the commercial manufacturing

FROM IDEA TO PRODUCT:

THE PATHWAY FROM ACADEMIC INNOVATION TO A

COMMERCIAL MANUFACTURING PROCESS

Timothy Fong, PhD, MBA

VP Technology & Product

Development

PCTCELLTHERAPY.COM | PROPRIETARY | 2

Forward Looking Statements

PCT is a wholly-owned subsidiary of NeoStem, Inc., effective January 19, 2011.

Included in this presentation are “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, as well as historical information. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements, or industry results, to be materially different from anticipated results, performance or achievements expressed or implied by such forward-looking statements. When used in this presentation, statements that are not statements of current or historical fact may be deemed to be forward-looking statements. Without limiting the foregoing, the words “plan," "intend," "may," "will," "expect," "believe," "could," "anticipate," "estimate," or "continue" or similar expressions or other variations or comparable terminology are intended to identify such forward-looking statements, although some forward-looking statements are expressed differently. Our future operating results are dependent upon many factors and our further development is highly dependent on future medical and research developments and market acceptance, which is outside our control. Forward-looking statements may not be realized due to a variety of factors and we cannot guarantee their accuracy or that our expectations about future events will prove to be correct. All forward-looking statements attributable to us are expressly qualified in their entirety by these and other factors. We undertake no obligation to update or revise these forward-looking statements, whether to reflect events or circumstances after the date initially filed or published, to reflect the occurrence of unanticipated events or otherwise, except to the extent required by federal securities laws.


Pathway to Commercialization

University or Academic Lab

Idea Conception and Preclinical Proof-of-Concept studies

University Hospital or Biotech Cell Processing

Facility

Process Development and Clinical Manufacturing

Product Characterization

Commercial Manufacturing

“Scale up and/or Scale out”

Volume and economies of scale


Challenges in Commercialization

of a Cell-Based Product

•Convert great science into clinical therapy

•Develop and Establish a robust manufacturing process

•Develop and Establish product specifications

(characterization and potency)

•Design and support clinical trials

•Optimize economics, manufacturing

and distribution logistics

•Develop and strengthen IP

•Manage evolving regulatory framework


Steps to a Robust Manufacturing Process

• Technology Transfer

• Process & Product Development

• Engineering & Qualification Runs

• Clinical & Commercial Manufacturing

• Storage and Distribution


Technology Transfer

• Technology transfer

• Transfer of knowledge

• Cell product characteristics, identity, purity, potency

(MOA)

• Procedures and protocols

• Tissue or cell sourcing

• List of materials and reagents

• Specialized or custom equipment and instruments

• Gap analysis


Process & Product Development

• Process Development

• Scaled up or scale out

• cell enrichment

• cell culture

• Closed systems

• cell enrichment

• cell culture

• Single-use supplies

• Operating parameters

• Interim product sampling and testing

• Product Assay Development

• Identity

• Purity

• Potency


NeoStem’s VSEL R&D Program

Differential Centrifugation

Percoll

Antibody magnetic bead

selection of cells

Flow cytometric sort and analysis

for VSELs

Cryo-preservation


NeoStem’s Athelos Treg R&D Program

Differential Centrifugation

Ficoll

Flow cytometric sort

for Tregs

Ex vivo expansion

Harvest and cryopreservation


Assay Development for Product Characterization

• Assay development and validation for product identity,

purity, potency

• In-process and final product testing for process run

parameters

• Process optimization or improvement

• Validation studies for product cryopreservation, storage

and shipping stability

CD4

SSC

CD25

CD

12

7


Engineering & PQ Runs

• Engineering Runs

• Full-scale “shake down” of the manufacturing process

• Data to support run parameters and product

specifications

• Finalization of production batch records

• Qualification Runs

• Full “dress rehearsal” prior to manufacturing clinical

trials

• Process Validation Prior to Commercial Manufacturing



cGTP / cGMP

• Manufacturing Process Control

• Facility design, construction, validation and

operations support

• Quality systems, development and implementation

21 CFR 210-211: Current Good Manufacturing Practices in Manufacturing,

Processing, Packaging or Holding of Drugs

21 CFR 610: Biological Products:

General, Subpart B - Establishment Standards

21 CFR 1271: Current Good Tissue Practice for

Manufacturers of Human Cellular and Tissue

Based Products

21 CFR Part 11: Electronic Records; Electronic Signatures


Storage and Distribution

cGMP standard operating procedures

in all phases of storage and transit

• Validation of storage conditions and

shipping container

• Secure point-to-point chain of

control and custody

• Real-time package tracking

• Specialized air and ground courier

network

• Quality assurance at each transfer

point


Steps to a Commercial Manufacturing Process

Technology Transfer

Process & Product Development

Engineering & Qualification Runs


Storage and Distribution

the commercial manufacturing

Documents