The Pharmaceutical Industry and The Process of

Drug Discovery

 What is a Drug?
 Types of Pharmaceutical Products
 What are the Important Disease Targets?
 How the Industry Has Evolved
 Drug Discovery and The Process of Getting
a Drug to Market - an overview
 What is a drug?
“A Chemical Substance that Interacts with a Living System
and Produces a Biological Response”

What criteria MUST drugs meet?

 Drugs must address a new need or provide a significant
“added benefit” over an existing medicine

 Drugs must also meet five criteria:

 Must be safe, effective, of high quality
 cost effective
 affordable
 Classification of Drug Types
 Ethical drugs
 Generic drugs (no longer under patent)
 “Prescription Only” vs “Over the Counter”
 “Off Label” applications
 Orphan drugs
 Biotechnology products
 Counterfeit drugs
 Street drugs!
 Major Therapeutic Targets
 Infectious disease – anti-infectives
 Anti-bacterial, anti-viral, anti-parasitic drugs
 Metabolic disease
 cancer, cardiovascular, diabetes,
inflammation, high blood pressure,
neurological disease, pain
 Other aspects of health care
 Hormonal treatments, contraception,
vaccines, immunosuppresents, anaesthetics,
nutraceuticals, “life style” drugs
 How do drugs work?
 The Biological Target - enzyme or receptor
 Where is the target - part of “us” or elsewhere

 Paul Ehrlich, Nobel Prize 1908, salvarsan;

 blood-brain barrier; “Lock and Key”
hypothesis; chemotherapy and “magic bullet”

The Lock - Active Site of

Enzyme/Receptor
The Key - the Drug
 The “Lock and Key” analogy

Key
Lock
Binding

 Here the KEY is the natural substrate

 Binding of the KEY to the LOCK (an enzyme
or a receptor) then causes a response – a
shape change in the protein/receptor
 The “Lock and Key” analogy

Key
Lock
Binding Biological
Response

 Here the KEY is the natural substrate

 Binding of the KEY to the LOCK (an enzyme
or a receptor) then causes a response – a
shape change in the protein/receptor
 But when an effective drug is present

Biological response
is altered OR shut down
vs.
Binding of Drug
is preferred

 Drug may bind preferentially to the “active site”

 Antagonist – binds and BLOCKS
 Agonist – binds and ACTIVATES
 Partial agonist – induces a partial response
 Who discovers drugs? Doctors?

 Identify biological target - biology

 Prioritise/ validate target – pharmacology and
chemistry
 Identify and optimise lead molecules –
chemistry/pharmacology
 Preclinical studies – chemistry/pharmacology/
toxicology
 Formulation - pharmaceutical sciences
 Clinical evaluation – medicine
 Manufacture - chemical engineering
 Getting a drug to market
 Disease target - possible drug candidates
 Pre-clinical testing; R&D (1-3 yrs)
 Toxicology, “ADME”
 Clinical R&D (2-10 yrs; Av. 5yrs)
 Phase 1 – healthy volunteers
 Phase 2 – small patient group
 Phase 3 – larger patient group
 Regulatory approval (2-10(!) yrs)
 Market
 Phase 4 – long term monitoring
 The Gamble - wastage and timescale

 For EACH DRUG approved, an average of 7500

compounds will have been made
 Of this 7500, an average of 21 will be tested for
subacute toxicology, 6.5 will be tested in humans and
2.5 will reach Phase 3 – 1 then gets to market………

 Entire process takes on average 12 years

 Costs $138M (1975); $800M (2000); $1.6Bn (2008)
 Development costs do NOT include pre-launch
marketing which can DOUBLE costs
The “Pay Off”……to the companies

 Typical R&D budget: 33% R and 67%D

 R&D = 15 to 25 % of sales turnover
 Patent protection – 20 years from filing
 On average, 11yrs. of productive market life
 Losec – $2.7Bn in 1998; Nexium (single
enantiomer) $7.7Bn in 2008
 Lipitor - $1Bn in 1998; $13.8Bn in 2008
 The “Pay Off”…….to us
 Massive contributions to health, quality of life,
reduced child mortality, life expectancy
 Vaccines have eradicated major disease –
smallpox; vaccines for malaria and pneumonia
soon……..?
 But costs and accessibility to healthcare are
becoming major social and geopolitical issues
 And, is there something seedy about making
money out of illness?
 What will happen into the future?
Major Therapeutic Targets

CNS
Metabolic
Cardiovascular
Anti-infectives
Respiratory
Gentio-urinary
Musculoskeletal
Oncology