During this interactive Webinar your expert presenter, Dr. John Ludlow, PhD, will cover the general requirements for manufacturing and testing cell-based products in a regulatory compliant manner, sponsor expectations, awardee responsibilities, project control, and publications rights. Key Take-Aways: Understand the general requirements for manufacturing and testing cell-based products in a regulatory compliant manner Learn how cell-based products are evaluated Study protocol development How to develop “Good Laboratory Practices” that meet the needs of the academic researcher and the biotechnology company researcher Acquire tissue engineered and regenerative medicine product definitions Why discussions regarding ownership of IP need to take place well in advance

1. Company-Sponsored Research Agreements:
What Academic Laboratories Should Know Before
Accepting
Presented by John W. Ludlow, Ph.D.
For more information visit
http://bit.ly/816webinar
www.principalinvestigators.org

2. Live Webinar on Thursday, August 16, 2012 at 2:00 PM EST.
Social Media Exclusive Promotion
First 5 registrants receive FREE Live Webinar Attendance
by entering coupon code Free0816 at check-out.
Five seats already taken? Receive 50% off by entering code
50%0816 at check-out. Offer valid until 08/16/2012. Free webinar valid only for Live format.
To Register click the Order Now button or Visit http://bit.ly/816webinar
Registration Includes:
•Access for one phone line (unlimited listeners)
•Expert answers to your tough questions
•Complimentary attendee package with presentation handouts
•Live Q&A session (you may also e-mail your questions in advance)
•No Risk! 100% satisfaction guarantee

3. Company-Sponsored Research Agreements:
What Academic Laboratories Should Know Before Accepting
• Biotech companies continue to look for cost-effective ways to
conduct studies in support of product development
• Academic laboratories are a practical solution due to their
lower cost of services compared to commercial Contract
Research Organizations (CRO)
• This is especially true for studies supporting development of
tissue engineered and regenerative medicine products, as
they often require unique services which are typically outside
the usual CRO catalogue
• Company-sponsored research agreements can serve
academic researchers well, given the downward trend of the
funding rate at NIH, NSF, and private foundations, due to
increasing applications coupled with stagnant budgets

4. Presentation Goals
1. Provide insight into the
regulated environment under
which biotech companies are
required to operate
2. Better position the academic
laboratory so that the needs of
the company sponsor can be
met
Areas of emphasis for academic laboratory positioning are
highlighted in yellow

5. Presentation Outline
1. Introduction
• Defining TE/RM products
• Product evaluation
2. Requirements for study conduct
• Protocol development
• Good Laboratory Practices (GLP)
3. Sponsor expectations and awardee responsibilities
• Project control
• Intellectual property and publication rights
4. Assets appealing to commercial sponsors
5. Suggested resources
6. Summary and closing remarks

6. Defining TE/RM products
Why use TE/RM products as the example?
• Tissue Engineered/Regenerative Medicine (TE/RM)
products are relatively new with respect to
commercial development of treatment strategies
• Regulatory agencies (ie: FDA) are still developing
guidelines
• CROs may be at a disadvantage with respect to the
services they can provide for TE/RM products
• These factors help to position academic laboratories
as the “go-to” place to have critical work performed
for biotech companies developing TE/RM products,
provided certain expectations are met by the
academic laboratory

7. Defining TE/RM
•products
Tissue Engineering/Regenerative Medicine
(TE/RM) refers to a broad range of emerging
technologies that employ cells, biomaterials or
cell/biomaterial combinations (referred to as
“constructs”) to reconstitute functional tissue
or organ-like structures ex vivo (neo-organs)
and/or to catalyze organogenesis de novo by
leveraging the body’s innate ability to
regenerate itself
• Tissue engineering and regenerative medicine
are two terms often used synonymously
• A subtle difference between these terms may
be that tissue engineering emphasizes the
biomaterials and engineering components,
while regenerative medicine accentuates the
cellular contribution

8. Defining TE/RM products - Cells
1. Cell populations with application in TE/RM may be
broadly divided into two categories:
• Stem and progenitor cells
• Committed cell types
2. The cell is the primary Active Biological Ingredient (ABI)
3. Mechanisms of action include
• Leverage the “classical” properties of stem cells
(self-renewal, multi-lineage differentiation potential)
• Action-at-a-distance paracrine signaling pathways, whereby native stem
and progenitor cell populations are recruited
• Release cytokines and growth factors that promote angiogenesis and
neo-vascularization, modulate inflammatory, fibrotic and apoptotic cascades
and interfere with the onset of pathology while promoting repair and
regeneration
• Niche-specific directed differentiation towards defined developmental
lineages as regulated by contextual signaling cues derived from the
surrounding tissue or organ parenchyma

