1

Chapter 1

Overview of

pharmaceutical

industry

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1. OVERVIEW OF PHARMACEUTICAL INDUSTRY:1.1 An Introduction

The Indian pharma industry currently tops the graph amongst India's science-

based industries with wide ranging capabilities in the field of drug technology and

manufacture. A well-organized sector, the Indian p’cal industry is estimated to be

worth $ 4.5 billion and growing at about 8 to 9 % annually. Indian pharma industry

ranks 3rd amongst all the world countries, when it comes to quality, technology and

the vast range of medicines that are manufacturing in India. Medicine ranges from

simple headache tablet to sophisticated antibiotics and complex cardiac NDDS

compounds; almost each type of medicine is now manufactures in the Indian

pharmaceutical industries. The Indian pharma sector is highly fragmented with more

than 20,000 registered pharma companies in 2010. It has expanded drastically in the

last 20 years. The Chemical and Pharmaceutical industry in India is an extremely

fragmented market with serious price competition and government price control

(DPCO). The Pharmaceutical industry in India meets around 70% of the India's

demand for drug intermediates, bulk drugs, pharmaceutical formulations, tablets,

chemicals, capsules, injectables and orals. There are approximately 250 large units

and about 8000 Small Scale units including 5 Central Public Sector Units, which form

the core of the pharmaceutical industry in India. The Government plays a vital role in

the development of the Indian Software Industry. The Indian government announced a

new software policy in 1986 which was assigned to serve as a catalyst for the

software industry in India. This was followed in 1988 with the establishment of the

Software Technology Parks of India (STP) scheme and The World Market Policy. In

addition to that, to attract foreign direct investment (FDI), the Indian Government

allowed foreign equity of up to 100 % and duty free import (DFI) on all inputs and

medicinal products.

1.2 Current Scenario

Indian pharma industry is expected to grow at 19% in 2013. Today, India is

among the top 5 pharmaceutical emerging markets. There will be new drug filings,

new drug launches and Phase II clinic trials throughout the year 2013. Apart from

increasing sales of generic medicines, continued growth in chronic therapies and a

greater penetration in rural markets. The domestic pharmaceutical market is expected

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to show a strong double-digit growth of 13-14 % in 2013 end. In addition, the

increasing population of the higher-income group will establish a potential US $ 8

billion market for multinational companies (MNCs) selling costly drugs by 2015.

Apart from this, the domestic pharmaceutical market is estimated to touch US $ 20

billion by 2015 end. It will make India a lucrative host for clinical trials for MNCS.

Further estimates that the healthcare market in India will reach to US $ 31.59 billion

by end of 2020.

1.2.1 Diagnostics Outsourcing / Clinical Trial

According to the estimates, the Indian diagnostics and labs test services is

expected to reach Rs.159.89 billion by the end of 2013. The domestic market for both

therapeutic and diagnostic antibodies is expected to rise exponentially in the future.

More than 60% of the total antibodies market is presently dominated by diagnostic

antibodies. Few of the major Indian pharmaceutical firms including Cadila

Healthcare, Piramal Life Sciences and Sun Pharma, had applied for carrying out

clinical trials on at least 12 new drugs in 2010 which indicates a growing interest in

new drug discovery research.

1.2.2 Generics

Generics will always continue to dominate the market while patent-protected

products are supposed to constitute 10 % of the pie till the end of 2015, according to

the McKinsey’s report, “India Pharma 2015 - Unlocking the potential of Indian

Pharmaceuticals market”.

Dr Reddy's Lab has launched a new Finasteride tablets which is a bio-

equivalent generic version of Propecia (Finasteride) tablets, in the US market. These

tablets are prescribed to treat male pattern hair loss.

1.3 Growth of Import-Export

Imports: - As per the data collected by Directorate General of Commercial

Intelligence and Statistics (D.G.C.I.S.) Kolkata, the value of imports of “Medicinal

and pharmaceuticals Products” for the latest period 2007-‘08 to 2010-‘11 is as under:

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Year Value of import of “Medicinal and

Pharmaceutical products” (Rs. In bn.)

Growth (%)

2007-08 67.34 14.79

2008-09 86.49 28.43

2009-10 99.59 15.15

2010-11 109.37 9.82

Table No. 1.1

The country is almost self-sufficient in production of most of formulations/

pharmaceuticals products. Manufacturers of Drugs & Pharmaceuticals are free to

produce any drugs approved by the Drug control authorities.

Exports: - As Per D.G.C.I.S. Kolkata Exports of “Drugs and Pharmaceuticals

and Fine Chemicals” for the period 2007-08 to 2010-11 are below:-

Year Value of Export of “Medicinal and

Pharmaceutical products” (Rs. In bn.)

