Why was lymerix taken off the market

Project Management ( Heparin: A Global Medicinal Disaster ) Case Study

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/main3896578.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.

http://www.cbsnews.com/stories/2008/03/01/eveningnews/main3896578.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 associated with 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

http :// www.cbsnews.com/stories/2008/03/01/eveningnews/main3896578.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 humanized monoclonal 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_Lyme_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