Biopreneurs: The Molecular Millionaires

i
B I O B U S I N E S S D E M Y S T I F I E D

BIOPRENEUR:
The Molecular Millionaires

iii
Biopreneur:
Ryan Baidya, PhD, MBA
California Takshila University
with
Miyuki Shiratani, MBA
Devicenet USA, Inc.
California Takshila University Press
Silicon Valley California

iv
Biopreneur:
Published by California Takshila University
Silicon Valley, California
Copyrght © 2008 Ryan Baidya
First Edition
All rights reserved. No part of this book may be reprinted or reproduced or translated
or utilized in any form or by any electronic, mechanical or other means, now know or
hereafter invented, including photocopying and recording, or in any storage or retrieval
system, without written permission from the publisher.
Library of Congress Cataloging-in-publication Data
is available from the United States Library of Congress.
ISBN -10: 0-9822001-0-2 (hbk)
ISBN-13: 978-0-9822001-0-0 (hbk)
ISBN-10: 0-9822001-1-0 (pbk)
ISBN-13: 978-0-9822001-1-7 (pbk)

v
About the Authors
Ryan Baidya, Ph.D., MBA
Dr. Baidya, an entrepreneur, has a rare combination of
expertise and professional background. He is a
business strategist, an inventor, a public speaker, a
thought leader (Frost & Sullivan), an educator (MBA-
faculty for CTU), a mentor and an expert in bio-
business. He has overall 15+ years of experience in the
biotech and IT -business development (domestic &
International), licensing and marketing. He serves as
an advisor to several technology-based companies in
USA, Japan and India.
Currently, he is a faculty for MBA at the California Takshila University,
Silicon Valley, California. He gave numerous lectures on entrepreneurship;
business-strategy and technology related topics at conferences, primarily in
USA, and Japan and served as a Thought Leader, Frost & Sullivan Executive
Summits. He authored articles, patents, and commentaries. Dr. Baidya
received an MBA at the San Jose State University; a doctoral degree in Science
at the University of California, Santa Cruz; and a Master Degree from the
Indian Institute of Technology (IIT) Kanpur. As a fellow of the Damon
Runyon Walter-Winchell Foundation he spent five years at the University of
Colorado Boulder.
Miyuki Shiratani, MBA
Mrs. Shiratani is a logistician with 12+ years of
experience in business development and international
business relation. She has worked several
multinational companies in Japan and USA. Her
early works include international business logistics
and corporate communications in the high-tech field
(Sharp Corp, Japan). Later she contributed
immensely in the business development of BioZak,
Inc., an antiviral drug discovery company and has
written on bio-businesses in Japan.
She currently works at DeviceNet USA in Silicon Valley and serves as an
adjunct faculty of Business at the California Takshila University. Mrs.
Shiratani received her BA in International Relation in Osaka, Japan and an
MBA at San Jose State University, California, USA.

vi
–"There
is
no
bigger
test
for
humanity
than
the
crisis
of
global
health.
Solving
it
will
require
the
full
commitment
of
our
hearts
and
minds.
We
need
both.
Without
compassion,
we
won’t
do
anything.
Without
science,
we
can’t
do
anything.
So
far,
we
have
not
applied
all
we
have
of
either."
~~
Bill
Gates,
World
Health
Assembly,
May
2005

vii
Dedication
To our Families and Friends, who have inspired, motivated
and supported us.
-- R.B. & MS

viii
BRIEF CONTENT
Chapter I: Entrepreneurship in Biotechnology
Chapter II: Biopreneurs
Chapter III: Understanding the Business of Biotechnology
Chapter IV: Pre-clinical Development
Chapter V: Clinical Development
Chapter VI: Beginning a Bioventure
Chapter VII: Funding for Bioventure
Chapter VIII: Fund Raising
Chapter IX: Valuation
Chapter X: Public Relations & Investor Relations
Chapter XI: Role of Marketing in Biotech Business
Chapter XII: Investment in Biotech Industry
Chapter XIII: Journey of a Biopreneur
Chapter XIV: It’s your Call
Chapter XV: Success
Supplements

ix
__________________________________________________________
THE GROUND RULE
Information  Knowledge  Wisdom
** time & experience drive the process of this conversion **

x
TABLE OF CONTENTS
Topic Pages
1) Prelude xvii-xix
Entrepreneurship in Biotechnology
2) Chapter I: 01-16
Biopreneurship: Entrepreneurship in Biotechnology 03
Crossing the Boundaries 03
Uncertainty and Biopreneurship 06
Uncertainty opens the Door for Opportunities 08
Molecular Millionaires 09
Steps towards Biopreneurship 10
Most of us dream to be a Biopreneur 12
A Calling 13
Biopreneurs
3) Chapter II 17-33
Who is a Biopreneur? 19
Valuable Opinions 21
Leadership: It is Expected 23
A Simple Philosophy 24
Inside the Minds of Biopreneurs 25
Paths to Success 27
Success Redefined 28
Summing it Up 31
Understanding the Business of Biotechnology
4) Chapter III 34-50
What is Biotechnology? 37
History and Development of the Industry 37

xi
Characteristics of the Industry 39
Understanding the Drug Discovery Process 40
Research and Development 41
Efficacy Studies - Animal Model Selection 43
The Casualty of R&D 44
Future Drug Development Process 45
Business Decision-Making Infrastructure 46
Conclusion 50
Pre-clinical Development
5) Chapter IV 51-78
Preclinical Development 55
Drug discovery: A Brief Story 55
Developability Decision 57
Establishing Developability 58
Pre-clinical Development Tasks 59
Animal Testing 62
History in Brief 63
Types of animals used 64
Safety Assessment
(in using Animals in Preclinical Studies) 67
Dose Selection 68
Pharmacodynamics—Biological Activities 69
Pharmacokinetics and Toxicokinetics 70
Immunogenicity 71
Investigational New Drug Application 73
Clinical Development
6) Chapter V 79-117
Clinical Research 81
What is a Clinical Trial? 82
Clinical Trial – the Process 84
Clinical Proof of Concept 85
A Few Important Notes 86

xii
Phases/Stages of Clinical Trial 87
Phase I 87
Phase II 89
Phase III 89
Phase IV 90
Regulation and Safety of Patient 92
Pre-clinical Safety Assessment 93
Pre-Approval Safety Assessment in Humans 93
Safety Assessment during FDA Regulatory Review 93
Post-Marketing Safety Supervision 94
Placebo and other sides of a trial 96
Benefits and risks of participating in a clinical trial 98
What are side effects and adverse reactions? 99
Sponsors 99
Beginning a Bioventure
7) Chapter VI 102-115
Business Plan and Business Planning 105
Business Plan 105
Executive Summary 106
Executive Summary Items 106
Mission statement 107
Company description 107
Technology Description 107
Market Analysis 108
Competitors and Competitiveness 110
Strategy 111
R&D 112
People and Assumption 113
Summary 114

xiii
Funding for Bioventure
8) Chapter VII 117-134
Financing: from Idea to IPO & Beyond 119
Financing Bioventure 123
Financing Strategy –From Idea to IPO 123
Equity capital 127
Angel Investments 127
Venture Investments 127
Debt Capital 129
Mezzanine Finance 129
Bank Loans 129
Convertible Loans 129
Corporate Bonds 130
Government’s role on a Bioventure development 131
Three Strategies –model for bioeconomy 132
Vitalization of bioventure businesses 133
Fund Raising
9) Chapter VIII 135-148
Fund Raising for your Business 137
Investors 138
Getting Ready for VC Meeting 139
VCs – an Introduction 140
VC Investment Features 143
Last Words 146
Valuation
10) Chapter IX 149-160
VALUATION OF A BIOBUSINESS 151
Valuation Methods 153
Comparable/Guideline Method 153
Discounted Cash Flow/Income Method 154
Risk adjusted discount factor 156

xiv
Company Specific Factors 156
Biobusiness Specific Factors 158
Public Relations & Investor Relations
11) Chapter X 161-172
Pitching the Bioventure Business 165
Strategic Plan for Media Relations 166
Less/Not so Expensive Media Exposure 167
Media Tips 167
Least Cost-effective Events for Bioventure 170
Expensive Media Exposure 170
Expected Expenditure 171
Communication Assets 171
What are the Communication Assets 171
Role of Marketing in Biotech Business
12) Chapter XI 175-190
Role of Marketing Biotech Business 176
Crossing the Boundaries 177
Marketing begins in our life before we even know it 178
Basics of Marketing in Bioventure 179
Market Segments 179
Niche Marketing & Scientists’ Crossover 180
Niche Marketing Strategy 180
Differential Strategy & Niche Marketing 182
Differential Model in Business 183
Fractional Differential Strategy 184
Earlier Differential Strategy 185
Differential Strategy &Time 185
Differential Strategy & Technology 186
Power of “DS”- From dust to Castle 187
Biopreneurs & “DS” 188
Biopreneurs and the Transaction Theory of Cost 188
Conclusion 189

xv
Investment in Biotech Industry
13) Chapter XII 191-202
Investment in the Biotech Industry 193
Biobusiness-a new Gold Rush 193
Paradigm of biobusiness 194
Common senses not common traits 195
Which sector offer short-term return 196
Which sector offers long-term return 196
How to evaluate biotech companies 197
Proprietary expertise 198
Robust pipeline and technology 198
Appropriate business model 199
Strong management 200
Financial resources 200
Market 201
Journey of a Biopreneur
14) Chapter XIII 203-211
Beginning of a Journey 205
Understanding the Reality 205
Questions of Biopreneurs 206
Revenue Based business model bound to succeed 209
It’s your Call
15) Chapter XIV 212-222
Where does the Inequality of Health Lie 215
Why do Biobusiness 217
Biotech business is more than just making money 218

xvi
Success
16) Chapter XV 223-228
Success-Definition 225
Success-Viewpoints of Others 225
Know Thyself 228
SUPPLEMENTS
Supplement –I 233
Package of Studies to Assess Developability
List of Studies Needed for IND Registration
Optional Tests Depending on Phase I/IIa Strategy
Clinical Trial Cost and % of Risk
Supplement –II 239
Time-Value-Money & Discounted Cash Flow
Supplement-III 243
Snap Shot of Bio-VC
Supplement-IV 249
Biotech Around the World

