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.