Lecture 2

Question 1

what are the 3 major organizational functions

Answer 1

-research and development
-manifacturing
-commercial

Question 2

what is in research and development

Answer 2

-discovery
-development (clinical development/product development)

Question 3

what is in manifacturing

Answer 3

-clinical studies and clinical trial supplies
-marketed products

Question 4

whats in commercial

Answer 4

-product launch
-product marketing
-sales

Question 5

pharma goals

Answer 5

Devoted to inventing medicines that allow patients to
liver longer, healthier and more productive lives

Question 6

development of new pharmaceutical products is driven by what

Answer 6

• Unmet medical needs and health economics (eg new HCV drugs vs liver transplant)
• Projected market demographics (e.g. an aging population; evolving health of population)
• Evolving disease profiles (e.g. addressing chronic conditions)

Question 7

what are the business needs for development of new pharmaceutical

Answer 7

• Addressing competitive environment
• Shareholder value
• Growing the business
• Maximizing market share, sales, profits, and ROI

Question 8

what occupies 50% of healthcare costs in the us

Answer 8

-hospitals and physicians and clinics

Question 9

Major pharmaceutical companies mainly focus on these therapeutic areas:

Answer 9

o Cancer/Oncology
o Cardiovascular Diseases
o CNS Disorders
o Psychological Disorders
o Prophylactic Vaccines
o Gastrointestinal Disorders
o Respiratory Disease
o Blood Disorders
o Dermatological Disorders
o Diabetes & Obesity/Metabolic Disorders
o Infectious Diseases/AIDS

Question 10

The key steps in the Discovery of a small molecule:

Answer 10

-target id
-target validation
-assays and lead ID
-lead optimazation
-candiate selection
-pre-clinical profiling
-development candidate/ NME

Question 11

what is in target id

Answer 11

• Basic Research
• Knowledge
• Bioinformatics
• Genetic Links
• Biochemistry
• Pathways

Question 12

what is in target validation

Answer 12

• Target Disease Link
• Reverse Genetics
• Animal Kock out
• Animal Data
• Health Databases

Question 13

what os in assays and lead id

Answer 13

• Binding Assays
• Enzyme Assays
• Cell-based Assays
• Compound Library
  Screens
• Hit ID
• De novo design
• Animal models/
• In vivo pharmacology
  assay development

Question 14

what is in lead optimazation

Answer 14

• Small molecule:
• Med chem
• Structure Activity
  Relationship
• (SAR)
• QSAR
• Modelling docking
• PK – pharmacokinetics
• ADME –adsorption,
  distribution,
  metabolism
• In vitro ADME
• In vivo ADME

Question 15

what is in candidate selection

Answer 15

• Patent applications
• Target potency and
  exposure requirements
• Free-drug levels
• Pre-clinical general and
  safety pharmacology
• NOAEL (no adverse
  effect level) targets
• Cross-species PK
• PK scaling: Human dose
  and exposure levels
• Back-up candidate
  defined
• TPP – target product
  profile drafted

Question 16

what is in pre-clinical profiling

Answer 16

• Scale-up process
• Pre-formulation studies
• GLP Toxicity testing –
  rodent and non-rodent
  species
• TPP – finalized
• Research, Medical and
  Marketing Agree to
  develop

Question 17

what is in development candidate

Answer 17

• IND – investigational new
  drug filing with FDA
• Major Investment
  Decision
• Product Development
  Team assumes
  responsibility

Question 18

The key steps in the Development of a drug candidate:

Answer 18

-development team
-phase 1 clinic
-phase 2 clinic
-phase 3 clinic
-new drug app/nda/bla
-post market monitoring

Question 19

what is in develop team

Answer 19

• Medical, Marketing,
  Research, Patents
• Long term animal
  toxicology – reprotox;
  carcinogenicity
• CMC – chemistry
  manufacture and
  control - GMP
• Scale-up process
• Pharmaceutics/
  Formulation
• Clinical PK/
  pharmacology
• Statistics
• Safety/
  Pharmacovigilance
• Clinical Development
  Plan: Trial protocols –
  GCP

Question 20

what is in Phase 1 clinic

Answer 20

• Small number of
  subjects
• Single dose escalation
  healthy human
  volunteers
• Single Dose PK
• Human PK
• Multiple ascending
  dose PK
• Confirm safety and
  human PK
• Drug – Drug
  Interactions studies

Question 21

what is in phase 2 clinic

Answer 21

• Small to medium
  number of patients
  (~50-100)
• Multiple Ascending
  Dose
• Safety and PK in
  patient population
• Assess treatment
  durations
• Effect (PD) in patients
• Assess clinical
  biomarkers
• Establish dose and
  duration for testing in
  phase III

Question 22

what is in phase 3 clinic

Answer 22

• RCT- randomized
  controlled clinical trial
• In large number of
  patients
• Blinded studies
• Registrational trials
• Two trials confirm
  efficacy and safety
  relative to comparator
  (placebo or existing
  treatment)
• Establish superiority or
  non-inferiority to
  comparator

Question 23

what is in new drug app

Answer 23

• NDA – New Drug
  application
• BLA – Biologics Licensing
  application
• Drug supply complete
• FDA review (1-2 years!)
  and approval
• Drug registration
• Submission in other
  jurisdictions

Question 24

what is in post market monitoring

Answer 24

• Lon-term Side effects
• FDA Adverse Event
  Reporting System
  (FAERS)
• Phase IV studies –
  special populations
• Post marketing
  commitments
• Pediatric Studies

Question 25

what is attrition rate target validation

Answer 25

49

Question 26

what is attrition rate pre clinical

Answer 26

31

Question 27

what is attrition rate phase 1

Answer 27

36%

Question 28

what is attrition rate phase 2

Answer 28

56%

Question 29

what is attrition rate phase 3

Answer 29

30%

Question 30

what is attrition rate submission

Answer 30

9%

Question 31

Organization of (Large) Pharmaceutical Company

Answer 31

-corporate team
-research leadership team
-development leadership team
-product launch and support