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In early 1940s, I was a young child who suered
several bouts of malaria. The only drug
available at the time was quinine which was sold
in the local post oce. No doubt it helped as a
cure, but many also died of malaria. I also realized
if anybody contacted TB, they would die in a short
time. The other prominent disease was smallpox.
If a patient contacts smallpox their survival rate
was very slim. People believed that it was due to
the curse of the local Goddess, and they would
perform rituals, poojas and prayers for eradicating
the disease. I can go on mentioning the gamut
of the health problems that people were facing
during those times. The life expectancy during
those years was less than 40 years. Today the
situation is totally dierent. Malaria as well as
TB are no more dreadful diseases. They can be
cured with proper medication. Smallpox has been
almost totally eradicated from the world due to
vaccination programs. Thus, the health of humanity
has improved, and the life expectancy has gone
up well beyond 70 years. How has this happened?
This is due to the relentless eorts of chemical and
pharmaceutical industries. We now live in a world
with lifesaving drugs, where many are available
as generics - o patent drugs available at a much
aordable price.
Even in India, domestic chemical manufacturers
provide various fertilizers, agrochemicals for our
food. We use colouring material such as dyes and
pigments to colour fabrics and for a variety of other
uses. The polymer industry has grown and entered
every aspect of our lives, from packing water,
milk, and food, for the clothes we wear, furniture,
automobiles, machines and electronics we use are
made from plastics. The list is long.
Indian
Chemical
Industry
By A V Rama Rao
Former Director, Indian Institute of Chemical Technology, Hyderabad
https://doi.org/10.51167/acm00035
*Curre nt Address: 7-102/ 54, Sai Enc lave, Habsig uda, Hydera bad – 500007.
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Chemical Industry:
Chemistry is at the center of all the action;
atoms form molecules which further aggre-
gate to everything in life. The subject has
grown, and its allied industries have evolved
to deliver everything that supports our lives.
The global chemical market is worth USD
4.73 trillion, and Europe was the largest
producer till recent years with China taking
over most of the global chemical production.
The German company BASF is the world’s
largest chemical company. The fast-growing
Chinese chemical industry is now valued at
over 1.5 trillion US dollars and representing
40% of the global chemical industry revenue.
Chemicals can be broadly divided as large
volume or bulk chemicals which include
petrochemicals, fertilizers, polymers, etc.
and specialty chemicals which are also
referred to as ne chemicals which have a
relatively higher value and used in making
pharmaceutical drugs, dyes, agrochemicals,
fragrances, and materials
The Indian chemical industry is valued
at over USD 200 billion (3% of the world
sales) and likely to reach USD 300 billion by
2025. Drugs and Pharmaceuticals normally
form a separate class and generally are not
included in the chemical sector. India has
played a major role in the production of
generic drugs (copies of o-patent branded
drugs that have the same chemical compo-
sition and intended for the same use as the
branded drug).
Before any pharmaceutical company
introduces a new drug in the market they
patent and protect their product to become
the sole manufacturer of the drug for the
patent duration (life of a patent is normally
20 years). Once the patent expires, other
companies can manufacture the same drug
with the same chemical composition and
purity, these are referred as generic drugs.
Today, India had the distinction of being
Dr. A V Rama Rao
Dr. A.V. Rama Rao was bor n in 1935 i n Guntur,
Andhra P radesh, and rec eived his B.Sc. in 196 0
from Bom bay Universit y and Ph.D. in 1964 from
NCL Pune w ith Dr. K. Venkataram an. While at
NCL, he too k a sabbatical le ave with Prof E.J.
Corey at Ha rvard Univer sity (1975-1977). In 1965
he beca me a Scientist B at N CL Pune and later
was Head of the Organic Chemistry Division there.
In 1985, He move d to the CSIR in Hydera bad as a
Director and transformed the Regional Research
Labor atory (RRL) into t he Indian Insti tute of
Chemical Technology (IICT). After retirement in
1995, he found ed the A. V. Rama Rao Res earch
Foundation, a non-governmental promoting
research and doc toral studies in c hemistry, and
the Avra Laboratories. This multi-million-dollar
pharm aceutical co mpany currentl y has over 600
employe es. Dr. Rama Rao has tr ained 112 Ph.D.
studen ts and publishe d more than 260 pap ers on
the isolation and structural elucidation of plant and
insect pigments and synthetic dyes, biologically
active natural products such as antitumor
antibiotics, macrolides, immunosuppressants,
and cycl ic peptides. He re ceived the Padm a
Shri (1991), Padma Bhu shan (2016), and the
techno logy award from th e World Academy of
Scien ces (TWAS). He is a fe llow of all scien ce
academ ies in India and a f ellow of the TWAS.
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along with the development of synthetic
drugs that could treat a gamut of diseases.
For example, in early 1930s, Gerhard
Domagk of Bayer in Germany tested vari-
ous azo-dyes against Streptococcal bacteria
and discovered Prontosil as an antibacterial
agent. In late 1935, he gave it to his dying
daughter suffering from a streptococcal
infection. She recovered although with a side
eect that turned her bright red. Prontosil
was not active in Vitro but in Vivo it was
converted to Sulphanilamide the main active
compound and this discovery gave birth to
various sulpha-drugs. He was awarded the
the Nobel Prize in 1939.
Another major and accidental discovery
was Penicillin. Alexander Fleming working at
St. Mary’s hospital, London in 1928 discov-
ered Penicillin a life-saving antibiotic drug.
Penicillin’s curative power and therapeutic
action was fully identied by Howard Florey
and Ernest Boris Chain and nally the drug
was mass produced and commercialized in
1941. During the second world war Penicillin
was extensively used to treat the wounded
soldiers. Currently, Penicillin is more a start-
ing material for the manufacture of several
semi-synthetic antibiotics such as Ampicillin
and Amoxicillin. During that period several
synthetic drugs also entered the market,
which include vitamins, hormones, psycho-
tropic drugs, antihistamines, and anesthet-
ics. However, in India before independence
most of these drugs were not made and not
easily accessible at aordable prices.