xvii
Prelude
We know that every business is related to either inventive or innovative
products or services and it must face some ups and downs throughout the
phases of its development. Ultimately, and quite fortunately, a stage
usually appears in typical development that can offer some comfort and
satisfaction to the participants of most business ventures. But purists in
any field will advocate neither satisfaction, nor comfort alone, for its
own sake. It is dedication, business zeal, will power to prove proficiency,
and the unforgettable love of a product that entices most people involved
to continue serving business goals. Our focus and our prime concern in
this book are to explore bioventure and the journey of a bioventurer.
Bioventure represents a microcosm of the world at large concentrated
into the small word of biological venture capital. As far as biopreneurs
are concerned we have to define a scenario with a different kind of
light—a light of a different color and temperature. It is an interesting and
exciting a time for people wanting to appreciate the world of bioventure.
And this is plainly because biotechnology, with emergent educational,
governmental, and industrial support, is moving toward its wave crest.
We can think of bioventure being a sleek aerodynamic car racing on
three wheels—technology, management, and capital. Each wheel is
extremely sophisticated, and must be taken care of appropriately to drive
the car to an ultimate and optimal destination. After spending many years
learning and teaching, when I joined the practiced field of authentic
business, I realized the need for the proper understanding of those three
driving wheels. As people from the field of research work, and
management, we may be aware of the greater issues related to our own
unique areas of interest, but to be a truly successful biopreneur we must
have a commanding grasp on all three driving wheels in our bio-business.
When we look at the world of bioventure we find several cases where
people intended to invest heavily, but due to a lack of suitable
knowledge they decided to shy away. There are instances where
companies having a potential to expand their horizons by meeting a mere

xviii
few necessities—such as patenting their ideas, and technology. Simply
having enough information and facts regarding selling intellectual
property or research-based material to pharmaceutical establishments
may help some budding bioventures to succeed. But insufficient
information also causes comparable ventures to lag behind other more
aggressive competitors.
When these realizations struck me, I felt there was a lack of one
extraordinary item in our immediate area which could solve our
collective problems. That extraordinary item was a quality study
curriculum that might be of assistance to all people in the field of
bioventure. My intent is that this study material must contain substantial
information for all—upcoming entrepreneurs, people from the field of
management, and suited investors. This would not only to serve getting
people from various fields under the one roof—bioventure—but it would
also create a feeling of unanimity within bioventure.
Working together has always been a fun for people like us. Now we have
the means to create that same fun—multiplied—by networking our
talents, invented drugs, and various other biotechnological products. At
the same time there could be an additional benefit waiting for each of us
involved, in the form of earned capital. In all honesty, that is simply one
future that I dream of for bioventure. The best possible future relies on
greater understanding among the people associated with this business.
This will be possible only if we can integrate our knowledge and
experience, and operate within each other’s respective fields of expertise.
If we can appreciate the views that those among us want to share, and
vice versa, then a treasure trove in bioventure is not far off.
Keeping all this in mind I started writing my book. Now the book is
ready to begin its journey. I hope it will travel a long way binding a bio-
world together for a better, cheerful future in bioventure. As we all know
every business has its commercial perspectives, and that is as it must be.
But at the same time we must keep our eyes open for the humanitarian
views. I have tried to focus on specific parts of bioventure that venture
capitalists, or other prospective investors, along with biopreneurs, might
always bear in mind, so that their actual goals of helping needy people is

xix
the foremost issue. And the money will flow if consumers are there to
buy the products, and that will happen if we don’t forget others needs.
Our book is targeted for everyone associated with the field of bioventure.
Whether you are preparing to start a business, a potential investor, a
person from the field of management, or you are a researcher, I hope you
will find reading this book essential. I have tried to say a lot, though I
possibly have missed things which I will need to revise in another issue.
I invite responses from you so that I can understand what you want,
making an ongoing and continued conversation, an enduring process to
exchange thoughts on the topic. After all we can build the future world
of bioventure together, by pooling our dreams together.
Ryan Baidya
Miyuki Shiratani

xx
“As
we
stand
at
the
dawn
of
a
new
century,
we
recognize
the
enormous
potential
that
biotechnology
holds
for
improving
the
quality
of
human
life…
President
Bill
Clinton

Chapter I
Biopreneurship:

2
Our Greatest glory is not in never-falling, but in
rising every time we fall.
- Confucius

3
BIOPRENEURSHIP:
Biotechnology, at its present stage, is incredibly complex, confusing,
expensive, particularly entrepreneurial, though fast-paced and highly
promising. Just getting out of its last phase of a closed setting,
biotechnology is now flying like a freed bird reaching multi-proportions in
the world of business. So then this is the most risky yet challenging period
to join a biotech-venture (bioventure).
I would like to start this chapter wishing you all “congratulations” for your
initiative in exploring and expanding your fields of interest. The
biotechnology business, often called bioventure or bio-business, is complex
and exciting. Biotechnology is the outcome of years of fundamental
research by thousands of researchers around the world. Biotechnology was
a very confined world until the early 1980s, when a group of researchers
decided to apply their research findings, to practical applications, for human
health. A rush of technological networks, or webs, began to accumulate
around the economic zones near university campuses such as the University
of California, San Francisco, UC Berkeley, MIT, Stanford, Harvard and
others.
This rush came with optimism and high expectations; however it lacked
persistence. The first round of the biotech rush died out shortly after 1992.
This first biotech rush taught researchers and supporters of biotech-
ventures—bioventure—valuable lessons and gave them a better
understanding of what was required to succeed. A few select few from the
first wave of the revolution are Amgen, Genentech, Roche and Genencor.
Crossing the Boundaries
There is a little bit of entrepreneurship in every one of us. In some it is
activated, and in others it gets transformed into something else, depending

4
upon environment and timing considerations. The late 20th
century and the
beginnings of 21st
century is a time for entrepreneurship and venture
capitalism. Capital ventures come from the urge to be free—such as in the
popular lines born to be free OR born to be wild. From birth we are free to
think and to do that which fits us best. However, more complete freedom
comes with economic freedom. Quite often entrepreneurs begin ventures
seeking to achieve economic freedom using innovative and exploratory
ideas. New entrepreneurs especially almost always fall into this category.
Biopreneurs are generally bio-scientists with practical approaches to
problems. Also many physicists, mathematicians, economists, financiers,
and liberal-arts majors become successful biopreneurs too. Biopreneurs,
from non-bioscience fields, normally focus on the business aspects of a
bioventure, while biopreneurs from bioscience can both drive the business
as well as develop the requisite science. One thing seems clear that if
someone is from the field of bioscience he or she has to gather information
about management and business, whereas a person from the business world
must acquaint himself with bioscience to understand and run a bio-venture.
Moving from a scientific frame of mind to a disciplined business mindset
could be very challenging and exciting. Since scientists always appreciate
challenges, we see more and more scientists becoming good biopreneurs
every day. Researchers are greatly focused and goal oriented. This trait,
when molded into the time-value-money concept, can produce excellent
biopreneurs. Crossing from one discipline into another is not difficult, but
requires willingness and an internal driving force to move forward.
Those who wish to venture into biotech fields require a good understanding
of the entire biotech process, and this should not be simply a single
biological process or a function based on a particular enzyme or molecule.
A scientist or non-scientist with little or no exposure to biotech fields can
quite easily expand their understanding of an entire drug discovery process
and varied business aspects of it. The following are highlights that make
the biotechnology industry unique and somewhat distinct:
Biotechnology: Science and business
Basics of the industry
Differences between the high-tech and the biotech

5
Drug development and scientific issues:
R&D – Processes and cost
Logistics of product development
How are new drugs found?
How are clinical studies carried out?
Regulatory issues:
How does FDA approval process work?
What are the concerns in the regulatory process?
Regulatory requirements and timelines
Business Development Issues:
Business Plan and Business Planning:
Markets and marketing
Licensing, collaboration and partnership in the bioindustry
Public relation and Investor Relation
Management issues:
What is the internal structure of biotech industry?
What is management protocol for R&D management?
Interpersonal skills and bio-scientist (bio-scientist-cum-manager)
Financial Issues:
Financing of a biotech endeavor, operating capital, sales and
marketing
Social issues:
The cost of drug to the society
Environmental and social issues
The RISK factors:
Intrinsic risk of biotechnology product development
Risk factor and patience

6
Uncertain Universe
It is not humanly possible to become proficient in all these fields; however,
biopreneurs should master as many as possible and acquire a good
understanding of all or most. Those biopreneurs, who were found to be
successful were those with more than one of the above expertise and they
were able to bring in people on to their team with expertise that the
biopreneurs did not have at the time of inception. Learning is a continuous
process and biopreneurs are often gains their understanding and strengthens
theirs knowledge as they go along with the bioventure.
Uncertainty and Biopreneurship
Uncertainty is a normal phenomenon of the universe. On the macro scale,
human beings are a speck in the universe. In 1927 Heisenberg predicted
uncertainty of the universe, known as the “uncertainty principle,” or
interdeterminancy principle, at the submicroscopic scale—a quantum
phenomenon. Heisenberg’s Uncertainty Principle (HUP) states - "The more
precisely the POSITION is determined, the less precisely the MOMENTUM is
known.”
An odd aspect of quantum
mechanics is contained in the
Heisenberg Uncertainty
Principle. The HUP can be
stated in different ways,
however, let’s first talk in
terms of momentum and
position.
If there is a particle, such as
an electron, moving through
space, we can characterize its
motion by telling you where it is—by position—and what its velocity is—
more precisely, its momentum. Now, let us say something strange about
what happens when we try to measure its position and momentum.
 Classically, i.e., in our macroscopic world, we can measure these two
quantities to infinite precision—more or less. There is really no
question where something is located and how great its momentum.