Growth

(%)

2007-08 293.54 14.37

2008-09 398.21 35.66

2009-10 424.56 6.62

2010-11 475.51 12.00

Table No. 1.2

1.4 Major Pharmaceutical Companies in India

Some of the Indian pharmaceutical player by their sales volume in INR Billion:

Company Name Sales in INR Billion

Cipla 69.77

Ranbaxy lab 76.86

Dr Reddy’s lab 66.86

Sun pharma 40.15

Lupin Ltd. 53.64

Aurobindo Pharma 42.84

Jubilant Life 26.41

Cadila Health 31.52

Ipca Lab 23.52

Wockhardt 26.50Table No 1.3

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1.5 Government Initiatives and Investments

1.5.1 Government Initiatives

The Union Finance Minister spotted few points in union budget of 2012-13:

It is proposed to extend the concessional basic customs duty of 5% with fully

exempted excise duty/CVD to six specified vaccines / life-saving drugs. These

are used for the treatment or prevention of diseases such as renal cancer, HIV-

AIDS etc.

Probiotics are a cost-effective means of battling bacterial infections. It is

expected to lower down the basic custom duties on these items from 10 % to 5

%.

Basic customs duty and excise duty lower down on Soya products to target

protein deficiency among women and children in domestic market. Basic

customs duty and excise duty lowered on Iodine too.

In the Indian pharma sector, marking a new trend of investments by foreign

players, the need for foreign investors to receive a no-objection from their JV (joint

venture) partner before spending out on their own or leashing in another local firm has

been wiped out by the Pharmaceuticals Export Promotion Council (Pharmexcil).

The Dept. of Pharmaceuticals has made a 'Pharma Vision 2020' document for

emerging India as one of the leading destinations for end-to-end drug discovery,

research and innovation and for that purpose, the Dept. provides required support by

way of internationally competitive scientific manpower for pharma research and

development (R&D), venture fund for research in the public, world class

infrastructure and private domain and such other measures.

1.5.2 Investments

Israel-based Teva Pharmaceuticals in JV with Procter & Gamble (P&G) plans

to set up world's largest over-the-counter (OTC) medicine production facility

at Sanand near Ahmedabad, Gujarat.

‘GlaxoSmithKline (GSK)’ and the Hyderabad based ‘Biological E Ltd’ have

collaborated for early stage research and development (R&D) of a 6 in 1

combination pediatric vaccine against the polio and other infectious diseases.

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Claris Life-sciences has entered into joint venture (JV) with 2 Japan based

drug makers Mitsui & Co Ltd and Otsuka Pharmaceutical for its injectable

business in Indian and other emerging markets.

Nipro Corporation has settled up India's 1st dialyser production facility at

Shirwal near Pune. This investment cost them Rs.700 cr. (US $130.60 mn).

Aurobindo Pharma Ltd has got approval from the US Food and Drug

Administration (USFDA) to produce and promote various medicines namely

Rizatriptan Benzoate tablets and Oxacillin injections in the US, apart from

Nafcillin and Ondansetron injection.

Eli Lilly and Strides Arcolab have covered a pact to increase delivery of

cancer medicines in the emerging markets. Agila Specialties which is the

specialties division of Strides Arcolab will make cancer medicines and Eli

Lilly will promote them in emerging markets.

1.6 Challenges

Over the past 10 years, pharmaceutical companies have entered into a difficult

period where the market, regulators and Shareholders have created remarkable

pressures for reform within the industry. The main issues for most of pharma

companies are patent expiration of number of block buster drugs, reduced

productivity of in-house R & D, increasing legal and regulatory concern and pricing

issue. As consequences larger pharmaceutical companies are reforming to new

business model with more outsourcing of clinical research, manufacturing and

discovery services.

Presently global financial conditions and a threat of a globe wide recession

accelerated the schedule for applying transformational changes in MNCs, as the

industry on fronts reduce corporate stock prices and an increasingly cost-sensitive

customer. Executives of the largest global pharmaceutical companies realised the

need for transformational change in their organizations, but will need wisely to move

swiftly to ensure sustained growth in company.

Transformations in the business model of global pharmaceutical industry spell

more Opportunities for Indian pharmaceutical companies. Pharma production costs

are almost 50 % lower in India than in western countries, while clinical trial expenses

around one-tenth and overall R&D costs are about one-eighth of western levels.

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The Indian stock market may fear a possible recession but Indian pharma

companies seem unfazed by slowdown dreads. Achieving on better sales in the

domestic and export markets, Indian pharma industry is expected to go on with its

good performance. Currently, Indian pharma Industry can look forward to the years to

come, with many expectations. The opportunities in expanding the area of generic

products as more molecule come off patent, outsourcing and above all, in

concentrating into drug discovery because more profits come from traditional plays.

