Additional Material, Lect #1 CHIRON case study.docxCHIRON’S FL.docx

Additional Material, Lect #1 CHIRON case study.docx
CHIRON’S FLU VACCINE CASE STUDY
Homework project.pptx
Homework
#2. Heparin - Blood-Thinning Drug Under Suspicion
http://www.cbsnews.com/stories/2008/03/01/eveningnews/main
3896578.shtml
The U.S. Food and Drug Administration stated that at least 81
deaths were believed linked to a raw heparin ingredient
imported from the People's Republic of China, and that they had
also received 785 reports of serious injuries associated with the
drug’s use.
3896578.shtml
Lect#3 Lymerix case study written project PM FINAL (2).docx
!Unexpected End of Formula
9/28/13

Project Management
LYMERIX: AN UNFORTUNATE END THAT COULD HAVE
BEEN AVOIDED
Lyme disease…
Lyme disease was first acknowledged in 1977 in Lyme,
Connecticut, when different clusters of the town’s residents
came down with cases of juvenile rheumatoid arthritis. At first,
it was thought to be derived from an autoimmune disease, but
that did not explain the vast outbreaks of rheumatoid arthritis
continuing to pop up in abnormally young populations
throughout the northeastern United States. Finally, researchers
were able to identify the previously unrecognized source: the
nasty, little, bacterial spirochete known as Borrelia burgdorferi.
The disease is spread by Ixodes Scapularis, more commonly
known as the deer tick, whose natural host is mice and deer (1).
The transmission of the bacteria to the human host occurs
over several hours when the deer tick bites and remains
attached. Most often, the deer tick goes unnoticed on the human
due to its near microscopic size, and is left uninterrupted to
transmit the bacteria. The only known indication of the disease
is the unmistakable bull’s eye type rash that develops around
the bite site several days or weeks after the host has been bitten.
Upon being diagnosed with Lyme disease, long doses of
antibiotics are prescribed. If the Lyme infection is left
untreated, a variety of flu like symptoms will often develop in
addition to Bell’s palsy and other neurological symptoms. In
about 60% of the patients, chronic arthritis often develops (2).
It is common even after treatment for the patient to exhibit
periodic “flare ups” of symptoms for months or years. Every
year well over 20,000 cases of Lyme disease are reported, and
even as much as three times as more go unnoticed (2).
The story of LYMErix…
In 1990s, an outer-surface, 31 kDa, lipoprotein known as
OspA on the B. burgdorferi was found. Although it was shown

to be highly variable, it was considered to be a promising
candidate for vaccination studies (1, 3). SmithKlineBeecham
took the consensus sequence of OspA and developed a Lyme
disease vaccination that used a recombinant OspA as their
immunogen, and called it LYMErix (1). Recombinant OspA,
when expressed in E. coli cells and subsequently injected into
mice in preclinical studies, protected against Lyme disease;
therefore, it was considered to be a highly, promising candidate
for vaccination (1-3). Immunization was shown to be antibody
driven, and offered protection from heterogeneous B.
burgdorferi driving its candidacy as a vaccine (3). In a safety
and efficacy trial in humans conducted by the University of
New Mexico’s school of medicine, recombinant OspA was
shown to be safe and effective. The trial was randomized,
double blinded, and placebo controlled. The participants
received two or three doses of the vaccine, and they were
followed for one year after the final dose (1,4). The only side
effects or adverse events that were reported were pain and
tenderness at the injection site, which subsided after three days
(4). When LYMErix underwent a similar, larger phase III,
clinical trial with 10,906 subjects, in an endemic area, 76% of
vaccinated individuals exhibited a reduction in Lyme disease
after a year with no significant side effects shown (1). As a
result, the FDA approved the three dose LYMErix vaccine for
Lyme disease in December 1998 (1).
The issues arise…
As soon as the FDA approved LYMErix for marketing
questions about its development began to arise. As pointed out
in the review article, The Lyme Vaccine: a cautionary tale there
were four major problems contributing to its market withdrawal
in 2002 (1). First, the vaccine was only efficacious for 76% of
the vaccinated individuals, which meant close to a quarter of the
vaccinated individuals would not receive any benefit. Second,
in order to maintain the titer for a year the vaccine had to be
given in three doses over a course throughout a year. There

