Untitled - Keck Graduate Institute

TEAM MASTER’S PROJECT PRESENTATIONS
The Team Master’s Project (TMP) is the capstone activity
for students in the Master of Bioscience (MBS) and the
Postdoctoral Professional Master of Bioscience Management
(PPM) degree programs at KGI. In accordance with KGI’s
mission of translating the potential of the life sciences into
practice, the TMP offers a rigorous and experiential learning
opportunity which immerses students in the type of work
many will pursue after graduation. TMPs are supported
by interdisciplinary teams made up of three to six students
who work with sponsoring companies to address real world
company objectives.
Replacing the traditional Master’s thesis work found in
standard programs, these projects provide students with the
opportunity to apply their marketing, business, financial
and science training to state-of-the-art corporate challenges.
Importantly, our teams are advised by both KGI faculty
and expert industrial liaisons to assure that academic rigor
is paired with pragmatic focus. Our typical TMP Team is
composed of MBS, PPM, and senior undergraduate students
from The Claremont Colleges (Harvey Mudd, Pitzer,
Claremont McKenna and Scripps) resulting in a rich and
diverse set of skills, backgrounds and expertise.
TMP activities emphasize problem-solving, project
management, new business opportunity, productive
teamwork, and effective communications skills that will be
critically important to KGI graduates as they pursue careers in
the bioscience industries. Representing about 35 percent of a
student’s final year of academic work, these contract research
projects are designed to produce valuable deliverables for the
sponsoring companies.
TEAM MASTER’S PROJECT PRESENTATIONS
WEDNESDAY, MAY 7, 2014
Program
7:30 am
Continental Breakfast
517 Bldg., Founders Room
8:00 am
Introductions
517 Bldg., Founders Room
8:20 am - 11:45 am
Team Presentations (Groups A and B)
Time
Group A
Location: 517 Bldg.,
Lecture Hall
Group B
Location: 535 Bldg.,
152 Classroom
8:30 - 9:00 am
Lilly “Data Mining”
Pfizer
9:00 - 9:30 am
Amgen “Regulatory”
Lilly “CHORUS”
9:30 - 10:00 am
BioMarin
Boehringer Ingelheim “Perfusion
Process”
10:00 - 10:15 am
Break
10:15 - 10:45 am
Gilead “Operational Excellence”
Tanner/CBS/Lambda/ Pomona
College
10:45 - 11:15 am
NuSil
Gilead “Value Stream”
11:15 - 11:45 am
Amgen “Supply Chain”
Edwards Lifesciences
11:45 - 12:45 pm
Lunch
517 Bldg., Founders Room
12:45 - 1:30 pm
Combined Corporate Liaisons’ Meeting
517 Bldg., Room 147
1:30 - 4:45 pm
Team Presentations (Groups C and D)
◆
Time
Group C
Location: 517 Bldg.,
Lecture Hall
Group D
Location: 535 Bldg.,
152 Classroom
1:30 - 2:00 pm
Life Technologies
Monsanto
2:00 - 2:30 pm
City of Hope “Epigenetic
Therapies”
Boehringer Ingelheim “Quality
Control”
2:30 - 3:00 pm
Brace Pharmaceuticals
Raptor Pharmaceuticals
3:00 - 3:15 pm
Break
3:15 - 3:45 pm
Lilly “Regulatory”
Sigma-Tau
3:45 - 4:15 pm
Regeneron
Sarepta Therapeutics
4:15 - 4:45 pm
City of Hope “HIV Therapies”
Project Summaries
Global Regulatory Landscape and U.S. Regulatory
Strategy for Lung Cancer, Hypercalcemia of
Malignancy and Graft Versus Host Disease
Sponsor Company
Students:
Jixi He
Jinghua ‘James’ Jia
Nathan Lyman
Tina Mathew
Nandaj Nair
Vishnu Sreedhar
Corporate Liaison:
Naseem Kabir
Faculty Advisor:
Susan Bain
Amgen focuses on areas of high unmet medical need
and leverages its biologics manufacturing expertise to
strive for solutions that improve health outcomes to
dramatically improve people’s lives. A biotechnology
pioneer since 1980, Amgen has grown to be the world’s
largest independent biotechnology company. As Amgen
continues to build a pipeline of therapeutic medicine
with breakaway potential, its current products provide
improved therapies to millions of patients around the
world.
The Amgen Regulatory TMP developed regulatory
landscapes for hypercalcemia of malignancy and lung
cancer during the 1st semester. During the second
semester, the team focused on a similar document for
Graft Versus Host Disease (GVHD). Finally, the team
developed a regulatory strategy for a hypothetical
GVHD product seeking approval in the US
marketplace. These landscapes and this strategy were
presented to the senior staff of Amgen. The team will
present the 2nd semester effort focused on GVHD.
To construct an FDA regulated landscape for therapies
directed at GVHD, the team first characterized the
disease demographics and pathologies. This work
was then expanded to include an examination of
the literature for previously approved therapies,
clinical studies and investigational treatments for this
disease. Ultimately, the team located essential public
information and compiled a series of milestone reports
with key observations and insights which might help
guide Amgen as it navigates the regulatory barriers for
GVDH disease. The Amgen TMP provided the student
team with an excellent experience in the regulatory
challenges associated hypercalcemia of malignancy,
lung cancer and GVHD. Ultimately, the TMP team
provided Amgen with detailed supporting information
for these diseases as well as some discussion of
the potential regulatory approaches to pursue
investigational drugs in these therapeutic areas.
Project Summaries
Benchmarking Study to Evaluate Best Practices in
Supply Chain Management
Sponsor Company
Students:
Jagan Choudhary
Disha Goswami
Hannah Huvard
Sheetal Khanna
Phillyne Shiu
Corporate Liaisons:
Aylene Bao
Kyle Mak
Andrew Mica
Faculty Advisor:
Craig Adams
Amgen, Inc., a world class biopharmaceutical
company, discovers, develops, manufactures and
delivers therapeutic products for the disease areas of
oncology, hematology, inflammation, bone health,
nephrology and cardiovascular diseases. Since its
founding in 1980, Amgen has grown rapidly to
attain a market capitalization of $91 billion with a
world-wide presence in over 50 countries. Amgen
currently produces 12 products for 20 different
disease indications while pursuing numerous
additional drugs through Amgen R&D. Amgen is
headquartered in Thousand Oaks, California and
employs 20,000 staff worldwide.
As Amgen’s network evolves and grows to supply
more countries with more products, their supply
chain will face increasing challenges in planning,
sourcing, and delivery. As a result of this growth,
Amgen has sought to evaluate optimal supply chain
models to ensure time to market, outstanding patient
supply and efficient delivery of its products across
world markets.
The Amgen Supply Chain TMP was asked to
benchmark supply chain best practices across a
number of selected industries. Model companies
were chosen, by brainstorming with Amgen
liaisons, from industries with high value products,
stringent regulations, or highly efficient supply
chain behaviors. The team gathered information
about supply chain management and supply chain
strategies for these prominent targeted companies
in the pharmaceutical, biotechnology, diagnostic,
consumer technology and e-commerce industries.
