The therapeutic equivalence of complex drugs.
When the patent of a small molecule drug expires generics may be introduced. They are considered therapeutically equivalent once pharmaceutical equivalence (i.e. identical active substances) and bioequivalence (i.e. comparable pharmacokinetics) have been established in a cross-over volunteer study. However this generic paradigm cannot be applied to complex drugs as biologics and a number of other therapeutic modalities. For copies of biologics the European Medicine Agency and other regulatory agencies have introduced a new regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. However for other complex drugs such as the iron-carbohydrate drugs, low molecular weight heparins (LMWHs), liposomal drugs and the glatiramoids regulatory guidance is still mostly lacking. In this paper we will discuss (therapeutic) experience obtained so far with these different classes of 'complex drugs' and their specifics to provide scientific arguments and criteria for consideration for a regulatory framework for the market authorization for these type of drugs.
Department of Pharmaceutical Sciences, Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands. h.schellekens@uu.nl
Huub
H
Schellekens
Ety
E
Klinger
Stefan
S
Mühlebach
Jean-Francois
JF
Brin
Gert
G
Storm
Daan J A
DJ
Crommelin
D000925:Anticoagulants / Q000493:pharmacokinetics; D001688:Biological Products / Q000493:pharmacokinetics; D003226:Congresses as Topic; D003257:Consumer Product Safety; D016568:Drugs, Generic / Q000009:adverse effects / Q000493:pharmacokinetics*; D019317:Evidence-Based Medicine; D005290:Ferric Compounds / Q000493:pharmacokinetics; D000077605:Ferric Oxide, Saccharated; D000068717:Glatiramer Acetate; D005937:Glucaric Acid; D006397:Hematinics / Q000493:pharmacokinetics; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D007880:Legislation, Drug; D008081:Liposomes; D010330:Patents as Topic; D010455:Peptides / Q000493:pharmacokinetics; D011506:Proteins / Q000493:pharmacokinetics; D018570:Risk Assessment; D013395:Sucrose / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
D000925:Anticoagulants; D001688:Biological Products; D016568:Drugs, Generic; D005290:Ferric Compounds; D006397:Hematinics; D006495:Heparin, Low-Molecular-Weight; D007166:Immunosuppressive Agents; D008081:Liposomes; D010455:Peptides; D011506:Proteins; D013395:Sucrose; D000068717:Glatiramer Acetate; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid