A outline of Biopharmaceutical market of the World

1. Biopharmaceuticals
Transforming proteins and genes into drugs
By-
Kuldeep Dabasby:
Prepared
XIIIth Batch

2. Flow of presentation
I. Biopharmaceutical
1.Definition
2 Structure
3.Type
4. Manufacturing
5. Top 10 Biopharmaceuticals(2008)
6. Top 10 Biopharmaceutical companies
II. Biosimilars
1.Definition
2.Regulation
3.Strategies
III. Challenges for Biologics
IV. Future
V. Conclusion
2

3. Terminology used
 Biologics
 Biopharmaceuticals
 Biosimilars
 Follow-on Biologics
 Biogenerics
3 Note- Following terms are used in different organization in different places

4. Cornerstones in biotechnology history which have influenced the
production of Biopharmceuticals
1953: Discovery of DNA structure
1973: Discovery of DNA restriction enzymes
1977: Genentech, first biotech-enterprise founded
1982: First biopharmaceutical approved by FDA: recombinant human insulin
1986: First recombinant vaccine (HepB) is approved for human use, first
recombinant anti-cancer drug (Interferon) is produced
2003: Human genome sequenced
4

5. Traditional Vs Biopharmceuticals
Traditional Biopharmceuticals
Multiple effect Specific effect
Short Acting Long acting
Non-Immunogenic Immunogenic
Species independent Species dependent
Small molecules Large molecules
Stable Heat sensitive
Oral administration Parenteral
General practice Hospital
5

6. Definitions of BiologicsBiopharmaceuticals
A biologic can be any therapeutic serum, toxin, antitoxin, vaccine, virus, blood, blood component or derivative,
allergenic product, or analogous product, or derivatives applicable to the prevention, treatment, or cure of
injuries or disease of human
Source – FDA
“A biological substance is a substance that is produced by or extracted from a biological source and for which a
combination of physico-chemical-biological testing and the production process and its control is needed for its
characterisation and the determination of its quality
Source – EMEA
“a substance which cannot be completely characterized by physicochemical means alone and which therefore
requires the use of some form of bioassay”.
Source – WHO
6 Note: Sources mentioned in the notes section of slide

7. Complexity of Biopharmceuticals
Structure
Epoetin Size
Aspirin
M
Stability
od
ifi
ca
tio
n
7

8. Types of Biologics
 Peptides
 Non-glycosylated proteins
 Glycosylated proteins
 Monoclonal antibodies
8

9. Manufacturing Process
Cell Bank
UPSTREAM
•Cell expansion
•Fermentation
Raw In
•Clarification
materials process
DOWNSTREAM
•Centrifugation
•Chromatography
•Ultra filtration
Drug substances
Drug release
substances
9

10. Biotech Process
A typical fermentation based biotech
process flow
10

11. FDA Approvals (2005-2009) Synthetic V/s Biopharmceuticals
25
21
20 19
18 18
16
Number of Approvals
15
10
6
5 4
3
2 2
0
2005 2006 2007 2008 2009
New molecular entities New biologic entities
11

12. EMEA Approvals (2005-2009) Synthetic V/s Biopharmceuticals
25
23
20
20 19
16
Number of Approvals
15
13
10
10
8
6
5
5 4
0
2005 2006 2007 2008 2009
New molecular entities New biologic entities
More number of Biopharmceuticals were approved by EMEA as compared to FDA in 2009
12

13. Benefits of Biopharmaceuticals
 Highly effective and potent action
 Fewer side effects
 Potential to actually cure diseases rather than merely treat the symptoms
 Longer half life
13