From this research, the Amgen Supply Chain
TMP identified best practices and common trends
within and across these industries. After analyzing
these industrial trends, the KGI team pursued two
focus areas in the spring semester: global trade
management and inventory management. Ultimately,
the team performed an in-depth qualitative analysis
of supply chain opportunities before making
recommendations to Amgen regarding their use of
new tools in global trade management and inventory
management.
Optimization of the Capital Asset
Procurement Process
Sponsor Company
Students:
Alison Blaschke
Wendy Chen
Srishti Goel
Michelle Plummer
Sean Reimer
Ryan Shade
Corporate Liaison:
Paul Lauer
Faculty Advisor:
Tina Etcheverry
BioMarin Pharmaceutical, Inc. began developing and
commercializing therapies for rare genetic diseases
in 1997. Their strategy to develop first-to-market
therapies with an orphan disease status has been
remarkably successful resulting in a product portfolio
with five approved products and multiple pre-clinical
and clinical candidates. Strategically, BioMarin intends
to continue to focus on areas of high unmet medical
need and to leverage their expertise to improve health
outcomes for patients.
BioMarin’s five-year trend reveals an average revenue
growth of 14% each year. This level of growth has
encouraged BioMarin to re-examine strategic aspects of
the operations organization to more efficiently support
the growing list of products. As BioMarin pursues
major milestones in 2014 including the launch of a new
drug, Vimizin, it is critical their processes withstand
the influx of new projects as well as the increasing
workload. BioMarin has undertaken the task of
defining their ‘Invest-to-Divest End to End Business
Process’ with an end goal of alignment, efficient
decision-making, and communication. The BioMarin
TMP team was tasked to analyze current business
processes and assist in developing the ‘Deliver Capital
Assets’ sub-processes.
Risks, resources, cost, and time-to-implement have
been identified as key performance metrics to consider
when devising recommendations for improved capital
procurement efficiency. By analyzing primary and
secondary literature and conducting interviews with
key stakeholders at BioMarin and industry leaders, the
team has exposed areas of inefficiencies in the process
and identified factors that differentiate BioMarin from
leaders in the industry. Upon completion of the project,
the team delivered five specific recommendations
outlining changes that might have the greatest potential
to benefit BioMarin. The team provided detailed
justification for implementing these recommendations
and has assigned a process owner within BioMarin to
facilitate the implementation of these solutions.
Project Summaries
Evaluating and Optimizing the Perfusion Process
for a CMO Universal Platform
Sponsor Company
Students:
Carlos Damas
James Miller
John Min
Robin Modi
Flaka Radoniqi
Melissa Reynoso
Corporate Liaisons:
Jon Coffman
Samantha Wang
Faculty Advisor:
KiriLynn Svay
Boehringer Ingelheim (BI), headquartered in Germany,
is one of the world’s leading contract manufacturing
organizations (CMO) and one of the largest privatelyheld life science companies. BI has an established
position in the biologics market having brought over
20 products successfully to the market for companies
such as Amgen, Bayer, Genentech, and Pfizer. Overall,
BI provides a comprehensive CMO platform with
diverse capabilities from cell line development to
product fill and finish, including the capacity to scale
from clinical to commercial production. BI’s mission is
to add value through innovation includes investigating
the potential benefits of the perfusion process.
The perfusion process offers an excellent solution for
the manufacturing of unstable proteins. Perfusion
allows proteins to be quickly removed from a cell
culture bioreactor and stored under stable conditions
for further processing rather than remaining in
a potentially damaging cell culture environment.
Furthermore, perfusion offers Boehringer Ingelheim
the opportunity to reduce costs by using smaller scale
bioreactors than the traditional setup for batch or fed
batch cell cultivation. The goal of the BI TMP was: to
grow and achieve a very high cell density on various
cell lines; compare the retention analysis for the BI
media versus commercial media; and, compare the
density and product concentration of the fed-batch and
perfusion process modes.
Successful perfusion experimental runs, for baseline
data analysis, were conducted during the fall semester
using commercialized media on various CHO
(Chinese Hamster Ovary) cells. During the spring
semester, the team ran various experiments utilizing
adapted cell lines and collected valuable information
which provided insights into the advantages of the
BI proprietary media over the commercial media. By
demonstrating, via the perfusion process, the ability
of multiple cell lines to reach and maintain a high
density in the BI media, the BI Perfusion Process
TMP validated important aspects of the perfusion
process. Ultimately, this information provided BI
with critical data which supported the potential of a
universal mammalian cell perfusion platform for the
manufacturing of pharmaceutical products.
Offering:
Master of Bioscience
Postdoctoral Professional Masters
Postbaccalaureate Premedical Certificate
PhD Programs
PharmD
www.kgi.edu
Project Summaries
Streamlining the Quality Control Method
Transfer Process
Sponsor Company
Students:
Michael Choy
Tiffani Sandoval
Ivan Xa
Corporate Liaisons:
Rio Denoga
Ken Gomez
Rong Wu
Faculty Advisor:
Larry Grill
Boehringer Ingelheim (BI), headquartered in Ingelheim,
Germany, is a family-owned global corporation founded in 1885 which is focused on Human Pharmaceuticals and Animal Health. The BI site in Fremont, CA is
a division of the Global Biopharmaceutical Network.
BI Fremont has state-of-the-art process development
and manufacturing equipment with the capacity to
annually produce over 200,000 liters (L) of cell culture
product. BI Fremont currently supports both GMP
clinical and commercial production, and has a global
track record of over 140 biologic projects including 22
commercial products.
Due to the commercial and clinical production capability, capacity, and flexibility of the BI facility, many
companies contract with BI as a Contract Manufacturing Organization (CMO). This contract business generates significant revenue to the company. Concomitant
to transferring the manufacturing process to BI, these
companies must also transfer analytical methods which
ensure the product’s efficacy, strength, purity, integrity,
quality, and safety. These methods allow on-site/realtime testing for in-process sampling, as well as release
and stability testing. Unfortunately, method transfers
can be tedious and may take up to 60-90 days to complete. Additionally, because there are approximately 10
method transfers per project, project transfer timelines
can take as long as 8-9 months. Lastly, because there
may be as many as 3-5 concurrent projects, the organization may be transferring 30-50 methods at a time.
The BI Quality Control TMP was tasked with analyzing the current method transfer processes and implementing solutions to streamline the process and reduce
method transfer times. The BI TMP team approached
this project using the DMAIC (Define, Measure,
Analyze, Improve, Control) methodology to construct
a current-state process map, identify bottlenecks, eliminate waste in the system, and develop a future-state
process map. Additionally, the team interviewed clients
to gain input from the customer and conducted industry research to determine how many methods might be
waived. This research and analysis enabled the team
to create and implement solutions to streamline the
method transfer process. In conclusion, the BI TMP
Team made recommendations which should enable
BI to expedite method transfers. It is hoped that these
recommendations might allow Boehringer Ingelheim to
reduce the cost and time required for method transfers
– and, ultimately allow BI to tackle more projects and
generate more revenue.