Several multinational companies had for-
mulation facilities in India and were using
imported active drug substances, these
included- Glaxo, Burrows Welcome, Ciba,
Roche, Parke-Davis, Merck, Hoechst, and
Wyeth.
Chemicals and Pharmaceutical Works
Limited in 1901. It gradually expanded and
had undertaken bulk drug production and
formulations. In addition, the company was
making some perfumes, cosmetics, surgical
equipment. Till 1960 the company-main-
tained leadership in technology after which
its sales slowly went down and became sick
in 1970. The Government of India nation-
alized it in December 1980, but it did not
recover and once again was declared sick
on 14 Jan 1993. Further attempts to revive
the company by infusing more money during
the Government’s 11th ve-year plan did not
help. Ray also established in 1919 Bengal
Immunity Company Limited to produce
Sera, vaccines and toxoids, based on their
know-how using indigenous raw materials.
An important life-saving contribution the
company made was the development of an
anti-snake venom serum which was eective
against the commonly encountered Indian
Cobra. The serum was prepared from con-
centrated and puried plasma obtained from
hyper-immunizing horses.
The second major chemical and phar-
maceutical company in India was Alembic
Chemical Works Company Limited started
by B D Amin in 1907 in Baroda with the
support of the Maharaja of Baroda. It has
grown into a multinational organization and
is involved in the manufacture of drugs and
intermediates. The company is a leader
in macrolide segments of anti-infective
drugs and also has expertise in peptide
manufacture.
In the US and Europe, modern drug devel-
opment witnessed a revolution and rapid
growth between 1930 to 1960, wherein
several breakthroughs were made with the
discovery of penicillin and other antibiotics
the second largest producer with USFDA
approved drug manufacturing units outside
the US. The Indian pharmaceutical compa-
nies have led so far more than 1218 ANDAs
(abbreviated new drug application) with the
USFDA which amounts 45.5% of all appli-
cations. The top 20 Indian pharmaceutical
companies constitute 80.5% of these appli-
cations and 40% of generic drugs used in
USA come from Indian manufacturers. The
country also has a well-evolved ecosystem
of highly skilled professionals to undertake
these tasks required for highly regulated
manufacturing. Further, 95% of its domestic
bulk drug requirements are met by the local
industries ensuring drug prices in India are
one of the lowest in the world.
Over the last 5 decades, I dealt exten-
sively with the Indian pharma industry and
watched it grow from its infancy to its current
leadership position.
Earlier History of the Indian drugs
and pharmaceutical industry:
Before the British invaded and took over
the country, the Indian medical system relied
on traditional Ayurveda and Unani, which
were the only indigenous forms that were
practiced for the health care and available.
The development of the drug industry in
India started around a century ago. In 1892,
Acharya Prafulla Chandra Ray (P C Ray),
started a small manufacturing factory for
chemicals and pharmaceuticals named as
Bengal Chemicals and Pharmaceuticals
in a rented house at “91, Upper Circular
Road, Calcutta” with a minimum capital of
Indian rupees 700. Ray was keen to exploit
the knowledge of ancient Indian medicine
by adopting modern methods for manu-
facturing. The company was converted as
a limited company in the name of Bengal
(Gerhard Domagk)
Discoverer of sulfa drug
(Alexander Fleming)
Acharya Prafulla Chandra Ray
(1861 – 1944)
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Technology from Bombay University; I real-
ized that the search for innovative solutions
to industry related problems could also be
done along with basic academic research. I
felt nding a new process to produce a drug
could be as exciting and gratifying as getting
a research article published in a scientic
journal. In this quest, I selected Diazepam
(Valium, an antianxiety agent produced by
Roche) as its sales were growing signicantly
globally while its production was only in kilo
gram quantities per annum. The process
that was patented by Roche was tedious
for the Indian manufacturers to scale-up.
The original Roche process made the key
intermediate – “2-methylamino-5-chloroben-
zophenone” starting from 4-chloroaniline
by reacting with benzoyl chloride in molten
zinc chloride and the resultant product was
subjected to acid hydrolysis to yield 2-ami-
no-5-chlorobenzophenone. This was then
subjected to N-methylation using a classical
method and nally converted to Diazepam.
I developed a simple process whereby the
They fought to amend the 1911 Patent Act,
a struggle which was culminated in the
enactment of the Indian Patent Act of 1970
which was passed by the Indian parliament
in September 1972. As a result, “all product
patents for drugs and agrochemicals were
abolished and only process patents were
allowed for a period of 7 years from the date
of ling the patent or 5 years from the date
of acceptance whichever is earlier”. This
allowed the Indian pharma industry to begin
its journey of drug development and manu-
facturing. In 1947, the Indian pharma industry
had a turnover of Rs.10 crores which had
gone up to Rs.360 crores by 1972 but this
was just over 1% of the world pharma mar-
ket value. By 1980’s there was phenomenal
growth; imports of pharmaceuticals was
marginal while India started exporting API’s
(Generic drugs) and their formulations to
various countries.
Indian Institutions and Industry
collaboration for developing
technologies for lifesaving drugs:
After enacting the new patent law, the then
Prime Minister, Mrs. Indira Gandhi who was
also the Pre sident of the Council for Sci enti c
and Industrial Research (CSIR) instructed all
the CSIR Directors, to initiate the develop-
ment for drugs and agrochemicals and help
the Indian chemical industry in technology
transfer and commercialization. Dr. B D
Tilak, the then Director of National Chemical
Laboratory (NCL), Pune, called a meeting of
various divisional heads including myself; I
happened to be a young project leader in
NCL. Dr Tilak stated the Government’s intent
to initiate work towards the process devel-
opment for some of the essential drugs.
