NIST

Visiting Committee on Advanced 

Technology

Bioscience Panel

Robert Deans, Athersys

Gaithersburg 6.9.15

The statements and discussions contained in this presentation that are not historical facts constitute forward-looking statements, which can be

identified by the use of forward looking words such as “believes,” “expects,” “may,” “intends,” “anticipates,” “plans,” “estimates” and analogous

or similar expressions intended to identify forward-looking statements. These forward-looking statements and estimates as to future

performance, estimates as to future valuations and other statements contained herein regarding matters that are not historical facts, are only

predictions, and that actual events or results may differ materially. We cannot assure or guarantee you that any future results described in this

presentation will be achieved, and actual results could vary materially from those reflected in such forward-looking statements.

Information contained in this presentation has been compiled from sources believed to be credible and reliable. However, we cannot guarantee

such credibility and reliability. The forecasts and projections of events contained herein are based upon subjective valuations, analyses and

personal opinions. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities. Such an offer or

solicitation, if made, will only be made pursuant to an offering memorandum and definitive subscription documents
Product Development Portfolio

MultiStem®

adherent adult 

stem Cell 

isolated from 

bone marrow

o CHF

o Peripheral vascular disease

Cardiovascular

o Acute Myocardial Infarction → phase 2

o Acute Respiratory Distress Syndrome

Neurological

o Ischemic Stroke: phase 2

o Traumatic brain injury & related

o Spinal cord injury

o Multiple sclerosis

Other 

o Orthopedic (e.g., allograft combo) → RTI Surgical

o Tissue repair (e.g., wound, muscle)

Immunological 

o HSC Transplant / GVHD → phase 2/3 

o Solid organ transplant: phase 1

o Inflammatory Bowel Disease w/ PFIZER: phase 2

2

Overview of MultiStem® Production Process

Lot Release & Product 

Characterization Testing

Sterility

Potency

Identity and Viability

Stable Cytogenetics

Absence of ectopic tissue 

potential in vivo

4
Production Overview

Isolation / 

processing of 

donor cells

Master Cell Bank 

establishment

Cell harvesting & 

cryopreservation

Working cell bank 

establishment Working cell bank 

establishment

Working Cell 

Bank 

establishment

Production runs Production runs Production runs

Production runs

Central storage

Central 

processing

Local storage

Local processing / 

use

Media, factors, 

materials

Media, factors, 

materials

Media, factors, 

materials

• Cell factory / 2D-based production

• Bioreactor-based production

• Volume reduction, cell washing, buffer exchange

• Fill, finish and freezing

CELL BANKS PRODUCT MANUFACTURING

DISTRIBUTION / LOCAL USAGE

Stability Product release

Safety testing

5

Next Generation Xeno-free formulation, bioreactors in development
Current Development Needs Outstrip 

Technology and Capacity

• Technology: current MFG platforms (eg., Mab) were not developed to 

harvest viable cell product

– Downstream processing tools do not exist for efficient viable cell 

recovery (50% of COGS) or uniform cryoformulation and fill

– Analytical methods insufficient for many determinations particularly 

those linked to in vivo function (biodistribution, potency)

• Capacity: current 2D technologies cannot meet commercial need 

– international contract mfg capacity is rate limiting

• Regulatory: standards are dynamic in this field

– Raw material control is already and will become increasingly utilized as 

a trade barrier

• Fetal calf serum, donor ethnicity

– Accelerated Regulatory approval has become strong component of 

development decisions
Scale-Up vs Scale-Out Manufacturing Options

• 40 Layer Cell Factory, Hyperstack

– direct path to scale up with existing 

technologies in 2-D format

• Suspension bioreactor using 

microcarriers

– 3-D footprint targeting large scale stirred tank 

bioreactors mimicking MAb technology 

• Disposable patient designated options

– Quantum Hollow Fiber Bioreactor (Terumo)

– Xpansion Bioreactor (ATMI)
Heavy Lifting Scale Up Comes with Costs

Courtesy of Jon Rowley, Lonza
What Are We Facing in MFG Challenges?

