The Two Main Goals of Bioequivalence Studies.

The principal goal of bioequivalence (BE) investigations has crucial importance and has been the subject of extensive discussions. BE studies are frequently considered to serve as procedures for sensitive discrimination. The BE investigation should be able to provide methods and conditions sensitively identifying relevant differences between drug products if such differences in fact exist. Alternatively, BE studies can be deemed as surrogates of clinical investigations assessing therapeutic equivalence. Bioequivalent drug products will be provided to patients for their benefits. Both points of view are valid since they represent two aspects of product performance. It has been argued that both should be equally sustained and applied. In practice, however, they collide when regulatory conditions and statements are developed. For instance, some regulators prefer to conduct BE studies following single drug administrations since these conditions are considered to provide the highest sensitivity of discrimination between pharmacokinetic profiles and thus, a product's in-vivo performance. Others suggest that, at least for modified-release products, BE investigations should be performed in the steady state since it represents clinical conditions. Preference for one point of view or the other pervades other regulatory statements including suggestions for subjects to be selected in studies and pharmacokinetic measures to be evaluated. An overview is provided on the disturbing inconsistency of statements within and between regulations. It is argued that harmonization would be highly desirable, and relevant recommendations are offered

Midrapidity antiproton-to-proton ratio in pp collisons root s=0.9 and 7 TeV measured by the ALICE experiment

The ratio of the yields of antiprotons to protons in pp collisions has been measured by the ALICE experiment at root s = 0.9 and 7 TeV during the initial running periods of the Large Hadron Collider. The measurement covers the transverse momentum interval 0.45 < p(t) < 1.05 GeV/c and rapidity vertical bar y vertical bar < 0.5. The ratio is measured to be R-vertical bar y vertical bar<0.5 = 0.957 +/- 0.006(stat) +/- 0.0014(syst) at 0.9 Tev and R-vertical bar y vertical bar<0.5 = 0.991 +/- 0.005 +/- 0.014(syst) at 7 TeV and it is independent of both rapidity and transverse momentum. The results are consistent with the conventional model of baryon-number transport and set stringent limits on any additional contributions to baryon-number transfer over very large rapidity intervals in pp collisions

Higher harmonic non-linear flow modes of charged hadrons in Pb-Pb collisions at sNN\sqrt{s_{\rm{NN}}} = 5.02 TeV

International audienceAnisotropic flow coefficients, v$_{n}$, non-linear flow mode coefficients, χ$_{n,mk}$, and correlations among different symmetry planes, ρ$_{n,mk}$ are measured in Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV. Results obtained with multi-particle correlations are reported for the transverse momentum interval 0.2 < p$_{T}$< 5.0 GeV/c within the pseudorapidity interval 0.4 < |η| < 0.8 as a function of collision centrality. The v$_{n}$ coefficients and χ$_{n,mk}$ and ρ$_{n,mk}$ are presented up to the ninth and seventh harmonic order, respectively. Calculations suggest that the correlations measured in different symmetry planes and the non-linear flow mode coefficients are dependent on the shear and bulk viscosity to entropy ratios of the medium created in heavy-ion collisions. The comparison between these measurements and those at lower energies and calculations from hydrodynamic models places strong constraints on the initial conditions and transport properties of the system.[graphic not available: see fulltext