Targeted development of biosimilar pharmaceutical products
Targeted development of biosimilar pharmaceutical products
Targeted development of biosimilar pharmaceutical products
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Fab<br />
Fc<br />
Using variability to identify CQAs<br />
Establishing structure- function relationships<br />
Afucosylated glycans as CQA<br />
Glycosylation impacts<br />
Effector functions<br />
- Complement interaction<br />
- Fc Receptor interaction<br />
- S - S -<br />
- S - S -<br />
� Minor glycan structure with high impact on in vitro potency 1<br />
� Established quantitative relationship between afucosylation<br />
and ADCC potency<br />
� Highly predictive model as ADCC = f(ManX,G0)<br />
1 Shields et al.(2002), Shinkawa et al. (2003), Kanda et al.(2007)<br />
HILIC glycan analysis<br />
30 | Thomas Stangler | EAPB SIG Regulatory Aspects for Bio<strong>pharmaceutical</strong>s | October 4th, 2010 | Business use only<br />
C H2 C H3<br />
Heavy chain<br />
S S<br />
S S<br />
G0<br />
G0F<br />
Man5<br />
21 23 25 27 29 [min]<br />
ADCC potency actual vs predicted<br />
ADCC Actual [%]<br />
500<br />
450<br />
400<br />
350<br />
300<br />
250<br />
200<br />
150<br />
100<br />
ADCC = f(ManX,G0)<br />
RSq=0,99 RMSE=11,298<br />
(filled circles only)<br />
50<br />
50 100 150 200 250 300 350 400 450 500<br />
ADCC Predicted [%] P
![Roy Forster [Kompatibilitätsmodus]](https://img.yumpu.com/7737040/1/190x135/roy-forster-kompatibilitatsmodus.jpg?quality=85)
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