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TRANSCRIPT
Point-of-Care Cell Processing Technologies
What’s in clinical use in the U.S.
R. Lee Buckler
8 September 2013
ISCT North American Regional Meeting. Philadelphia, PA
consultant
www.celltherapygroup.com business development industry intelligence analysis strategy
blogger | commentator | analyst
www.celltherapyblog.com
www.twitter.com/celltherapy
facilitator & connector
www.linkedin.com – LI cell therapy industry group
www.alliancerm.com – Co-Chair of Communications & Education
Committee, Alliance for Regenerative Medicine (ARM)
Entrepreneur
www.regenerativemedicinejobs.com | www.celltherapyjobs.com
www.cellwasher.com
R. Lee Buckler
Disclosure
Director: Hemostemix (www.hemostemix.com)
Disclaimer I just pulled an all-
nighter
POINT-OF-CARE CELL PROCESSING
AN OVERVIEW OF TECHNOLOGIES IN U.S. CLINICAL USE
Goals 1. To identify the primary categories and types of point of-care cell processing
technologies currently in clinical use in the United States
2. To provide examples of different technology platforms
3. To introduce top-level regulatory and commercial implications associated
with the different types of technology
Disclaimers & Definitions
Subject-Matter Disclaimers:
1. Not my area of expertise
2. Impossible to answer what’s in clinical use in the U.S.
• Lack of FDA enforcement
• Surgeons are...well...surgeons
Assumptions & Definitions:
“Point-of-Care” = when clinicians deliver cells to patients at the time of care
- most often perioperative (pre-, intra-, post-operative) but may be
associated with non-surgical procedures (e.g., injections)
“used in the U.S.” = what’s used – not what’s approved, legal, or compliant
Disclaimers & Definitions
Assumptions & Definitions (con’t):
“Cell Processing” = processing of cells at (or immediately prior to) the time
of cell delivery to a patient
• Autologous end-to-end processing (collection, separation,
processing, delivery)
• ‘Upstream’ processing – collection, separation
• ‘Downstream’ processing – post-manufacture, pre-administration
processing (e.g., thaw, wash, volume reduction, formulation)
“Cells” – any product containing (or likely to contain) live cells when
delivered to the patient
“Technologies’ – kits and devices not services or clinical
POINT-OF-CARE CELL PROCESSING
AN OVERVIEW OF TECHNOLOGIES IN U.S. CLINICAL USE
Goals 1. To identify the primary categories and types of point of-care cell processing
technologies currently in clinical use in the United States
2. To provide examples of different technology platforms
3. To introduce top-level regulatory and commercial implications associated
with the different types of technology
POINT-OF-CARE CELL PROCESSING
AN OVERVIEW OF TECHNOLOGIES IN U.S. CLINICAL USE
Goals 1. To identify the primary categories and types of point of-care cell processing
technologies currently in clinical use in the United States
2. To provide examples of different technology platforms
3. To introduce top-level regulatory and commercial implications associated
with the different types of technology
Primary categories of POC cell processing technologies
in clinical use in the United States
Collection Cell
Separation POC
Processing Delivery
Formulation
Intraoperative Stem Cell Therapy
M.B. Coelho, J.M.S. Cabral, J.M. Karp
Annu Rev Biomed Eng. 2012; 14:325-349
Post-Mfg POC Processing
Primary categories of POC cell processing technologies
in clinical use in the United States
Collection Cell Separation POC
Processing Post-Mfg POC
Processing Delivery
Formulation
Intraoperative Stem Cell Therapy
M.B. Coelho, J.M.S. Cabral, J.M. Karp
Annu Rev Biomed Eng. 2012; 14:325-349
Primary categories of POC cell processing technologies
in clinical use in the United States
Collection
Liposuction (canula, aspirator,
cannister)
Bone Marrow (syringes, filters,
containers)
Whole Blood (needles, tubing,
containers)
Apheresis Blood (apheresis devices)
Cell Separation
Centrifugation
Rosetting
Filtration
Antibody - flow cytometry
(e.g., MACS)
Adherence
Microfludic
