by different manufacturing steps covering upstream processing (USP), downstream
processing (DSP), formulation, and fill and finish operations. Typical USP operations are the manufacturing of the Master Cell Bank (MCB) and Working Cell Bank
(WCB), seed cell production, and cell expansion at L-scale. DSP operations include
cell harvest, cell separation, washing as well as concentration procedures, and
medium exchange. Different economic studies have demonstrated that the USP,
and in particular the hMSC expansion, represents the main cost driver when examining the whole manufacturing process [3, 13, 14]. To reduce the number of
experiments and to increase the process knowledge during either the design and
development or the optimization phase, virtual representations of the hMSC production process, so called “Digital Twins,” are helpful. These virtual models allow
an approximation of real process conditions, a fact that is particularly important for
Table 1 Available hMSC-based products (as of May 2020)
Medicinal
product
Company
Therapy/cell type
Indication
Market
Allostem
AlloSource
Allogeneic ASC
Bone regeneration
USA
Alofisel
TiGenixTakeda
Allogeneic ASC
Anal fistula in Crohn’s
disease
EU
AstroStem
Biostar
Autologous ASC
Alzheimer’s disease
Japan
aJointStem
Biostar
Autologous ASC
Degenerative arthritis
Japan
Cartistem
Medipost
Allogeneic UCM
Degenerative arthritis
Korea
Cupistem
Anterogen
Allogeneic ASC
Anal fistula in Crohn’s
disease
Korea
Grafix
Osiris
Therapeutics
Allogeneic
BM-MSC
Soft tissue defects
USA
HearticellGramAMI
FCB
PharmiCell
Autologous
BM-MSC
Acute myocardial
infarction
Korea
Neuronata-R
Corestem
Allogeneic
BM-MSC
Amyotrophic lateral
sclerosis
Korea
OsteoCel
NuVasive
Allogeneic
BM-MSC
Spinal bone regeneration USA
OvationOS
Osiris
Therapeutics
Allogeneic
BM-MSC
Bone regeneration
USA
Prochymal
Osiris
Therapeutics
Allogeneic
BM-MSC
Acute graft vs. host
disease
Canada
Stemirac
NIPRO Corp
Autologous
BM-MSC
Spinal cord injury
Japan
Stempeucel
Stempeutics
Allogeneic
BM-MSC
Critical limb ischemia
India
TemCell
JCR Pharm.
Allogeneic
BM-MSC
Acute graft vs. host
disease
Japan
Trinity Elite
Orthofix
Allogeneic
BM-MSC
Bone regeneration
USA
Trinity Evolution Orthofix
Allogeneic
BM-MSC
Bone regeneration
USA
190
V. Jossen et al.
processing (DSP), formulation, and fill and finish operations. Typical USP operations are the manufacturing of the Master Cell Bank (MCB) and Working Cell Bank
(WCB), seed cell production, and cell expansion at L-scale. DSP operations include
cell harvest, cell separation, washing as well as concentration procedures, and
medium exchange. Different economic studies have demonstrated that the USP,
and in particular the hMSC expansion, represents the main cost driver when examining the whole manufacturing process [3, 13, 14]. To reduce the number of
experiments and to increase the process knowledge during either the design and
development or the optimization phase, virtual representations of the hMSC production process, so called “Digital Twins,” are helpful. These virtual models allow
an approximation of real process conditions, a fact that is particularly important for
Table 1 Available hMSC-based products (as of May 2020)
Medicinal
product
Company
Therapy/cell type
Indication
Market
Allostem
AlloSource
Allogeneic ASC
Bone regeneration
USA
Alofisel
TiGenixTakeda
Allogeneic ASC
Anal fistula in Crohn’s
disease
EU
AstroStem
Biostar
Autologous ASC
Alzheimer’s disease
Japan
aJointStem
Biostar
Autologous ASC
Degenerative arthritis
Japan
Cartistem
Medipost
Allogeneic UCM
Degenerative arthritis
Korea
Cupistem
Anterogen
Allogeneic ASC
Anal fistula in Crohn’s
disease
Korea
Grafix
Osiris
Therapeutics
Allogeneic
BM-MSC
Soft tissue defects
USA
HearticellGramAMI
FCB
PharmiCell
Autologous
BM-MSC
Acute myocardial
infarction
Korea
Neuronata-R
Corestem
Allogeneic
BM-MSC
Amyotrophic lateral
sclerosis
Korea
OsteoCel
NuVasive
Allogeneic
BM-MSC
Spinal bone regeneration USA
OvationOS
Osiris
Therapeutics
Allogeneic
BM-MSC
Bone regeneration
USA
Prochymal
Osiris
Therapeutics
Allogeneic
BM-MSC
Acute graft vs. host
disease
Canada
Stemirac
NIPRO Corp
Autologous
BM-MSC
Spinal cord injury
Japan
Stempeucel
Stempeutics
Allogeneic
BM-MSC
Critical limb ischemia
India
TemCell
JCR Pharm.
Allogeneic
BM-MSC
Acute graft vs. host
disease
Japan
Trinity Elite
Orthofix
Allogeneic
BM-MSC
Bone regeneration
USA
Trinity Evolution Orthofix
Allogeneic
BM-MSC
Bone regeneration
USA
190
V. Jossen et al.