The same time, the Indian Pharmaceutical Industry would have to assert with several

challenges particularly the

Effects of new product’s patent

Drug price control over (DPCO)

Regulatory reforms affair

Infrastructure development

Quality management and

Conformance to the global standards.

1.7 Future Growth

According to consulting firm Grant Thornton, India is expected the largest

number of merger and acquisitions (M&As) in the pharmaceutical and healthcare

sector. A survey conducted across the 100 companies has revealed that one- fourth of

the respondents were optimistic about acquisitions in the pharma sector.

According to a Barclays Capital Equity Research report on India Healthcare &

Pharmaceuticals, The Indian pharma market is expected to grow at a CAGR

(Compounded Annual Growth Rate) of 15.3 % during 2011- 12 to 2013-14. The

growth of Indian pharma companies will also be dragged by the fastest growing

molecules in the skincare, eye care and diabetes segment.

Moreover, the pharma companies such as Ranbaxy, Cipla, Lupin and Dr

Reddy's Labs might soon be part of the government's most expected 'Jan Aushadhi'

project. To commercialize the project, the Government is likely to rope in the private

sector units to bulk-procure generic drugs from them. Today, there are 117 “Jan

Aushadhi” stores across the country and the ambition is to expand to at least 600 in

the next 2 years and 3,000 by the end of 2016.

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Chapter 2

INTRODUCTION to

Organisation

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2. INTRODUCTION TO ORGANISATION:

Cadila Pharmaceuticals Ltd. is one of the largest privately held pharmaceutical

companies in India. Its headquarter is at Ahmedabad, Gujarat. In the last five decades,

it has been developing and producing pharmaceutical products. It is selling and

distributing pharmaceutical Products in over 50 countries around the world. It

provides integrated healthcare solutions with pharmaceutical products; it caters to

over 45 therapeutic areas that include respiratory agents, cardiovascular, haematinics,

anti-infective and antibiotics, gastrointestinal, analgesics, anti-diabetics and

immunologicals. The company focuses on providing appropriately priced, high

quality products to its customers and supports all these with dedicated customer

service. Cadila Pharmaceuticals has a multinational, multilingual and multicultural

workforce of over four thousand employees including more than two hundred people

outside India in forty-nine countries of Africa, CIS, USA and Japan.

The company has one of the best Research and Development (R&D) setups in

India, having crewed by more than three hundred and fifty scientists and engineers

from various disciplines including pharmacology, biology, chemistry, clinical

research, toxicology, phytochemistry. The company also participates in Public-Private

partnerships (PPP) for developing curative, preventive and diagnostic pharmaceutical

and diagnostic products.

Cadila Pharmaceuticals Ltd. is the first Indian company to get IND approval by

USFDA for the clinical trials to be conducted in India. After that, the company has

filed 4 more INDs with USFDA. Of the five filed INDs filed, one is for pulmonary

tuberculosis; and the trial is supported by Department of Biotechnology, Govt. of

India. The remaining four INDs are for various types of cancers, e.g., Prostate cancer,

Lung Cancer, Bladder Cancer and Melanoma. Thus all the filed INDs are for

providing solutions to major global health care problems. The clinical trials on Lung

cancer, Prostate cancer and Bladder cancer are supported by Department of Science

and Technology to encourage innovations.

The company has “state-of-the-art” manufacturing facilities conforming to the

most stringent international cGMP norms vis-a-vis WHO, WHO-GMP, Geneva (GDF

site for Anti- TB), USFDA, TGA Australia (PIC/S), MCC-South Africa, UK- MHRA,

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ISO 9001 and ISO 14001. Spreaded over hundred acres of land, Cadila

Pharmaceuticals Ltd.’s manufacturing facility at Dholka is very well equipped with

world-class production facilities. The CPL’s two Active Pharmaceutical Ingredients’

(API) units at Ankleshwar manufacture a wide-range of APIs and intermediates

including 3 USFDA approved products. The production facility at Samba, near

Jammu started its operational activities in August 2006. The first overseas formulation

producing facility of Cadila Pharmaceuticals Ltd. has started its operations in

Ethiopia.

As a responsible corporate citizen, they are conscious of their duty towards

various sections of the society; Cadila Pharmaceuticals Ltd. nurtures young talents;

runs an ultra-modern charitable hospital in a remote area with facilities like

Telemedicine in association with Apollo Ahmedabad; works closely with NGOs by

assisting and supporting for mid-day meal programmes to village schools, among

other initiatives.

A Prelude

Cadila Pharmaceuticals Ltd. Ahmedabad, India exemplifies a spirited Indian

Enterprise. Cadila Pharmaceuticals Ltd.’s phenomenal growth is a corporate

milestone, an era in time nurtured by fifty-two years of caring, rich heritage. With a

chase of creditable milestones, Cadila Pharmaceuticals Ltd. today has emerged to

become the undisputed leader in Indian Pharmaceutical sector, with largest

therapeutic groups, its operations spanning over 50 countries. Cadila Pharmaceuticals

Ltd. is multi-locational, with its various global corporate offices and manufacturing

houses.