were questions about the long efficacy of the vaccine, such as
how often a booster would be needed (1,3), which in turn,
brought up questions about the cost effectiveness of the
vaccine. Third, SmithKlineBeecham never conducted studies in
children: the most at risk population for Lyme disease. Fourth,
LYMErix was only effective against the North American strain
of B. burgdorferi eliminating the international market. Despite
being aware of these issues, SmithKlineBeecham went forward
with the launch.
The public view…
Lyme disease became a “hot topic” as did the LYMErix vaccine.
LYMErix benefits were the main emphasis in advertisements
with little regard for its potential side or long term effects. The
media encouraged the public to speak to their physicians if they
lived in a high prevalence area. Between 1998 and 2000 more
than 1.4 million doses of the LYMErix vaccine were distributed
in the United States, a mere fraction of the total number of flu
vaccinations distributed every year (5).
The “glory days” for LYMErix were short lived. In the early
1990s the FDA created the Vaccine Adverse Event Reporting
System (VAERS) as a way to keep post licensure surveillance of
vaccines. According to the VAERS, 905 adverse events were
reported during the two year time span. Of the 905 adverse
events, 7.4% reported events were deemed serious, requiring
hospitalization; however, these events were not necessarily
caused by the vaccine, and were considered to be not significant
by both the FDA and SmithKlineBeecham (5). The majority
(56%) of the adverse events were the typical associated vaccine
redness, swelling at the injection sites, and flu like symptoms
not lasting longer than three days (5). Among these events there
were also 59 reported cases of arthritis that developed within 30
days after the vaccination. There were 49 cases of arthritis were
reported in the placebo recipients (6). These results translate to
a reported cumulative arthritic incidence of 333 per 100,000
doses in vaccine recipients and 308 per 100,000 doses in

placebo recipients (6). Since arthritis was considered to be an
adverse event, it received significant attention; although, the
reported cases were lower than in the estimated background
population the cases were not considered to be out of the
ordinary. If only half of the 1.4 million doses of LYMErix were
administered, it would be expected that at least 2000 individuals
would have reported arthritis. Approximately the same number
of the placebo recipients would have also developed arthritis
(6). Thus the number (59) reported to VAERS was far below the
expected incidence rate in the background (6). Also, there was
no temporal association found between the administration of
LYMErix and the onset of the symptoms (5). The FDA had no
reason to deem the LYMErix unsafe; however, the media
refused to let the adverse events go, and hunted down these
“vaccine victims” putting a human face to suffering (1).
Despite the supporting evidence that LYMErix was safe,
the media focuses its attention on the fact that there were
serious adverse symptoms associated with the vaccine. Lyme
disease public action groups were soon publicizing the
controversy. As a result, more and more allegations began to
surface that were unreported adverse events associated with
LYMErix (1, 5). The media began to question the credentials of
physicians. Collectively this caused a public uproar leading to
a class action suit against SmithKlineBeecham in December of
1999 (5). The suit claimed that LYMErix caused harmful side
effects, and the SmithKlineBeecham withheld information about
its potential risk (1).
FDA’s response…
With all the negative press coverage and allegations
around LYMErix, the FDA was obligated to take action. The
FDA reexamined the phase III clinical trial that lead to
licensure. Upon examination it was found significantly more
vaccine recipients than controls had minor side effects
associatedwith all immunizations (1). Most of the side effects
occurred within 48 hours of injection and were gone within a

week without any treatment. The FDA followed the participants
for year and concluded there were no more arthritic symptoms
than in the control group (1). There were no apparent short
adverse events that the FDA found justifiable to revoke
licensure; although, the long term side effects remained
unknown.
SmithKlineBeecham’s response…
With the rising accusations, SmithKlineBeecham launched
a post licensure safety and efficacy case control study trial.
Initially, they were planning on following the patients over a
four year period and enrolling 25,000 LYMErix recipients and
another 75,000 to serve as controls; however, due to a lower
than expected recipient population, the study was only
conducted for a two year time span and enrolled only 10% of
what SmithKlineBeecham had anticipated (1). The results were
still consistent with the prior trials; there were no significant
adverse events to support the allegations.
Around the same time of SmithKlineBeecham’s post
licensure trial researchers began to develop a better
understanding of Lyme disease. It was found that people who
genotypically expressed human leukocyte associated antigen
DR4+ after being infected with Lyme disease had a greater
chance of developing chronic arthritis (1). These patients
produced a high level of autoantibody to OspA in their joints.
These findings suggested that these genetically predisposed
individuals when injected with LYMErix could develop an
arthritic autoimmune response. Developing a genetic test to
prescreen these individuals would have just added cost to the
vaccine development potentially causing more harm than good
(1).
The final Chapter…
The trial was highly publicized, and as a result an FDA
advisory panel reconvened to discuss the case. After hearing
compelling testimonies from both sides, the FDA finally sided