Processing
Ultrasound activation
Laser activation
Photoactivation
Culture activation
Post-Mfg Processing
Washing excipients
Volume Reduction
Activation
Formulation
Input into clinical syringe or other
delivery tool
Combination with other products (e.g., scaffold)
POINT-OF-CARE CELL PROCESSING
AN OVERVIEW OF TECHNOLOGIES IN U.S. CLINICAL USE
Goals 1. To identify the primary categories and types of point of-care cell processing
technologies currently in clinical use in the United States
2. To provide examples of different technology platforms
3. To introduce top-level regulatory and commercial implications associated
with the different types of technology
Examples of POC cell processing technologies
in clinical use in the United States
Collection Cell Separation POC Processing
(other than separation)
Often collection and separation are packed together into the kit or device but occasionally they are separate. BioAccess BM Collection System Fenwal BM Kits Microaire PAL Cannula Whole blood needles
Pall Purecell Cytori Celution GID 700 / LifeCEll Resolve TerumoBCT Harvest Smart PreP2 Depuy Cellect EmCyte Genesis CS KanekaMSC Cell Separation Kit GE Ficoll-Paque & Percoll Arteriocyte Magellan Cytomedix Autologel or Angel BioSafe Sepax2 CellCoTec INSTRUCT Charter Medical
Typically POC cell processing is simply cell separation / isolation / enrichment / purification but occasionally other processes are involved such as some type of cell activation. Adistem AdiLight Intellicell
Terumo BCT Elutra / Optia Fenwal Amicus Ageless Regenerative Medicine system
Primary categories of POC cell processing technologies
in clinical use in the United States
Delivery Formulation
Typically formulation into a format ready for clinical administration is the final stage of the processing platform . In some instances formulation is a unique step in the process such as is the case for CellCoTec’s INSTRUCT which seeds the tissue-separated cells and bone marrow-derived cells on a scaffold then ready for implantation.
Post-Mfg POC Processing
BioSafe Sepax
Devices awaiting launch (Fenwal, GE, etc)
Primary categories of POC cell processing technologies
in clinical use in the United States
Collection Cell Separation POC
Processing Post-Mfg POC
Processing Delivery
Formulation
Intraoperative Stem Cell Therapy
M.B. Coelho, J.M.S. Cabral, J.M. Karp
Annu Rev Biomed Eng. 2012; 14:325-349
• Blood disorders
• Oncology
• Orthopedics (cartilage, muscle)
Commercial Implications
Types of Indications
1. Soft tissue
2. Aesthetic / Cosmetic
3. Inflammation
4. Pain
5. Arthritis
6. Multiple sclerosis
7. (everything)
POINT-OF-CARE CELL PROCESSING
AN OVERVIEW OF TECHNOLOGIES IN U.S. CLINICAL USE
Goals 1. To identify the primary categories and types of point of-care cell processing
technologies currently in clinical use in the United States
2. To provide examples of different technology platforms
3. To introduce top-level regulatory and commercial implications associated
with the different types of technology
Commercial Implications
Types of Companies
1. Bioprocessing companies • GE Healthcare
• BioSafe
• Pall
2. Medical device companies • MicroAire
• Fenwal / Fresenius
• Depuy, a J&J company
• TerumoBCT
• Biomet
3. Founder/Inventor companies • GID
• SynGen
• StemCell Partners
4. Cell Therapy companies • Cytori
• Cytomedix
Artreus Dr. Shin’s Thrombo Kit
PAL Cannula
Sepax2
Amicus
Magellan
Commercial
Implications
Types of Cell
Sources & Output
Company Device Cell Source Adistem Adistem kits & AdiLight2 Adipose
Cytori Puregraft Adipose
Celution 800/CRS Adipose
GID GID 700 Adipose
SVF-1 Adipose
Intellicell Intellicell sytem Adipose
Lipogems Lipogems Adipose
Medi-Khan Lipokit / 416D / Celltibrator Adipose
Microaire Lipofilter Adipose
StromaCell Adipose
Millennium Medical Technologies Nutational Infrasonic Cell Acquisition Adipose
Tissue Genesis Icellator Adipose
Viafill Viafill System Adipose
Ageless Propietary system & training courses Adipose, BM, Blood
TerumoBCT Arteus; REVOS Blood
BioCUE Platelet Concentration System BM