Project Summaries
Evaluation and Recommendation of Investment
Opportunities in Rare Diseases
Sponsor Company
Students:
Mirza Ahmed
Nikitha Bollipalli
Pranay Madan
Haley Patoski
Fernando Pimentel
Mrudang Shah
Corporate Liaisons:
Thiago Brasil
Vinzenz Ploerer
Faculty Advisor:
Tim Cote
Brace Pharmaceuticals, Inc., is an investment company
created by EMS S/A, the largest pharmaceutical
company in Brazil. Brace Pharmaceuticals is looking
for partners interested in co-developing pharmaceutical
products that complement its corporate and product
development strategy. These opportunities include
innovative, life-changing therapies for diseases with
high unmet medical need, including orphan diseases.
Brace Pharmaceuticals intends to diversify its
project portfolio by investing 80% of its funds in
late-stage clinical phase projects and 20% in earlier
phase projects. Brace’s initial investments have been
completed and evaluation of additional feasible
projects is ongoing. The Brace TMP’s main objective
was to identify a short-list of projects that complement
Brace’s investment strategy in the area of rare diseases.
The team focused its initial efforts on evaluating
potential candidates that have been granted orphan
designations, orphan product approvals and/or
awarded FDA grants to support clinical studies for
rare diseases. These viable candidates were then
analyzed based on scientific and medical rationale,
regulatory considerations, intellectual property rights,
and commercial potential. Future efforts will focus on
identification and evaluation of candidates which have
been approved in other markets.
Development and Commercialization Strategy for
Novel Epigenetic Cancer Therapy
Sponsor Company
Students:
Christine Chen
Brandon Hunter
Joanna Naymark
Sergio Villegas
Corporate Liaison:
David Horne
Faculty Advisor:
Animesh Ray
City of Hope is a renowned non-profit organization
focused on world-class research and treatment for
cancers and other life-threatening diseases. The
Beckman Research Institute (BRI) is one of six
key strategic research programs at City of Hope,
responsible for expanding the world’s biological
understanding of diseases such as cancer, HIV/AIDS
and diabetes. The BRI encompasses over 60 years of
expertise in scientific research, where investigators are
committed to identifying opportunities at the cellular
and molecular level to predict, prevent, diagnose, treat
and cure such serious diseases.
The BRI is interested in cancer related epigenetics,
particularly in gene-regulatory proteins involved in
cancer expression. Epigenetic regulators alter gene
expression without changing actual DNA sequences.
A class of proteins important for epigenetic regulation,
histone methyltransferases (HMTs), plays multiple
important roles in certain cancers. The BRI has recently
developed a novel class of chemical entities that
target a specific HMT for potential cancer treatment.
This class of compounds targets a promising new
therapeutic area that may have significant application
in a number of cancer indications.
The City of Hope Epigenetics TMP team was
tasked with creating a product development and
commercialization plan for a potential epigenetic
cancer therapy, based on a novel HMT inhibitor
developed at the Beckman Research Institute.
Throughout the project, the team investigated
standards of care in a number of cancer indications,
conducted detailed interviews with key opinion leaders
in the field, and performed market and competitive
analyses to evaluate the commercial potential of a
new epigenetic cancer therapy. This effort resulted
in the final deliverable which included a strategic
recommendation outlining the critical steps needed to
maximize the potential for commercial, clinical, and
regulatory success of this new therapy.
Project Summaries
Developing a Business Plan for HIV
Stem Cell Therapies
Sponsor Company
Students:
Brigette Duran
Melissa Campos
Varant Shirvanian
Corporate Liaison:
Dave DiGiusto
Faculty Advisor:
Joel West
City of Hope is a leading research and treatment
center for cancer and other life-threatening diseases.
It includes the Comprehensive Cancer Center, the
Beckman Research Institute, and the Irell and Manella
Graduate School of Biological Sciences. The City of
Hope celebrated its 100th anniversary in 2013 and is
located in Duarte, California. Research at the City of
Hope focuses on cancer biology, diabetes, immunology,
and virology.
The Beckman Research Institute at City of Hope has
developed a novel gene-modified stem cell therapy
to treat HIV. To support this therapy, the City of
Hope has just completed a human clinical trial
which demonstrated the safety of the autologous
stem cell product. To help the Beckman Research
Institute commercialize its technologies, the City
of Hope engaged KGI to assess the feasibility of
commercialization through creation of a spin-off
company.
The City of Hope HIV Therapies TMP team
was charged with creating a business plan and
commercialization strategy for this stem cell therapy. To
accomplish this goal, the team: conducted a competitive
analysis of current HIV therapies; performed primary
and secondary market research regarding the RNAbased science of this therapeutic technology; and studied
the unique challenges of commercializing a genetherapy product. After reading key scientific articles and
speaking to subject matter experts in venture capital,
regenerative medicine, regulatory approval, technology
transfer, and biotech operations, the team developed a
comprehensive business plan. The plan highlights the
market potential for HIV gene therapeutics; identifies
critical marketing risk factors; and recommends an IP,
marketing, operations and development strategy for
the new firm. The business plan also includes detailed
financial projections and identifies a series of funding
milestones for equity investors to fund its operations.
Project Summaries
Design, Implementation, and Testing of a
New Biomedical Engineering Test Bench
Sponsor Company
Students:
Andrew Barajas
Anthony Capili
Stanley Chang
Colin Costello
Ryan Hernandez
Frank Lam
Luis Valenzuela
John Wu
Corporate Liaison:
Alex Holland
Faculty Advisor:
Hsiang-Wei Lu
Edwards Lifesciences is the global leader in the science
of heart valves and hemodynamic monitoring. Founded
in 1958, Edwards has grown into a global company
with a presence in approximately 100 countries and
more than 7,800 employees around the world. Edwards
focuses on medical technologies that address large
and growing patient populations in which there are
significant unmet clinical needs, such as structural heart
disease and critical care monitoring.
Edward’s hemodynamic monitoring instruments
measure cardiovascular parameters that are derived
from sensor data. Typically, sensors are attached to,
or integrated within catheters, which are inserted
into blood vessels. Catheter associated sensors then
generate signals that allow healthcare personal to
make conclusions about patients’ health. Sophisticated
algorithms within Edward’s patient monitoring
software interpret these cardiovascular signals so
that advanced health information can be displayed.
Unfortunately, the only way Edwards can test these
algorithms and their patient monitoring devices is
through the use of animal studies and recorded patient
data from a limited patient population. Further,
many of Edward’s available test benches are limited
in function and cannot be used for complex R&D
investigations. Yet test bench analysis is essential in
understanding the various cardiovascular signals found
in the field.
The core goal of the Edwards TMP was to facilitate
software design, implementation, and testing of
a new biomedical engineering test bench which
would permit the testing and validation of Edward’s
products. The project focused on four interrelated
subprojects: physiological modeling, embedded systems
development, and physical experimentation. The key
objective of the physiological modeling group is to
further develop Edward’s cardiovascular modeling
tools making them more robust and easier to use. The
key objective of the embedded systems development
and the physical experimentation subgroup is to
create a reliable and fully developed test bench which
accurately simulates cardiovascular signals and
expands Edward’s cardiovascular research capabilities.
In conclusion of the Edwards TMP, the team developed
a signal test bench which is expected to enhance
Edwards research capabilities. This test bench utilizes
Python™ tools for aortic pressure signal generation
and modeling, and a physical test bench with protocols
for performing frequency response experiments with
Edwards products.