with SmithKlineBeecham. The FDA believed the benefits from
LYMErix outweighed the risk, and could remain on the market;
although, the phase IV trial was to continue (1). At this point,
SmithKlineBeecham had had enough. They were tired of being
ridiculed and fighting the media. Consequently, in 2002, they
pulled LYMErix off the market. Soon after in 2003 the law suit
was settled. SmithKlineBeecham paid the prosecuting fees, but
the alleged “vaccine victims” received no compensation (1). To
this day, SmithKlineBeecham, now GlaxoSmithKline, denies
their vaccine caused harm, and they insist LYMErix was taken
off the market due to financial concern.
SmithKlineBeecham Project Management Analysis…
The fact of the matter was that public image was everything for
SmithKlineBeecham. It did not matter that their vaccine was
safe and effective in an area with high prevalence of Lyme
disease. A mere 59 out the 905 patients that reported adverse
events with LYMErix may have developed arthritis as the result
of the LYMErix vaccine. The media took a small risk and blew
it completely out of proportion which resulted in a bad public
image and dwindling sales. The project managers at
SmithKlineBeecham made the right decision from an economic
standpoint.
The choice came down to two options: 1) Write off the losses or
2) continue to fight a losing battle and hope to win the war.
Option 1 was simple. Quit then, take LYMErix off the market to
satisfy the public and prevent future losses, while hopefully
saving SmithKlineBeecham’s public image. At this point
SmithKlineBeecham was already in the hole, there was no point
to dig it any further.
Option 2 was to continue to fight a losing battle and hope to win
the war. To go with this option SmithKlineBeecham would have
had to continue to invest money into studies to show LYMErix
was safe, while continuing to combat the allegations and
fighting with the media. Then, if the safety studies came out
showing that a small subset of the population that contained a

predisposed genotype had autoimmune responses after being
vaccinated with LYMErix, then SmithKlineBeecham would risk
more law suits. Not only would they have to spend money to
settle those suits, SmithKlineBeecham would have to admit
LYMErix caused harm. Then in order to keep LYMErix on the
market they would have had to come up with a genetic test for
screening the recipients, or started over again at the preclinical
stage altering the vaccine. Millions if not billions could have
been spent, which quite possibly could have ended in failure
anyways. If the target population wasn’t already scared off by
the media, the increase in cost because of the diagnostic test,
which may or may not be covered by insurance, would surely
ward off more. So with the remaining hand full of the target
population, it was no longer cost effective for
SmithKlineBeecham to produce it.
If SmithKlineBeecham continued the LYMErix project, not only
would it require more excessively, large, monetary investments,
but time as well. Time in the biotechnology/pharma world is
limited. The longer a company spends on development and
clinical trials the shorter the patent exclusivity becomes. All a
competing company would have had to do is come out with a
Lyme disease vaccine slightly better than LYMErix, that
doesn’t need a diagnostic test and LYMErix would be gone.
Clearly, the project managers at SmithKlineBeecham made
the right decision. The budget had its limits, and the project was
not going to produce the return they had expected. There was no
way to add value to the project to make it worthwhile to save.
Further development would have cost millions, and the patent
clock would have continued to tick away time.
SmithKlineBeecham did the best thing it possibly could from
the company’s standpoint and terminated LYMErix.
LYMErix was a safe vaccine, the FDA found no definitive
evidence that LYMErix actually caused arthritis. Vaccines have
to be designed with a strong safety profile, because they are
going into healthy people to avoid future disease. Prior to
licensing LYMErix, SmithKlineBeecham, could have better

