2. History
Biotechnology in some way is as old as human history,
our ancestors harnessed living organisms to make bread,
curd and wine
It was just during the early 20th century when the term
biotechnology came into use
The term was coined in 1917 by Karl Ereky, a hungarian
engineer & professor
3. What are biosimilars
A biosimilar is a copy of a commercially available
biopharmaceutical (reference product) which no longer is
protected by patent which has:
• undergone rigorous analytical
& critical assesment in
comparision to its reference product
•has been approved by a regulatory
agency to a specific pathway or
biosimilar evaluation
A biosimilar is highly similar to its reference product in
physiochemical characteristics, efficacy and safety
4. Cont…
It is a drug created by means of biotechnology, especially
genetic engineering: primarily rDNA protein &
monoclonal antibody
Typically derived from living organisms(living cells,
bacteria, viruses & yeast)
Includes:
•therapeutic proteins(cytokines, hormones & clotting
factor), insulin, DNA vaccines, monoclonal antibodies
•new experimental modalities such as gene therapy,
stem cell therapy etc..
6. CONDITIONS WHICH CAN BE TREATED
BY USING BIOLOGIC MEDICINES
Blood conditions: leuko/neutro/pancytopenias
Cancers: colon and breast cancer
Immune system disorders: rheumatoid arthritis, psoriasis &
crohns disease
Neurological conditions: multiple sclerosis
More than 400 biologics are in clinical trials
These includes therapies for cancers, alzheimers disease,
heart disease, diabetes, HIV/AIDS & autoimmune disorders
7. THE FIRST BIOLOGIC DRUG
Biosynthetic human insulin
Marketed: since 1982
8. THE CHALLENGES IN
MANUFACTURING BIOLOGICS
The manufacturing process:
complex and very sensitive
Slight changes in temp and other factors:
impact the final product
Changes in manufacturing process or facility:
may affect purity as well as potency of drug
9. MANUFACTURING OF BIOLOGIC
AGENTS
Develop host cell
Identify the human DNA sequence for the desired protein
Isolate the DNA sequence
Select a vector to carry the gene
Insert the gene into the genome of a host
Modification of cells recombinant technology
The exact DNA sequence & type of host cell used will
significantly influence the characteristics of the product
10. STEPS INVOLVED IN MANUFACTURING
OF BIOLOGIC AGENTS
Modify the selected cell
Growing a cell line from the original modified cell
Growing a large no of cells from cell line
Cultivating them to produce the desired protein
Seperating the proteins from cell
Purify the collected protein
11. EFFECT OF VARIABLES IN THE
MANUFACTURING OF BIOLOGICS
Even small changes in production(minor equipment/env
variation)
Significant changes in behaviour of the cells & changes in the
protein
Alterations in 3 dimensional structure of protein
To assure high quality & consistency of the final product,
production process requires a high level of monitoring &
testing throughout the process
A biologic drug typically has around 250 in process tests during
manufacturing, compared to around 50 tests for small molecule
drugs
12. USES OF BIOSIMILARS IN
DERMATOLOGY
Infliximab-
psoriasis:- psoriatic arthritis and plague psoriasis
dose- 5 or 10 mg I.V over a period of 2 hours at
week 0, 2 and 6
Adalimumab-
multiple inflammatory diseases
dose-40 to 80 mg s.c every week
13. Etanercept-
used in pyoderma gangrenosum
used in connective tissue disorder
Rituximab-
used in type 2 hypersensitivity reactions
14. LIMITATIONS IN USE OF BIOSIMILAR
AGENTS
Increased incidence of infections
Relapse during treatment or inadequate response
Used in special population-
pediatrics and geriatrics
pregnancy and lactation
Carcinogenic potential
15. FEW BIOSIMILARS APPROVED IN INDIA
Epoetin alpha- erythropoetin
produced by rDNA tech
stimulates erythropoiesis
treatment of anemia
Darbopoetin alpha- re-engineered from erythropoeitin
contain 5 amino acid chain
stimulates erythropoiesis
16. Insulin glargine- long acting insulin analogue
microcrystals that slowly release insulin
Reteplase- thrombolytic agent
longer half life than ateplase
