Biopharmaceuticals Production

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

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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

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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)

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Complexity of Biopharmceuticals

Structure
Epoetin Size

Aspirin

M
Stability
od
ifi
ca
tio
n

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 Manufacturing Process
Cell Bank

UPSTREAM
• Cell expansion
• Fermentation
Raw • Clarification In
materials process
DOWNSTREAM
• Centrifugation
• Chromatography
• Ultra filtration

Drug substances
Drug release
substances 7
Biotech Process

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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 Biopharmceutical Brands Company Sales(08)(US$ million) Therapeutic area
s
1 Etanercept Enbrel Amgen, Wyeth $6,580 Rheumatoid Arthritis
J&J, Schering Plough,
2 Infliximab Remicade 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 $2,871 Anemia
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 Top 10 companies in Biopharmceuticals
Sales/Revenues In R & D spending (In
# Rank Company Therapeutic area
US$ Million) 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 therapy ,
3. Novo Nordisk 8,989 1,550
Hormone replacement therapy
Neurodegenerative Diseases, Oncology, Fertility, Endocrinology, Autoimmune
4. Merck Serono 7,338 1,580
and Inflammatory, Cardio metabolic care
5. Baxter biopharma 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,
CSL ltd
8. 2,961 202 Central nervous system, Analgesia, Emergency Care, Obstetrics and
Gynecology
Allergan Neurosciences, Medical Dermatology and Urology, Eye Care, Medical
9. 1,311 798
Alexion Aesthetics, Obesity Intervention
10. Pharma 259 63 Hematology
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 Cost of Biopharmceuticals
Drug Indication Cost Duration
Cerezyme Life-threatening enzyme $200,000 to 12 Month
deficiency $500,000
Trastuzumab (Herceptin) Breast Cancer $36,000 6 Month

Rituximab (Rituxan) Non-hodgkin’s lymphoma $32,500 2 Month

Bevacizumab (Avastin)/
Metastatic Colorectal Cancer $28,500 2 Month
Cetuximab (Erbitux)

Infliximab (Remicade), Rheumatoid arthritis $18,000 -

Infliximab Crohn’s disease $16,500 -

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Cost for indication listed are for 2005 Source- MONROE 2006