7
 In the world of quantum mechanics, there is a breakdown in the
concept that we can measure things precisely. Let’s state this notion
more accurately. Suppose a particle has momentum p and position x.
In quantum mechanics, we should not be able to measure p and x
precisely. There is an uncertainty associated with each measurement,
e.g., there is some dp and dx, which we can never get rid of, even in a
perfect experiment! This is due to the fact that whenever we make a
measurement, we must disturb the system. In order for us to know
something is there, we must bump into it. The size of the uncertainties
are not independent, but they are related by:
dp x dx > h / (2 x pi) = Planck's constant / ( 2 x pi )
As a result of this uncertainty, it is not possible state where a particle is
located with 100% precision. Its location can only be described in terms of
probability. For example, we can say that an atom is at some location with a
99% probability, but there will be a 1% probability it will be somewhere
else—in fact, there will be a small but finite probability that it will be found
somewhere across the universe. So, the fact is if I measure x exactly, the
uncertainty in p (dp) must be infinite, in order to keep the product constant.
We do not know if this indeterminism is actually the way the universe
works because unifying theories, within quantum mechanics, are still
incomplete. That is, we do not know if the universe actually behaves in a
probabilistic manner—such as, there are many possible paths a particle can
move, and the observed path taken is probabilistic. Conversely, if the
universe were in fact deterministic it would behave in a manner where I
might be able to predict a particle’s path with 100 % certainty.
We can make an analogy between aspects of life as we experience it, versus
quantum mechanics and the HUP. For example, in bioventure we can
compare technology with position, and success with momentum. In order to
measure the success of a bioventure, biopreneurs and investors evaluate the
technology. However, it is always uncertain and predictability is less than
1%. Therefore, we can conclude that bioventure is a probabilistic
phenomenon.

8
So, seeing it from a different point of view we may ask why are there so
many biopreneurs? Even after all these uncertainties or negatives! It may
simply be because life as such is extremely risky and uncertain, just as it is.
Human living is full of uncertainty and the environment around us is also
fairly uncertain.
This should not be surprising for an entrepreneur. If you compare
uncertainty in life and uncertainty in the environment where we live, to the
uncertainty in the success of a bioventure business, one can easily see the
difference is minuscule, i.e. differential risk in life and bioventure is very
small, so it is not surprising that more and more people are becoming
biopreneurs.
Uncertainty Opens the Door for Opportunities
Once, inside the socio-democratic environment, corporate jobs were secure
for a lifetime, and the government provided most of our other basic services.
When that certainty became uncertain, people in Japan and in other socio-
democratic environments became more and more entrepreneurial.
Traditional pharmaceuticals companies are no longer a place for life-time
employment, due to globalization of the bio-industry, which presents
economic shifts and many challenges. Former mid-level managers from
there are now hedging their futures on bioventures. This is probably a good
outcome from inherent uncertainty.
As you can see in the graph biopreneurship and professional job security,
are inversely proportional to each other. As biopreneur traits increase in
ones life, uncertainty in job-security creeps in and grows. Most of the
biopreneur-minded professionals stay to the right side of the threshold bar,
because a higher-level of activation energy— risk—is required to cross
from the traditional career mindset to venture mindset.
In the US life has always been full of uncertainty, beginning during the
wild-west and gold rush periods, continuing through and into the cold-war
era. Hiring and firing is part of the normal career path. So, it is no surprise
to see entrepreneurs popping up like mushroom in that particular

9
environment. The US has been enjoying this paradigm for several decades.
Currently, biopreneurship in US not only flourishes but also creates many
Molecular Millionaires.
Molecular Millionaires
Many bio-scientists who have become successful biopreneurs have been
described as Molecular Millionaires by the Genetic Engineering (&
Biotechnology) News, which publishes a yearly list of the top 100
financially successful biopreneurs in the US. In the year 2003, when the
economy was beset by heightened geopolitical uncertainties, it was
nonetheless staggering in the many parts of the world including the US and
Japan. Bio-economy continued showing promise and maintained its growth.
Many biotechnology companies strengthened their products pipeline and
advanced their R&D projects to preclinical and clinical stages. During the
year 2003, the top 100 molecular millionaires collectively held $3.2 billions
in stocks. Don’t be stunned to learn that 98% of those molecular
millionaires held doctorate degrees. In 2006 18 out of top 20 molecular
millionaires were PhDs.
Comparison of biopreneurs with traditional professionals

10
In terms of the amount of dollars invested in biotechnology by the public of
the United States shares-market, California, followed by Massachusetts, led
the investment list. There are also several hundreds publicly traded
biotechnology companies outside of US, each of which has a large number
of molecular millionaires. For examples, in Japan newly traded bioventure
companies such as Anges and Transgenic have created several new
molecular millionaires.
Steps towards Biopreneurship
Two career paths can meet professional goals for each individual:
a) Traditional Career Path
b) Venturing Career Path
The traditional career path leads an individual through a structured process,
where the individual goes to high school, graduates, gets a degree from
college, then takes a secure job in an established company and eventually
retires.
On the other hand the venturing career path is quite complex and has
multiple entry points. For example, an individual can enter into a venture
right after high school, and not need to complete a college degree
curriculum. The most cited examples are Bill Gates, Steve Jobs and many
like them. The most common trend for the venture path is to enter after
gaining sound familiarity, and hands-on expertise, in a particular field.
In Japan and India however, the model is quite different. Many individuals
start their career journey as traditional employees in a relatively stable firm
then become an intrapreneur—an inside entrepreneur—within the big firm
while having nominal career security. Later they can move on to become
real entrepreneurs.
One parting thought, an important thing that we should keep in mind,
successful entrepreneurs never get retired! They move on to inspire and
guide, as mentors to young entrepreneurs while building new ventures.
Hence the cycle and the spirit of biopreneurship goes-on forever.

11
A – Lateral Biopreneurism
B – Infrequent path
C – Rare path
D – Most common path
Career Path : Biopreneurism
High School
University
Practical Experience
Management Training
Well Managed,
High Growth Firm
Venture Business
Again Bioventure
Investor (Angel or VC)
Never Retire
High School
University
Big Company
Retire
Traditional Career Path Venture Career path
A
C
D
Vertical
Biopreneurism
B

12
Dream
Zone
Vision
Zone
Realism
Zone
Biopreneurship
Zone
Most of us Dream to be a Biopreneur
We think about it, talk about it, and we dream about it—afraid to take the
initiative to break out of the threshold region (see image—Comparison of
biopreneurs with traditional professionals). Yet a significant number among
these dreamers begin to see their dreams and their visions in concretion.
Vision is part dream and part reality. Vision works as the connecting bridge
between dream and reality, making the dream become concrete-truth for
dreamers. Those, who have dreams without vision never reach the
important reality stage. While those, who have dreams and visions but lack
realism, also fail to reach the final goal in a fierce competitive business
world.
Those, who have a balanced mix of dream-vision-realism, become
successful biopreneurs. Individuals with a confluence of all three zones
reside in the shaded region of the above diagram.

13
Building a bioventure is a teamwork endeavor and if the leader of the team
collectively possesses all three aspects—the dream, the vision and the
realism—the bioventure will likely be a successful one.
Those, who inhabit in the dream zone, are excellent artists, writers and
musicians. People with highest realism are excellent managers and business
people. They excel in big corporate environments, where processes are well
structured.
People with dream and vision are great leaders, for example, Martin Luther
King, Mahatma Gandhi. And people with vision and realism are very strong
corporate executives, e.g., Leis Gustner (IBM).
A Calling
We invite all young scientists to break down emblematic walls with
brainpower and the wisdom of well seasoned professors. I invite you the
professors, the PhDs, and the postdoctoral fellows, to join hands with
investors, individuals, and institutions, and to venture into a new frontier,
the new territories of biopreneurship.
This is not just for profit, but also for the promotion of our future health and
wellbeing. Scientific research alone cannot create new drugs and neither
can just funding. In biotechnology, science and money have to meet and
combine into one, well in advance—usually 7-10 years prior, in order to
have a drug catered to a specific human need.
We know that after passing the age of 40 we usually need eyeglasses and
our immune system function drop dramatically. We can resist acceptance of
these realities and hope that someone will take a lone financial risk to
develop newer drugs as we need them. These drugs that you and I—all of
us—may need are drugs for diabetes, cancer, Alzheimer’s, anti-viral drugs,
and so on. Even my little kid, Akianand, needs drugs for a number health
problems. Am I a responsible father? Am I taking enough of an active role
in advancing new drug development? Or am I expecting someone else to
take the risks incurred in developing these new drugs so my kid, and I can,
utilize them as the need arises? He and I ask you the same question.

14
So, you see, we have plenty of reasons to jump onto a new wave of
enthusiasm—one of bioventurism. Come on scientists, investors, and bio-
patrons! Lets get energized and search for technology that has a reasonable
potential to bring new and effective drugs to light. Let’s not just think
about IPO’s and ROI’s. Let’s focus on new development.
Everyone knows that with success comes ample reward. To the scientist:
you know how difficult and how much dedication it took to reach your
present position. If anyone can bring a drug to the market it surely is you.
Don’t let anyone tell you how over-focused you are, or how it is done
differently in the business world. Investors and future bio-patrons can
guide you through the complexities of the business environment. Science
and technology is 30% of the puzzle, while the remaining 70% lies ahead;
the first steps are in science.
The business world! Of course, there are certain subtleties in business. I
suggest that each biopreneur spend at least 20% of his or her time reading
business related journals and books, while trying to set-up a new
bioventure. Learn from your peers, learn from your mistakes, learn from
doing it again, and again. Don’t wait any longer; it’s your turn. Make it
work! Remember all the experiments that didn’t work, until you finished
that thirteenth trial? Eventually, you made it work. Or I should say Just Do
It—which golfer Tiger Woods can insist is the Nike way.
------------------

16
According to Mr. Olaf Isachson, the author of Joining the
Entrepreneurial Elite, there are ten traits that biopreneurs have:
1. They are in charge of their own destiny.
2. They are non-conformists, able to be-stand-alone or be with
people.
3. They move beyond the local, the provincial, the familiar and the
tried and true.
4. They avoid time-consuming trifles and are swift to make
decisions.
5. There are no obstacles, only challenges and temporary
setbacks.
6. The harder they work the more energy they generate.
7. They love what they do, and their devotion and passion allows
them to move beyond the confines of the ordinary.
8. They are visionaries and their biggest competitors are
themselves.
9. They seldom give up. Failure is not in their vocabulary
10. They firmly believe there are no sins of commission—only those
of omission.