Most of the senior scientists did not take his
message seriously and some even refused
expressing that they were working in the NCL
with a meager salary only for the academic
pursuit of fundamental research and if they
had to do industrial research, they could as
well go to industry and earn a salary at least
10 times higher than what they were being
oered in NCL. I was a graduate of Chemical
These multinational companies operating
in India took advantage of the prevailing
Indian Patent Act of 1911 and almost all the
new drugs introduced in India were priced
higher compared to New York or London
prices. Realizing the need for affordable
health care, the Indian Government encour-
aged the production of drugs by starting
state-owned public-sector units. Thus,
Hindustan Antibiotics was started in Pune
in 1955 to produce penicillin and strepto-
mycin and their formulations with aid from
WHO and UNICEF. Similarly, Indian Drugs
and Pharmaceuticals Limited (IDPL) was
incorporated in 1961, with the sole objec-
tive of creating self-suciency through the
domestic manufacturing of essential life-
saving drugs. IDPL’s facility in Hyderabad
started manufacturing several synthetic
drugs including sulfa drugs and vitamins ini-
tially with assistance from the former Soviet
Union (USSR) government.
IDPL - Hyderabad played a major role
in developing infrastructure for the growth
of the Indian drug industry especially the
bulk drug industry which involved the mass
production of active ingredients. Later some
the technical sta left IDPL and started their
own companies based on the knowledge
that they acquired from IDPL. Several of
these former employees went on to become
successful entrepreneurs while laying the
foundation for the private pharmaceutical
industry. Unfortunately, the growth of the pri-
vate sector led to downfall of the state owned
IDPL which was finally liquidated on 9th
February 2021 by the Government of India.
The city of Hyderabad owes its success and
reputation as the pharma capital of India to
IDPL. The two states of Andhra Pradesh
and Telangana together have 2500 pharma
companies with most of them having their
headquarters in Hyderabad.
Several Indian companies came together
and formed the Indian Drug Manufacturing
Association (IDMA) in 1961, with the sole
aim of boosting domestic manufacturing. Dr. Yusuf K Hamied
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crop. The state government started pro-
curing these dried leaves and were keenly
looking for an institution to develop an indig-
enous approach to isolate the two valuable
dimeric alkaloids. In 1978, I approached
the Maharashtra Government for funding to
take up this project and was given a grant.
My research group quickly worked out a
simple process of isolating vinblastine using
a solvent extract technique from the vinca
dried leaves thereby totally avoiding the
tedious chromatography column separation.
We then converted it by a simple potassium
permanganate oxidation to give Vincristine.
We also worked out a way to formulate the
drug substance by way of lyophilizing in
the form of vials with the help of Hindustan
Antibiotics Limited (HAL). For the rst time,
we demonstrated that the bioavailability of
the drug was identical with Eli Lilly’s imported
vials with assistance from the Head of the
Chemotherapy at the Tata Cancer Hospital,
Mumbai. The entire technology including its
formulation process was passed on to Cipla
for commercialization. Cipla introduced both
these two natural anticancer agents in 1983
in India and subsequently in 1985 started
exporting these two compounds to US and
Europe. This was the second example of
successfully achieving a solution to a di-
cult problem where better technology was
developed in NCL and commercialized by a
domestic company.
Eli Lilly came to India to look at the Indian
medical system and the plant materials that
were used as herbal remedies. They carried
with them the Vinca dried leaves and looked
for antidiabetic agents from the leaf extract.
They could not nd any active compo nent for
the treatment of diabetes but were surprised
to realize that the extract contained an anti-
cancer agent. The plant contains nearly 95
alkaloids which were mostly monomers but
a small fraction of the alkaloids were dimeric.
The Eli Lily team separated the active vin-
ca-alkaloid named Vinblastine using a very
tedious alumina column chromatography.
Further, they also isolated another minor
component named Vincristine which was
more active and an eective treatment for
pediatric leukemia. Based on these positive
results they were importing huge quantities
of dried vinca leaves from India. With the
growing demand some of the traders who
were exporting dried vinca leaves became
greedy and started adulterating the vinca
leaves. Faced with this problem of getting
good quality raw material from India, Eli Lilly
started their own plantations near Houston
in the southern parts of US where the cli-
mate was suitable to grow the Madagascar
periwinkle plants. Around the early 1970’s,
sourcing of the leaves from India was
stopped. This led to a political problem
with the Maharashtra government having
to deal with livelihood of many people who
were growing and harvesting this medicinal
same intermediate could be made starting
from 4-nitrochlorobenzene using simple
operations which made the product dras-
tically cheaper compared to the original
patented process. In 1973, I met Dr. Y K
Hamied, who was then the Director of R&D
in CIPLA and informed him about my work
on Diazepam. He was so impressed with my
approach that he decided to buy the route
of synthesis without waiting for our process
scale up. He met Dr. Tilak and told him that
he would like to make a one-time payment
on nonexclusive basis for the laboratory
process developed by Rama Rao. This was
the rst drug process technology sale from
CSIR-NCL that was successfully commer-
cialized by an Indian industry.
Rama Rao’s Contributions to
Indian Drug Industry - Consultancy
and contract research:
After my return from Harvard University
working in Prof. E J Corey’s group, it was
my intention to continue working on impor-
tant industrial projects. The isolation of
Vinblastine and Vincristine, two complex
alkaloid molecules from Madagascar peri-
winkle - Vinca Rosea leaves seemed like a
colossal challenge to take on. Vinca Rosea
(Catharanthus roseus) was widely grown in
India and known for its medicinal properties.
In fact, even today some people in Kerala use
the dry leaf decoction believing that it cures
diabetes. In late 1950’s, a delegation from
CSIR-Indian Institute of Chemical Technology
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March 20 23
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converting it to chloro and subsequently to
cyano and then perform an alkaline hydrol-
ysis to give Ibuprofen. Cheminor, scaled up
this technology and made several process
improvements to produce Ibuprofen. They
proceeded to obtain a USFDA clearance to
export to the US market. Anji Reddy went
on to consolidate his business by setting
up Dr. Reddy’s Laboratories in 1984. They
produced Methyldopa both for Indian con-
sumption and international markets. Dr.
Reddy’s moved into formulating and market-
ing his own branded products when India’s
two main formulators at the time, Cipla and
Ranbaxy refused to buy his Noroxacin and
Ciprooxacin APIs. Dr Reddy’s introduced
these two drugs in the market at a third of the
existing prices and achieved a great success
and brand recognition. Within a short time,
Dr Reddy’s grew into a multinational and
today has revenue around USD 2.5 billion
manufacturing over 60 API’s and is the fth
largest pharma company in India.
