Presentation introduction on new drug development Prof. JanHasker G. Jonkman

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INTRODUCTION ON NEW DRUG DEVELOPMENT (INT-S.)
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INTRODUCTION ON NEW
DRUG DEVELOPMENT
Prof. JanHasker G. Jonkman,
Ph.D., F.C.P., F.R.Q.A., R.Ph.,
Clinical Pharmacologist
University of Groningen (NL)
Professor Quality Management in Drug Research and Manufacturing
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INTRODUCTION ON NEW DRUG DEVELOPMENT (INT-S.)
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TABLE OF CONTENTS
• Worldwide Sales of Medicines
• Costs of Research and Development
• New Drug Approvals
• Development of a New Drug
• Synthesis
• New Drug
• Pharmacology/Toxicology
• Clinical Pharmacology
• Phase I – studies
• Phase II – studies
• Phase III – studies
• Market Authorization
• Phase IV – studies
• Conclusions
INTRODUCTION ON NEW DRUG DEVELOPMENT
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TABLE OF CONTENTS
• Worldwide Sales of Medicines
• Costs of Research and Development
• New Drug Approvals
• Development of a New Drug
• Synthesis
• New Drug
• Pharmacology/Toxicology
• Clinical Pharmacology
• Phase I – studies
• Phase II – studies
• Phase III – studies
• Market Authorization
• Phase IV – studies
• Conclusions
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Sales % of worldwide
Country (billion US $) sales
North America 342 39.1
Europe 250 28.6
Asia (excluding Japan),
Africa and Australia 129 14.8
Japan 99 11.3
Latin America 53 6.2
TOTAL 875 100.0
WORLDWIDE SALES OF MEDICINES:

BY REGION (2010)
(Source: PAREXEL R&D Sourcebook, 2011/2012)
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WORLDWIDE SALES OF TOP 10 MEDICINES:
BY THERAPEUTIC CLASS (2010)
Sales % of worldwide % of growth
Rank Therapeutic Class (billion US $) sales (vs 2009)
1. Cytostatics 56.0 6.4 + 6.7
2. Cholesterol &
Triglyceride reducers 36.4 4.2 + 2.0
3. Respiratory agents 35.9 4.1 + 7.0
4. Antidiabetics 34.4 3.9 + 12.2
5. Anti-ulcerants 28.0 3.2 - 6.5
6. Angiotensin-II inhibitors 26.6 3.0 + 4.5
7. Antipsychotics 25.4 2.9 + 9.0
8. Autoimmune agents 20.7 2.4 + 14.7
9. Antidepressants 20.2 2.3 + 3.4
10. HIV Antivirals 15.4 1.8 + 13.2
(Source: PAREXEL R&D Sourcebook, 2011/2012)
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WORLDWIDE SALES OF TOP 10 MEDICINES:
BY PRODUCT (2010) (1)
Sales
Rank Product (billion US $) Company
1. Lipitor 12.7 Pfizer
(atorvastatin; antilipidic agent)

2. Plavix 8.8 Sanofi-Aventis
(clopidogrel; antithrombic agent)
3. Seretide 8.5 GSK
(salmeterol/fluticasone;
asthma/COPD)
4. Nexium
(esomeprazol; antiulcer) 8.4 Astra Zeneca
5. Seroquel
(quetiapine; antipsychotic agent) 6.8 Astra Zeneca
(Source: IMS Health World Review, 2010)
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WORLDWIDE SALES OF TOP 10 MEDICINES:
BY PRODUCT (2010) (2)
Sales
Rank Product (billion US $) Company
6. Crestor 6.8 Astra Zeneca
(rosuvastatine; antilipidic agent)
7. Enbrel 7.3 Wyeth
(etanercept; antirheumatic agent)
8. Remicade 6.0 Schering-Plough
(infliximab; antirheumatic agent) (Merck&Co)
9. Humira 6.0 Abbott
(adalimulab; antirheumatic agent)
10. Zyprexa
(olanzapine; antipsychotic agent) 5.7 Eli Lilly
(Source: IMS Health World Review, 2010)
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WORLDWIDE SALES OF MEDICINES:
BY COMPANY (2010)
Pharma sales
Rank Company (billion US $)
1. Pfizer (US) 58.2
2. Sanofi-Aventis (F/Ger) 40.3
3. Merck & Co (US) 39.8
4. Novartis (Swi) 39.1
5. GlaxoSmithKline (UK) 36.1
6. Roche (Swi) 35.6
7. AstraZeneca (Swe/UK) 33.3
8. Johnson & Johnson (US) 22.4
9. Eli Lilly & Co (US) 21.1
10. Abbott (US) 19.9
(Source: Scrip 100, 2011)
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TABLE OF CONTENTS
• Worldwide Sales of Medicines
• Costs of Research and Development
• New Drug Approvals
• Development of a New Drug
• Synthesis
• New Drug
• Pharmacology/Toxicology
• Clinical Pharmacology
• Phase I – studies
• Phase II – studies