18
“Failure
is
one
of
the
major
milestones
of
an
entrepreneur,
and
each
obstacle
is
an
opportunity.”

19
Who is a Biopreneur?
Biopreneurs or bio-entrepreneurs are normally adventurous, innovative,
analytical, problem solvers. PhD training in any given field gives the
primary skills and core knowledge of that field. However, there is another
whole set of skills and understanding that is not covered in normal PhD
training. That aspect is the understanding of entrepreneurship itself, which
makes it easier to manage and administer the aspects of a specific business.
With bioventure comes extreme complexity that requires business
knowledge and understanding. To become an established and successful
bio-entrepreneur no one can avoid the business aspects of such a venture. A
successful biopreneur must acquire and command the necessary basic
knowledge of general business practices. Planning a business and the
execution of that plan—to achieve real success—are two completely
different aspects of bionventure, or of any business. A person may have to
go through an intermediary phase, or phases—becoming a technical
manager—and might also have to be a lead scientist or researcher as well.
The transition from technical contributor to technical manager is not easy.
Globally, in biotechnology, scientists are often given the responsibility for
projects and people without much thought or additional management
training. This is especially true in the case of biopreneurs who want to
establish a business without outside administrative help. If they transition
perfectly—i.e. they understand the proper place and roles of administrative
people and mold themselves in accord with that—they’ll gain the same
outcome as having outside managers brought into the team. The fact is that
some biopreneurs make the transition rather well, though many experts
agree that the industry has had a rough time in such transitional phases; it
needs improvement. So, to reach the peak in your business, you cannot
underestimate the need for efficient management styles.
Try to understand what happens within the minds of many biopreneurs.
Failure in the transitional stage to manager occurs because most people with
a PhD in biotechnology, while chalking out a business plan, focus on the
scientific and technological aspects of the whole matter. As they consider
their potential product and related incidentals, they see it only from a
scientist’s point of view. Thus when it comes to the administrative aspects

20
of the venture, they believe that implementing supervisory skills is simply a
matter of time and gaining experience. They expect it to be a basic learning
situation while they operate their new business.
Stan Sewitch, a human resources (HR) consultant in San Diego, contradicts
that all too common belief saying, "Management is not an additional set of
responsibilities requiring new skills to be added to one's professional
repertoire," he continues, "Management is an entirely different career from
that of the individual contributor in science." Sewitch, former director of
human resources for Mycogen, San Diego, CA, USA, adds that technical
professionals too often believe that managing people is a skill-set to be
acquired. In most cases, they find out too late that this isn't the case. It’s
best to take Sewitch’s advice seriously from the very outset of a project.
A researcher willing to set up a business based on his or her concept in
biotechnology, known as a biopreneur in the industry, must achieve several
useful qualities to reach the goal of becoming a successful businessman.
Along with gaining managerial awareness it is also advantageous to know
how they themselves are different from other businessmen. It surely helps
them to smooth out any pertinent difficulties while adding indispensable
qualities. It is essential to prospective biopreneurs to prepare for the future
TRAITS OF A RESEARCHER AND A BUSINESSPERSON
RESEARCHER
(Science)
BIOPRENEUR
(Science+ Business)
Determinant & Stubborn Determinant
Ambitious Ambitious with realism
Problem solver Problem solver & delegator
Unbound Explorer Disciplined Exploration
Risk taker Risk taker & hedger
Leadership (some cases) Leadership & Team Player
Cheer leader (some cases) Cheer leader
Sales person (some cases) Sales person
Hard worker Hard worker
Characteristic differences between
Researcher and Businessperson

21
by learning and planning for their bio-venture. They must understand, along
with other things, prior to commencing their business, their own drawbacks
and weaknesses and how they may overcome them or at least be prepared to
face them.
From the above chart it is quite clear that researchers and biopreneurs are
different in fundamental ways. You can recognize one thing clearly; if you
are willing to become solely a researcher you may follow one path,
inventing new things day in and day out. But if your goal is to become a
successful businessman you will have a somewhat different pathway to
take. If fortune is inviting you to become a biopreneur you must choose a
special lifestyle— one where you must play both roles—researcher and
businessman. Along with the characteristics that a researcher exhibits a
biopreneur carries additional attributes which demand particular attention.
For example, a researcher’s character-set insists on being ambitious. In
contrast the character of a biopreneur requires ambition based on reality.
That “reality” makes an ideal situation because in bioventure you must
work to promote yourself along with your company’s brand. There is no
place for airy ambition as you are required to make a profit for your
investors. In the case of bioventure, you will be forced into certain
obligations such as: competitive intelligence, task-management, finding
investors and funding, tax concerns and monetary returns for your investors,
marketing strategies, concrete branding—the future of your brand,
reworking corporate structure etc. These things will prevent you from
exploring new product-lines without ample concern for profit in the venture.
Thus, still retaining characteristics of a researcher, which you truly are, you
will also think and execute things like a businessman. That means not to
embellish, so that you will become an ideal biopreneur.
Valuable Opinions
Co-founder and Chairman of Responsys, Inc., Anand Jagannathan talked
about the characteristics required to be an entrepreneur. Entrepreneurs need
to have determination and drive, the ability to face rejection, and they need
to be risk takers. They must know their “value proposition” with respect to
customer “pain points.” Most successful entrepreneurs, Jagannathan
suggests, have a clear definition of their personal success that goes beyond
reaching the IPO stage, an ability to listen and adapt to customer’s

22
requirements, and the ability to recognize and seize opportunity. Though it
may be easy to read or listen to this, it’s really very difficult to follow
through. And, to materialize the whole concept is even harder.
Mr. Bipin Shah, a successful entrepreneur, now a V.C. in the Silicon Valley,
once presented advice to the new entrepreneurs:
 Start only if you are committed for the long haul and prepared to
go through the ups and downs.
 Start only if you have the deepest passion for what you are going
to do.
 Start only if you are prepared to “fail” if things go “wrong” and
they “do…”
 Start only if you are absolutely convinced that you are killing a
real pain that exists in the market today.
Though an old familiar story but probably novel to new entrepreneurs—
starting anything new always has risk factors, which could lead to failure. If
you are inclined to stop at this point, or move on to other tangential visions,
you may never return to your dream of establishing a real bio-venture and it
will remain merely a fantasy. Whether it’s a new, or an established venture,
risk is always an innate part of the game. But you have to stick to your
original choice of acquiring success. Gururaj “Desh” Deshpande rejected
thoughts of returning to his life as a professor and software engineer—Re:
book titled From Financial Flop to Billionaire. After his first failure,
Desphande stayed the course, always true to his original vision. Now a very
successful entrepreneur, he relates: “A manager means doing things (the)
‘right way’ and a leader means doing the ‘right things.’” If it's something
you really believe in, he asserts, "…you're going to make it happen."
Here, before you decide which role fits you best, you have to know exactly
what right thing and exactly which right way… Reading theories and
building a business plan, based on theory alone, is not very hard, maybe
even a little too easy. Your planning must be based first on reality. After
that you have to be prepared to pursue essential intermediate goals in order
to achieve success. First and foremost, you must consider possible risk
factors that you or your company may need to face. Risks have to be faced;
not succumbing to your fears will make you an ultimate winner.

23
Leadership—It is Expected
Outstanding leaders in business have the ability to convince others. You
must have the ability to inspire your peers and to execute things at the right
time. You have to motivate investors and partners to have faith in your
abilities and concepts, so that they do not waver to invest or support your
decisions.
It is particularly true that gaining something is frequently easier than
retaining it. Leadership is that same sort of thing. As a leader you may have
to make decisions without having all the information at hand, but your
decisions will have to be a strong enough so that no one will want to oppose
you afterward. Though only real experience helps true leaders to make
decisions effectively, nonetheless, many times intuition, based on personal
and concrete understanding, is also a great and positive assist.
You have to stick to your decisions until a time when you find significant
flaws in them. Here you will have to mindful that as a leader you must not
play the part of a dictator. Good and generous leaders have their goals
focused on their team’s goals. You have to be always ready to listen to your
people because they may, in fact, have better ideas in mind than you. You
must build a good team to execute what you think. Thus capable minds
should surround you—their suggestions, comments and interpretations will
always be helpful. You should try to remain the center-point of the team,
and so your communicating skills will keep them in concert. You have to be
strongly connected to your team-members, ready to listen to and talk to
them as needed.
It may appear to be the job of managers but you also must learn how to
separate your inner being—compartmentalizing yourself as required for a
group venture. You must know how to gain the qualities needed to
accomplish the duties of full leadership. You have to sanction yourself with
powers like ego-power, self-power and agency-power. And it is your soul-
power—the power of your spirit—that will keep you totally responsive to
all appropriate feedback. That power will never lead you to feel-on-top of
anyone, nor beneath anyone either. Also ego, if used positively, can make
you self-aware; it can increase positive values in your life. But remember,

24
your ego-power must not become tactless egotism—self-centered
selfishness—optimally it should lightly touch egoism, i.e. self-interest. That
difference subtlety prevents you from losing your humanity.
As Deepak Chopra has shared, you as a leader have to have the ability to
look and listen—not normal looking, and listening—you must not be
blinded to observing reality. For the best possible future of your business,
you must not be deaf to free-flowing ideas and advice from your partners
and your subordinates.
Interestingly, this vision is not only for you, but also for the sake of social
justice and environmental responsibility. After all you must be responsible
for any harm caused to ambient surroundings if it’s caused by your
bioventure. So you ought to cultivate a sense of consciousness, and social-
environmental awareness. Consciousness differentiates tangled hierarchies.
Consciousness is necessary to virtually connect with reality. And so, it is a
sense of consciousness, and awareness, that every human being, whether in
business or any field or job, must possess, for the betterment of society and
the environment in general.
A Simple Philosophy
Business is a service for society, and money is the by-product of that
service. Every time you think of building a new venture, you ought to
remind yourself of that fact. The by-product of the business is your profit,
and it is the living blood of your company. The service you provide to
society must not be any less than the vital need of oxygen. That might be
considered yet another thing to do, but as a leader you have to be prepared
for such responsibility.
Leadership is dependent on time and circumstances. Be prepared to prove
your abilities every time you are faced with requisite circumstances. You
have to create a wholly positive environment for ongoing projects. As a
leader you have to have synchronicity—a sense of co-ordination and
harmony within several jobs. A leader feels, visualizes, takes a risk, and
accomplishes a commitment as he or she moves along to meet various goals.
A leader never loses the winning spirit in the face of setbacks.