14. Top 10 Biopharmceuticals in 2008
#Rank Biopharmceuticals Brands Company Sales(08)(US$ million) Therapeutic area
1 Etanercept Enbrel Amgen, Wyeth $6,580 Rheumatoid Arthritis
J&J, Schering Plough,
2 Infliximab Remicade $5,934 Rheumatoid Arthritis
Mitsubishi
3 Bevacizumab Avastin Roche $5,777 Colorectal cancer.
4 Rituximab Rituxan Roche $5,653 Head and Neck Cancer
5 Adalimumab Humira Abbott $5,488 Rheumatoid Arthritis
6 Epoetin alfa Epogen Amgen $5,033 Renal anemia
7 Trastuzumab Herceptin Roche $4,890 Breast cancer
8 Insulin Lantus Sanofi Aventis $4,180 Diabetes
9 Pegfilgrastim Neulasta Amgen $3,355 Neutropenia
10 Darbepoetin Aranesp Amgen $2,871 Anemia
14 Source- La Merie Business intelligence (R&D Pipeline news 10 March 2010)

15. Top 10 companies in Biopharmceuticals
Sales/Revenues R & D spending
# Rank Company Therapeutic area
In US$ Million) (In US$ Million)
1. Amgen 14,687 $2,900 Oncology, kidney disease, rheumatoid arthritis
Oncology, Immunology, Tissue Repair, Neuroscience, Ophthalmology
2. Genentech 10,531 2,800
Diabetes care , Haemostatic management , Growth hormone
3. Novo Nordisk 8,989 1,550
therapy , Hormone replacement therapy
Neurodegenerative Diseases, Oncology, Fertility, Endocrinology,
4. Merck Serono 7,338 1,580
Autoimmune and Inflammatory, Cardio metabolic care
Baxter biopharma
5. 5,308 868 Hemophilia, Biotherapeutics, Regenerative Medicine, Vaccines
solutions
6. Biogen Idec 3,968 1,072 Neurology, Oncology, Immunology, Hemophilia, Cardiopulmonary
Genetics Diseases, Cardio metabolic and Renal, Oncology,
7. Genzyme 3,751 750 Orthopaedics/Biosurgical Specialties, Transplant,
Genetics/Diagnostics
Dermatology, Urology, Cardiovascular, Antibiotics, Anaphylaxis,
8. CSL ltd 2,961 202 Central nervous system, Analgesia, Emergency Care, Obstetrics and
Gynecology
Neurosciences, Medical Dermatology and Urology, Eye Care,
9. Allergan 1,311 798
Medical Aesthetics, Obesity Intervention
10. Alexion Pharma 259 63 Hematology
15 Source-Contract Pharma Articles » 2009 » July/August 2009

16. Cost of Biopharmceuticals
Drug Indication Cost Duration
Cerezyme Life-threatening enzyme deficiency $200,000 to $500,000 12 Month
Trastuzumab (Herceptin) Breast Cancer $36,000 6 Month
Rituximab (Rituxan) Non-hodgkin’s lymphoma $32,500 2 Month
Bevacizumab (Avastin)/ Cetuximab
Metastatic Colorectal Cancer $28,500 2 Month
(Erbitux)
Infliximab (Remicade), Rheumatoid arthritis $18,000 -
Infliximab Crohn’s disease $16,500 -
Cost for indication listed are for 2005 Source- MONROE 2006
16

17. Biosimilar

18. Definitions and Terminologies
A biosimilar medicine is a medicine which is similar to a biological medicine that has already been authorised (the
‘biological reference medicine’)1
Source – EMEA
“A follow-on biologic (FOB) is “a protein product which is intended to be a similar version or duplicate of an already
approved or licensed protein product”.4
Source – FDA
A new biological medicinal product claimed to be “similar” with regard to quality, safety and efficacy to an already
approved reference medicinal product3
Source – WHO
“A drug to be developed by a different marketing approval holder as a drug that is bio-equivalent/quality-equivalent to
biotechnology-derived drug already approved domestically” 2
Source – PMDA ,Japan
Commonly used
terminologies/synonyms
• Biosimilars
• Biogenerics
• Follow on Biopharmceuticals
• Follow on Protein
18 Note: Sources mentioned in the notes section of slide

