This document discusses definitions, classifications, and trends related to cell therapy. It defines cell therapy as the administration of cells to the body for therapeutic purposes and regenerative medicine as replacing or regenerating tissues to restore function. Classifications of cell therapies include immunocellular vs regenerative approaches and autologous vs allogeneic cell sources. The trends show growing interest in immunocellular therapies and use of mesenchymal stem cells and adipose tissue-derived cells. Regulatory classifications of cell therapies vary between countries and agencies and certain cell therapies can be difficult to clearly define, creating potential confusion.

1. Alexey Bersenev, MD, PhD
Advanced Cell Therapy Laboratory,
Yale-New Haven Hospital, Yale University www.celltrials.info
8th the BioProcessing Summit, Boston, Aug. 15, 2016
CELL THERAPY –
Definitions, Classifications and Trends

2. 56 58
85
117
133
111
179
243
259
293
0
50
100
150
200
250
300
2011 2012 2013 2014 2015
industry academia
Total number of cell therapy trials: academic vs. industry

3. • Cell therapy – administration of cells to the body with
therapeutic purpose
• Regenerative medicine - replaces or regenerates
human cells, tissues or organs, to restore or establish
normal function
• Cellular immunotherapy – using immune or other
types of cells for modulation of host immune system
or direct elimination of pathogen/ tumor
Definitions:

4. What if cell is just a vehicle for therapeutic agent?
Is irradiated cancer cell line a cellular therapy?
Is manipulation of cell in vivo (cells are not
administered) a cell therapy?
Is cell-based therapy better term?
Problem with definitions -
Cell (cellular) Therapy

5. cells
tissue
engineering
Scaffold
(matrix)
genes
small
molecules
Regenerative Medicine as generic term
Regenerative
Medicinebio-
molecules device

6. RM is not equal to cellular immunotherapy. Equation
is confusing!
Tissue engineering was rebranded as RM
RM and Cell Therapy may have different challenges
and obstacles (example: EPO as regenerative)
Organizations successfully exploit RM brand to attract
public trust, money, and lobby politicians (CIRM, ARM)
Problem with definitions -
Regenerative Medicine

7. • Immunocellular
• Regenerative
Classification based on
mechanism of action

8. 46 62
137 156 174
121 175
191 220 252
0%
20%
40%
60%
80%
100%
2011 2012 2013 2014 2015
Immuno- Regenerative-
Trend: Immunocellular therapy vs. cell-based
regenerative medicine

9. • Autologous
• Allogeneic
• Auto + Allo
• Xenogeneic
Classification based on donor cell origin

10. Industry is not in favor of allo- model
Total
number of
registered
clinical trials
31 26
48
70
79
24 29
34
45
54
0
20
40
60
80
100
120
140
2011 2012 2013 2014 2015
allo
auto
Trend: Allo- vs. auto- commercial trials

11. Origin:
• Somatic cell therapy
• Germline cell modifications
Differentiation:
• Stem cells
• Progenitor cells
• Mature (differentiated) cells
Cell types classifications

12. 52
80
90
116
140
22
42
60
81
96
38
25
13
22
26
3 3
8
11
41
32
17
0
20
40
60
80
100
120
140
2011 2012 2013 2014 2015
MSC total
T-cells
BM MNC
HSPC
adipose SVF
ESC
DC
NK cells
Trend: Interest to major cell types

13. 23 24
19
28
40
31
58
71
89
100
0
20
40
60
80
100
2011 2012 2013 2014 2015
industry academic
Cell therapy trials: cell type – mesenchymal stem cells

14. 5
9
13 22
26
6
13
10 18
37
0%
20%
40%
60%
80%
100%
2011 2012 2013 2014 2015
Fresh SVF Adipose SC expanded
Trend: Interest to adipose tissue-derived cells

15. Based on:
• Degree of cell manipulation
• Homology
• Risks to recipient
Disregard:
• Cell biology, cell type and origin
• Therapeutic intention
Regulatory classifications

16. Cell Therapy
(somatic cell,
including stem
cells)
Gene Therapy
Devices related
to cells
351 HCT/P (drug, biologic or device)
361 HCT/P (tissues)
cartilage, bone, tendon, skin,
ocular tissue, reproductive cells
and tissues…
HCT/P
Regulatory classification: USA
Cells & Tissues but not HCT/Ps:
(blood and blood components, minimally manipulated bone marrow for
homologous use, xenogenic cells/ tissue…)

17. Regulatory classification: EU
Cell-based/ gene therapy
Biologic - ATMP (EMA – CAT)
Somatic
Cell
(including stem
cells)
Gene
Therapy
Transplants/
TransfusionsTissue
Engineering

18. Regulatory classification: Japan
Class I
(iPS/ ES cells,
gene-modified cells,
allo-)
Class II
(auto- somatic cells
– cultured/
nonhomologous
use)
Class III
(auto- somatic cells
– homologous use,
Processed somatic
cells)
Regenerative Medical Product Blood Transfusions
HPC transplantation
Assisted Reproduction
(no gene modification, not derived
from stem cells)
Processed cells (manufacturing)
Not processed or
Specific processed cells

19. Cell Therapy Gene Therapy
Tissue
Engineering
Biologics (medicinal product)
Human Tissue
cartilage, bone, ligament, tendon,
skin, heart valves, blood vessel,
fascia, amnion
MFDS (former KFDA)
Regulatory classification: South Korea
Cell Therapy as medical practice
(minimally manipulated auto- or allo- cells)

20. Some products hard to fit in definitions (ATMP or
361/351). To avoid confusions, contact regulators as early
as possible
Not always clear difference between ”product” and
“medical procedure” / “tissue for transplantation”
Autologous not gene-modified cells freshly used at point-
of-care is not easy to fit in definitions of “regulated
product”
Immunocellular therapy called “regenerative medical
product” (Japan)
No definitions for ”stem cell product”
Confusions about regulatory definitions