25
Nearing the end of this section, I would like to recap and philosophize. It’s
not wrong to say that leaders and followers co-create each other. Leaders,
followers, and environments co-arise within the same space and time. It is
rule itself that differentiates the ruler from others. Although there are
several points or characteristics that may help an entrepreneur to manage
the role of the ruler, there is nothing that is fixed in any business. Rules
work for business, but business is never for the sake of rules. Rules or basic
guidelines to prepare your business are conceived from previous business
experiences and observation.
As a leader you will have to make your own rules according to the time of
the micro and macro environment. Why follow other’s rules? You are
looking to make the best rules to serve your vantage point, reflecting your
understanding and the avoidance of non-productive rules.
Knowledge is only a stairway that leads you to a level of success—you have
to become successful first, by devising your own strategy. When your
strategy is proven, you will establish your own rules in which to rule your
business, as you see fit. This tipping point will be perceived as the birth of a
real industry leader. …Hats off!
Inside the Minds of Biopreneurs
Now you know or at least have a vague notion of what a biopreneur is, a
hint of the managerial aspects of the job, as well as the role and the ways of
a leader. Now let’s take a brief journey through the mind of a biopreneur.
What they hold in their minds makes them different from other researchers,
as it also makes them known to the world! What is the inspiring source of
such strong will-power! According to Mr. Olaf Isachson, the author of
Joining the Entrepreneurial Elite, the ten most traits of entrepreneurs,
including biopreneurs possess, are:
 They are in charge of their own destiny. Contradicting this, anyone
can say that every man is the master of his own destiny, it is true!
But the winning drive is this: Like other people, entrepreneurs, when
problems arise, do not leave their destiny in hands of an unforeseen
circumstance.

26
 They are non-conformists, able to be stand-alone or be with people.
It is their iron mettle that helps them to face any situation. They
know how to mold themselves in accordance with a given situation.
 They move beyond the local, the provincial, the familiar and the
tried and true. In short they are true risk-takers.
 They avoid time-consuming trifles and are swift to make decisions.
True leadership is always a part of their character. Always, even in
the roughest and hardest situations, they remain cool and calm—to
make the right and best decisions.
 There are no obstacles, only challenges and temporary setbacks.
The word obstacle does not exist in the vernacular of biopreneurs. It
is a merely a challenge, as they love to call it, and obviously it is a
challenge that makes them so excited and charged.
 The harder they work the more energy they generate. They
generally possess nonstop energy to go on, and on, and on…
 They love what they do, and their devotion and passion allows
them to move beyond the confines of themselves. The passion and
love for what you are about to do will make its outcome much better,
and of course generally positive.
 They are visionaries and their biggest competitors are themselves.
It is ultimately their unique vision and decisions that make up
responsibilities for the future of their ventures. Certainly, if they are
wrong, they will reverse an imminent catastrophe.
 They seldom give up. Failure is not in their vocabulary. Just like
the word obstacle they are not ready to think of failure. A small
piece of advice here: it is better to have confidence, not thinking of
failure or obstacles, but you have to keep your eyes open for
anything of that sort too, so that you find yourself and your people
ready to face it, if it appears in the future.

27
 They firmly believe there are no sins of commission—only those of
omission. That may differ depending on the individuals. However, it
is also a particular trait that biopreneurs possess quite proudly.
Paths to Success
We always like to know and teach, especially when we know a lot about
business, leadership, etc., or about a formula that may bring success. I do
not think there is any generalized formula or equation that can be used to
define success. However, this does not prevent us from exploring and
finding a cluster of formulas, or sets of characteristics, that may give us a
foreseeable indication of a pathway to success. In bioventure this
information is quite valuable. It is actually based on experience as well as
the experiments of others who might inform us about possible, though not
100% flawless, paths to success. One thing might be applicable to X,
though it may not equally be applicable to Z, and so on. A group of
scholars at MIT’s Sloan School of Management did research on this subject
for five years. According to their studies here is their model for success:
 Success takes a balance of forces. Technology is not always
necessary and is almost never sufficient.
 Due to the power of open communication by the virtue of the
Internet revolution, the business model of future company
might be a huge corporation or it might be a very small
enterprise.
 Decentralization is key phrase of the future. In order to be
successful one must make decisions based on ones proximity to
the knowledge of his or her customers.
 True activities, not the corporate organization charts, will
become the primary building blocks in a business. Out-
sourcing and alliances will eliminate the need for huge
personnel, and becomes the enabler of the small
businessperson intent on staying lean but growing into a big
business.

28
 Companies large and small will be both global and local. They
will need the local touch and all will face global competition.
 The most impacting discovery of this research is regarding the
coming golden era of micro-enterprises—a vision that is
saturated in the power of Internet. Given the low cost of
communications, everyone can be well informed and thus will
make good decisions. The highly motivated, the creative and
innovative, the biopreneur, will convert imparted data and
knowledge into business wisdom, and build successful
companies to compete with gorilla-corporations.
As I already have mentioned these are possible ways; it depends upon you,
as you are the sole responsible agent for the future of your company. It is
useful and a wise decision for the time being to read these ideas to
comprehend the right way before you make any hasty decisions. No one and
nothing in particular will bring success unless you understand and decide
what is good for you. It is well said that success is the progressive
realization of a worthy goal. Success comes from the ability to feel
compassion.
Success Redefined
Inderjit Singh, founder and CEO of Infiniti Solutions and also TIE
Singapore, a member of parliament in Singapore, he has shared the story of
his entrepreneurship. Acquiring a seat in government or joining a
multinational company formerly defined success in Singapore. This might
resonate with many of us who have known success in Japan, or have
equated it to signing-up with a multinational organization, or gaining a
government position. Singh climbed the ladder of success in Singapore
through the same means. But then he attempted something a bit different; he
was able to acquire venture funding from inside of Singapore, and from
abroad. In doing this he ultimately realized his entrepreneurial dream by
changing previously construed, or tacitly defined, limits.
He said, as a member of parliament he championed the cause of
transforming Singapore from a corporate based economy into an
entrepreneurial one by addressing all concerns, impediments, and

29
challenges to entrepreneurship—his mission leaving: “no stone left
unturned.” According to him the key characteristics required to be a
successful entrepreneur are as follows:
1) Determination
2) Risk-taking
3) Leadership
4) Number one salesperson and number one cheerleader
5) Problem solver
So you see the basic traits required to be a successful entrepreneur stay
same. It is only the method of utilizing these traits that change. Over the
course, methods change with things such as the mind, time, and
circumstances.
Though not directly connected to bioventure let us share another important
success story. A well circulated story, if not well known, is one in which
Ireland was looking to become a major center for Microsoft and wanted a
major server hub. Unfortunately, Microsoft’s investigation revealed that
Ireland’s electronic infrastructure could not support it because it did not
have enough resident bandwidth. So everything stopped. What to do now!
There was no looking back and no crying tears of woe. Ireland took on the
enterprise, implementing the required bandwidth building it to the latest
specifications in a very short span of time. The rest is history, thus
establishing Ireland as a global center of excellence in Internet activity. And
that is how one should be prepared for any forthcoming or unforeseen,
unexpected, problem. Now then two questions arise:
How would another country have dealt with such a challenge?
How are other countries prepared to participate in similar
dynamic and global marketplaces?
Problems and their solutions will remain in the background; we just have to
find them. Now that we have enjoyed a couple success stories let’s explore
some new ways to attend to success:

30
Some Critical Success Factors In Biopreneurs
 Strong Will Power That Can Motivate Others.
 Early Contact With Successful Entrepreneurs.
 Exposure To Success Stories And Case Studies.
 Gain Practical, Real World Experience Before, During And
After PhD.
 Be Willing To Be Unusual or Unconventional.
 Agree To Embrace Risk, And Possibly Failure.
 Be Ready To Leave A Large Company.
 Start With Great Ideas.
 Excellent And Passionate Team—Near And Long Term Vision.
 Able To Change Course, Mid Stream.
 Execution, Execution, Execution!
 Strategic And Marketing Brilliance.
 Frugality And Excellent Cash Management.
 Support Network—VCs, Board, Advisory Panel, Other Value-
Added People.
It may look like I’m bringing the same old ideas the forefront again, but I’ll
remind you once more that these things need not be strictly followed or
adhered to. These are guiding principles; as such they are important yet
completely flexible rules. These are tools for the sake of your business—
your business is not there to prove the rules practical worth. Every leader
creates his or her rules, but rules come after you are sure you can call
yourself a leader in business.

