Lecture 2 Flashcards
what are the 3 major organizational functions
-research and development
-manifacturing
-commercial
what is in research and development
-discovery
-development (clinical development/product development)
what is in manifacturing
-clinical studies and clinical trial supplies
-marketed products
whats in commercial
-product launch
-product marketing
-sales
pharma goals
Devoted to inventing medicines that allow patients to
liver longer, healthier and more productive lives
development of new pharmaceutical products is driven by what
- 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)
what are the business needs for development of new pharmaceutical
- Addressing competitive environment
- Shareholder value
- Growing the business
- Maximizing market share, sales, profits, and ROI
what occupies 50% of healthcare costs in the us
-hospitals and physicians and clinics
Major pharmaceutical companies mainly focus on these therapeutic areas:
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
The key steps in the Discovery of a small molecule:
-target id
-target validation
-assays and lead ID
-lead optimazation
-candiate selection
-pre-clinical profiling
-development candidate/ NME
what is in target id
- Basic Research
- Knowledge
- Bioinformatics
- Genetic Links
- Biochemistry
- Pathways
what is in target validation
- Target Disease Link
- Reverse Genetics
- Animal Kock out
- Animal Data
- Health Databases
what os in assays and lead id
- Binding Assays
- Enzyme Assays
- Cell-based Assays
- Compound Library
Screens - Hit ID
- De novo design
- Animal models/
- In vivo pharmacology
assay development
what is in lead optimazation
- Small molecule:
- Med chem
- Structure Activity
Relationship - (SAR)
- QSAR
- Modelling docking
- PK – pharmacokinetics
- ADME –adsorption,
distribution,
metabolism - In vitro ADME
- In vivo ADME
what is in candidate selection
- 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
what is in pre-clinical profiling
- Scale-up process
- Pre-formulation studies
- GLP Toxicity testing –
rodent and non-rodent
species - TPP – finalized
- Research, Medical and
Marketing Agree to
develop
what is in development candidate
- IND – investigational new
drug filing with FDA - Major Investment
Decision - Product Development
Team assumes
responsibility
The key steps in the Development of a drug candidate:
-development team
-phase 1 clinic
-phase 2 clinic
-phase 3 clinic
-new drug app/nda/bla
-post market monitoring
what is in develop team
- 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
what is in Phase 1 clinic
- 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
what is in phase 2 clinic
- 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
what is in phase 3 clinic
- 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
what is in new drug app
- NDA – New Drug
application - BLA – Biologics Licensing
application - Drug supply complete
- FDA review (1-2 years!)
and approval - Drug registration
- Submission in other
jurisdictions
what is in post market monitoring
- Lon-term Side effects
- FDA Adverse Event
Reporting System
(FAERS) - Phase IV studies –
special populations - Post marketing
commitments - Pediatric Studies
