Maarg Manthan · Topic 11.7

Biopharmaceuticals and Therapeutic Proteins

Science & Technology › Biotechnology – Applications · Topic 11.7

Biopharmaceuticals are medicines made from living cells or by biotechnology, instead of by chemical synthesis. Most are therapeutic proteins such as insulin, growth hormone, erythropoietin, clotting factors, interferons, monoclonal antibodies and vaccines. They are made by recombinant DNA technology in host cells such as bacteria, yeast, insect cells or mammalian cells grown in bioreactors. Human insulin, marketed as Humulin by Eli Lilly in 1982, was the first recombinant DNA drug approved. Because biologics are large, complex molecules, copies of an approved product are called biosimilars, not generics, and need their own comparison studies. In India they are regulated by the Central Drugs Standard Control Organisation along with the Review Committee on Genetic Manipulation.

5 min read · UPSC Prelims · Science & Technology · Biotechnology – Applications

At a Glance

First rDNA drug Humulin insulin, 1982
Examples Insulin, EPO, interferon, antibodies
Host cells E. coli, yeast, mammalian cells
Copies Biosimilars
Regulator CDSCO and RCGM
Exam link UPSC Prelims, Science & Technology: Biotechnology – Applications

Where Does It Fit?

This topic follows single-cell protein and fortification. It returns to the medical use of genetic engineering, where microbes and cells become factories for human proteins. Previous topic: Single-Cell Protein Production and Food Fortification. Next topic: Brain Fingerprinting Technology.

Which Therapeutic Proteins Are Made and How?

Product	Use and host
Insulin	For diabetes. Made in E. coli or yeast. Replaced insulin taken from pig and cattle pancreas
Human growth hormone	For growth failure in children. Made in bacteria. Earlier taken from dead bodies, which carried disease risk
Erythropoietin	Raises red blood cells in kidney disease and anaemia. Made in mammalian cells
Clotting factor VIII and IX	For haemophilia. Made in mammalian cells
Interferons	Antiviral and anticancer proteins, made in bacteria
Monoclonal antibodies	For cancer and autoimmune disease. Made in mammalian cells, as in Antibody-Antigen Interaction and Detection Methods
Hepatitis B vaccine	The first recombinant vaccine. The surface antigen is made in yeast

How Are Biopharmaceuticals Produced and Regulated?

Gene cloning: the human gene is isolated and put into a vector, as in Recombinant DNA technology Cutting tool Restriction enzymes Joining tool DNA ligase Carriers Plasmids and other vectors India…">Genetic Engineering: Procedure and Applications
Choice of host: bacteria are cheap, but cannot add sugar groups to proteins, so complex proteins need yeast or mammalian cells such as Chinese hamster ovary cells
Fermentation or cell culture: cells are grown in bioreactors, as in Bioprocess and Fermentation Technology
Purification: chromatography and filtration give a pure product
Quality control: biologics are tested for purity, activity and immune reactions
Biosimilars: follow-on products shown to be highly similar to an approved reference biologic
Indian guidelines: India issued Similar Biologics Guidelines in 2012 and revised them in 2016 and again later. Check the current version
Pricing: biologics are costly, and biosimilars lower prices and increase access

What Else Should You Remember?

Humulin: approved in 1982 in the United States, developed by Genentech and marketed by Eli Lilly
Genentech: founded in 1976 by Herbert Boyer and Robert Swanson, the first biotechnology company
Indian firms: Biocon, Serum Institute, Bharat Biotech, Dr Reddys and others make biologics and biosimilars. Biocon was founded by Kiran Mazumdar-Shaw in 1978
Insulin access: India has a large diabetic population, and local production of insulin is important for affordability
Animal and plant systems: proteins can also be made in milk of transgenic animals or in plants, as in Genetically Modified Animals and Transgenic Animal Techniques
Immune reactions: patients may make antibodies against the drug, which can reduce effect
Cold chain: most biologics must be stored cold, which makes delivery in hot regions hard
Glycosylation: adding sugar groups affects the activity and life of a protein in the body
Cell and gene therapies: newer biological medicines such as CAR-T cells are also called advanced biologics, as in Gene Editing (CRISPR) and Gene Therapy
Patents and prices: patent expiry opens the market to biosimilars, a point linked to Protection of Biotechnological Inventions: Patents, Trade Secrets, Plant Breeders’ Rights
Production Linked Incentive: the pharmaceutical PLI scheme includes biopharmaceuticals among categories
Policy: the National Biopharma Mission, supported by the Department of Biotechnology and a World Bank loan, supports development of vaccines, biologics and devices
Insulin types: rapid, short, intermediate and long acting insulin analogues are made by changing amino acids so that the drug acts faster or lasts longer
Vaccine platforms: protein subunit vaccines, such as those for hepatitis B and HPV, use recombinant proteins made in yeast or insect cells
Orphan drugs: biologics for rare diseases, such as enzyme replacement for Gaucher disease, have very high prices and need special policy support
Quality scandals: poor quality control can lead to contamination or reduced effect, which is why good manufacturing practice is checked by inspectors
Skills: biopharma needs scientists, process engineers and regulators, so the National Biopharma Mission also funds training

Why Does It Matter for the Exam?