The city of Hyderabad continued to pro-
duce many great pharma entrepreneurs
and is home to majority of the country’s
top pharmaceutical companies. Aurobindo
was founded in 1986 by Mr. P V Ramprasad
Reddy; Divi’s Laboratories founded in 1990
by Murali Divi; Hetero Drugs founded Dr.
B Parthasaradhi Reddy in 1993. All above
three were colleagues and associates of Dr.
Anji Reddy.
Today, Hyderabad accounts for 40% of
total Indian bulk drug production and 50%
of them are exported and is regarded as a
“Bulk Drug Capital of India”.
Cipla was founded by Dr. K A Hamied
in 1935 and in the beginning the company
conned to formulations and did not man-
ufacture drugs. In 1960, his eldest son Dr.
Yusuf K Hamied completed his Ph.D. in
chemistry from Cambridge University joined
Cipla as its R&D Head. He realized that
Cipla would not grow unless it has its own
drug manufacturing facilities. Cipla was the
rst company to introduce steroids in the
country and later went on to manufacture
almost all the major generic drugs and their
formulations. Having had the training in syn-
thetic organic chemistry, Dr. Yusuf Hamied
also pioneered the concept of academic and
industry interaction and sponsored several
projects with my research group at NCL and
subsequently at IICT. In 1991, I approached
him to commercialize Zidovudine, com-
monly known as AZT, which at that time
such as Atenolol and Metoprolol for Cipla
and for the rst time in India made a chiral
drug - Timolol and passed on its technology
to FDC, Bombay.
Subsequently, I moved to Hyderabad as
Director, Regional Research Laboratories
(RRL) in 1985 which was renamed as the
Indian Institute of Chemical Technology (IICT)
in 1988. Here, I continued to work closely with
Indian pharma industry. At IICT, we devel-
oped technology for making an anticancer
drug, Etoposide and successful transferred
the technology to Cipla for its manufacture.
We also developed a laboratory process for
Noroxacin and Ciprooxacin for Cipla. We
were also instrumental in developing several
other processes for Indian pharma which
include Flurbiprofen (for FDC), Astemizole
and Gembrozil (for Cadila), Meoquine and
Sulbactam (for Unichem).
Indian Pharma Revolution after
1972:
Many Indian companies were very keen
to take advantage of the new 1972 patent
law in India and started copying some of
the new and essential drugs which were
being made internationally and were keen
to introduce them in Indian market. The
demand for talented chemists and chemical
engineers spiked as more R&D and produc-
tion units were established. Several entre-
preneurs with technical expertise ventured
into starting their own companies. One such
successful example was Dr. K Anji Reddy, a
graduate in chemical technology from UDCT
and obtained his Ph.D. in chemical engineer-
ing from NCL and joined IDPL as technical
ocer in 1968.
He was directly involved in taking up R&D
projects of IDPL, scaling up on pilot plant and
manufacturing. He was very keen to go on
his own and set up a company - Uniloids with
two other partners in 1974. They started pro-
ducing Metronidazole which became a big
hit in the Indian market. Later he parted ways
and founded Standard Organics Limited in
1980 to manufacture Sulfamethoxazole and
Trimethoprim. Standard Organics quickly
became the leader in the domestic market
for these two drugs and also started export-
ing them to other countries. Anji Reddy
started another company named Cheminor
in 1981 with Mr. Murali Divi to exclusively
manufacture Ibuprofen. Anji Reddy was
a family friend, both at UDCT and subse-
quently at NCL before he left for Hyderabad
to work at IDPL. He consulted with me
to know more about the Ibuprofen pro-
cess which we had developed and trans-
ferred to Cipla on a non-exclusive basis.
I had some new ideas and suggested to
use a process starting from 4-isobutylace-
tophenone, reducing the ketone to alcohol,
Another example which came out from
the National Chemical Laboratory was
Vitamin-B6. The work on Vitamin-B6 was ini-
tiated at NCL in 1958 based on the directive
from the Government of India to work on an
indigenous process technology and pass it
on to the Indian Drugs and Pharmaceuticals
Limited (IDPL) in Hyderabad for commercial-
ization. NCL started working on the original
twelve step process based on Harris and
Folkers method of Merck. When NCL sci-
entists initiated the work in 1958 the cost of
vitamin-B6 in international market was 450
USD per kilo but by 1963 the price came
down to 80 USD per kilo. This dramatic
change happened based on a publication
by Kondratyers from USSR stating that
substituted hydroxypyridines could be made
by a simple Diels Alder reaction involving
substituted oxazole with dimethyl acetylene
dicarboxylate. Pursuing this new nding, the
project was once again taken up by NCL
based on Merck process and carried out
on pilot plant scale by 1973. But by then
the price of vitamin-B6 came down to 30
USD, which the NCL process was not able
to meet, and the project was shelved. Later,
when I took over as the Head of the Organic
Chemistry Department in 1980 at NCL and
I was keen to revive the process to work on
the vitamin-B6 despite the then Director’s
reluctance. We realized what went wrong
with the earlier process. They used 4-Methy-
5-ehtoxyoxazole as the diene, which is very
unstable to heat and resulted in lower yields
after Diels Alder reaction. Contrary to it,
we used 4-methyl-5-cyanooxazole as the
diene, which is relatively stable to heat and
reacted with cis-1,4-butene diol acetonide
as the dienophile. By this way, the process
worked out better, successfully carried out
on pilot scale and finally commercialized
by Lupin Laboratories in their Ankleswar
unit in 1985. I continued to associate with
Indian industries and taken up several pro-
jects under sponsorship or what is referred
to as contract research today. I was also
an active consultant with several Indian
pharmaceutical companies. We worked
on developing processes for beta-blockers
N
N
H
N
OH
CH
3
N
H
O
CH
3
CH
3
O
O
CH
3
O
O
CH
3
O
O
CH
3
H
HO
H
R
Vinblastine: R=Me
Vincristine: R=CHO
Dr. Kallam Anji Reddy
(1939 – 2013)
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contraceptive. The drug is marketed under
the trade name Saheli by Hindustan Latex
Limited and used by many women as an
oral contraceptive taken one pill per week.
