the range 0.80–1.25. Tmax should also be similar between the products.
  There are tighter requirements for drugs with a narrow therapeutic index and/or saturable metabolism – thus no generic products exist on the Australian market for digoxin or phenytoin for instance.