Selection of subjects
The subject population for bioequivalence studies should be as homogeneous as possible; studies should therefore generally be performed with healthy volunteers so that variability, other than in the pharmaceutical products concerned, is reduced. Clear criteria for inclusion/exclusion should be established. If possible, subjects should be of both sexes; however, the risk to women will need to be considered on an individual basis and, if necessary, they should be warned of any possible dangers to the fetus if they should become pregnant. They should normally be in the age range 18-55 years and of weight within the normal range according to accepted life tables. Subjects should preferably be non-smokers and without a history of alcohol or drug abuse. If smokers are included, they should be identified as such. Volunteers should be screened for suitability by means of standard laboratory tests, a medical history, and a physical examination. If necessary, special medical investigations may be carried out before and during studies, depending on the pharmacology of the drug being investigated.
If the aim of the bioequivalence study is to address specific questions (e.g. bioequivalence in a special population), the selection criteria will have to be adjusted accordingly.
Phenotyping and/or genotyping of subjects may be considered for safety reasons.
Patients versus healthy volunteers
If the active substance is known to have adverse effects and the pharmacological effects or risks are considered unacceptable for healthy volunteers, it may be necessary to use patients under treatment instead. This alternative should be explained by the sponsor.
Monitoring the health of subjects during the study
During the study, the health of volunteers should be monitored so that the onset of side-effects, toxicity, or any intercurrent disease may be recorded, and appropriate measures taken. Health monitoring before, during and after the study must be carried out under the supervision of a qualified medical practitioner licensed in the jurisdiction in which the study is conducted.