Post-prior equivalence

Urine samples collected from two human subjects, prior to (minus 24 to 0 hours) and after (plus 2 to 6 hours) oral administration of 30 mg A9-THC, were hydrolyzed and extracted as described in the experimental section. Pre- and post-drug extracts corresponding to equivalent urinary creatinine levels were separated by reverse phase HPLC. The pre-drug extract was used as a... 

Given these definitions, FOPs would likely be considered pharmaceutical alternatives if one presumes that pioneer and follow-on proteins are identical at a precursor stage, prior to potential post-translational modification. This presumption may also be consistent with the similarity standard the agency applies to ascertain orphan drug status (see discussion in Section 1.2.6). Follow-on proteins cannot be considered to be therapeutic equivalents since they are not pharmaceutical equivalents and cannot be expected to have the same clinical effect and safety profile in the absence of testing. This assertion is supported by the following ... 

Levels of radioactivity were highest in the liver and kidneys of male and female rats at two hours post final dose and averaged 3.A63 ug equivalents/g and 4.073 ug equivalents/g in male and female rat liver, respectively, and 2.383 and 2.132 yg equivalents/g in male and female rat kidney. Urine samples were analyzed by direct injection onto the HPLC column, whereas feces and liver samples were homogenized and extracted with methanol and subjected to solid phase extraction (if necessary) prior to HPLC analysis of the organic extract. The major radiolabeled component in male and female rat urine co-chromatographed with flunixin. Lesser amounts of the two hydroxylated metabolites, 5-hydroxyflunixin and 2 -methyIhydroxyflunixin, were also detected. Two major radiolabeled residues, identified by retention characteristics as flunixin and 5-hydroxyflunixin, were observed in rat feces. The major radiolabeled component in male and female rat liver co-chromatographed with authentic flunixin standard. The monohydroxymetabolite, 5-hydroxyflunixin was also detected in male rat liver. 

It is often argued that formal analyses of safety data are inappropriate, usually because pre-specified hypotheses are not available. This raises the issues of multiplicity and intentions (in designing the experiment) for a frequentist analysis. For a Bayesian analysis the equivalent problem is raised of having to establish prior distributions after the data are in. Neither mode of inference deals well with carrying out post-hoc analyses. 

R. W. Emmons and S. H. Suck. Equivalence between the prior- and post-interaction forms in the distorted-wave Born-approximation transition amplitude. Phys. Rev.. 25A. 2385-7 (1982). 

If only one pH and/or conductivity sensor are utilized it is usual to locate them after the column to monitor the column eluent. They may, however, be additionally located prior to the column to act either in an alarm only mode to protect the column from extremes of pH due, for instance, to failure of a caustic dilution step, or to enable equilibration of a column to be continued until the pre and post column pH or conductivity measurements are equivalent. 

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