Treatment of Inflammatory Bowel Disease with Biologics

264

Scientific Criteria for Demonstration of Biosimilarity

Issues in Biosimilar Manufacturing

Many of the synthetic and manufacturing processes involve proprietary techniques
to produce a biosimilar of the reference product. Specific manufacturing features
are summarized in Table 15.1. A large number of variables exist, among other fea-
tures, in the choice of the cell vector and cell expression system and cell line and
master cell banks. Likewise, conditions for expansion of the cell lines are proprie-
tary, and variables which may be highly controlled are not known to the biosimilar
manufacturer and may play into intellectual property concerns after drug approval
(Fig.15.1). Differences in synthesis can potentially result in different posttransla-
tional modifications, possiblyaffecting efficacy, safety, and immunogenicity of the
product [ 8 ]. For both the biosimilars for IFX and ADA, the FDA closely considered

Cloning and protein expression

Cloning into DNA vector

Source

DNA

Target DNA

Cell

expansion

Different cell line,
growth media,
method of expansion

Different cell line,

growth media,

bioreactor conditions

Different

operating

conditions

Different binding and

elution conditions

Different methods,

reagents, reference

standards

Purification through

chromatography

Characterization and

stability

Purified

bulk drug

Recovery through

filtration or

centrifugation

Cell production in

bioreactors

Protein production, purification and validation

Possibly same

gene sequence

Probably different

vector

Different cell expression

system

Transfer into host cell

expression

screening/selection

Fig.15.1 Biological drugs manufacturing: reprinted from Ref. [ 74 ]

C.Y. Ha and A. Kornbluth