Selection of subjects
The subject population for bioequivalence studies should be as homogenous as possible and therefore studies should generally be performed with healthy volunteers in order to reduce variability other than in the pharmaceutical products. Clear criteria for inclusion/exclusion should be stated. If feasible, they should belong to both genders (however, the risk to women will need to be considered on an individual basis and, if necessary, a warning issued to them about any possible dangers to the foetus if they should become pregnant). They should normally be in the age range of 18-55 years with a weight within the normal range according to accepted life tables. The subjects should preferably be non-smokers and without a history of alcohol or drug abuse problems. If smokers are included they should be identified as such. The suitability of the volunteers should be screened using 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 individual drug being investigated.
In case the aim of the bioequivalence study is to address specific questions (e.g., bioequivalence in a special population) the selection criteria have to be adjusted accordingly.
Phenotyping and/or genotyping of subjects may be considered for safety reasons.
Patients versus healthy volunteers
If unacceptable pharmacological effects or risk may ensue because of known adverse effects of the active substance for healthy volunteers, it may be necessary to use patients under treatment rather than healthy volunteers. 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 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 takes place.