communicated the general risk associated with any vaccines.
Vaccines are taken with a small upfront risk to avoid a serious
risk later; whereas, with most pharmaceuticals the side effects
have to be weighed against the disease or condition they are
fighting.
The media played a huge role in the outcome of LYMErix. They
constantly communicated how bad the alleged adverse events
were, and nothing was stated about how people benefited from
LYMErix. The media changed the risk benefit ratio, forcing the
public to believe LYMErix was a horrible thing.
SmithKlineBeecham should have communicated the risk better
and emphasized the benefits of the vaccine. The company and
FDA could have stated the facts about Lyme disease and how
difficult it is to treat. Instead, they let the media turn the risk
benefit ratio toward the unfavorable risk associated with the
vaccine. The company should have asked physicians and FDA to
emphasize the benefits of vaccines in general, and explain that
there is always a small, inherent risk associated with any
vaccination.
FDA Project Management Analysis…
The FDA requires vigorous preclinical studies and very in depth
clinical trials with any vaccines to prove vaccines are safe and
efficacious before going into the healthy individuals. In the
LYMErix cases the FDA should have also communicated the
benefits and risk associated with vaccines. The FDA did the
right thing remaining neutral, and reporting just the facts. The
facts were that the LYMErix vaccine was safe, efficacious and
did not appear to cause any harmful, adverse effects. They did
not see any evidence to consider removing the LYMErix
licensure. They could have also explained that there is an
inherent risk with anything put into the human body. They could
have pushed the ill effects of Lyme disease and difficulties with
treatment, and how many people the disease affects.
Implications for Today…

LYMErix was made out to be the scapegoat in the spot light.
Lyme disease should have been the bad guy then, just as it is
today. Today, Lyme disease continues to affect thousands of
people every year, and in 2012 it was 7th on the list of CDC’s
most common notifiable diseases in the United States (7). The
deer tick population is booming, and yet still no vaccine has
come to the market for Lyme disease. The FDA and
SmithKlineBeecham let the media kill an efficacious remedy
through bad risk communication. It could happen again today!
Companies need to emphasize the risks associated with getting
the disease, and the benefits of their vaccination. Diseases need
to be put into the spot light as the bad guy, and that cannot be
turned around. Today, there are diseases that were nearly
eradicated making a comeback because ignorant people are
refusing to get vaccinated. The burden falls not only on the
company but on the FDA as well to relay the safety and benefits
of vaccination to the public.
References
1. Nigrovic LE and Thompson KM. The Lyme Vaccine: a
cautionary tale. Epidemiol. Infect. (2007) 135, 1-8.
2. The history of the Lyme Disease Vaccine.
http://www.historyofvaccines.org/content/articles/history-lyme-
disease-vaccine.
3. Nardell DT, Munson EL, Callister SM, and Schell RF. Human
Lyme disease vaccines past and future concerns. Future
Microbiol. (2009) 4, 457-469.
4. Keller D, Koster FT, Marks DH, Hospach P, Erdile LF, Mays
JP. Safety and immunogenicity of a recombinant outer surface
protein A Lyme Vaccine. JAMA. (1994) 271, 1764-1768.
5. Shen AK, Mead PS, and Beard CB. The Lyme disease
Vaccine—A public Health Perspective. CID (2011) 52, S247-
S252.
6. Lathrop SL, Ball R, Haber P, Mootrey GT, Braun MM,
Shadomy SV, Ellenberg SS, Chen RT, Hayes EB. Adverse event

reports following vaccination for Lyme disease: December
1998-July 2000. Vaccine 2002; 20:1603–1608.
7. http://www.cdc.gov/lyme/stats/
Lect#3 The Impact of Organizational Size on Drug Project
Management 2016.pptx
BIOL 581 – Essentials of Biotechnology Project Management
#3 The Impact of Organizational Size on Drug Project
Management
P3M book, chapters 2, 3
Drug Development is a sequence of phases
Discovery
Research
~ 2 years
IDEA
Preclinical
Development
~ 2-4 years
Clinical Development
Phase I……Phase II
~ 2-4 years
POC
Demonstration
IND/
CTA
Lead
Compound
Clinical