“Anytime you get students who are learning, they ask questions and
draw unique conclusions. They raise ideas and bring up points you
may not have thought of otherwise. They're in a different paradigm,
than people who are in the company and heading down a certain path
just because that path was decided on.”
–Bonnie Anderson, CEO and co-founder, Veracyte, Inc.
“KGI makes the process easy, even the contracting, and its students
are coming from a different perspective, developing creative new ideas
we haven't thought of before.”
–Tom Lester, BioMarin
Project Summaries
Establishment of a Capital Project Management
Process for the Engineering Team at Gilead,
San Dimas
Sponsor Company
Students:
Abasi Ene-Obong
Kekoaponolani Iobst
Ashi Jain
Pancham Parikh
Nitesh Singhvi
Corporate Liaisons:
Steven Brannan
Chris Deitz
Fred Kilpatrick
Catherine Kuo
Mark Nelson
Faculty Advisor:
Jennifer Ton
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes
innovative medicines in areas of unmet medical need.
Gilead was founded in 1987 in Foster City, California.
Over the past 25 years, it has grown to become one of
the world’s largest biopharmaceutical companies, with
approximately 6,000 employees across five continents.
Gilead has a portfolio of products and a pipeline of
investigational drugs directed at therapies for HIV/AIDS,
liver diseases, serious respiratory and cardiovascular
conditions, cancer and inflammation. The Gilead site in
San Dimas, one of the three manufacturing sites owned
by Gilead, is a 200,000 square foot facility.
The San Dimas operation supports manufacturing, filling,
packaging and labeling for a variety of products representing over 70% of Gilead’s products destined for the
“Americas”. To support these operations, the engineering department at San Dimas, manages capital projects
ranging from $3,000 to over $40 million using different
management tools. Unfortunately, Gilead’s current capital
management approaches, adapted from the chemical
industry, do not address pharmaceutical industry specific
requirements such as aseptic manufacturing. In addition,
the lack of a uniform predefined business process may
introduce capital management errors which can lead to
extended project timing and increased costs.
The Gilead TMP team was responsible for designing a
‘Business Process’ to enable the planning, prioritization,
management, monitoring and evaluation of all capital projects at San Dimas. Additionally, the team was
responsible for creating documentation including SOPs,
guidelines and templates to support the capital process.
To achieve these objectives, the team identified industry
best practises for the capital project management process
through literature review and input from key stakeholders. The team was able to establish a standard ‘Business
Process’ tailored specifically for projects at San Dimas.
32 key documents for engineering and project management aspects were identified and developed to support
the implementation of these processes. After launch of
the process, Gilead, San Dimas should be able to adopt
a streamlined approach to all its capital projects, leading
to significant savings in terms of time and money. In the
future this process may potentially be expanded to other
sites at Gilead.
Project Summaries
Commercial Solutions to Improve
Operations Efficiency
Sponsor Company
Students:
Cassy Chang
Rohan Sukumar
Naoya Sun
Kelly Theel
Corporate Liaison:
Gwen Steavens
Faculty Advisor:
Jim Osborne
Gilead Sciences is a research-based biopharmaceutical
company that discovers, develops and commercializes
innovative medicines in areas of unmet medical need.
Its focus is to transform and simplify care for people
with life-threatening illnesses around the world. Gilead’s
portfolio of products and investigational drugs includes
treatments for HIV/AIDS, liver diseases, serious respiratory and cardiovascular conditions, cancer and inflammation. Gilead has several manufacturing facilities.
Gilead’s San Dimas facility is a sterile-fill facility which
is responsible for the manufacturing of an antifungal
agent, AmBisome®; the packaging and labeling of Gilead’s antiviral products; and, the distribution of products
to the America’s and the Pacific Rim.
Pharmaceutical manufacturing processes are strictly
regulated and accurate documentation is of paramount
importance. Every step in the manufacturing process
must follow established protocols. Documentation,
during the manufacturing process, provides a summary
of real-time events and confirms all validated processes
were carried out according to specifications. Currently,
Gilead’s San Dimas facility has highly manual methods
of documenting manufacturing processes. Key documented processes include data entry by shift leaders
to account for labor allocation and the compilation of
FDA-mandated batch records. Each of these processes
is manually carried out by employees. While the San
Dimas’ manual documentation methods are sufficient
to ensure that their products meet FDA standards, their
manual documentation methods do not provide management the level of visibility needed to track and assess
performance and overall equipment efficiency (OEE).
The Gilead Operational Excellence TMP team was
tasked with understanding data gathering systems currently in place in the manufacturing department at the
San Dimas facility. Further, the team was asked to recommend improvements or to recommend new systems
for Operational Equipment Effectiveness (OEE) studies
which would include the analysis of labor and process
tracking. After analyzing the current data gathering
systems, they identified equipment, process and people
tracking needs and prioritized them in the form of a user
requirement specification list (URS). A comprehensive
search for commercial OEE solutions was performed
which identified the top options. Eventually, the team
identified solutions for high, mid, and low tier automated options as well as an improved manual option. These
recommendations were followed by a SWOT analyses
of the solutions to evaluate how well they meet San Dimas’s needs. Finally, the team provided an implementation plan for the improvement/new system in the facility.
Analysis of the Pharmaceutical Industry’s
Approach to Measuring and Controlling Subvisible
Particulates in Parenteral Drug Products
Sponsor Company
Students:
Carrie Cao
Luigi Mendoza-Ochoa
Nandaj Nair
Nikhilesh Sanyal
Corporate Liaison:
Danny Chou
Faculty Advisor:
Anastasia Levitin
Since 1987, Gilead Sciences has worked to discover,
develop, and commercialize medications in order
to advance the care of patients suffering from lifethreatening diseases in areas of unmet medical
need. In just over 25 years, Gilead has become a
leading biopharmaceutical company with a portfolio
of 16 marketed products, a growing pipeline of
investigational drugs and approximately 5,800
employees in offices across five continents. Gilead
Science’s primary areas of focus include HIV/AIDS,
liver disease, and serious cardiovascular, metabolic, and
respiratory conditions. Gilead’s office in Oceanside,
California is responsible for the clinical manufacture
and process development of biologics candidates in
preclinical, Phase 1 and Phase 2 testing.
The Gilead Particulates TMP was asked to perform an
in depth analysis of the biopharmaceutical industry’s
efforts to use the characterization and quantitation
of subvisible particulates as a tool to control the
quality of biological drugs. The size and count of
protein particle aggregates within biopharmaceutical
formulations is a major quality concern which can
negatively impact safety and/or efficacy of drug
products. It is thus important to carefully monitor and
characterize these particles. The current regulatory
size limit for particles in formulation is 10 microns, as
defined by FDA and ICH guidance. However, recent
research has shown that this standard is not sufficient
because of the prevalence of subvisible particles below
10 microns in size.
The aim of this project was to assess the advancement
in regulatory and industrial standards, as well as in
technologies used to monitor these subvisible particles
(SVPs) in parenteral drug products – within the
size range of 0.1 to 10 microns. Through in-depth
literature research and interviews with key opinion
leaders (KOL) within academia, industry, the FDA,
and commercial vendors, the team gained insight into
the progress of regulatory standards and identified the
latest technologies that are most suitable for use in the
surveillance of SVPs. The results of this study were
compiled into a final report, which was submitted to the
team’s corporate liaison at the conclusion of the project.
