biopharmaceuticals (transforming proteins and genes into drugs)
DESCRIPTION
A outline of Biopharmaceutical market of the WorldTRANSCRIPT
Biopharmaceuticals Transforming proteins and genes into drugs
Prepared by:
By-
Kuldeep DabasXIIIth Batch
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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
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Terminology used
Biologics
Biopharmaceuticals
Biosimilars
Follow-on Biologics
Biogenerics
Note- Following terms are used in different organization in different places
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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
Cornerstones in biotechnology history which have influenced the production of Biopharmceuticals
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Traditional Vs Biopharmceuticals
Multiple effect
Short Acting
Non-Immunogenic
Species independent
Small molecules
Stable
Oral administration
General practice
Specific effect
Long acting
Immunogenic
Species dependent
Large molecules
Heat sensitive
Parenteral
Hospital
Traditional Biopharmceuticals
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Definitions of Biologics\Biopharmaceuticals
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
Note: Sources mentioned in the notes section of slide
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Complexity of Biopharmceuticals
Size
Structure
Modification
Stability
Epoetin
Aspirin
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Types of Biologics
Peptides
Non-glycosylated proteins
Glycosylated proteins
Monoclonal antibodies
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Manufacturing Process
UPSTREAM •Cell expansion•Fermentation•Clarification
DOWNSTREAM•Centrifugation•Chromatography•Ultra filtration
Raw materials
In process
Drug substances release
Cell Bank
Drug substances
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Biotech Process
A typical fermentation based biotech process flow
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FDA Approvals (2005-2009) Synthetic V/s Biopharmceuticals
18 18
16
21
19
4
23
6
2
0
5
10
15
20
25
2005 2006 2007 2008 2009
Nu
mb
er
of
Ap
pro
va
ls
New molecular entities New biologic entities
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EMEA Approvals (2005-2009) Synthetic V/s Biopharmceuticals
5
16
19
13
23
4
10
8
6
20
0
5
10
15
20
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2005 2006 2007 2008 2009
Nu
mb
er
of
Ap
pro
va
ls
New molecular entities New biologic entities
More number of Biopharmceuticals were approved by EMEA as compared to FDA in 2009
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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
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Top 10 Biopharmceuticals in 2008
#Rank Biopharmceuticals Brands Company Sales(08)(US$ million) Therapeutic area
1 Etanercept Enbrel Amgen, Wyeth $6,580 Rheumatoid Arthritis
2 Infliximab RemicadeJ&J, Schering Plough,
Mitsubishi $5,934 Rheumatoid Arthritis
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 $2,871 Anemia
Source- La Merie Business intelligence (R&D Pipeline news 10 March 2010)
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Top 10 companies in Biopharmceuticals
# Rank CompanySales/Revenues
In US$ Million)
R & D spending
(In US$ Million)Therapeutic area
1. Amgen 14,687 $2,900 Oncology, kidney disease, rheumatoid arthritis
2. Genentech 10,531 2,800 Oncology, Immunology, Tissue Repair, Neuroscience,
Ophthalmology
3. Novo Nordisk 8,989 1,550Diabetes care , Haemostatic management , Growth hormone
therapy , Hormone replacement therapy
4. Merck Serono 7,338 1,580 Neurodegenerative Diseases, Oncology, Fertility, Endocrinology,
Autoimmune and Inflammatory, Cardio metabolic care
5.Baxter biopharma
solutions 5,308 868 Hemophilia, Biotherapeutics, Regenerative Medicine, Vaccines
6. Biogen Idec 3,968 1,072 Neurology, Oncology, Immunology, Hemophilia,
Cardiopulmonary
7. Genzyme 3,751 750
Genetics Diseases, Cardio metabolic and Renal, Oncology,
Orthopaedics/Biosurgical Specialties, Transplant,
Genetics/Diagnostics
8. CSL ltd 2,961 202
Dermatology, Urology, Cardiovascular, Antibiotics, Anaphylaxis,
Central nervous system, Analgesia, Emergency Care, Obstetrics
and Gynecology
9. Allergan 1,311 798Neurosciences, Medical Dermatology and Urology, Eye Care,
Medical Aesthetics, Obesity Intervention
10. Alexion Pharma 259 63 Hematology
Source-Contract Pharma Articles » 2009 » July/August 2009
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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
(Erbitux)Metastatic Colorectal Cancer $28,500 2 Month
Infliximab (Remicade), Rheumatoid arthritis $18,000 -
Infliximab Crohn’s disease $16,500 -
Source- MONROE 2006Cost for indication listed are for 2005
Biosimilar
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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
Note: Sources mentioned in the notes section of slide
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Pre-Clinical
Clinical
Biosimilars -Scientific basis for abbreviated pathway
New Biologic Extensive Characterization
Pre-Clinical
Clinical
Demonstrate Quality, Safety, Efficacy
Surv
eill
ance
Regula
tory
Appro
val
Biosimilar
Extensive Characterization
Extensive Comparison to
Reference
Pre-Clinical
Regula
tory
Appro
val
Surv
eill
ance
Clinical
Allows for abbreviated pre-clinical & clinical
Regulation of Biosimilars
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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
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Biosimilars – Regulatory Perspective
Comparability studies are
required to substantiate evidence
for safety, efficacy and quality5
Guidelines, including specific
clinical and non-clinical data
requirements for four product
types:
Recombinant insulin, human
growth factor, erythropoietin and
CSFs 6
10-year period for innovator
exclusivity, with the opportunity
for an additional year for new
indications5
Currently there is no clear guidelines
and authority for approval of
biosimilars
No equivalent of ANDA under PH&S
act for approval of biosimilars6
A biosimilar could not be approved
until 12 years after the date on which
the reference product was first
licensed5
Requires only Phase III clinical
trials for 100 patients
Pharmaceuticals and medical device
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
Pharmaceuticals and medical device
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
Well Defined FrameworkWell Defined Framework
EUROPEAN5 UNION
Under process of DevelopmentUnder process of Development
USA5
JAPAN 1
No or Minimal FrameworkNo or Minimal Framework
CANADA 4
INDIA2
CHINA 4
Note: Sources mentioned in the notes section of slide
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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
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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
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Biosimilars successful if all hurdles passed
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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
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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
Regulation of Biologics
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Challenges in front of Biopharmceuticals
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)
From Industry perspective
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Continue…
No guidelines (Since Biopharmceuticals are in Nascent stage)
Adverse - effects
From Govt. perspective
From Patients perspective
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Future of Biopharmceuticals
More diseases will come under the treatment
Effective manufacturing
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Conclusion
Biopharmceuticals or PERISH!!!!!!!
Traditional drug1st generation Biopharmceuticals (small
molecules)2nd Generation Biopharmceuticals (large molecules)
Follow on Biopharmceuticals Biobetters ….….What next???
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