Transcript Poster Presentation - The University of Oklahoma

New Anthrax Countermeasure*
Vi Pham**, Zachary Taylor** and Miguel Bagajewicz
University of Oklahoma - Chemical Engineering
(*) This work was done as part of the capstone Chemical Engineering class at the University of Oklahoma
(**) Capstone undergraduate students
Key Agent Research & Production
Abstract
In this work , we investigated the production of a novel new anthrax treatment with minimal side
effects and virtually no possibility of bacterial resistance. The probability of successful laboratory
development is analyzed in detail. Next, a thorough evaluation of the FDA process for drug approval
is described to assess failure risk. Finally, an in depth economic analysis is performed on the entire
drug production process – from laboratory work to final product. Approval of this drug is expected
to take seven years and cost approximately $12M.
Fundamentals
Pre-Clinical & FDA Modeling
Pricing & Profitability
Pricing Models
FDA Approval Process for Countermeasure Drugs
Comparison of Anthrax Survival With and Without Key Agent
Model 1
Macrophages
Nuetrophils
Engulf Bacteria
Secrete Enzymes to Kill Bacteria
Preclinical
Development:
Preclinical
Development:
Animal trials
-safety
-pharmacokinetics
-proof of concept
efficacy
Discovery
-safety
-efficacy
Clinical Trials
-safety
-pharmacokinetics
Production
&
Stockpiling
Model 2
Human
Efficacy
Trials
in the event of
product use
H1 = our benefits
H2 = competitor’s benefits
 = constant based on consumer preference
P2 = competitor’s drug price
P* = price to make us equal to our competitor
in terms of benefits and cost
-
Types of Infection
Models valid for:
0.75 < H2/H1 < 2.05
Preclinical Research and FDA Approval Process Flow Diagram
Macrophages A. Macrophages with anthrax not treated with key agent have not engulfed any bacteria. B. Macrophages with anthrax treated with one of
key agents have engulfed many bacterial cells.
Neutrophils A. Neutrophils with anthrax treated with key agent have killed all of the anthrax. B. Neutrophils with anthrax not treated with one of our key
agents have not killed all of the anthrax.
A.
B.
Anti-Infective Mechanism
Process Flow Diagram
(modified agent 1)
Anthrax is one of the most significant bioterrorism threats to the United States today. Left untreated, inhalational
anthrax, the form most likely to be employed in a bioterrorism event, would claim at least 75% of those infected.
Although treatments and a vaccine against anthrax do exist, these also produce adverse side effects and are
susceptible to bacterial resistance..
We performed 500 profitability trials for the development of a modified agent to treat anthrax. The
program considered the following parameters: the probability of success for each pre-clinical experiment
and FDA approval phase, the cost of each experiment and phase, the manufacturing cost based on the
number of doses needed and the concentration required for each dose, and the pricing model developed
for the final product.
A. A flow diagram of the initial experiments required for pre-clinical
research. The projected time and costs are given for each stage. (Gray
boxes cover sensitive material)
Inhalation of anthrax
spores into the lungs.
B. A flow diagram of the in vitro and in vivo experiments required for preclinical research for each successful modified key agent from the previous
stage. The most successful modified key agent will proceed to the FDA
approval process. The projected time and costs are given for each stage.
Survival of anthrax bacteria after treatment with key
agent and incubation with human neutrophils for two hours.
This kinetic data was used to determine dosing
concentrations.
Spores are engulfed by
macrophage cells.
C. A flow diagram of the stages required for the FDA approval process. It
is assumed that Priority Review was obtained. The projected time and
costs are given for each stage.
Anthrax bacteria cleave the
macrophage cells and attack
neighboring cells, eventually
resulting in organ failure and death.
Spores are able to
change into toxic
bacteria cells and
proliferate within the
macrophage cells.
Conclusions
*The projected time and cost are based on detailed experimental protocols
not shown here.
Macrophage cells
with the engulfed
anthrax spores travel
to the lymph nodes
for further
instruction on how to
proceed with the
invader. The anthrax
spores, however, are
undetected by the
immune system.
C.
•Our key agent is effective as an anthrax prophylactic.
•Our key agent can be cheaply produced in large quantities.
•The probability of successfully developing our key agent as a
pharmaceutical is approximately 30% with a predicted profit of
Marketing Strategy
approximately $600M.
•The predicted average loss for unsuccessfully developing the key
agent as a pharmaceutical is approximately $2.4M with a
Project BioShield
Dept. of Health & Human Services
$5.6 billion for improved
vaccines and drugs against
CBRN agents.
RFP seeking 10,000-200,000
treatments for inhalational anthrax
disease.
Anthrax bacteria cleave the macrophage cells, but the drug
eliminates the proliferated bacteria before they can attack
neighboring cells.
Project BioShield Contract
This graph shows the effect of varying pharmacokinetics
on serum concentration for a drug administered three times
over 60 days.
Must be “licensable”
Must be able to mass produce
Delivery within 8 years
Process flow diagram (PFD). (Gray boxes cover sensitive material)
-
Intended Market
Stockpile, Military
maximum loss of $12M.
Major Incentives
Key agent is newer and more effective.
Cheap to produce.
Lobbying
$1.8 Million
Fast Track (Priority Review)
$1 Million
Acknowledgements
We would like to thank Prof. David Schmidtke and Yahya Lazrak.