Changing paradigms in bioequivalence trials submitted to the EMA for evaluation - A clinical and regulatory perspective.
BACKGROUND
The selection of a robust bioequivalence (BE) study designs for registering a generic product remains still a hard task. This task is still challenging despite the fact that generic products are much needed by health care providers in economical terms. Thus, BE study designs could be a means to allow companies to reduce costs and reach the market earlier. We therefore investigated whether different approaches in various products assessed by the European Medicines Agency during the approval phase resulted in a reduction in resources required to show bioequivalence for different medicinal products.


METHODS
European Public Assessment Reports (EPARs) for off-patent medicinal products authorised within the European Union (EU) through the centralised procedure during the period 2007-2015 were retrieved and reviewed to identify the clinical studies that resulted in fewer number of subjects, the number of centres or trial duration versus the two-period crossover design.


RESULTS
7 studies out of 108 were considered as having benefitted from having a different design. Differences noted included having a different dose allocation scheme, having a different number of dosing periods, having a different number of treatment arms, and having one study evaluating different strengths. Benefits noted included a decrease in the number of subjects and centres required, decreases in study duration and a reduced number of studies required to demonstrate bioequivalence.


CONCLUSIONS
Bioequivalence studies can be designed in a specific manner to require fewer resources to carry out. Fewer resources required to register a medicinal product, could impart an advantage to companies (such as to be first on the market) or could even translate to making medicines more accessible (such as cheaper) to patients.
Medicines Authority, Sir Temi Żammit Buildings, Malta Life Sciences Park, San Ġwann, Malta.
Nathaniel
N
Refalo
Medicines Authority, Sir Temi Żammit Buildings, Malta Life Sciences Park, San Ġwann, Malta.
Daniel
D
Chetcuti
Medicines Authority, Sir Temi Żammit Buildings, Malta Life Sciences Park, San Ġwann, Malta.
Amy
A
Tanti
Medicines Authority, Sir Temi Żammit Buildings, Malta Life Sciences Park, San Ġwann, Malta; Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
Anthony
A
Serracino-Inglott
Medicines Authority, Sir Temi Żammit Buildings, Malta Life Sciences Park, San Ġwann, Malta; Department of Biology, School of Pharmacy, University of Tor Vergata, Rome, Italy.
John Joseph
JJ
Borg
API, active pharmaceutical ingredient; BCS, Biopharmaceutics Classification System (BCS); BE, bioequivalence; BSA, body surface area; Bioequivalence; CHMP, Committee for Medicinal Products for Human Use; EMA, European Medicines Agency; EPAR, European Public Assessment Report; EU, European Union; Generic medicinal products; MA, marketing authorisation; Marketing authorisation; NHS, National Health System