DePuy Cellect BM
Fenwal BM Collection Kits and Filters BM
CellCoTec INSTRUCT BM and knee cartilage
EmCyte Genesis CS BM, Whole blood
Kaneka BM MSC Separation Device Bone Marrow
Thermogenesis MxP Bone Marrow
Res-Q Bone Marrow
Harvest SmartPReP2 hole blood
Fresenius Blood Cell Separator PB
Fenwal Amicus PB, BM
SynGen SynGenX PB, BMA, Adipose
Axis-Shield & Stem Cell Technologies LymphoPrep & SepMate PB, UCB, BM
Biosafe Sepax 2 RM UCB, BM, Blood
Arthrex Double Syringe (ACP) System Whole blood
Biomet Clotalyst Autologous Serum Activation Solution Whole blood
GPS III Whole blood
Blood System Medical Yes PRP Kit Whole blood
Cytomedix AutoGel Whole blood
Angel Whole blood
Estar Medical / Medira Tropocell / MyCells Whole blood
Grand Aespio Puch-Man Thrombo Kit Whole blood
Vivostat Vivostat system Whole blood
RegenLab RegenKit Whole blood, Adipose, BM
Arteriocyte Magellan Whole blood, BM
Pierce Surgical ClotMaster "Hula Cup" Whole blood, BM
GE Healthcare Ficoll-Paque and Percoll Various
Miltenyi Biotec CliniMACS Various
Of 43 devices reviewed:
Sources
Adipose = 38%
BM = 38%
WB or PB = 52%
Other = 12%
Output
ADRCs / SVF / fat graft
36%
PRP / PPP
38%
MNCs / TNCs
24%
Other
19%
Commercial Implications
Benefits of the device model
1. Circumvents many of the limitations and challenges of exogenous cell therapy
by avoiding processing which takes it over the ‘minimal manipulation “threshold,
removes the process from costly cGMP-compliant processing facilities and
personnel, and may not require as extensive clinical testing prior to market.
2. Traditionally the regulatory pathway for medical devices has been much quicker
and less costly than biologics but where the device is processing and outputting
a biologic that line is blurring.
Commercial Implications
A Few Observations
1. There are many device companies willing to push well beyond regulatory
boundaries because enforcement is so remarkably slow
1. Claims
2. Facilitating (if not encouraging) off label use
3. Selling into markets without appropriate approvals
2. FDA regulation is tightening, approvals now require much higher thresholds of
evidence and claims are more restrictive. CBER is now governing most cell
processing devices. But when combined with lack of enforcement this leads to
double-standard in the marketplace
3. Surgeons are incentivized (and phenotypically engineered) to push the
envelope, be innovative and use novel devices and products
4. Devices are capable of delivering an end product very competitive with
autologous biologics with a far different (often lower) regulatory and cost
structure.
Commercial Implications
A Few Observations
5. Poorly designed and power trials have generated piles of unconvincing data.
6. Almost never is the issues of final product heterogeneity, characterization, cell
count, release specification addressed.
7. As PRP illustrates obtaining reimbursement for these device-based procedures
is often very difficult.
8. Device developers have a history of racing to market . Their bold and
aggressive development pathway matches the surgeons appetite but often runs
afoul of regulators.
9. There are some who suspect that the FDA’s recent letter to MiMedx re it’s
claimed s.361 status will have some spill-over into those walking a similarly fine
line in the cell processing device industry.
Commercial Implications
Challenges
10. There are significant knowledge gaps the different types of device developers
Bioprocess companies often don’t
understand the medical surgery
market.
Not prepared for regulatory
hurdles. Users are very
different. Clinical studies and claims are
foreign.
Medical device companies often don’t appreciate the complexities
of and risks related to
bioprocessing
Surgeons often don’t
appreciate the complexities
and risks associate with cell processing.
Cell therapy and cell processing
people / companies don’t appreciate the
parameters of the medical market .
Tendency to over-
engineer. Often
underestimate complexity of
device development.
science develops.
so should your strategy.