With a clinical campaign producing 50 billion cells, 

a 5 trillion annual production requirement would entail 100 

campaigns per year in robotic 2D

5 trillion cells equates to 5 2000L bioreactor runs yielding 10e12 

cells: industry average $10 / million cells = $2 MM per run
In Process and Lot Release Quality Metrics

• Lot Release Template

– Sterility 

– Cytogenetics (sampling size; relevance of high sensitivity testing)

– Identity and viability (FACS based with options for long term cell cell viability)

– Potency (generally in vitro surrogates for presumed clinical mode of action)

– GAPS: testing for recovery post thaw for in vivo surrogates of function 

(attachment, biodistrubtion) and correlating in vitro function to in vivo 

hypotheses

• In process testing

– Marked gap in real time analytical tools to determine cell health and 

surrogates of in vivo function (emphasizing biophysical measurements of 

cytoskeletal integrity)

– Particulates and residual testing are complicated (microcarriers and fragments 

are particulates inseparable from cells

• Next generation cell manufacturing platforms and cell processing instruments are 

emphasizing automated sampling but need to be informed 
Cell Characterization Approach (Do We Like Big Data?)

Roobrouck 2011

Vaes 2013
Quality Approaches in Clinical Delivery

Clinical product flow – Clinical centers on study did not have stem cell 

processing lab capacity

Cryoformulation for direct infusion, optimal temperature storage became key 

development challenges

Past

Future

Reformulation of product at MFG facility with drop shipment for infusion w/o 

further testing

Formulation enables shipment at 4 degrees with 36 hour stability window
Clinical Measurements and Standards

• Biodistribution tools and sensitivity 

• Analytical markers for donor cell persistence 

• Biomarkers of disease response for treatment decisions 

• Companion diagnostics to determine response to treatment

Current emphasis is on emerging epigenetic tools as surrogates 

for clinical effect and brings computational standards into mix

– Transcriptional profiling

– Gene methylation 

– miRNA fingerprints
Going Forward

• Visibility and authority

– Center of Excellence for Cell Standards can provide guidance and 

nucleate resolution between engaged parties – currently lacking

– NIST has very effectively led industry engagement in ISO cell standards 

activity 

• Leading by science -- driving consensus

– Anticipating gaps and building tools with necessary sensitivity, 

durability

– Promoting non-competitive co-development options

• Gains industry segment endorsement and validation 

• Promotes international harmonization 
Working Group 4: 

Analytical Technology:

Tasks Tactics Deliverables Time-Line

(Months)

Define environments for 

deployment of 

technologies

• Brainstorm categories with team 

and align with WG3

• Cell Type: allogeneic vs. 

autologous cells

• Formulation: single cell vs. multicell (tissue engineered product)

• Point of Care versus centralised

•List of environments with 

required attributes for 

deployment in selected 

workflows 3-5

Defining available

technologies

•Review and categorize existing 

platforms using relevant criteria

•Register of technologies 

with objective mapping to 

relevant criteria

4-6

Pair relevant bioassays 

with technology 

•Align technologies with bioassays •Mapping of technologies 

to WG3 assays 

•Identification of gaps 

required

5-8

Define validation 

pathway 

•Validate identified assays on 

suitable platforms

•R&D investment to 

validate use of platforms 

on identified assays

8-12

NIST / Alliance for 

Regenerative Medicine 

Initiative
NIST

Visiting Committee on Advanced 

Technology

Bioscience Panel

Robert Deans, Athersys

Gaithersburg 6.9.15

The statements and discussions contained in this presentation that are not historical facts constitute forward-looking statements, which can be

identified by the use of forward looking words such as “believes,” “expects,” “may,” “intends,” “anticipates,” “plans,” “estimates” and analogous

or similar expressions intended to identify forward-looking statements. These forward-looking statements and estimates as to future

performance, estimates as to future valuations and other statements contained herein regarding matters that are not historical facts, are only

predictions, and that actual events or results may differ materially. We cannot assure or guarantee you that any future results described in this

presentation will be achieved, and actual results could vary materially from those reflected in such forward-looking statements.

Information contained in this presentation has been compiled from sources believed to be credible and reliable. However, we cannot guarantee

such credibility and reliability. The forecasts and projections of events contained herein are based upon subjective valuations, analyses and

personal opinions. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy any securities. Such an offer or

solicitation, if made, will only be made pursuant to an offering memorandum and definitive subscription documents