Project Summaries
Understanding Molecular Diagnostic Testing
Laboratories’ Needs and Decision-making Process
Sponsor Company
Students:
Maria Filippou
Timothy Han
Krissia Manansala
Jason Ross
Corporate Liaison:
Vicki Singer
Faculty Advisor:
Yvonne Klaue
Life Technologies Corporation (Life Tech), now
the Life Science Solutions Group of ThermoFisher
Scientific, is a global biotechnology business dedicated
to improving the human condition. Life Tech provides
a wide variety of tools designed to assist the life
science community and is a global leader in genetic
analysis through its real-time PCR (qPCR), capillary
electrophoresis (CE) and next generation sequencing
(NGS) platforms.
Molecular diagnostic labs face difficult decisions
regarding which platforms to choose for testing of
different diseases (e.g. cancer, inherited diseases, etc.)
and clinical indications (e.g. screening, diagnosis,
staging, therapeutic choice, etc.). These decisions
are further complicated by an industry that is
undergoing drastic changes including the introduction
of new technology and a complete overhaul of the
reimbursement system. This Team Master’s Project
aimed to better understand the needs and the decisionmaking process of diagnostic testing laboratories
regarding qPCR, CE, and NGS platforms.
In order to understand how these laboratories make
decisions, the KGI team conducted extensive research.
The team began by consulting secondary sources such
as scientific literature and market research reports to
gain an understanding of the industry. This knowledge
was used to structure interviews with key opinion
leaders, which provided the team with a qualitative
understanding of their thought processes. Based on
these results, the team constructed and administered a
survey to labs across the country to obtain actionable,
quantitative data. These results helped the team
develop a strategy to guide Life Tech in their efforts
to effectively market these platforms to the most
applicable sectors of the molecular diagnostics industry.
Chorus Value Proposition Identification
and Communication
Sponsor Company
Students:
Nimish Gopal
Andrea Itskovich
Rhea Jain
Ariel Johnson
Ellen Margolis
Corporate Liaisons:
Eyas Abu-Raddad
Paul Owens
Liean Schenck
Faculty Advisor:
Ted Slocomb
Chorus is an autonomous group within Eli Lilly and
Company that functions to determine the proofof-concept of new clinical development molecules
(assets) quickly, efficiently, and at low cost. Chorus
was initially developed by Lilly as part of a fast-to-fail
approach for secondary internal assets. It was hoped
that this approach would reduce the cost of failed
molecules yet accelerate the development of molecules
with a successful proof-of-concept outcome by rapidly
delivering them to the internal Lilly pipeline. Since its
inception Chorus additionally developed assets from
sources outside of Lilly—specifically assets funded
directly or indirectly by Lilly’s Capital Funds Strategy.
These assets, selected for development by Chorus, were
from therapeutic areas that matched those of Lilly’s
portfolio.
During the transition from developing “internal only”
Lilly assets to developing assets from outside sources,
some confusion has developed about the role of Chorus
within Lilly. Simultaneously, the value of Chorus to
external customers and Lilly’s internal research engine
has changed. Chorus has no desire to become a solely
contract research organization which develops assets
on a fee for service basis. Consequently, Chorus needed
to identify their core capabilities and clarify their
value to both their internal Lilly R&D as well as their
external customers. Finally, Chorus wished to identify
areas of research which were of particular value to
their customers.
To support Chorus’ goals, the KGI team was tasked
with interviewing and surveying Chorus team
members to identify the internal perceptions of their
key capabilities as well as the areas they need to
improve. Additionally, the team interviewed current
and potential customers to crystallize their view of
Chorus’ strengths and weaknesses, the value of their
capabilities, and to compare the internal and external
customer perceptions of Chorus’ capabilities. After
generating a complete list of capabilities, current and
potential customers were segmented based on their
motivation and their needs in seeking development
activities from Chorus. Lastly, the team analyzed the
competitive landscape, and made recommendations
for improving the communication of Chorus’ value to
current and potential customers.
Project Summaries
Social Media Data Mining for Patient Insight into
Pharmaceutical Product Design
Sponsor Company
Students:
Michael Bartoli
Brian Cohn
Lakshmi Dharmarajan
Swati Munshaw
Anjali Narayakkadan
Eoin Nugent
Eter Rodriguez
Corporate Liaison:
Tony Zhang
Faculty Advisor:
Jay Chok
Eli Lilly and Company is a global, research-based
pharmaceutical firm headquartered in Indianapolis,
Indiana. Founded more than 135 years ago, Lilly
is at the forefront of pharmaceutical research and
development in both small molecules and biologics.
Lilly’s portfolio contains products that meet
medical needs in the therapeutic areas of oncology,
cardiovascular disease, diabetes, musculoskeletal disease,
neuroscience, critical care and men’s health. Eli Lilly’s
products are sold in more than 125 countries and
include the blockbuster drugs Evista®, Cymbalta®,
Humalog®, Gemzar® and Cialis®.
Eli Lilly believes that social media could represent a
viable channel to understand patients’ needs better.
People regularly discuss their health and treatment
options online. These conversations on social media
websites may offer different points of view from
traditional venues and may provide unique insight to
drive pharmaceutical product design and innovation.
The Eli Lilly TMP team was asked to conduct a
feasibility study to determine if valuable patient insight
could be obtained from Twitter for the therapeutic
areas of rheumatoid arthritis and Alzheimer’s disease.
To accomplish this goal, the TMP team worked with a
third-party vendor to procure Twitter datasets. The team
then analyzed these datasets utilizing Big Data analytic
approaches to provide Lilly with recommendations
on ways to apply these insights in product design.
Additionally, the team provided Lilly with an algorithm
which can be applied to other therapeutic areas of
interest. In conclusion, the Lilly Data Mining TMP
team provided an analysis of the potential options
and limitations of leveraging the social media space.
Furthermore, the TMP team clarified the constraints
of leveraging social media in a highly regulated
environment. As a follow-up to the Lilly Data Mining
TMP research, the team expects to present its findings at
a national conference in June.
Project Summaries
Regulatory Competitive Intelligence: Opportunities
and Advantages Associated with Regulatory Interactions with the FDA
Sponsor Company
Students:
Ricardo Kim
Akhilesh Kumar
Laura Mixon
Jeanne Ngo
Sharifia Wills
Corporate Liaisons:
Marija Popovic
Shanthi Sethuraman
Faculty Advisor:
Steven Casper
Eli Lilly & Co. is an Indianapolis- based company
founded in 1876 with a vision to make medicines that
help people live longer, healthier, and more active lives.
The company continues to be committed to making
a significant contribution to humanity by improving
global health in the 21st century. Lilly has developed a
diverse portfolio in several therapeutic areas, i.e. bone
muscle joint, cardiovascular, diabetes, men’s health,
neuroscience and oncology. Lilly was the first company
to mass-produce penicillin, the Salk polio vaccine and
insulin. Lilly has locations in 18 countries and their
products are sold in 125 countries.