9. Defining TE/RM products - Biomaterials
• The most straightforward classification of
biomaterials is based on source, which may be of
natural or synthetic origin
• Examples of naturally occurring biomaterials
include gelatin, fibrin, hyaluronic acid (HA),
chitosan, silk, collagen and alginate
• Such naturally derived biomaterials are typically
well tolerated upon introduction within the body
and tend to reflect properties of native
extracellular matrix (ECM) well
• Naturally sourced biomaterials are potentially
problematic, presenting difficulties in sourcing,
quality control, reliability and reproducibility
across lot to lot
• Synthetic biomaterials such as poly-co-glycolic
acid (PGA), poly-lactic-co-glycolic acid (PLGA)
and poly-L-lactic acid (PLLA), offer better
reliability and reproducibility

10. Defining TE/RM products - Construct
1. Any TE/RM product or product candidate
incorporating a cellular ABI may be defined as a bi-
component “construct” or combination product
composed of:
• Cellular ABI
• Biomaterial or scaffold
2. As currently understood, the role of biomaterials
within today’s TE/RM products may include:
• Providing space for tissue repair and
regeneration
• Providing a foundation for the expansion and
delivery of therapeutic exogenous cell
populations
• Serving as a framework for the deposition of
extracellular matrix and paracrine signaling
factors
• Providing a foundation for the regeneration of
neo-tissue and neo-organs in a manner
appropriate to the local micro-environment

11. Product Evaluation
1. There is an established pathway for pharmaceutical compound development and
review by the FDA. Developers of TE/RM products have to improvise certain parts
of this established pathway, especially when it comes to ADME Tox testing
•Adsorption
•Distribution
•Metabolism
•Excretion
•Toxicity
2. Both in vitro and in vivo animal testing is required before the FDA will allow any
medicinal product to be tested in humans. These studies need to be well defined,
controlled, and monitored
3. TE/RM products rarely, if ever, lend themselves to such pharmacologic and
toxicologic studies as the ‘small molecule’ drug compound development programs
have

12. Product Evaluation
1. TE/RM product parameters to be tested in vitro often include cell viability,
morphology, phenotype, function, cryopreservation, biocompatability
2. Biomarker analysis of TE/RM products is the best correlation to the established
regulatory path of ADMET testing which pharmaceutical compounds go through,
and may include:
• Multiplex cytokine array and secretome analysis to address function,
potency, and fitness of use
• Flow cytometry and immuno-histochemical staining to assess protein
expression and phenotype
• Automated biochemical analyzers for metabolite analysis
• Real-time polymerase chain reaction to quantitate gene expression

13. Protocol Development
• Preclinical studies, sometimes referred to as preclinical development or
nonclinical studies, focus on obtaining safety data prior to testing in humans
during a clinical trial
• Data from iterative and feasibility testing is also collected and analyzed
during the pre-clinical studies
• The protocol contains the study plan
• This document allows for investigators at multiple sites to conduct the study
in an identical manner, which is critical for the data to be combined and
analyzed together
• The protocol serves as a reference tool for study managers and
administrators, in addition to providing the investigator with a description of
their duties and responsibilities
• In general the protocol explains the objective of the study, its design and
methodology
• The academic investigator should work with the sponsor on protocol
development

14. Protocol Development
• Title - name of what is being tested
• Testing Facility and Sponsor Facility information - contact info
• Study objectives – what is to be accomplished
• Regulatory compliance – following of SOP, GLP
• Animal welfare compliance
• Study personnel – names, titles, training
• Study schedule – when start, timelines, when completed
• Test system information – animals used
• Study design – a description of sequence and duration
• Test device information – what is being tested (test article)
• Technical and analytical procedures - include chain of custody
• Data analysis – usually statistical
• Reporting – a final report that has been audited for accuracy
• Biosafety precautions
• Collection and retention of source data - electronic, notebook
• Protocol amendments/deviations – changes made during progression of the study

15. Good Laboratory Practices (GLP)
• Good Laboratory Practice (GLP) ensures consistency and reliability of
non-clinical laboratory and research organization results by instituting a
quality system of controls
• GLP guidelines focus on the processes undertaken for non-clinical
safety study planning, performance, monitoring, recording,
achievement, and reporting
• GLP certification was established by regulatory agencies to garner a
degree of confidence that the work submitted to them is properly
conducted and adequately documented to allow for anyone skilled in the
art to replicate the results
• GLP study costs are approximately 10-times the cost of conducting a
non-GLP study, and are not necessary until an organization needs to
obtain regulatory approval for further product development
• Since many academic laboratories do not have the infrastructure to
rigorously comply with these guidelines, having an outside auditor come
in and assess the level of compliance, and provide a detailed report,
may be advised