This drug is distributed free of cost through
government hospitals.
The present global API market is around
USD 200 billion while the global pharmaceu-
tical market is valued at USD 1.4 trillion. While
these numbers appear attractive, the busi-
ness itself is very competitive with more than
2000 rms and 5000 manufacturing sites.
Currently, India has a reputation in producing
high quality and low-cost generic drugs in
the world. This industry has been valued at
USD 42 billion by 2020. India is the third larg-
est provider of generic medicines by volume
and having 20% of global market share. It is
also the largest supplier of vaccines to the
world by volume and accounting for more
than 50% of all vaccines manufacturing in
the world. Indian pharmaceutical business
is showing an annual average growth of
11% per annum and is expected to reach
60 billion USD in value by 2024. The future
of the pharmaceutical business in India is
promising and investments into this sector
are only increasing, but the area of concern
where India needs to achieve self-suciency
is in the production of raw materials used for
making APIs. Most of the Indian companies
depend on the import of key starting mate-
rials from China and this accounts to 58%
by value and 80% by volume. Most of the
fermentation products especially antibiotics
and almost all steroids are being imported
into India from China. Although India is
known as the largest producer of Metformin
in the world which is used for treating dia-
betes; two key intermediates for making this
drug are imported from China. To counter
this dependence on China, in recent years,
the Indian government came out with incen-
tives to be given to domestic companies that
can produce products without the need for
any raw materials being imported.
For the last two decades several entre-
preneurs have entered the pharmaceutical
business with start-ups offering a gamut
of research services along with testing and
manufacturing capabilities. I was one of the
early entrants who believed in the contract
research as a business story. After my retire-
ment at the age of 60 as the Director of CSIR-
Indian Institute of Chemical Technology (IICT)
in 1995, I started my own venture named
Avra Laboratories Private Limited to oer
R&D services to multinational companies.
Avra grew quickly and built a reputation for
being able to work on complex problems
and oer low-cost solutions. Our success
led many other companies to take notice
of the opportunities and join in this space
of contract research and manufacturing.
was included in the act. The Government
can sanction compulsory licensing wher-
ever required for domestic use. The Indian
patent act of 2005 specically stated that
incremental changes will not be regarded
as exclusive right. Based on this analogy,
drug controller of India did not allow its
product patent for Novartis for Imatinib. They
appealed to supreme court, even then the
court ruled that it was an improved version
and not a new invention. India also issued
its rst compulsory licensing in March 2012
to NATCO Pharma to manufacture Bayer
anticancer drug “Nexaver”.
After the new patent law, Indian compa-
nies invested large sums of money for drug
discovery. Dr. K Anji Reddy founder of Dr.
Reddy’s was a pioneer and made huge
investments in the search for new drugs
in therapeutic areas such as antidiabetic,
cardiovascular and analgesics. These eorts
led to development of the two antidiabetic
drug candidates which were taken up by
multinational companies for further clinical
trials. Unfortunately, as is the case with sev-
eral drug candidates, they could not provide
the required results to make it to market.
So far there is only one indigenous drug
in the Indian market and this was devel-
oped by the Central Drug Research Institute
(CDRI), Lucknow. Thanks to the eorts of its
former Director, Dr. Nitya Anand, the com-
pound known as Centchroman (Generic
name – Ormeloxifene) was introduced in
India in 1991 and is a nonsteroidal oral
was the only drug available for treating HIV
and AIDS patients. Initially he was reluctant
to introduce this drug as he felt the market
was limited. I convinced him that HIV would
soon be a major problem in India. Further,
I pleaded with the Government of India to
waive the impor t duty on the starting material
Beta-Thymidine to help lower the cost of the
drug production. I also impressed on the
Drug Controller of India on the importance
of AZT production by Cipla to facilitate clin-
ical trials to the extent possible within the
country. By the combined efforts of the
Government and my research group, Cipla
commercialized the AZT production in 1993
and marketed the 100 mg capsule formula-
tion at 1/6th of the then prevailing international
price. Later Cipla developed several anti-HIV
medications and oered the world’s rst tri-
ple single drug cocktail named Triomune at
a price of less than one USD per patient per
day. Being HIV positive is no longer a death
sentence and can be treated as a chronic
disease with aordable medicines, thanks
to Cipla and several Indian companies that
are manufacturing these drugs at low cost.
Future of Indian Drug Industry:
In 1994, India joined the World Trade
Organization and accepted the TRIPS man-
date. The Indian Patent Act of 1972 was
amended on 26th December 2004 and came
into eect from January 2005. By this act all
product patents were allowed in all sectors,
license of right deleted, it also allowed micro-
organisms to be made patentable while the
pre and post grant opposition provision
Inaugural function of Cipla Patalganga factory in 1984 (from Right – Dr. A V Rama Rao,
Dr. Y K Hamied, Dr. G S Sidhu, DG-CSIR, Hamied’s Mother)
www.asiachem.news
March 20 23
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25
acid D coupling with tyrosine to yield laccaic
acid C, decarboxylation gave laccaic acid
E which on acetylation of the amino group
gave the major laccaic acid A with its distinct
red colour. The pure lac dye was found to
be totally non-toxic and could be used as
a food colouring agent. Unfortunately, the
purication cost is very expensive, and the
costs prohibited its use in pure form. In the
past the natural resin was used to make
gramophone records and telephone equip-
ment, today, its resin is used as a commodity
by the paint industry.
The Advent of Synthetic dyes:
Th e rst synth etic dye, Mauve was dis cov-
ered by W H Parkin while carrying his Ph.D.
program to synthesize quinine at the age of
18 years. The compound was bright red and
dyed fabric which was not washable. He led
a patent in August 1856 and established the
rst factory to manufacture synthetic dyes
in Greenford, near London. He became rich
at a very young age. After this, many major
chemical industries such as BASF and Bayer
in Germany started working on synthetic
dyes in a major way. Indigo which was a
most important natural dye from India was
rst synthesized by Adolf Von Baeyer who
reported its synthesis in 1878 and commer-
cialized its manufacturing in 1890. Baeyer
received the Nobel prize in chemistry in 1905
for his contribution to the synthesis of Indigo.