Development
(DP1)
Phase III
~ 4-5 years
NDA/
MAA
Approval
Initial
Indications
Launch
Commercial
Development
Phase IV
5+ years
LCP
ETC.
Life Cycle Development Plan (DP3)
Life Cycle
Development
Plan (DP2)
TO MARKET
Drug Development Program (business part)
Drug Discovery Phase
Preclinical Phase & IND
Phase I-III Clinical Development and NDA
Notice of Claimed Investigational Exemption for a New Drug
(IND)
Proof of Concept (POC)
New Drug Application (NDA) to the FDA
Life Cycle Plan (LCP), DP1…..N (Development plans)

“Pharmaceutical & Biomedical Project Management in a
changing global environment”, by S.D. Babler, Chapter 4
2
The Impact of Organizational Size on Drug Project
Management.
Drug Development is a fairly well understood and regulated
process.
Effectively implementing this process is another story!
DD&D success is often related to successful Project
Management.
Skills and expertise in execution are not directly related to the
size of the organization.
Size however does influence how drug development is
conducted.
The impact of organizational size
Organizational culture is dependent on:
Size
Science needed for product development
Geographical location
Ownership
Actual & Intended market
Organizational Structure
The size of the organization influences the number of functions
that exist, as well as number of therapy areas, and number of

projects
The more functions company performs, the bigger and more
complex organizational matrix is (see P3M book, pg. 26)
Organizational Structure
Size Definition
Organizational size is determined by:
Number of employees
Largeness of its operation
Market reach and share
Idea:
Small organizations are build for innovation
Large - for operational efficiency
SME – small/medium enterprise
Project Management in SMEs
The nature of SMEs
Several different definitions of SMEs have been proposed. The
European Commission defines medium, small and micro
enterprises:
Medium: have fewer than 250 employees and turnover of less
than 50 million Euro.
Small: have fewer than 50 employees, and turnover of less than
10 million Euro.
Micro: have fewer than ten employees, and turnover of less than
2 million Euro.

Skills necessary for entrepreneurship are quite different from
that of running a large and diverse organization
Management Focus of Attention:
Small biotech – stretching the budget
Idea to do as much job is possible for
as little money as possible
E.g., rare to do multiple Phase II trials
Approaches:
Risk identification
Developing multiple plans to face unexpected events
Select right partners (outsourced contract research organization)
Identification of the right number and geographical location of
study sites and decisions
There is often only one chance to get studies right!
If not…
End of the project
If the company is lucky, the product is sold to another company
Management Focus of Attention:
Large companies– managing a much larger portfolio of drug
projects (>150 is not uncommon)

Less focus on individual projects
Focus on success of larger number of projects within a big
portfolio
More focused on their reputation
This often results in:
Unforeseen risks occurring
Significant delays
Small business mind-sets
Small companies – share “whatever it takes” passion
Every project and every activity is a priority
Project manager becomes the “Chef d’orchestre”
~ 60 employees + 1 PM manage 4 projects at different stages of
development
PM plays a critical coordination and documentation role
PM do not have any time to care about company maturity or
how business is conducted
Approaches:
Bringing in consultant with specific expertise, contract research
organizations
Automation of work: clinical trials management, protocol
development.
Communication
Small biotech (advantage)
Communication is easier
PM has the ability to go straight to the CEO.
Large companies (difficulty)
This can be challenging is large biotech companies

PMs need to find a systematic planned way to communicate
with
Management teams
Portfolio committees
Science committees
Approaches (for PMs in large companies):
Manage & document meetings
Distribute draft meeting minutes within 24 hours of the meeting
and the final version within 12 hours – insures fast and
consistent communication .
Prioritizing Projects
Projects often run over time and over budget
Inadequate project definition
Shortage of key human and other resources
Poor management skills
Conflicting priorities
Clear need for a systematic, integrated approach to improve the
performance
PM role: Assignment of prioritization of individual projects
(resources – money, people, equipment)
Most large pharma/biotech companies have this process in place
But having a process, and following that process, is not the
same thing
Prioritizing Projects
Many small companies have only one product in the pipeline.