16. Good Laboratory Practices (GLP)
A GLP study requires:
• Staff documentation, including responsibilities for all personnel involved
• An approved and valid study design
• A quality management program
• Personnel training documents
• Standard Operating Procedures (SOP)
• Study performance (including study plan and how the study will be
conducted)
• Statistical analysis of study data (where applicable)
• Results reporting
• Records and reports storage

17. Good Laboratory Practices (GLP)
• The purpose of quality
management is to make sure that
mistakes are not made during the
study which can negatively impact
the outcome
• Quality management will focus on:
• Controls
• Record keeping
• Personnel competence for
the assigned tasks

18. Good Laboratory Practices (GLP)
•The effectiveness of GLP
•Personnel training:
• Controls
• Record Keeping
• Personnel competence
for the assigned tasks

19. Good Laboratory Practices (GLP)
1. A Standard Operating Procedure (SOP)
is an approved, written procedure
describing how a task or operation is to
be performed
2. It ensures that operations are
performed over time in as close to an
identical manner as possible, and that
this performance is in compliance with
applicable regulations
3. The following is a list of information
essential to all SOP:
• Heading
• Approval or Effective Date
• Version Control
• Introduction
• Scope
• Purpose
• Approval Signature
• Document History

20. Good Laboratory Practices (GLP)
• Information headings for the
remainder of the document
• The procedure itself should be
described in short steps

21. Project Control
• The project, which is a set of interrelated tasks, should be
‘under control’ (maintaining the output within a desired
range) by strictly adhering to the protocol
• Careful attention to detail during protocol development
should alleviate the need for amendments/deviations
• The sponsor has project control regarding protocol
amendments/deviations
• The academic investigator has project control regarding
execution of the protocol

22. Intellectual Property (IP)
• Intellectual property is defined as creations of
the mind for which property rights are
recognized under intellectual property law
• Owners of IP are granted certain exclusive
rights, thereby denying others the right to
perform the same action or produce the same
product in the same manner
• These exclusive rights permit the owners to
benefit from the property they have created,
thereby producing a financial incentive for
creating and investing in IP
• A patent by itself does not grant the inventor
the right to commercialize the protected
technology; a patent grants the right to
exclude others from commercializing it

23. Intellectual Property (IP)
• Continuing to secure additional IP,
as well as leverage existing IP, are
critical to a company’s success
• Ultimately, IP needs to be translated
into a revenue-generating product for
a company to enjoy some degree of
financial stability
• A discussion regarding ownership of
IP needs to take place well in
advance of any work performed

24. Publication Rights
• A clear description of
publication policy (i.e.: who
owns the data, who needs to
be consulted as to if or when
the data can be published, who
is responsible for publications)
should be included in the
Protocol
• This description is often
provided by the sponsor
• Work with the sponsor to
ensure that this policy is
compatible with the academic
laboratory/institution policy

25. Assets appealing to commercial sponsors
• Cell-based assays, culturing
techniques
• Unique in vitro and in vivo models
• Biomaterials synthesis,
characterization
• Specialized equipment
• A reasonably regulatory compliant
operation
• Commercial-friendly technology
transfer office

26. Suggested Resources
• GLP Guidelines
CFR Code of Federal regulations Title 21
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=58
• SOPs
http://www.biopharminternational.com/biopharm/Article/Assuring-the-Effective-Use-of-Standard-Operating-P/Arti
• Personnel training and documentation
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/QualitySy
stemsRegulations/MedicalDeviceQualitySystemsManual/ucm122447.htm
• Biotechnology Centers
http://www.biotech.sunysb.edu/
http://www.ncbiotech.org/
http://www.pabiotechbc.org/biotech/directory.htm
• University Technology Transfer Office
http://www.techtransfer.umich.edu/

27. Summary and Closing Remarks
• Company-sponsored research agreements
can serve academic researchers well
• Follow GLP guidelines as close as possible
• Adherence to the study protocol, timetable,
and final reporting are crucial

28. Live Webinar on Thursday, August 16, 2012 at 2:00 PM EST.
Social Media Exclusive Promotion
First 5 registrants receive FREE Live Webinar Attendance
by entering coupon code Free0816 at check-out.
Five seats already taken? Receive 50% off by entering code
50%0816 at check-out. Offer valid until 08/16/2012. Free webinar valid only for Live format.
To Register click the Order Now button, Visit http://bit.ly/816webinar or
Call 800-303-0129 ext 506.
Registration Includes:
•Access for one phone line (unlimited listeners)
•Expert answers to your tough questions
•Complimentary attendee package with presentation handouts
•Live Q&A session (you may also e-mail your questions in advance)
•No Risk! 100% satisfaction guarantee