19. Biosimilars -
Scientific basis for abbreviated pathway
Demonstrate Quality, Safety, Efficacy
Surveillance
Regulatory
Extensive
Approval
New Biologic Clinical
Characterization
Pre-Clinical
Clinical
Extensive
Regulatory
Surveillance
Characterization
Approval
Clinical
Biosimilar
Extensive Pre-Clinical
Comparison to Pre-Clinical
Reference
Allows for abbreviated
19 pre-clinical & clinical

20. Regulation of Biosimilars

21. No Harmonized Worldwide Regulatory Framework for
Biosimilars
 Small molecule generics model is inappropriate
 In many regions limited or no regulatory processes exist
 Lack of minimum regulatory standards presents a risk for patients
because of the potential issues relating to the quality, efficacy and safety
of biosimilars developed and approved without defined requirements
21

22. Biosimilars – Regulatory Perspective
Well Defined Framework Under process of Development No or Minimal Framework
EUROPEAN5 USA5 INDIA2
UNION  Currently there is no clear guidelines
 Comparability studies are required and authority for approval of biosimilars  Requires only Phase III clinical
to substantiate evidence for safety, trials for 100 patients
 No equivalent of ANDA under PH&S act
efficacy and quality5
for approval of biosimilars6
 Guidelines, including specific clinical CHINA 4
 A biosimilar could not be approved until
and non-clinical data requirements
12 years after the date on which the
for four product types:
reference product was first licensed5
Recombinant insulin, human
growth factor, erythropoietin and
CSFs 6
 10-year period for innovator
exclusivity, with the opportunity for
JAPAN 1
an additional year for new
 Pharmaceuticals and medical device
indications5
Agency (PMDA )
Japan's regulator, expects to finalize a
new guideline for the regulation of
follow-on Biopharmceuticals this year,
 First draft put out for public comment
last September
CANADA 4
22 Note: Sources mentioned in the notes section of slide

23. Biosimilars In the Market Today
 Europe - Sandoz –Omnitrope (hGH), Binocrit (“EPO” or erythropoietin);
Biopartners -Valtropin (hGH);
Hexal –EPO version;
 U.S. –Sandoz -Omnitrope
 China –EPO versions, Interferons, IL-2, IL-11, GM-CSF, hGHs
 India –hGH. EPO, Interferon alpha 2b, insulin
 Australia –Omnitrope (Sandoz)
 Cuba, Egypt, Africa –EPO versions
23

24. Strategic Options to Tap Biosimilar Market
Generics firms enter successfully into the biosimilars
market
Pharmaceutical companies expand their Biopharmceuticals
business and enter biosimilars market opportunistically
New types of cooperation between Pharma, Biotech
or Generics
24

25. Biosimilars successful if all hurdles passed
25

26. The other side of the Biopharmceuticals…….
Safety issue …………??????????
 Biologic drugs are orders of magnitude more complex than small
molecule drugs
 Safety & efficacy of final product is exceptionally sensitive to small
changes in manufacturing process
 It is difficult to impossible to predict the effect of these small changes—
experience counts
 Potential for dramatic negative health consequences
26

27. Key Success Factors for Biosimilars
1. Consistent long term strategy
2. Healthy financial structure
3. Comprehensive competitive intelligence
4. Core competencies for manufacturing process
5. Deep clinical development and regulatory expertise
6. Effective marketing & sales skills
27

28. Regulation of Biologics

29. Challenges in front of Biopharmceuticals
From Industry perspective
 Long and costly clinical trials
 Efficacy
 Difference in Sero – Prevalence (Virus etc) and Genetic makeup (Human
beings)
 Low cost advantage (due to costly raw materials, equipments and labor)
 Difficult to copy (Standardization process)
29

30. Continue…
From Govt. perspective
 No guidelines (Since Biopharmceuticals are in Nascent stage)
From Patients perspective
 Adverse - effects
30

31. Future of Biopharmceuticals
 More diseases will come under the treatment
 Effective manufacturing
31

32. Conclusion
 Biopharmceuticals or PERISH!!!!!!!
 Traditional drug1st generation Biopharmceuticals (small
molecules)2nd Generation Biopharmceuticals (large molecules)
Follow on Biopharmceuticals Biobetters ….….What next???
32

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