The similarity question for biologicals and non-biological complex drugs.
For small - low molecular weight - molecule medicines a robust regulatory system has evolved over the years. This system guarantees high and constant quality of our (generic) medicines. Pharmaceutical equivalence and bioequivalence assessment are the pillars under that system. But there are complex medicines where the question of equivalence is more challenging to answer. For biologicals the paradigm of similarity rather than equality (the emergence of 'biosimilars') was developed in the past decade. This has been a program where an evolutionary, science based approach has been chosen by the frontrunner regulatory body, the EMA, with a 'learn and confirm' character. In addition, there is another group of complex drugs, the non-biological complex drugs, NBCDs, where the generic paradigm can be challenged as well. The NBCDs are defined as: 1. consisting of a complex multitude of closely related structures; 2. the entire multitude is the active pharmaceutical ingredient; 3. the properties cannot be fully characterized by physicochemical analysis and 4. the consistent, tightly controlled manufacturing process is fundamental to reproduce the product. NBCDs encompass product families such as the glatiramoids, liposomes, iron-carbohydrate colloids and many candidates of the group of the upcoming nanoparticulate systems. Following the main principles of regulatory pathways for biologicals (with appropriate product-by-product adjustments), instead of that for small molecules, would be the more logical strategy for these NBCDs. The status and outstanding regulatory issues for biosimilars and NBCD-similars/follow on versions were discussed at a conference in Budapest, Hungary (October 2014) and this commentary touches upon the issues brought up in the presentations, deliberations and conclusions.
Dept. Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, UIPS, Utrecht University, The Netherlands.
Daan J A
DJ
Crommelin
North Potomac, MD 20878, USA.
Vinod P
VP
Shah
Semmelweis University, Department of Pharmaceutics, Budapest, Hungary.
Imre
I
Klebovich
Nanotechnology Characterization Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.
Scott E
SE
McNeil
Teva Pharmaceutical Industries, Ltd., Discovery and Product Development, Global Research and Development, Netanya, Israel.
Vera
V
Weinstein
Vifor Fresenius Medical Care Renal Pharma Ltd., Glattbrugg, Switzerland.
Beat
B
Flühmann
Vifor Pharma Ltd, Glattbrugg, Switzerland; Dept. Pharmaceutical Sciences, Unit of Clinical Pharmacy and Epidemiology, University of Basel, Switzerland.
Stefan
S
Mühlebach
Dutch Top Institute Pharma, P.O. Box 142, 2300 AC Leiden, The Netherlands.
Jon S B
JS
de Vlieger
D000818:Animals; D001688:Biological Products / Q000009:adverse effects / Q000737:chemistry / Q000145:classification / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000737:chemistry / Q000145:classification / Q000627:therapeutic use*; D017277:Drug Approval; D016568:Drugs, Generic / Q000009:adverse effects / Q000737:chemistry / Q000145:classification / Q000627:therapeutic use*; D017408:Guidelines as Topic; D006801:Humans; D015394:Molecular Structure; D061214:Patient Safety; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000145:classification; D018570:Risk Assessment; D013329:Structure-Activity Relationship; D009626:Terminology as Topic; D013810:Therapeutic Equivalency
D001688:Biological Products; D059451:Biosimilar Pharmaceuticals; D016568:Drugs, Generic; D004364:Pharmaceutical Preparations
Biologicals; Biosimilars; Glatiramoids; Iron–carbohydrate complexes; Liposomes; Nanomedicines; Non-biological complex drugs