The drug development process in the U.S. is highly regulated by the Food and Drug Administration (FDA), and
it assesses safety and efficacy of the drug products to be
used by the patients. Since it takes 9-12 years to bring a
drug to the market, pharmaceutical companies diligently
look for ways to improve the overall drug development
paradigm, minimize the time to the product launch, provide timely valued medicines to patients and to decrease
the duration of drug development and total cost. The
conversations that take place between the Sponsor and
the FDA during the development of a drug product appear to be instrumental in the drug’s successful preclinical and clinical assessment and ultimate launch. Presently, it is unclear which types of interactions between
the Sponsor and the FDA may be the most impactful to
the successful development of a product. Therefore, it
would be ideal to understand optimal interaction strategies between the Sponsor and the FDA and proactive
approaches the Sponsor could undertake to improve the
robustness of their internal portfolio development.
The Lilly Regulatory Affairs (Lilly-RA) Team Master’s
Project (TMP) team was asked to investigate the impact
of formal and informal interactions, in the pharmaceutical industry, between the Sponsors and the FDA
from 2009-2014 (last 5 years) by focusing on successful submissions of the New Drug Applications (NDAs)
and new Biologics License Applications (nBLAs). To
accomplish this objective, the Lilly-RA team: performed
literature research on current FDA guidance’s; devised
and launched an industry-wide survey; interviewed experienced industry experts in the field of US-regulatory
affairs; and, gathered publicly available documents.
Upon consolidating the data from this research, the team
assessed the industry’s best practices. Ultimately, the
team made recommendations to Lilly which describe the
optimal interactions between the Sponsor and the FDA
as well as the timing of these interactions to improve
successful drug development.
Project Summaries
Design of a Portable Device for the Detection
of Soil Pathogen
Sponsor Company
Students:
Zach Cooper
Kevin Kim
Jamin Leung
Chinobu Mihara
Hari Purushothaman
Diego Silva
Corporate Liaisons:
Luis Jurado
Susan McIsaac
Kirsten Skogerson
Faculty Advisor:
Anna Hickerson
Monsanto is a sustainable agricultural company.
Founded in 1901, Monsanto has been at the forefront
of many scientific advancements in the agricultural
industry. Monsanto is devoted to delivering agricultural
products that support farmers all around the world.
Current work at Monsanto is focused on increasing
yields in core crops with a combination of advanced
plant breeding, biotechnology, and improved farm
management practices.
As plant diseases lead to significant annual crop losses,
disease management strategies are an important element
of Monsanto’s goal to increase crop yields. This requires
the accurate detection and monitoring of the presence of
pathogens in the field. Current methods require samples
to be transported to a centralized lab. Monsanto would
like to develop a method for pathogen detection that can
be used in a field setting. This would reduce the time and
cost of detection and allow a more immediate response
to a crop disease.
The Monsanto TMP team developed a method that can
be used to detect a fungal pathogen in a field setting. To
achieve this objective, the team identified various gold
standard protocols designed for a lab setting, modified
the procedures so that they can be performed on site
with minimal training and equipment, and tested their
performance. Ultimately, the Monsanto TMP team
used a pre-existing instrument to develop a device
which permits sample extraction and DNA purification
that is coupled to target sequence amplification and
quantitative detection on.
Project Summaries
Investigating Novel Market Opportunities for
Silicone Drug Delivery Devices in Women’s Health
Sponsor Company
Students:
Pamela Bonar
Alec Contag
Neha Dafria
Thomas Luu
Akhila Nair
Corporate Liaisons:
Jim Lambert
Scott Mraz
Brian Reilly
Faculty Advisors:
Vivek Gupta
John Krstenansky
NuSil is the leading global manufacturer of medical
grade silicone. Founded in 1979, NuSil is a privately
held company headquartered in Carpentaria, California.
Notably, with approximately 400 global employees,
NuSil has additional facilities located in California,
Texas, and France. The company focuses on the
manufacturing of silicone compounds for the healthcare,
aerospace, electronics, and photonics industries. The
healthcare division is further divided into long-term and
short-term implantable silicones, skin care, and drug
delivery.
During phase I of the NuSil TMP project, the team
was assigned the task of identifying novel commercial
opportunities for silicone drug delivery devices. To
complete this task, the team evaluated areas of women’s
health, wound healing, and antimicrobials. For each
of these market opportunities, the team investigated
market size, current research, competing biomaterials in
addition to the intellectual property surrounding the use
of silicone in each of these defined markets.
Upon the identification of women’s health as the most
promising commercial opportunity through secondary
research and KOL interviews, the team was tasked with
identifying strong opportunities in women’s health. We
successfully characterized over 30 disease indications
in women’s health, and ranked them according to
market opportunity. The top four disease indications
were the selected for further market research analysis.
The team’s analysis included areas ranging from unmet
clinical need, disease prevalence and demographics,
adoption rates, socio-economic analysis, technical
feasibility, regulatory pathways, IP considerations and
risk management. Ultimately, the NuSil TMP team
produced an abbreviated business plan, which NuSil
can use as a tool for the identification of new investment
opportunities.
30 Years Since the Orphan Drug Act:
A Comprehensive Database and Current Trends
Sponsor Company
Students:
Nikhilesh Sanyal
Donald Tan
Melanie Ufkin
Chendhore Veerappan
Naren Vinayak
Corporate Liaison:
Sukirti Bagal
Faculty Advisor:
Alan Rothfeld
The orphan drug act (ODA) was passed in 1983 to
encourage the development of drugs aimed to treat
rare diseases that affect fewer than 200,000 Americans.
Some of the incentives under this act include market
exclusivity for the drug maker, tax/financial incentives
and expedited review by the FDA. Given the increasing
cost of developing large market ‘blockbuster’ drugs and
breakthroughs in the understanding of the molecular
basis of disease progression, there is a rapidly growing
interest in the development of drugs designed to treat
rare diseases.
Pfizer, the world’s largest pharmaceutical company in
revenues, is currently exploring the rare disease space
which is currently dominated by biotech companies.
Pfizer’s current diversified global health care portfolio
includes medicines, vaccines, nutritional products, and
many of the world’s best-known consumer products.
To help guide Pfizer in making informed decisions in
pursuing orphan drug development, a comprehensive
centralized resource of all orphan designations since the
passing of the ODA was developed. The database will
additionally serve as a guiding resource for patients and
caregivers.
The goal for this team was to create a database whichincludes all orphan drug designations (current as of May
2014), with associated disease area classification, stage
of development, incidence/prevalence numbers, support
group and sponsor information. Within the database
there are 3000 plus orphan disease designations.
Each designation was classified into major disease
focus groups and further sub classified into specific
disease therapeutic areas. The staging of development
information for therapeutics in this area was derived
from clinicaltrials.org. Support group information and
incidence/prevalence data were obtained from reliable
federal and state websites and peer-reviewed journals.
A user-friendly front-end application to analyze and
filter the database on the disease area, designated drugs,
phase of development, etc. was also developed. By using
the developed database, the team analyzed historical
and current trends within the data to determine
opportunities and areas of need for various rare disease
classifications.