Firsts: first rDNA drug, first recombinant vaccine
Hosts: which proteins need mammalian cells
Terms: biosimilar versus generic
Current affairs link: insulin pricing and biosimilar approvals
Common errors: calling a biosimilar a generic or saying insulin is made by chemical synthesis

As an analytical point, biologics are among the fastest growing medicines but cost much. Indian biosimilar makers can widen access if regulation stays strict and prices are controlled.

Why Is This Topic Important?

Examples Insulin and EPO
Hosts Cell choice
Access Biosimilars

What Came Next?

The next topic covers brain fingerprinting technology. Next topic: Brain Fingerprinting Technology.

Key People and Terms

Biologic Medicine from living cells
Biosimilar Follow-on biologic
rDNA Recombinant DNA
Glycosylation Sugar addition to protein
Cell line Cultured cells for production
Reference product Original approved biologic

Exam Corner

Points to Remember

First rDNA drug: Humulin, 1982.
First recombinant vaccine: hepatitis B.
Biocon founded: 1978.
Complex proteins need mammalian cells.
Biosimilar is not a generic.

Do Not Confuse With

Biosimilar and generic Complex biologic copy versus simple chemical copy
Biologic and vaccine Biologics include vaccines but also proteins and cells
Insulin from pancreas and recombinant insulin Animal source versus microbial

Memory Hook

Boyer began, Humulin led; microbes make the human proteins we need.

Mains Angle

Questions ask about examples, hosts and policy on biosimilars. These points help.

Importance Access to medicines
Challenges Cost and quality
India Biosimilar leadership

A Question You May Face

An original practice question, not a past paper question.

“Discuss the importance of biopharmaceuticals and the policy measures needed for India to become a leader in biosimilars.”

How to Answer

Meaning Biologic drugs.
Examples Insulin, antibodies.
Challenges Cost, quality.
Way Regulation and R and D.

GS Relevance

Prelims: examples, host cells, biosimilars, Indian firms. GS Paper 3: science and technology, biotechnology, pharmaceuticals and health.

Frequently Asked Questions

What are biopharmaceuticals?

Biopharmaceuticals are medicines made from living cells or produced by biotechnology rather than chemical synthesis. Most are therapeutic proteins such as insulin, growth hormone, erythropoietin, clotting factors, interferons and monoclonal antibodies, made by recombinant DNA technology in microbes or mammalian cells grown in bioreactors.

Which was the first recombinant DNA drug?

Humulin, human insulin made by recombinant DNA technology in Escherichia coli, was the first recombinant DNA drug approved. It was developed by Genentech and marketed by Eli Lilly after approval in the United States in 1982. It replaced insulin extracted from the pancreas of pigs and cattle.

What is a biosimilar?

A biosimilar is a biologic medicine that is highly similar to an already approved reference biologic in structure, safety and effect, and is made by a different manufacturer. It is not called a generic because biologics are complex and cannot be copied exactly, so biosimilars need comparison studies before approval.

Why are mammalian cells used for some biopharmaceuticals?

Mammalian cells such as Chinese hamster ovary cells are used because they can add sugar groups and fold complex proteins correctly, as human cells do. Bacteria cannot do this, so proteins such as erythropoietin, clotting factors and monoclonal antibodies are usually made in mammalian cell cultures.

Which Indian companies make biopharmaceuticals?

Biocon, founded by Kiran Mazumdar-Shaw in 1978, is a leading maker of insulin and biosimilars. Serum Institute of India and Bharat Biotech make vaccines, and several other firms produce biologics. The National Biopharma Mission of the Department of Biotechnology supports development of vaccines and biologics in India.

PYQ Practice — Statement Analysis

1 Humulin was the first recombinant DNA drug.

True

Human insulin approved in 1982.

2 Biosimilars are identical chemical copies called generics.

False

They are highly similar, not identical.

3 The hepatitis B vaccine was the first recombinant vaccine.