Have tendency to push their unique project through all stages of
drug development whether it makes sense or not.
Canceling this product could mean the end of the company or at
least significant change in size.
Phase III – phase when it often happens.
Mature companies cancel their only one product after Phase II.
DD&D in small & start-up biotech and how we can do it better
It is common in small biotech that founders responsible for
start-up remains as de facto leaders of the company.
They have strong scientific mind-set but rarely possess
expertise in late stage drug development and commercialization
of their products.
At that
Biotech industry is highly competitive with high failure rates
High cost of drug development (on average $850 million,
including cost of failed projects) + an equal amount is spent on
efforts to brand and market products.
Knowledgeable and experienced managing team is needed to
compete and survive in industry.
Biotech versus Pharma
The Challenge of Transition from Research to Development (at
least 4 factors)
#1. Many small biotech companies are not aware of the exact &
stringent FDA requirements.
Additional resources and costs to follow these requirements are
often not included
Developing constructive and collaborative relationship with the
FDA is often underappreciated.
#2. Manufacturing and controls for biologics can be more

difficult from a technical perspective than for small molecules
(pharma) because production takes place through live cell
systems.
Meeting product quality specifications is more complex and
costly compared with methods developed for small molecules
over several decades.
The Challenge of Transition from Research to Development
#3. Opportunities for small biotech are limited because industry
is dominated by large companies – as a result, many startup
companies are investigating unmet medical need in niche, and
usually more difficult to treat patient populations.
Difficulties associated with clinical studies are even more
complex due to increased emphasis on ethic of these trials.
Impacted by slower enrolment and are forced to conduct trials
worldwide to locate sufficient number of patients.
The Challenge of Transition from Research to Development
#4. The administration of biologics is a challenge compared to
small compounds (subcutaneous, intramuscular, intranasal, and
intravenous routes).
Specials centers have to be created – increases cost.
Developing the image or device to administer products trough
these routes is more challenging and costly.
As an example, regulatory authorities will require a company to
develop methods to ensure particle size and total doze
administered is known and consistently delivered through an
intranasal aerosol device (far more difficult than to show the
same with an oral tablet).
The administration of biologics medication creates many
problems: delivery, packaging, stability, distribution, storage.

Managing the Pipeline of New Drugs
In contrast to established big pharmaceutical companies, many
small-biotech companies are not generating any revenue. But
it’s expected by investors and shareholders.
The pressure to meet these expectations and to generate
revenue quickly can influence the dynamic of decision making.
If small biotech companies have several R&D products, it’s a
challenge to manage them at the same time.
A single bad decision may cause the small biotech company to
fail.
Project Management Support
PM has a key role in helping the company to understand the
realism and structure of its long-term plan.
If small companies have more project opportunities than their
R&D budget can fund, PM defines a process and establish
criteria for selecting the best candidate(s)
Before any compounds enters clinical trials PM needs to define
criteria for the selection of the most technically feasible, and
financially valuable project candidates.
PM should play a lead role in creating standard methods for
collecting the data and information and establishing a
disciplined process for ensuring that regulatory criteria are met.
An accepted role for PMs is estimating and managing resources
and recourse constraints (e.g. to plan to use subcontractors and
consultants when needed rather than full-time employees).
Summary
Main idea: The approach taken to achieve outcome is often
different btw small and large companies
PM in small companies:

Getting results might seem easier at first.
Communications are enhanced by open-door policy.
However, small companies constantly face budget problems.
PM in large/ medium-sized biotech/pharma:
Money is likely to be less of a day-to-day concern.
Can afford to have a dedicated PM group.
Communication & decision making can be a challenge.
Written Project Requirements:
Choose you case study!
Scientific component (not less than 1 page)
What was the compound used for;
What caused the problem/tragedy (adverse reaction, drugs
interactions, etc.).
Identify and describe the problem from public side. What
happen? (not less than 1 page).
Describe the consequence of the steps that led to the
problem/tragedy. Include information about both the company
and the regulatory agency; (not less than 1 page).
Imagine, you are a Project Manager inside the company working
on this project. What would you do differently? (not less than 1
page).
Imagine, you are a Project Manager at the FDA (other
regulatory agencies). Your steps? (not less than 1 page).
Can you imagine this situation happening in 2018? Why?
FEEL FREE to MODIFY these questions!
Students are encouraged to use schemes, figures, diagrams,
tables, graphs, bullet-points. Microsoft Word or Power Point
presentations can be used, but for the Power Point make sure
you adjust the number of slides accordingly. For instance, when
using large fonts, make sure the information is still sufficient.
Do not afraid to be creative!