The synthetic indigo replaced the natural
product in 1914 and only 4.1% of the total
production of natural dyes came from plants.
The rst synthetic dye was made in 1856
and in subsequent years several dierent
classes of dyes entered the market and last
class of reactive dyes came from UK from ICI
in 1956. Dyes are classied by their method
of application to a substrate and placed in
categories such as direct dyes, reactive
dyes, vat dyes, disperse dyes, azoic dyes,
and other types.
Most of the dyes were manufactured
using big reactors by utilizing batch opera-
tions. With time several improvements were
made in the production of synthetic dyes in
the form of workup, drying using agitated
thin lm dryers, and falling lm evaporators.
Much of the research work was focused on
the dye application on cotton, polyester, and
polyamide fabrics. Eorts were also made
to achieve very high xations using reac-
tive dyes on cotton and leather, to reduce
dye discharges from entering into euent
streams.
Indian Dye Stu Industry:
The first dye stuff industry unit in India
was the Associated Research Laboratories
now called ARLab, established in 1941 near
Pune, the next big facility in the organized
Ferric sulphate, copper sulphate and other
polyvalent metal ions that form a coordina-
tion complex with dye and attach to the fab-
ric. Examples of such traditional natural dyes
include Tyrion, Crimson, Kermes, Indigo,
Saron, and Madder.
Till the end of the 18th century, Indigo
was much sought after from the blue colour
it imparts to the fabric. The oldest indigo
coloured fabric was discovered in Peru and
dates to around 6000 years ago. India was a
major center for its production and process-
ing where the plant was cultivated in Bengal.
Cutch is another Asian dye from the wood
of Acacia tree, commonly found in India for
dyeing cotton to give green, brown colours
using an iron-based mordent and an olive
brown colour when used with copper salts.
Turkey red used for dyeing cotton and was
isolated from madder root of the Rubia plant,
a process that was developed in India and
spread to Turkey. Indian Madder (Rubia cor-
difolia) is found in the Himalayan regions and
still used by craft dyers in Nepal. Besides the
spice trade, it was these dyes that brought
the Europeans and the East India Company
to trade and later colonize parts of India and
Asia.
Lac dye is the colouring matter of the
lac resin produced by the insect Kerria
lacca. The structure of Lac dye eluded the
scientists more than ve decades after its
isolation. The dye known as laccaic acid
was rst isolated in 1887 and regarded as
a single compound. However, efforts to
obtain pure laccaic acid eluded scientists
for a long time. Renowned Indian chem-
ists, Prof. K Venkataraman, and Prof. T R
Sheshadri dedicated a lot of time and eort
to identify to its structure and see whether a
synthetic alternative could be commercially
produced. Prof. K Venkataraman’s group
spent more than 10 years between 1955 to
1965 and could not elucidate its structure.
However, they demonstrated that the dye
was a mixture of at least two compounds,
one of them having an aliphatic nitrogen in
the form of an amine present as the major
component. In 1965, I was appointed as a
scientist in Venkataraman’s group, and he
assigned me the task to continue the search
for the structure of lac dye. As I worked on
this project, I found that the compound was
a mixture of two major compounds, one
containing a nitrogen as was anticipated
along with two more minor components
that were named laccaic acid D and laccaic
acid E. We were able to determine all the
structures based on NMR and mass spectral
data. We learnt that one component was
missing in the lac dye referred as laccaic acid
C derived from tyrosine. We also established
a biogenetic synthesis starting from laccaic
Within a span of a decade, India became a
preferred destination for global pharmaceu-
tical companies to source both products
and research services. Besides succeeding
as a contract research organization, Avra
became the first company to produce a
complex anticancer drug Irinotecan by total
synthesis. Originally, this drug was made
from a starting compound Camptothecin, a
natural plant alkaloid which has the complex
core and is converted to Irinotecan through
a semisynthetic approach. Today Avra is a
global leader oering advanced intermedi-
ates that allow for the facile production of
Camptothecin related derivatives.
Dyes & Pigments - Introduction:
Human beings always use colours to dec-
orate themselves, garments, tools, and their
surroundings for beautication. Traditionally
colours were derived from natural sources.
India was known for centuries for producing
natural colours derived from plants or insects
to dye fabrics. Even during the bronze-age
civilization of Mohenjo-Daro, there is evi-
dence of the use of natural colours being
applied to fabrics, pottery, and other items.
Archaeological data shows evidence of dye-
ing fabrics with colours derived from plants
and insects traced back to about 5000 years
in places from the Fertile Crescent, a region
in the Middle East considered the cradle of
civilization and China.
Natural dyes are derived from plants,
invertebrates, or minerals. While most col-
ouring agents are of plant origin others are
obtained from biological sources such as
insects and fungi. Many natural dyes require
the use of chemical compounds called mor-
dents to x the dye to the fabrics. Mordents
are normally inorganic salts such as alum,
Dr. Nitya Anand
26
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March 202 3
www.f acs.website
dyes and pigments manufacturers in India
include: Poddar Pigments, Priya Limited,
Sadhana Nitro, Sudharshan Chemicals,
Sree Hari Chemicals, Ultramarine, Vidhi
Dyes, Vipul Organics and others.
Agrochemicals- Introduction:
In the year 1960, as I started my career as
a research fellow at the National Chemical
Laborator y (NCL), Pune, working for my Ph.D.
degree. Growing up in India, we were familiar
with droughts, food shortages and famines
in the country. Around that time, Norman
Borlaug had become famous for his suc-
cess in growing high yielding wheat strains
in Mexico. Renowned Indian Geneticist, M S
Swaminathan wrote a letter to the Director
of the Indian Agricultural Research Institute
that they should invite Norman Borlaug to
learn more about his techniques and if they
could be applicable in India. In 1963 Dr.