Project Summaries
Mapping the Clinical Landscape of
Huntington’s Disease
Sponsor Company
Students:
Shravani Bobde
Josh Finley
Sara Herrmann
Alexander Lagadinos
Xinzhu “Nancy” Li
Jane Sur
Corporate Liaisons:
Kai Brown
Ben Cadieux
Faculty Advisor:
Luann Bangsund
Raptor Pharmaceuticals Inc. is a publicly traded
biopharmaceutical company that develops and
commercializes therapeutic drugs for rare inherited
diseases. The company was founded in 2005 by former
executives from Biomarin Pharmaceuticals Inc., and they
have been actively pursuing the development of multiple
drugs in several disease indications. Their current
lead product is a small molecule therapeutic known
as Procysbi® (delayed release cysteamine bitartrate),
which was approved for the treatment of nephropathic
cystinosis in April 2013. Raptor is currently seeking to
expand the utility of this active ingredient, RP103, into
other potential indications such as for Huntington ’s
disease (HD).
In February of 2014, Raptor reported the completion
of an 18-month Phase 2/3 clinical trial conducted
by the Centre Hospitalier Universitaire d’Angers
(CHU) in France, which indicated that the therapeutic
administration of RP103 attenuated the total motor
decline of HD patients. The current Standard Of Care
(SOC) for HD management aims to treat chorea, one
aspect of the motor decline experienced by HD patients.
Given that there are currently no drugs that slow the
disease progression, the CHU trial results indicate
a promising potential for this first-in-class drug. In
order to streamline the development and potential
commercialization of RP103 for treatment of HD, the
team focused on identifying signatures of HD diagnosis,
disease progression and treatment outcomes.
The project was divided into three phases. In Phase I, the
team conducted an extensive literature review in order
to establish the landscape of HD. This was accomplished
by curating published data on HD pathogenesis, patient
Quality Of Life (QOL), clinical trials, current SOC and
alternative therapies. Additionally, this data was used as
a basis of information for the next project phase. Phase
II focused on designing questions for patient and Health
Care Provider (HCP) surveys, which were conducted
by a contracted market research firm. These surveys
helped identify patient referral pathways, HD diagnosis
protocols and unmet clinical needs through consistencies
and discordances among primary and secondary
research. In the final phase, the team identified key
opinion leaders (KOLs) using quantitative weighting
measures, and began to address the clinical need for
HD patient outcomes research by utilizing a proprietary
insurance claims dataset. It is expected the output from
this TMP will give Raptor insights into signature issues
associated with HD treatment and economics, and
support the marketing strategies for RP103.
Evaluation of Continuous Bioprocessing Practices
for Production of Monoclonal Antibodies &
Fc Fusion Proteins
Sponsor Company
Students:
Arundhati Ghosh
Irene Ghozalli
Jacob Justus
Chas Syndergaard
Yash Ravishankar
Corporate Liaisons:
John Mattila
Ashley Witmer
Faculty Advisor:
David Vetterlein
Regeneron is a leading science-based biopharmaceutical
company based in Tarrytown, New York that discovers,
invents, develops, manufactures, and commercializes
medicines for the treatment of serious medical
conditions. Regeneron markets medicines for eye
diseases, colorectal cancer, and rare inflammatory
conditions. Additionally, Regeneron has product
candidates in development for other areas of high unmet
medical need, including hypercholesterolemia, oncology,
rheumatoid arthritis, allergic asthma, and atopic
dermatitis.
The Regeneron TMP team was asked to evaluate aspects
of continuous bioprocessing including: 1) available
types of equipment; 2) the impact of this technique on
cost of goods; and 3) a continuous bioprocessing plant’s
capacity for the production of monoclonal antibodies
and Fc fusion proteins. As part of the TMP team’s
effort, an initial survey was conducted to determine
industry trends and best practices regarding the use of
upstream and downstream continuous bioprocessing.
Additionally, a second survey was conducted to evaluate
the equipment used in continuous bioprocessing. The
project culminated in the production of a final report
detailing the global cost of goods and associated plant
capacity analysis related to the implementation of
continuous bioprocessing technologies.
In order to complete the initial survey related to industry
trends and best practices centered on continuous
bioprocessing, the Regeneron TMP team constructed
and deployed a digital survey to key opinion leaders
in the pharmaceutical industry. The second survey
focused on making direct contact with equipment
manufactures and vendors with knowledge of state-ofthe-art bioprocessing technologies, in order to document
the available equipment for continuous processing
applications. Using a Greenfield facility as a basis, the
team’s final project task was to perform a cost of goods
and plant capacity assessment of continuous processing
versus fed‐batch processing at a commercial scale. The
results and the analysis of the first survey were conveyed
to Regeneron in early January of 2014, and results of
the second survey and the Greenfield analysis were
presented to Regeneron in early May 2014.
Project Summaries
Evaluation of the Market Potential and Development
Feasibility of Seven Rare Disease States
Sponsor Company
Students:
Aimee Lake
Horrace Owino
JP Ruiz
Jaanhvi Vaidya
Corporate Liaisons:
Bo Cumbo
Emily Naughton
Faculty Advisor:
Mikhail Martchenko
Sarepta Therapeutics is focused on developing firstin-class RNA-based therapeutics to improve and save
the lives of people affected by life-threatening rare and
infectious diseases. The company’s long-term vision is to
become a leading, independent biotech company capable
of sustainably developing a pipeline of breakthrough
therapeutics and bringing them to the patients who need
them. To accomplish this vision, Sarepta has a unique
phosphorodiamidate morpholino oligomer (PMO)
technology at its disposal that is uniquely versatile,
allowing for the development of a range of therapeutic
candidates that target different types of RNA.
Sarepta’s pipeline currently includes its lead clinical
candidate, eteplirsen, for the treatment of Duchenne
muscular dystrophy as well as potential treatments for
influenza and Marburg hemorrhagic fever virus. Sarepta
is interested in adding candidates to its pipeline that
are based on its platform PMO technology. However,
Sarepta has devoted its resources to gaining approval for
its current pipeline and hasn’t formally evaluated which
disease state the company should pursue next.
The Sarepta TMP team was tasked with evaluating
the risk/benefit profiles of 7 disease states to determine
which indications would provide the highest return on
investment (ROI) while limiting risk. To accomplish
this task, an IP landscape and competitor analysis was
conducted to look for areas with freedom to operate.
Next, the feasibility of conducting and designing
successful clinical trials that would support a regulatory
pathway with limited clinical endpoints was analyzed.
Finally, a financial analysis that compared the potential
market opportunity to the costs of development of a
therapeutic for each disease was completed to ascertain
ROI. In support of the original objective, a report which
included a high level comparative analysis of the risks
and benefits of developing a therapeutic was performed
for each of the variables being examined to form the
prioritization strategy for Sarepta.
