Equivalence of glatiramer acetate products: challenges in assessing pharmaceutical equivalence and critical clinical performance attributes.
INTRODUCTION
This review discusses the challenges to characterize and evaluate the peptide based drug glatiramer acetate (GA) and its follow-on products used for treatment of multiple sclerosis patients.


AREAS COVERED
GA is a highly complex mixture of peptides consisting of four amino acids. The various (physico)-chemical approaches and bioassays used for characterizing this complex drug product are described. It is not possible to link data from preclinical performance to outcomes observed in clinical trials as no critical attributes suitable for predicting the clinical performance in MS patients have been identified yet. The limited insight into the precise mechanism(s) of action of GA may explain why these critical clinical performance attributes still have not been identified.


EXPERT OPINION
The complexity of GA and lack of understanding of critical clinical performance attributes leads to a number of issues to be resolved as they hamper industry and regulatory bodies in designing and evaluating follow-on/generic applications of GA. The following questions are waiting to be addressed: Preclinical characterization vs clinical outcome: what is the relation? What are possible biomarkers? How to choose the right patient group? What is the experience with existing follow-on versions? Is there a place for GA 'betters'? How to evaluate existing and draft new guidance documents and pharmacopoeial monographs?
['Borchard|G|G|', 'Crommelin|D J A|DJA|']
D016568:Drugs, Generic D000068717:Glatiramer Acetate D006801:Humans D007166:Immunosuppressive Agents D009103:Multiple Sclerosis D013810:Therapeutic Equivalency
glatiramer acetate multiple sclerosis Copaxone European medicines agency (EMA) Food and Drug Administration (FDA) Glatiramoids Glatopa follow-on versions/generics genetic profiling physico-chemical characterization