Borlaug visited India and brought with him
four promising strains of wheat that were
planted in Northern India. These seeds
worked perfectly in the Indian climate and
were also resistant to rust. A report in the
New York Times notes, “In pre-Borlaug
1963, wheat grew there (in India) in sparse,
irregular strands, was harvested by hand,
and was susceptible to rust disease. The
maximum yield was 800 lb per acre. By
1968, thanks to Borlaug’s varieties, the
wheat grew densely packed, was resistant
to rust, and the maximum yield had risen
to 6,000 lb per acre.”. It was also during this
time, India adopted IR-8, a semi-dwarf rice
variety developed by the International Rice
Research Institute. Soon the yield of wheat
and paddy in the country went up to 5 to 6
times higher per hector. A green revolution
had begun in the country. This dramatic
increase in wheat and rice production was
attributed to new strain of seeds along with
the use of fertilizers to promote plant growth,
and pesticides for crop protection which was
coupled with better irrigation facilities. India
was on the path towards self-sucie ncy in its
food production and in the subsequent years
it became a major exporter. Norman Borlaug
was awarded Nobel Peace Prize in 1970.
Prof. M S Swaminathan was responsible for
this transformation and is regarded as the
father of Indian green revolution.
In recent years, India’s need for food grains
is growing steadily due to increase in pop-
ulation (1.3 billion people) and at the same
time there is constant decline of the culti-
vable land as much is lost to growing cities
with expanding infrastructure for living and
industry. For this reason, the Government
of India is being forced to enhance farming
methods by the use of fertilizers and crop
protecting agents.
two volumes were the main source of infor-
mation related to the dye stu technology
and were so popular that they were trans-
lated into 13 international languages.
Pigments:
Pigments are also colouring matter and
dierent from dyes. Pigments are not soluble
in solvents, that they can only be suspended
in a medium with the help of a binder, on the
contrary dyes are substances that go into
solution and can impart colour to the fabric.
There are two types of pigments where most
of them are inorganic pigments while the rest
are organic pigments. Inorganic pigments
consist of minerals and metal content that
imparts their colour and are primarily based
on oxide, hydroxide, silicate, sulphate and
carbonate types and classified into four
groups: white pigments, black pigments,
coloured pigments and specialty pigments.
They are manufactured by a simple pro-
cess involving operations such as wash-
ing, drying, powdering, sieving and nally
formulating.
Organic pigments are also natural prod-
ucts which change the colour of reected
light because of wavelength-selection
absorption. Carotenoids are pigments in
plants that produce as variety of red to yellow
colours as they absorb violet to green light.
The red colour of roses is due to pigments
that absorb all colours of normal visible
light except red which is reected giving the
rose its red colour. The leaves of plants are
green due to the pigment chlorophyl, while
the colour of our skin is due to the pigment
melamine.
Synthetic pigments are compounds that
are made in the laboratory and produced
on a commercial scale with a greater control
over their production. These pigments are
widely used in paints, polymers, synthetic
bers, ink and more recently in electronic
devices. A good pigment has the follow-
ing properties: they mix freely, they show
chemical resistance, they are normally bril-
liant and show resistance to light, wetness,
and abrasion. In addition, their particle size
range is between 0.2 to 0.4 and have an
excellent dispersion property and because
of scientic advances in eld of synthetic
pigments several shades of pigment are
available for a variety of uses. The red colour
of the Ferrari car is from a pigment based on
an organic compound called DPP (diketo-
pyrrolopyrrole) which was rst synthesized in
1974 by Donald G Farnum at Michigan State
University. Pigment Red 254 aka Ferrari Red
was developed and patented by Ciba-Geigy
in 1983.
In India dyes and pigments are made by
several manufacturers. Among the major
sector was set up by Atul Industries in 1947
in Bulsar where a variety of dyes were pro-
duced from 1957. Indian textile industry,
which was originally using natural dyes,
now totally switched over to synthetic dyes.
Two well-known industries in Mumbai in the
years between 1960 – 1980, were Amar Dye
Limited and the Indian Dyes Industries (IDI).
Along with Atic (Atul in collaboration with ICI),
was the largest dyestu industry meeting
most of the Indian demand.
The Indian dyes and pigment industries
have contributed signicantly to the over-
all growth of the Indian chemical industry.
Approximately Rs. 48,000 crores (USD 60
billion) was generated by this industry in
the year 2022. This is still a growing sector
creating jobs and contributing to exports
from India.
In India the top 50 manufacturers of dyes
and intermediates have nearly 65% of the
total dyestu market share, the rest of the
35% come from the unorganized sector of
small and medium industries of more than
several thousand units.
Among the synthetic dyes, the reactive
dyes are much in use with a production
capacity of around 100,000 tons. For direct
dyes the production quantities are nearly
20,000 tons, while disperse dyes, basic, sul-
phur, and others have a capacity of approx-
imately 10,000 tons per annum. These dye
stus nd several applications in industries
where 80% of the dyes are consumed by
the textile industry. The growth of the textile
and leather industries is a consequence or
supplement for the growth of dye industry. In
India, nearly 90% of dye stu manufacturing
conned to Gujarat and Maharashtra states.
In the year 2017 India exported dyes worth
approximately 2.4 billion USD. Among them
US constitute 8%, Turkey 7.1%, Bangladesh
6%, China 5.7%, Germany 4.6%, Italy 4.3%,
Brazil, 3.9% and rest for other countries.
Although organic chemistry as a subject
was popular and research labs were started
in most Indian institutions and universities,
not much attention was given to the chem-
istry of dyes. There was only one institute
in the country, the Institute of Chemical
Technology (ICT) in Mumbai which carried
out research devoted to textiles chemistry as
well as dyes right from its inception in 1934
and now has the Department of Fibres and
Textile Processing Technology.
The rst Indian Director of the University
Department of Chemical Technology (pres-
ently ICT) was Prof. K Venkataraman, he was
an expert on synthetic dye s and also the rst
academic to write two volumes on synthetic
dyes and their intermediates in 1952. These
www.asiachem.news
March 20 23
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27
Exports:
The global agrochemical market was
around USD 225 billion in 2021 and is pro-
jected to reach USD 300 billion by 2030.
