The immunosuppressant cyclosporine is generally considered a critical-dose
drug. The validity of standard criteria to establish bioequivalence between
cyclosporine formulations has recently been challenged, Recommendations in
cluded establishment of individual bioequivalence rather than average bioeq
uivalence, establishment of bioequivalence in transplant patients and in su
bgroups known to be poor absorbers, as well as long-term efficacy and safet
y studies in transplant patients. However, at the moment individual bioequi
valence is a theoretical concept, the practical benefits of which have not
statistically been proven. The proposed patient pharmacodynamic studies can
be expected to require an unrealistically high number of subjects to achie
ve sufficient statistical power. It is well established that the common pra
ctice of blood-concentration-guided dosing of cyclosporine efficiently comp
ensates for interindividual and intraindividual variability and allows for
safely switching cyclosporine formulations as bioinequivalent as Sandimmune
and Neoral. Recent studies comparing the generic cyclosporine formulation
SangCya with Neoral, including individual bioequivalence, bioequivalence in
transplant patients, and long-term safety after switching from Sandimmune
to SangCya, confirmed that it was valid to conclude bioequivalence of both
cyclosporine formulations based on standard average bioequivalence criteria
. Present FDA guidelines for approving bioequivalence can be considered ade
quate and sufficient for generic cyclosporine formulations.