Team Master’s Projects range from highly technical to businessoriented. KGI offers its students experiential learning opportunities that
prepare them to translate their education into practice in industry. Past
project categories have included:
• Therapeutic and diagnostic market opportunity evaluation
• Product launch model and go-to-market strategy development
• Pharmacoeconomic and cost-effectiveness analysis
• Bioprocessing technical feasibility assessment
• Medical device prototyping, including VOC input
Project Summaries
Epidemiological Landscape of cerebrotendinous
xanthomatosis (CTX) and Recommendations for the
Implementation of a Newborn Screening Test
Sponsor Company
Students:
Courtney Hanlon
Anamika Jha
Roberto Rodriguez
Leeor Zilbermintz
Corporate Liaisons:
Karen Kuphal
Joe Testa
Faculty Advisor:
Ian Phillips
Sigma-Tau Pharmaceuticals is dedicated to helping
patients affected by rare diseases. The FDA defines a
rare disease as a disease that affects fewer than 200,000
individuals in the United States. Sigma-Tau’s core belief
and dedication is that the study of rare diseases should
be an integral part of its research activity. Consequently,
Sigma-Tau has chosen to specialize in these diseases by
discovering novel therapeutics to help patients suffering
from these rare conditions.
Sigma-Tau Pharmaceuticals is in the process of
exploring and expanding their rare disease product
profile for cerebrotendinous xanthomatosis (CTX).
Unfortunately, there is no current standardized
screening method in the United States for CTX.
Consequently, without proper disease detection, CTX
patients can remain undiagnosed or misdiagnosed
until their disease state has progressed. Sigma-Tau is
interested in generating a road map for the inclusion
of CTX in newborn screening. The establishment of
a standard for the CTX screening of newborns will
help patients by providing a more timely diagnosis
of disease, provide patients with earlier therapeutic
intervention and increase the market opportunity for
Sigma-Tau Pharmaceutical’s CTX-related products.
The Sigma-Tau TMP team was given two main goals:
1) gain an in-depth understanding of the epidemiology
of CTX; and, 2) generate a road map for the possible
adoption and implementation of a test for CTX in
the existing newborn screening panel. To accomplish
these objectives, the team performed a comprehensive
literature search and interviewed Key Opinion Leaders
of CTX to understand unmet clinical needs associated
with CTX diagnosis and treatment. The team then
synthesized collected information to produce an overview of CTX diagnosis within the United States and to
develop a strategy for the newborn screening of CTX.
In addition, the team identified diseases mechanistically
related to CTX and compiled an Orphan Drug Application (ODA) involving a promising new indication for
one of Sigma-Tau’s CTX-related products. This ODA
was provided to Sigma-Tau for possible submission
to the FDA. Upon project completion the TMP team
provided Sigma-Tau a CTX status report which included: all available CTX epidemiologic and diagnostic
data; identified current unmet clinical needs associated
with CTX; explored and identified the role of patient
advocacy groups within the CTX community; provided
recommendations to increase CTX awareness; and,
recommendations regarding the implementation of a
newborn screening test for CTX.
Project Summaries
Diagnosing Ventilator Associated Pneumonia
through Analysis of Volatile Organic
Compound Biomarkers
Sponsor Company
Students:
Alexandra Antonoplis
Elizabeth Henderson
Samantha Noronha
Franco Pillsbury
Constance Wu
Corporate Liaisons:
Angelika Niemz
Charles Taylor
Faculty Advisor:
Angelika Niemz
The National Science Foundation (NSF), under its
“Partnerships for Innovation” (PFI) program, provides
funding for collaborations between academic institutions
and small companies, to facilitate the translation of academic discoveries into novel products. This TMP team is
working on an NSF-PFI funded project involving Keck
Graduate Institute (KGI), Pomona College, and four
small business partners: Tanner Research, Claremont
Biosolutions, Lambda Solutions Inc, and Synedgen. The
goal of this project is to develop and market a device
that will allow for the early non-invasive diagnosis of
Ventilator-Associated Pneumonia (VAP) through analysis
of Volatile Organic Compound (VOC) Biomarkers.
Patients on ventilator support are frequently colonized
with pathogenic bacteria that grow as biofilms inside
the endotracheal tube. However, the presence of such
biofilms does not necessarily lead to active pneumonia.
The gold standard for VAP diagnosis therefore involves
quantitative culture of a bronchoalveolar lavage sample,
which is highly invasive and involves long turnaround
times, thus leading to high costs, presumptive treatment prior to confirmed VAP diagnosis, and over-use of
antibiotics. The overall goal of the NSF-PFI project is to
enable early, noninvasive, differential diagnosis of VAP
by measuring changes in VOCs exhaled by patients on
mechanical ventilator support.
To identify unique VOC signatures that can differentiate
bacteria present as biofilm versus infectious, planktonic
form, the team developed a setup to grow bacterial
biofilms and collect emitted VOCs, followed by analysis
via GC-MS. Through literature searching and bioinformatics tools, the team investigated the scientific background and identified differentially regulated metabolic
pathways that may be involved in production of unique
VOC signatures.
The partnering organizations of this NSF PFI project are
developing a device, consisting of a disposable sample
collector, and a compact instrument, that can be used
to identify VOC signatures from the exhaled breath of
mechanically ventilated patients. To better understand
how this device could be integrated into current clinical
practice, the team is conducting primary user research to
identify unmet needs and clarify product requirements.
Furthermore, the team is analyzing the competitive landscape and market potential, and is identifying potential
strategic partnerships. By developing a preliminary
commercialization plan, the team aims clarify alternative
paths for market entry.
Abbott Medical Optics
Abbott Nutrition
Allecure
Allergan
American Commercialization
Institute
Amgen
Amylin
Applied Biosystems
Arterial Light Sciences
AVI Biopharma
Beckman Coulter
Biocatalytics
BioHelix
BioMarin
Boehringer-Ingelheim
Brace Pharmaceuticals
Bristol Myers-Squibb
Broadley-James
Ceres
Children’s Hospital of Los
Angeles
City of Hope
Clear Springs Land Company
Dow Agrosciences
Edwards Lifesciences
Eidogen
Eli Lilly and Company
Equigene Research
Genomatica
Genentech
Gilead Sciences
Health IQ
Illumina
Invitrogen
Ionian Technologies
Kinetic Concepts
KGI/Sun Micro Systems
Legendary Medical Information
Systems
ThermoScientific Life
Technologies
Lnx Research
Medco
Monsanto
Nanostream
Navigant Biotechnologies
Northrup Grumman
NuSil Silicon Technology
Ortho Clinical Diagnostics
PBS Biotech
Pfizer
Pioneer Hi-Bred International
Prairie Ventures
Raptor Pharmaceuticals
Sarepta Therapeutics
Sigma-Tau
Syngenta Seeds
Tecan
Theravance
UVP
Veracyte
Waters
Zuyder
Keck Graduate Institute would like to thank all our sponsors for
their generous support of the Team Master’s Project.
For more information about TMPs contact
Diana Bartlett Assistant Vice President,
Corporate Partnerships
at Diana_Bartlett@kgi.edu
Mission
Keck Graduate Institute is
dedicated to education and
research aimed at translating into
practice, for the benefit of society,
the power and potential of the
life sciences.
Culture
KGI seeks to sustain an
interdisciplinary and entrepreneurial
culture, working in partnership with
industry to develop leaders for the
biosciences, while promoting
academic freedom and the highest
ethical standards.
Core Values
• Entrepreneurial and Reflective
• Ethical and Responsible
• Collaborative and Independent
• Interdisciplinary and Applied
535 Watson Dr.
Claremont, CA 91711
www.kgi.edu