31
Summing it up
As someone once said our best of us is not what we do, but what we inspire
in others. So when we share our experience and knowledge, it increases us.
Whatever way we choose or wherever we move to work, the basic
knowledge and methods will remain the same.
We may face failure and obstacles only to remember “Failure is one of the
major milestones of an entrepreneur, and each obstacle is an opportunity.” It
is not merely theory; theory is also based on what we learn from our failures
and experiments. Our own failures and flaws will teach us the right way to
success. This will make us winners one day.
Everything depends what is in our mind—the Silicon Valley is not a
geographical location it is just a state of mind. Think like a winner and you
will find yourself a winner. If you loose the vigor of your mind you will
wind up nowhere in the future.
If experimentation is the only thing that you have to play with, do it
sincerely, genuinely and with matchless passion. With human life spans
longer, and the business cycle shorter, opportunities are immense for those
with motivation and the guts to do it. There is no one-way, and there will
be no one-way. It’s the biopreneur’s way, and it will be the biopreneur’s
way.
~~~~~~~~~~~~~~

33
Biopreneur
Science + Business

35
Chapter III
Understanding the Business of
Biotechnology

36
Most
extraordinary
discovery
came
from
accidental
discovery—
serendipity.
The
most
prominent
example
is
penicillin
discovered
by
Alexander
Flaming
in
1928.
Also
notable
is
aspirin,
the
wonder
drug
from
willow
bark,
and
more
recently
Taxol
from
the
yew
tree
of
the
Himalayan
region.
There
are
also
a
large
number
of
painkillers
which
come
from
the
poppy
plant
seed.

37
What is Biotechnology
Finding an easy way to understand the business of biotechnology will be
easier when the technology itself is easily defined. Simply speaking
anything to do with the bio or life is biotechnology. Making medicine using
fancy reactions and chemical processes or fermentations of grains to make
alcohol, or making tofu, are distinct parts of biotechnology. A more broad
definition of biotechnology should be:
Biotechnology: The use of living organism, or their products, to modify
human health, and the human environment.
Early biotechnological processes were making wine, yogurt, and soy sauce.
And modern biotechnology has gone through a long development process
while there is still a long way to go. The information imparted there is
supposed to get your attention and arouse your interest in the development
of your bioventure.
History and Development of the Industry
It was in the early stages of civilization when people understood the
necessity of natural processes to utilize organic waste materials by
converting them into fertile soil. But until the invention of the modern
chemistry and microbiology the processes were not fully understood. Today
can visualize the same utilization of biotechnology, for producing necessary
foods. In understanding the whole biochemical process we have ascribed a
name, Green Biotechnology. For the sake of controlling pests, fertilizing
land, and restoring or securing the nitrogen balance to the soil, we use
several organic products. Several other experiments regarding the breeding
plants with other plants, modifying plants, genetic and artificial selection,
were carried out to facilitate agricultural improvements.
Regarding using biotechnology in other fields, the process of brewing was
probably the first. It is actually a method of using yeasts with
carbohydrates—malted grains—to produce alcoholic beverages. It has been
observed that methods, using antibiotics, and vaccines, to immunize people
against infection was known as early as 200 BC.

38
Recombinant DNA or rDNA came into the field which changed the style of
modern biotechnology forever. Stanley Cohen and Herbert Boyer
discovered rDNA in California in 1973, and it created quite a revolution.
Simply defined this is a process where the DNA of two different organisms
are recombined to produce a genetically advanced DNA. The most common
organism in this process is Escherichia Coli bacteria.
With the discovery of rDNA, as mentioned, a modern trend in
biotechnology was at on the threshold of a new revolution. In 1976, Boyer,
with Robert Swanson, established Genentech. Two years later Genentech
began the synthesis of human insulin. This success led to the establishment
of Biogen, Amgen, Chiron, and other university-led biotech firms. The first
biotech boom hit in the early 1980s, as the US economy emerged from
high-inflation during the Carter administration—a severe recession resulted
from an attempt to control it under the Reagan administration. There were
calls for a need to create employment. At that same time, there were several
developments at the federal level that helped boost the burgeoning biotech
industry. Among them:
 In 1979, Congress revised the Employee Retirement Income Security
Act to allow parts of pension funds to be used as Venture Capital
(VC), which increased available venture funding.
 In 1980, Diamond vs. Chakrabarty, a patent case, the US Supreme
Court handed down a decision saying any human invention, whether
animate or inanimate, could be patented—in this instance
genetically engineered bacterium. This decision, as one summary
puts it, “opened the floodgates to the suits of biotechnology-related
subject matter, now available for patenting.”
 Also in 1980, the University and Small Business Patent Procedures
Act, popularly known as the Bayh-Dole Act, expanded in 1984,
facilitated the commercialization of federally funded research.
 In 1982, the Small Business Innovation Research (SBIR) program
was established. It directed each federal agency with an R&D
budget in excess of 100 million, in order to “expend not less than

39
2.5% of that budget specifically for the SBIR program.” This
requirement greatly helped small firms which were exploring
biotech possibilities.
 In 1986, the Federal Technology Transfer Act authorized
government laboratories to enter into cooperative R&D agreements
with private firms, and to license inventions that may result from
such arrangements.
In 1990, the Department of Energy in co-operation with the National
Institutes of Health embarked on the Human Genome Project. Ten years
after a working draft of the DNA sequence of the human genome was
completed.
Charactistics of the Industry
The US biotech industry is characterized by two features:
 Regional concentrations and the leadership roles are played by
academia, large drug manufacturers, and medical institutions.
Recently, state governments—i.e. California—have been promoting
biotech as the potential economic boosters, comparable to
information technology during the 1990s.
 The largest biotech concentrations occurred in Gene Town, near
Boston, and Biotech Bay, near San Fransisco. Gene Town, with
Harvard University, MIT and Massachusetts General Hospital as
major academic backers, boasts nearly 250 biotech ventures,
whereas Biotech Bay, with Stanford University and the University of
California, San Fransisco, as preclinical academic backers, boasts
over 200 ventures. They took large NIH grants, with Biotech Bay
receiving $2,248 million and Gene Town $1,534 million in FY-
2000. Among other such clusters are Pharma Country (PA, NJ, NY,
CT), Bio Capital—Washington D.C. and Biotech Beach—San
Diego.

40
Understanding the Drug Discovery Process
Drug discovery processes has two major components:
(1) Research and Development (R&D) and
(2) Human Clinical Trials.
Research begins long before any a company considers pursuing a drug
discovery project. Normally scientific discovery is made in a research
institution or in a university, which notably is based on hundreds of research
and scientific projects prior to a particular discovery. Once a discovery is
made and shows promise for tangible commercial applications, companies
will bring that discovery to the industry for further research and
development
work. It may
take another 3-5
years and $5-
10M to reach
the point where
a possible drug
candidate can
be envisioned.
The next step in
the process is
human clinical
trials: Before those trials, a bioventure has to prove that the drug candidate
is non-toxic to animals. Additionally, it must perform a series of
pharmacological research trials for short-term and long-term effects on
animals. Collectively, those steps are referred to as pre-clinical.
Once the pre-clinical studies are completed, the bioventurer submits its all
findings to the regulatory agencies for clearance to perform human studies.
Once they receive the clearance, the company moves to the most expressive,
and most critical, stage of the drug development process. Human clinical
trials have 3 + 1 steps – three phases of clinical trials— phase-I, phase-II
and phase-III—and post approval surveillance studies, also known as phase-
IV.

41
The following figure depicts the different stages of the drug development:
Research and Development
There are two essential ways a drug can reach the hands of people:
 Targeted drug discovery process
 Accidental finding of a novel molecule
The molecules could be a small chemically synthesizable, or a
macromolecule, such as an antibody, enzyme, or oligonucleotides. Most
extraordinary discovery came from accidental discovery—serendipity. The
most prominent example is penicillin discovered by Alexander Flaming in
1928. Also notable is aspirin, the wonder drug from willow bark, and more
recently Taxol from the yew tree of the Himalayan region. There are also a
large number of painkillers which come from the poppy plant seed.
Discovery
phase
R & D
0 4 7 10
Toxicity
Study
Development
R&D
Marke
t
IND
P1
P２
P３
Clinical trials Regulatory
Approval
16
13
Preclinical
10,000 250 5
Drug Candidate
and
Application
Research
&
Experiments
P4
Year
Drug Development Stages

42
The story of penicillin’s discovery is particularly extraordinary and an
example of the gift of persistence. Penicillin not only saved million of lives,
but it additionally set the landscape for modern drug development.
A large number of drugs came to the market due to long-term targeted drug
discovery processes. A prime example of this is Augoron (Pfizer) a
pharmaceutical protease inhibitor, viracept, for AIDS.
It is important to note in a targeted drug discovery process of 10,000
screened targets only 250 become viable candidates for pre-clinical testing.
Therefore, serendipity in discovery seems mainly desirable and very
economical. Unfortunately chance discoveries are rare and may happen
once in every million times, and that is only if observations are made by a
persistent scientist—not just a talented one. In the targeted drug discovery
process, when lead candidates show promise in a laboratory setting, in a
cell-culture or tissue culture systems, those candidate drugs go to animal
efficacy testing. If animal testing shows positive efficacy, a selected drug
candidate can then move on to pre-clinical and safety studies.
Alexander Fleming's photo of the dish with
bacteria and Penicillin mold

43
Efficacy Studies—Animal Model Selection
It is important to select animals for parallel efficacy studies. Some studies
may provide misleading results. It has been reported in the past that while
rat and mice studies show little or no efficacy value, dog and/or pig models
can provide excellent efficacy in testing a given drug or substance, as a
candidate. It is therefore important to understand what pathway or cellular
structure is targeted. On that basis, one should select animal models that are
closest to the human cellular/organ structure and the morphology which is
being targeted. Sometimes it is not possible to find a proper animal model;
in those cases tissue cultures—if available—is the next best option.
An example of this would be the silent killer Hepatitis-C (HCV). There is
no widely accepted or economically viable animal model for HCV except
chimpanzees. On the top this, there is also no widely used tissue culture
system for a high throughput screening of drug candidates. A company I
was formerly associated with was one of the few establishments with a
system to screen small molecules for HCV in a tissue culture.
35.9 35.9
13.1
2.1
Casulties of drug development processes
Over 70% of all development projects are discontinued
due to lack of Efficacy or high Toxicity

44
The Casualty of the R&D
Over 35% of leading drug candidates are abandoned due to poor
