Glycosylation technologies for biosimilars and ‘biobetters’

Biosimilares/Investigación | Posted 10/03/2010 post-comment0 Post your comment

According to Mr Hans Baumeister and Mr Steffen Goletz of Glycotope, human cell lines providing a human glycosylation pattern – such as those of Crucell (PER.C6), Cevec (CAP) and Glycotope (GlycoExpress) – have attracted increasing amounts of attention over the past years. In the case of biosimilars, regulatory approval now requires an extensive programme of bioequivalence studies to be undertaken to characterise the product in terms of its biochemical properties, safety and activity. As a consequence, glycosylated biosimilars need to be equipped with a similar pattern of glycosylation. For example, the degree of sialylation should not deviate by more than 20% from that of the original product. Hence, the chosen cell clone with high productivity has to be able to provide post-translational modifications as closely related to the originator’s cell line as possible. However, since glycosylation differs within clones, during the bioequivalence study it is often realised that the product carries different carbohydrates, usually resulting in a hyposialylation; this requires the screening process to be repeated in order to identify a new cell clone that is able to provide the equivalent glycosylation. Several glycosylation analysis technologies are available for the development and production of glycosylated biotherapeutics, applicable to both biosimilars and second-generation ‘biobetters’ (see Table 1).

picture14

Table 1: Glycosylation analysis technologies for biosimilars and ‘biobetters’

GlycoProfiling Characterisation of the cellular glycosylation machinery
(mRNA, enzymatic) and analysis of key structures on cell
colonies, cell lines and recombinant products
GlycoAnalytics Analysing the structure of N- and O-glycans attached to
recombinant proteins in detail
GlycoAccess The preclinical development of glycosylated
biotherapeutics including in vitro and in vivo bioassays
GlycoEngineering of cells Engineering of cell lines with a novel and stable
glycosylation profile without necessarily generating a
genetically modified organism for biopharmaceutical production
GlycoProtein engineering Recombinant protein and antibody engineering and
optimisation, such as addition/omission of glycosylation
sites, humanisation and chimaerisation
Glyco-Optimisation Optimisation of biotherapeutics to achieve a favourable
glycosylation pattern by targeting the fucosylation,
sialylation, galactosylation, antenarity and bisecting N-
acetylglucosamine to get an optimal bioactivity,
bioavailability and stability
GlycoBodies Generation of monoclonal antibodies specifically
recognising carbohydrates and carbohydrate-protein
mixed epitopes

Reference:

Hans Baumeister and Steffen Goletz. Novel Glycosylation Technologies for the Development of Biosimilars and Biobetters. Innovations in Pharmaceutical Technology. pp 52-58. December 2009.

Source: Innovations in Pharmaceutical Technology

comment icon Comments (0)
Post your comment
Most viewed articles
Sobre GaBI
INICIO/Sobre GaBI Posted 06/08/2009
EU guidelines for biosimilars
EMA logo 1 V13C15
INICIO/Directrices Posted 08/10/2010