The Indian agrochemical industries valued at
around USD 5.72 billion USD in 2020-2021,
with domestic consumption around USD
2.72 billion and exports at USD 3 billion. The
forecast was exports is growing and many
Indian companies like United Phosphorous,
Gharda Chemicals, Excel industries and PI
are now increasing their global footprint.
A vast majority of the pesticides that are
being used are formulations of generics
– products whose patent life has expired.
Generic pesticides account for 60% of the
global crop protection market. In the next
ten years (2021-2030) around 22 patented
pesticide compounds will become generic.
These are Bixafen, Chlorantraniliprole,
Cyantraniliprole, Fenpyrazamine,
Flubendiamide, Fluopicolide, Fluopyram,
Fluxapyroxad, Isopyrazam, Mandipropamid,
Penflufen, Penthiopyrad, Pinoxaden,
Pyriofenone, Pyroxsulam, Sedaxane,
Thiencarbazone-methyl, Valifenalate,
Benzovindiflupyr, Sulfoxaflor, Saflufenacil,
and Aminopyralid. This would create a 3
to 5 billion USD opportunity for generic
manufactures.
Bhopal Gas Tragedy was considered as
the world’s worst industrial disaster due to
a pesticide industry in India purely by not
implementing safety measures and the neg-
ligence of the work force.
market in the country is growing steadily
along with improper use which impacts the
revenue and reputation of the organized
se ctor.
Indian Institutions and Industry
Interaction:
After the abolition of the Indian product
patent laws in 1972, The government of India
directed CSIR laboratories to work on pro-
cesses for both drugs and agrochemicals.
The National Chemical Laboratory (NCL),
Pune and the Indian Institute of Chemical
Technology (IICT), Hyderabad, initiated tech-
nology development programs, performed
pilot scale studies and nally helped design
chemical plants for pesticide production.
NCL worked out on Endosulfan and com-
mercialized the product by transferring tech-
nology to industries. IICT initiated a major
program on organophosphate pesticides
such as Monocrotophos, Chlorpyriphos,
Cyhalothrin (pyrethroid) insecticides, and
Butachlor herbicides. Chlorpyriphos was
much in demand and IICT prepared plant
designs to enable the production of 300-400
tons per annum and the technology was
transferred to over a dozen Indian com-
panies. In addition, we worked on. IICT
also carried out work on developing Neem
based biopesticides having Azadiractine
(13%) for commercial production. IICT was
also involved in developing technology for
promoting the use of biopesticide - Bacillus
thuringiensis, a soil dwelling bacterium and
its spores and insecticidal proteins are used
in pest control.
The history of Indian fertilizer
industry:
Back in 1906, the rst fertilizer factory in
India was opened at Ranipet (Tamil Nadu).
In terms of the scale of investment, the fer-
tilizer industry is regarded next to steel. The
present global fertilizer market size is around
USD 190 billion and there was a 12% growth
from the previous year. also is expected to
reach double the requirement. Fertilizers are
essential for food security. With the available
limited land, farmers must use fertilizers to
enhance the nutrients in the soil that were
taken up by previous crops.
The top 3 Indian fertilizer companies
have a market size of around 57% with
Chambal Fertilizers and Chemicals Limited
Coromandel International Limited leading
and having an installed capacity of 1.5 mil-
lion tons per annum (MTPA). The state of
Gujarat is the top producer of fertilizers,
while Pondicherry tops the consumption
(in kilos per hector) followed by Telangana
and Punjab.
Pesticide industry in India:
Pesticides are compounds used as crop
protecting agents and include insecticides,
herbicides, rodenticides, and fungicides.
292 pesticides are registered in India and
of these 40% are organochlorines. Rice has
the highest rate of pesticide usage (29%)
followed by cotton (27%), vegetables (9%)
and pulses (9%). In India, there are about 125
technical grade manufacturers including 10
multinational companies and 800 formula-
tors with several distributors. The formula-
tions are made from technical grade active
ingredients by adding inert carriers, adju-
vants, emulsions, solvents, and surface-ac-
tive agents. The Indian agrochemical market
is challenging and suers from high inventory
and long credit periods to farmers, thereby, it
requires huge working capital. However, its
strength comes from low cost manufactur-
ing and qualied personal making India is the
4th largest exporter of pesticides in the world
after China, USA, and France.
The main pesticide manufacturers in India
include United Phosphorus Limited (UPL),
BASF, PI Industries, Bayer Crop Sciences,
Syngenta India, and Rallis India where the
top ten companies control almost 80% of the
market share. These large players have an
extended product portfolio and are regularly
introducing new molecules. New global stra-
tegic alliances and acquisitions are allowing
for greater global reach increasing their
market share.
In recent years, the Indian government has
been advocating integrated pest manage-
ment and there is also a demand for organic
farming. In addition, the spurious pesticide
References
1. Hamied, Y.K., Indian Pharma Industr y: Decades of struggle and achievements. 2nd April 2005 Lecture
at IICT, Hyderabad
2. Rama Rao, A.V., Vishwakarma Medal Lecture – 1991, Proc. Indian Natn. Sci. Acad. 58, 1992: 287-311
3. Generic Drugs – Saving lives with Generosity, Kavita Tiwari – Indian Science Transforming India, A look
back on its 70-year Journey
Indian National Science Academy – 2018
4. Indian Drugs and Pharmaceuticals Limited
https://www.idplindia.in
5. Annual repor t 2020-21 – Departme nt of Pharmaceuticals, Government of India
https://www.pharmaceuticals.govt.in
6. Global Dyes Market outlook 2018-2022, Robust Growth
https://www.prnewswire.com, 14th February 2019
7. Dyes and Pigment market size, Global Intelligence Report
https://www.globenewswire.com, 08th October 2021
8. Rama Rao A.V., Venkataraman K., Insect pigments derived from hydroxyanthraquinones
Recent D evelopment in the chemistr y of Natural Products. Prentice – Hall of India Pvt. Ltd., New Delhi,
1972
9. Agrochemicals and their importance in Agriculture
https://www.researchdive.com
10. Indian Organic Chemical Industry: Decades of Struggle and Achievements
A V Rama Rao, Indian Journal of History of Science, 49, 399 (2014)