• Phase III – studies
• Market Authorization
• Phase IV – studies
• Conclusions
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•
World wide expenditure on R&D of new medicines
approximately $ 130.000.000.000 per year
• Of which costs of clinical research: $ 75.000.000.000
COSTS OF RESEARCH & DEVELOPMENT (2010)
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TOTAL INDUSTRY R&D vs PHARMA R&D
• Pharma R&D is approximately 10% of total Industry R&D
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R&D spend R&D as
Rank Company (US $ billion) %of sales
1. Merck & Co 11.0 27.6
2. Pfizer 9.4 16.2
3. Roche 8.7 24.4
4. Novartis 7.7 19.7
5. GlaxoSmithKline 5.9 16.3
6. Sanofi-Aventis 5.8 14.4
7. AstraZeneca 5.3 13.2

8. Eli Lilly 4.9 22.7
9. Johnson & Johnson 4.4 19.6
10. Abbott 3.7 18.6
COSTS OF PHARMA R&D (2010)
(Source: PAREXEL R&D Sourcebook, 2011/2012)
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CLINICAL PHARMACOLOGY (2)
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TABLE OF CONTENTS
• Worldwide Sales of Medicines
• Costs of Research and Development
• New Drug Approvals
• Development of a New Drug
• Synthesis
• New Drug
• Pharmacology/Toxicology
• Clinical Pharmacology
• Phase I – studies
• Phase II – studies
• Phase III – studies
• Market Authorization
• Phase IV – studies
• Conclusions
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• Number of New Molecular Entities (NMEs) or New
Chemical Entities (NCEs) approved for marketing:
 approximately 20-60 per year
NUMBER OF NEW DRUG APPROVALS (1)
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NUMBER OF NEW DRUG APPROVALS (2)
27
24
17
21
36
20
22
18
21
26
21
25
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
(Source: U.S. FDA)
New Molecular Entities
Approved in U.S.A.
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NUMBER OF NEW DRUG APPROVALS (3)
42

32
39
24
34
24
51
64
50
39
22
21
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
(Source: EMEA)
New Molecular Entities
Approved in the EU
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INTRODUCTION ON NEW DRUG DEVELOPMENT (INT-S.)
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But:
• Also withdrawals: approx. 2-3 per year
e.g. Vioxx (rofecobix, COX-2 inhibitor; Merck & Co)
• 80 million people worldwide were using Vioxx:
sales were $ 2.5 billion in 2003
• Widely promoted (but 21 studies by
Dr. Scott S. Reuben with fabricated positive results)
• Severe side effects:
 according to FDA; 88.000 – 139.000 heart attacks
(of which 30-40% fatal)
NUMBER OF NEW DRUG APPROVALS (4)
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INTRODUCTION ON NEW DRUG DEVELOPMENT (INT-S.)
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TABLE OF CONTENTS
• Worldwide Sales of Medicines
• Costs of Research and Development
• New Drug Approvals
• Development of a New Drug
• Synthesis
• New Drug
• Pharmacology/Toxicology
• Clinical Pharmacology
• Phase I – studies
• Phase II – studies
• Phase III – studies
• Market Authorization
• Phase IV – studies
• Conclusions
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DEVELOPMENT OF A NEW DRUG (2)
• Synthesis of the molecule
• Studies in animals
• Studies in healthy volunteers
• Studies in patients
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INTRODUCTION ON NEW DRUG DEVELOPMENT (INT-S.)
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TABLE OF CONTENTS
• Worldwide Sales of Medicines
• Costs of Research and Development
• New Drug Approvals
• Development of a New Drug
• Synthesis
• New Drug
• Pharmacology/Toxicology
• Clinical Pharmacology
• Phase I – studies
• Phase II – studies
• Phase III – studies
• Market Authorization
• Phase IV – studies
• Conclusions
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SYNTHESIS (1)
(the development of a new therapeutic effective
molecule = drug / medicine)
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SYNTHESIS (2)
12%
88%
2005
2010
Biotechnology Organic Chemistry
18%
82%