performance in animal efficacy studies, another 35% are dropped due to
toxic effects on animals. An additional 15% of drug candidates discarded
for financial and funding related reasons. In the end only a lucky few move
on to the next level.
Drug development processes grew longer with the better understanding of
molecular science. In the 1960s our knowledge was limited to the concept
that behavioral biology and drugs came mainly from plants that had been
used in traditional remedies. In the 1970s, came combinatorial science and
high-throughput screening—researchers screened large pools of plant
extracts, chemically synthesized compounds and other molecules, as drug
candidates.
At the same time the concept of molecular biology began to emerge; it
thusly influenced the requirements for clinical testing.
0
2
4
6
8
10
12
14
16
18
20
1960s 1970s 1980s 1990s 2000s 2010
Y
e
a
r
Period
Approval Clinical Trials
Pre-clinical R&D

45
In the 1980s, molecular biology was in full swing, with the invention of
PCR, recombinant technology, and newer modern equipment. Hence
regulatory agencies demanded, rightfully so, more data and information on
drug candidates, so to ensure the safety of the human life. Therefore, the
span drug development processes grew to be in the range of 13-14 years.
That has remained about the same for the last 25 years.
With the appropriate advancement of genomincs and pharamcogenomics,
we can expect a faster drug development process in the near future. Patient
populations can be divided according to their pharmacogenetic make-up.
This will eliminate ambiguity in the study results. Also, if one can devise
batteries of assessment systems to evaluate the propensities of drug
candidates to become new drugs, during the R&D and pre-clinical stages, it
would save huge amounts of capital resources and equally valuable time.
So, how does the future of the drug discovery process look?
Future Drug Development Process
As the knowledge and understanding of gene and gene function grows, the
resulting drug discovery process becomes more and more specific and
target oriented. Before the genome project we had only a handful of targets
Targets for screening new drugs.

46
for screening new drugs. Now we have over 10,000 targets. This number is
expected in increase to 50,000 or more in short order. The more we learn
about gene products, proteins, and their functions, the greater the
opportunity to find at least 10-50 targets per protein molecule in the human
body.
Bioventures as well as pharmaceutical companies are taking advantage of
new tools and assay systems in the drug development process. Strategies are
now built with information from the pathway-mechanisms, target-
characteristics, screening-protocols, and process-optimization.
Implementation of drug discovery strategies is guided by informatics—e.g.
genomics, pharmacogenomics and toxicogenomics.
At this point in time, out of existing processes, these newer processes seem
exceptional and are very promising. Biotech corporations will now move or
discard drug candidates faster, preparing to change or modify any required
molecules more quickly.
Business decision-making Infrastructure
Executives of bioventures or pharmaceutical companies need a clear
snapshot view of the entire drug discovery process based on dynamic-
phasing. This will allow executives to make prudent decisions and allocate
proper resources for the development of drug candidates. In the past, this
decision-making process was chiefly responsible for delaying in drug
development which resulted higher costs during the project.
The following schematic diagram represents the coordination and
deployment of different types of profiling and assays in various, specific
phases, of drug development. These highly integrated processes not only
bring forth the most effective drugs in a timely manner, but they also save
significant cost and time in drug development.

47
State of the art tools, assay systems, and bio-information technology (IT)
protocols can provide a just-in-time analysis of drug development processes.
The following schematic plainly shows how different sub-processes interact
with each other, and how the information generated from each process helps
to make early decision-making tasks less complicated.
The genome project not only brought understanding of biological process
closer to the molecular level, but it also created a complex system of
information and a virtual data jungle. Unless we implement a high-level
computer data gathering, analysis, and reporting systems, drug development
processes will surpass the current 14 years term, to 24 years.
New Technologies increase Quality and Quantity of Output

48
Fortunately this problem has presented sophisticated IT professionals with
sharp challenges to deal with—notably concurrent with the post dot.com
nosedive. IT professionals are now paying very close attention to making
drug discovery processes more efficient and cost effective.
As information technology modernized financial institution and businesses,
the IT industry is now also converging on bio-industry to give it a needed
face-lift. As a result a new discipline called Bio-IT has emerged.
Corporations like, IBM, Oracle, Intel, Motorola and HP joined the bio-
fields to take-on a share, from the $20B. Bio-IT is now lending a helping
hand in streamlining the drug discovery process, from start to finish. In drug
discovery processes there are enormous inefficiencies at every stage.
In R&D the lack of coordination among researchers, between research
teams, and between business teams, increases the time from the lab to the
pre-clinical stage. As a result, time and money are lost. Similarly, pre-
clinical and clinical processes require high levels of coordination, control,
and vigilant monitoring. These processes also create enormous mountains
Application of Pharmacogenomics in Drug Discovery and
Development will allow Decision Knowledge Base early on

49
of data that need to be handled and packaged in an efficient, digestible,
manner.
The current stage of the drug discovery processes has thus become much
more complex and extremely sophisticated. In the future, drug discoveries
and their inherent infrastructures could produce drugs in more efficient and
cost effective ways. A prospective, future, infrastructure could integrate the
most efficient data-gathering, analysis, high-powered computing, and
report-generating systems—along with state of the art chemical and
biological computer processing.
Infra-structure for Drug Discovery Process

50
-DRUG DISCOVERY-
RISKS
 High Cost, one drug /$100-300 millions
 Long time: 14 year from discover to approve
 Use out of exiting chemical libraries
REWARDS
 High Pay-off, 0.1-1 billion per drug for 10-12 years
 Save huge social cost for different diseases
 Huge social benefits
Conclusion
The ever expanding field of biotechnology is not only fascinating, but
equally full of practical promise. Since 1980s it has come a long way and
has seen variety of bio-travelers. Unlike other industries, this industry can in
fact modify human living standards to a great extent. But its yet greatest
possibilities are not easily conceived at this stage of development. One
might think of previous success stories in this field, while at the same time
think of immense possible futures. We still need a number of case studies
and information to understand the business of biotechnology. So, simply go
on reading this survey book of information, continue inventing and
innovating—all for the sake of increasing the markets in biotechnology.

51
From Lab to Patient:
D r u g D e v e l o p m e n t
P r o c e s s e s
AND QUALITY OF HUMAN LIFE

53
CHAPTER IV

54
....pre-clinical development is a stage, or period, when development of a
new drug begins prior to clinical trials, and before testing on humans can
start—it’s when important safety and pharmacology data is collected. ..

55
Pre-clinical development is defined by many pharmaceutical establishments
as a process to invent a new chemical or molecule, lead it through different
stages, and allow it to be tested on human volunteers, so that a new
medicine might arrive in market for the betterment of humanity. So then,
pre-clinical is just one stage of a new drug development that is executed
before the clinical stage—here we acquire important safety measurements
and pharmacological data to make experimental drugs for humans effective
and safe.
In other words, pre-clinical development is a stage, or period, when
development of a new drug begins prior to clinical trials, and before testing
on humans can start—it’s when important safety and pharmacology data is
collected. The main purpose of pre-clinical studies is to gather information
on a drug's pharmacodynamics (PD), pharmacokinetics (PK), ADME and
toxicity through animal testing. This data allows researchers to
allometrically estimate safe doses of a drug for upcoming clinical trials in
humans. Pre-clinical studies must accumulate data by behaving in
accordance with Good Laboratory Practices (GLP) in ICH Guidelines to be
acceptable for submission to regulatory agencies such as the Food & Drug
Administration in the United States.
Drug discovery: A Brief Story
Before we proceed in our overview, to the several stages or requirements of
pre-clinical studies, it is best to have some idea about how a new drug
reaches the market for the general population. In each case, inventing new
drug, we first have to find our target chemical or molecule. The process of
inventing a particular chemical is called drug discovery.
New Chemical Entities (NCEs) are the compounds that come out of the
process of drug discovery. As a result of drug discovery, new NCEs will
certainly have promising attributes against a particular biological target
thought to be important in a particular disease. But having these NCEs at
our disposal doesn’t mean that we know every aspect of the new element.
That is because information about the safety, toxicity, pharmacokinetics and
metabolism of the NCE in humans are still unknown.

56
The goals of the non-clinical or preclinical safety evaluation include: a
characterization of toxic effects with respect to target organs, dose
dependence, relationship to exposure, and potential reversibility. This
information is important in estimating an initial safe starting dose for human
trials, and for the identification of parameters in clinical monitoring for
potential adverse effects.
The non-clinical safety studies, although limited at the beginning of clinical
development, should be adequate to characterize potential toxic effects
under the conditions of the supported clinical trial. A major objective of
drug development is to make a recommendation of the dose, and schedule
to be used, the first time an NCE is used in a human in clinical trial which is
also known as First-in-Man (FIM). At the same time we have to evaluate
during this process the physicochemical properties of the NCE—that means
its chemical makeup, stability, and solubility. It will be further examined for
its suitability as well as its effectiveness to be made into capsules, tablets or
intravenous formulations. Together these processes are known in preclinical
development as CMC: Chemistry, Manufacturing and Control.
However, the research team must keep in mind that they have to satisfy the
licensing authority to clear the legal aspects of releasing the drug into the
market. In doing this they have to move through several other tests, as well.
These generally constitute a number of tests designed to determine the
major toxicities of a new or novel compound prior to first use in man (FIM).
It is a legal requirement that assessments of major organ toxicity be
performed such as on the heart and lungs, brain, kidney, liver and digestive
system, as well as other parts of the body which might be affected by the
drug—i.e. the skin if the drug using the skin for delivery. While,
increasingly, these tests can be made using in vitro methods, with isolated
cells, but many tests can only be made by using research animals. This is
simply because the tests performed on an intact organism can aid in
examining the complex interplay of metabolism and drug exposure on
toxicity. Even after clinical trials, tests continue in order to determine if the
drug is free from side effects on the immune system, reproduction, and
fertility related problems. Tests are also done to see if it has any noticeable