#1. New England Compounding Center meningitis outbreak
http://www.cdc.gov/hai/outbreaks/currentsituation/
Wikipedia: In October 2012, an outbreak of fungal
meningitis was reported in the United States. The U.S. Centers
for Disease Control and Prevention (CDC) traced the outbreak
to fungal contamination in three lots of medication used
for epidural steroid injections. The medication was packaged
and marketed by the New England Compounding
Center (NECC), a compounding pharmacy in Framingham,
Massachusetts. Doses from these three lots had been distributed
to 75 medical facilities in 23 states, and doses had been
administered to approximately 14,000 patients after May 21 and
before September 24, 2012. Patients began reporting symptoms
in late August, but because of the unusual nature of the
infection, clinicians did not begin to realize that the cases had a
common cause until late September. Infections other than
meningitis were also associated with this outbreak, which
spanned 19 states.
As of March 10, 2013, 48 people had died and 720 were being
treated for persistent fungal infections.
#2. Heparin - Blood-Thinning Drug Under Suspicion
3896578.shtml
The U.S. Food and Drug Administration stated that at least 81
deaths were believed linked to a raw heparin ingredient
imported from the People's Republic of China, and that they had
also received 785 reports of serious injuries associated with the
drug’s use.

#3. VaxGen and Anthrax Vaccine
Vaxgen had focused its recent efforts on a new form of Anthrax
Vaccine, for which it was awarded a $877 million dollar
contract to provide the vaccine. In December 2006, HHS
unilaterally withdrew the $877 million dollar contract, sending
the stock tumbling as low as $1.20 per share.
http://www.cidrap.umn.edu/news-perspective/2006/12/hhs-
cancels-vaxgen-anthrax-vaccine-contract
Later events:
http://www.cidrap.umn.edu/news-perspective/2008/05/vaxgen-
sells-anthrax-vaccine-rival-firm
#4. Troglitazone
Troglitazone was the first thiazolidinedione approved for use in
the United States and was licensed for use in type 2 diabetes in
1997, but withdrawn 3 years later because of the frequency of
liver injury including acute liver failure associated with its use.
http://livertox.nih.gov/Troglitazone.htm
How did they achieve blockbuster status without any clear
evidence of advantage over existing therapy?
#5. ZMapp
Wikipedia: ZMapp is an experimental biopharmaceutical drug
comprising three humanizedmonoclonal antibodies under
development as a treatment for Ebola virus disease.[1] It was
used to save eighteen monkeys who were given lethal doses of
the Ebola virus. The drug was first tested in humans during the
2014 West Africa Ebola virus outbreak and was credited as
helping save lives, but it has not been subjected to a randomized

clinical trial to prove its safety or its efficacy.
The ZMapp drug is being developed by Mapp
Biopharmaceutical Inc., a result of the collaboration between
Mapp Biopharmaceutical (San Diego), LeafBio (the commercial
arm of Mapp Biopharmaceutical), Defyrus Inc. (Toronto), the
U.S. government and the Public Health Agency of Canada. The
antibody work came out of research projects funded by the U.S.
Army more than a decade ago, and years of funding by the
Public Health Agency of Canada.
You are a senior level PM at Mapp Biopharmaceutical. Suggest
your detailed life cycle plan for Zmapp.
Cannot be used this year, but I will provide an example
The History of the Lyme Disease Vaccine
A first generation vaccine worked quite well. However it was
was pulled from the market in 2002
http://www.ncbi.nlm.nih.gov/pubmed/19416014 (let me know if
you need pdf of this article, CUA does not provide an access.
http://www.aldf.com/pdf/Aronowitz_The_Rise_and_Fall_of_Ly
me_Vaccines.pdf
.
“Real Option Analysis” paper (Merck “Project gamma” case
study is to discuss next time
It’s also useful to read the interview here
http://hbr.org/1994/01/scientific-management-at-merck-an-
interview-with-cfo-judy-lewent/ar/1
Pay attention to this addition

Additional Material, Lect #1 CHIRON case study.docxCHIRON’S FL.docx

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