cacogenic effects.

57
After going through as many possible tests as required by law, the drug
appears with information such as its efficacy, dose schedules to be used,
possible side effects, target populations, age group, etc. before an
organization employed to assess new drugs. In the US we have the FDA for
that purpose. A file that carries the aforementioned information and other
things related to the new drug is called New Drug Application (NDA).
Observations show that most NCEs fail to hurdle this entire procedure and
reach final approval.
The present chapter deals with only one part of drug developent known as
pre-clinical. As already known to some extent, the stages used in taking
new drugs into the market allows us, for the present, to make pre-clinical
our main area of concern. In later chapters we will discus in detail the latter
clinical stages of drug development. While exploring the whole concept we
will encounter several terms related to these other topics. We should
continue, adjunct to the main thrust, discussing those terms as well.
From Develop(ability) Decision,
to Clinical Proof of Concept
Let’s presume your bioventure passed through the exploratory
investigational phase in the laboratory. At this stage biopreneurs need take
into consideration the requirements of the regulatory agencies. Most of the
work done now will be used to file for regulatory reviews. Bioventures and
regulatory agencies take extraordinary measures to ensure the safety and
efficacy of all approved prescription medicines. The processes hereafter
become very expensive. So it is important to take extra measures to make
sure the drug-candidate has real potential as a drug.
The product has shown academic and scientific charm, and has potential for
piquing a scientific quest for knowledge. We have passed the dream and
vision cones of the biopreneurs’ universe; now it’s time to enter the realism
cone. Here product has to be tangible and feasible for commercial
production. Next step: establish the development-ability of the drug
candidate.

58
Establishing Develop(ability)
Once our lead molecule has been identified, it is prudent to evaluate the
develop(ability)—develop-ability—of the molecule using less expensive
tests which have been proven to identify problems with safety and drug
delivery in later development. It’s important, before starting expensive pre-
clinical processes, to evaluate the ability of any molecule with inherent
possibilities.
Questions to be answered
Can the parent molecule be measured in biological matrices over the
right concentration range and according to GLP standards?
Is the large molecule stable in biological matrices under normal
sample handling and storage conditions?
Is the large molecule stable in the formulations to be used in early
studies?
Is the large molecule degraded or metabolized and if so, to exactly
what?
Does the large molecule cross human intestinal epithelium as
predicted by Caco-2 cell permeation studies?
Does the large molecule penetrate membranes as predicted by the
MDCK cell culture model?
What is the plasma half-life in rats and dogs following single dose
intravenous administration?
Is the large molecule mutagenic or cytotoxic by in vitro (bacterial or
mammalian) genotoxicity screens?
At what dose does the large molecule show limiting toxicity after
acute administration to rodents?

59
At what dose does the large molecule show limiting toxicity after
repeated dose administration to rats and dogs?
What are the target organ systems of toxicity?
What should be the subchronic tox species for study based on
metabolism and pharmacokinetic considerations?
Preclinical study involves several stages or steps to satisfy researchers and
examining teams, such as the Institutional Review Board (IRB), in order to
get a license to conduct clinical studies of an Investigational New Drug
application (IND). We must also keep in mind other institutions that look
after the welfare of animals. These tests require several animal species, and
we might also assess possible, or intended, results of our tests. All those
steps or required tests with adjunct related information—which, we might
term preclinical development tests—are listed below to enable a swift
glance at the possibilities of preclinical study.
PRECLINICAL DEVELOPMENT - TASKS
Chemistry and Analytics: -
Chemistry, Manufacturing And
Controls
Supplies
-Up And Process
Development
Manufacturing
Manufacturing
Analytical/Bioanalytical Capabilities

60
Pharmacology and Toxicology tests –
Pharmacology
oncology, CV, CNS)
pharmacology/toxicology
studies
PK / ADME
Tissue distribution/mass
balance
Toxicology Services
carcinogenicity)
developmental toxicology
models
General Toxicology Studies
-range finding
biodistribution
Species
including
transgenics
Canines
-human
primates

61
Pathology tests –
Pathology // Histopathology
evaluations
Clinical Pathology
differentials
In addition to the aforementioned information, the develop-ability in
preclinical studies needs greater clarification to make that information clear.
This includes topics like estimated costs, kinds of testing required to satisfy
assessment, and on what exactly are those tests are executed. I have tried to
gather potential information in a short list, to give you a fairly quick
informational track—see Appendix I; table titled: Package of Studies to
Assess Develop-ability. These lists will undeniably help you to build a
model of what is what, in preclinical development. The rest of this chapter
will inform you about remaining study information.
Typically, both in vitro and in vivo tests are performed for the sake of safety
and research values. Studies of a drug's toxicity include which organs are
targeted by a drug, as well as if there are any long-term carcinogenic effects
or toxic effects on mammalian reproduction.
In vitro is a Latin term meaning within the glass. The term in vitro
represents the technique of performing a given experiment in a test tube, or
to express in a better way, in a controlled environment, outside the living
organism. In vitro fertilization is a well-known example of this. Many
experiments in cellular biology are conducted outside organisms or cells.
Thus, results may not correspond to those results inside an organism.
Consequently, experimental results are often annotated as in vitro.
In vivo is just the opposite of in vitro process. It is, however, also a Latin
term meaning within the living. So, it is easily understood as a process that

62
A S S E S S I N G D E V E L O P M E N T
Single IV/Oral Dose
Pharmacokinetics in Dog or
Monkey (DM4)
Single IV/Oral Dose
Pharmacokinetics in Rat (DM3)
Single (acute) Dose IV in
Mouse (TX1)
Ames bacterial
mutation (GT1
Mouse
lymphoma assay
(GT2)
Bioanalytical Method Validation
(BA1)
Crossvalidation
– Rat Plasma
(BA2)
Crossvalidation
– Dog Plasma
(BA3)
In Vitro Metabolism – Metabolic Stability
Caco-2 Cell Permeability (DM2)
Single (acute) Dose IV in Rat
(TX2)
Repeat Dose Range Finder &
Toxicokinetics in Rat (TX4)
Repeated Dose Range Finder &
Toxicokinetics in Dog or Monkey
(TX5)
Lead Identified
Is Lead
Developable
?
Go to
Flowchart 2
Identify New Lead Compound
Yes
No
Pharmaceutical Development Assessment: Solubility, Stability, Synthesis
takes place inside an organism. In science, in vivo refers to experimentation
done in, or on, the living tissue of a whole, living organism as opposed to a
partial or dead one. Animal testing and clinical trials are forms of in vivo
research.
Both in vitro and in vivo processes require more information and we will
continue with this later in this chapter.
Animal Testing
Animal testing or animal research represents the utilization of non-human
animals in experiments, to know the primary effects and related side-effects
on them. As it is done prior to a clinical study, it is easy to understand that
its purpose is to see if an invented molecule, or chemical, is applicable to

63
human beings. It is estimated that 50 to 100 million animals worldwide—
from fruit flies and mice to non-human primates—are used annually in
various scientific experiments. This research is carried out at universities,
medical schools, pharmaceutical companies, farms, defense-research
establishments, and commercial facilities that provide animal-testing
services to industry.
Nobel Prize winning research such as organ transplantation in dogs,
penicillin in mice, etc., has proven the necessity of animals in the medical
research sectors. Counter arguments claim—as opponents reveal—it is
unnecessary to use animals for research. Using rationales such as: animal
research is not only inhuman but it increases expenditures, and it is ‘bad
science’ to use animals in such ways, antagonists have many reasons to
support their position. However, in my judgment, that may not resolve our
situation. My job is mainly to deliver the when, how, and which, kinds of
information as is related to animal testing in preclinical studies. Expedience
is an end-all imperative, in my view.
History in brief
It is not the current state of preclinical testing activity that witnesses animal-
testing in drug development, but it still bears a reputation of long existing
practice. History tells us that the Greeks started it as early as third and
fourth century BC. They were first to use animals for this purpose.
According to history, Aristotle—384 to 322 BC—and Erasistratus of
Chios—304 to 258 BC—were the first among the Greeks to execute such
experiments on living animals—Re: Cohen and Loew, 1984. To add to this,
it is general knowledge that Galen is the “Father of Vivisection”. Galen, in
second century BC, dissected pigs and goats in Rome.
Mentioned earlier, animals have had a role in numerous and notable
experiments. I might also mention the name of Louis Pasteur who explained
germ-theory by experimenting with anthrax in sheep during the 1880s.
Insulin, which plays a considerable role in the treatment of diabetes, was
first isolated and produced from dogs in 1922. Before trying the multi-drug
antibiotic treatments for leprosy on humans, it was tested on armadillos in
1970s. And the most noted of them all, Dolly the sheep, the first cloned
mammal from an adult cell, was born in 1996.

64
We can also add Xeno-transplantation research, for example in the
development of modern medical science using animals. It primarily uses
non-human primates as the recipient of pig hearts. The British Home Office
released figures in 1999 showing that 270 monkeys had been used in xeno
research in the UK during the previous four years. In 1999, three baboons
and 79 cynomolgus macaques were also used.
Types of Animals Used
As in vitro tests is simply not enough to collect necessary toxicity and other
information. We have to depend on in vivo processes. Using animals, which
impart relevant information regarding an invented molecule/chemical, is
still the only way to move toward fruitful drug development. The intention
of any test in drug development, whether it is preclinical, or clinial, is to
estimate efficacy of a drug, safety measurements, possible schedules, and
the amount of intended doses—its side effects both in short and long term,
its target users, etc.
Thus, every way you have at your disposal to satisfy various queries related
to these fields and tests should be arranged in as many possible ways to
assist your efforts. The number of animals used in research work—both in
purely research-based and in applied research—as data shows, changes day
by day. You may also do single-instance research when applicable.
According to the U.S. Department of Agriculture, the total number of
animals used in that country in 2002 was 1,137,718, not counting birds,
mice, and rats, which make up around 85% of research animals—excluding
invertebrates. Other sources estimate the percentage of all lab animals
which are rats, mice, or birds at 85-95%. The Laboratory Primate Advocacy
Group has used these specific figures to estimate that 23-25 million animals
are used in research annually in America.
In 1986, a report produced by the U.S. Congress Office of Technology
Assessment reported that "estimates of the animals used in the United States
each year range from 10 million to upwards of 100 million," and that their
own best estimate was "at least 17 million to 22 million.” In 1966, the
Laboratory Animal Breeders Association estimated in testimony before

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Biopreneurs: The Molecular Millionaires