2.1.Milestones1951-

Shri Indravadan A Modi thinks to start a Pharmaceutical unit.

1952-

Cadila starts its production, On March 13th.

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1967-

Cadila shifts to its factory premises with operations full-fledged spanning

Marketing, Production and R&D.

1970-

Shri Indravadan A Modi represents the Indian Pharma industry and plays a

important role in shaping the Patents Act, 1970.

1982-

Karnavati Engineering Limited (KEL), Kadi (the machinery-manufacturing

arm of Cadila) commences operations.

1986-

Shri I A Modi plays a pivotal role in shaping the 1986 Drug Policy.

1992-

Tissue Culture Laboratory starts its operation at Hirapur, near Ahmedabad.

1995-

Cadila restructured and becomes Cadila Pharmaceuticals Ltd.

1997-

GUSSACON (Gujarat State Surgeons Conference) felicitates Shri I A Modi at

its 23rd Annual Conference for his outstanding contribution to the industry.

1999-

Cadila Pharmaceuticals Ltd. (CPL) ventures in the US market by establishing

CPL Inc.

2000-

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1. Cadila Pharmaceuticals Ltd. moves to an ultra-modern Corporate Campus at

Bhat, near Ahmedabad.

2. Cadila Pharmaceuticals Ltd. ties-up with various institutions for research;

Department of Biotechnology, UDSC, in New Delhi; Lala Ram Sarup Institute

of TB & Respiratory diseases, in New Delhi; IISc, in Bangalore; RRL, in

Jammu; CSIR, in New Delhi; CDRI, in Lucknow; Advanced Transfusion

Medicine Research Foundation, in Ahmedabad; National Institute of

Immunology, in New Delhi and Talwar Research Foundation, in New Delhi.

3. Cadila Pharmaceuticals Ltd. introduces World’s First IMMUVAC, an unique

Immunomodulator.

2001-

Cadila Pharmaceuticals Ltd. launches NEVA HIV, Which is world's First

whole blood Rapid HIV detection kit.

2002-

1. Cadila Pharmaceuticals Ltd. ventures in Japan and sets up Kadera Yakuhin

Ltd.

2. Cadila Pharmaceuticals Ltd. becomes India's First indigenous manufacturer of

natural Streptokinase – STPase.

2003-

Shri I A Modi honoured with the Express Pharma Pulse Lifetime Contribution

Award.

2004-

1. Cadila Pharmaceuticals Ltd. launches world's first Parenteral Formulation of

Rabeprazole (Rabeloc I.V.).

2. Cadila Pharmaceuticals Ltd. submits first IND (Investigational New Drug)

with the USFDA for pulmonary tuberculosis.

2005-

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1. KEL’s new production line becomes operational and dispatches first

machinery to USA.

2. Shri I A Modi getss a Lifetime Achievement Award by Gujarat Chamber of

Commerce and Industry for his valuable contribution to the Industry and

society.

3. Cadila Pharmaceuticals Ltd. publishes and presents a series of scientific

papers on IMMUVAC, Itza and Rabeloc I.V. at UEGW (United European

Gastroenterology Week, Prague), APDW (Asia Pacific Digestive Week,

Beijing), AGW (Australian Gastroenterology Week), DDW (Digestive

Diseases Week, Chicago, USA), ASCO (American Society of Clinical

Oncology), WCOG (World Congress of Gastro).

2006-

1. Cadila Pharmaceuticals Ltd. acquires Pfizer's API facility at Ankleshwar.

2. The formulation facility at Samba near Jammu, starts its operation.

3. Cadila Pharmaceuticals Ltd. enters into a Joint Venture with Apollo Hospitals

Group to manage Apollo Hospitals in Ahmedabad.

4. Cadila Pharmaceuticals Ltd. submits four more INDs (Investigational New

Drug) with the USFDA for Prostate cancer, Lung Cancer, melanoma and

Bladder Cancer.

2007-

1. “Divya Bhaskar” honours Shri I A Modi with Lifetime Achievement Award

2. As a part of efforts to prevent lifestyle diseases, Cadila Pharmaceuticals Ltd.

commences large clinical trials aimed at prevention of Cardiovascular disease

and stroke by using an innovative polypill.

3. Cadila Pharmaceuticals Ltd. inaugurates its first overseas manufacturing

facility in Ethiopia, Cadila Pharmaceuticals (Ethiopia) PLC.

2008-

1. Shri I A Modi figures in the “Gujarat Glories annual power list of 50

businessmen”.

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2. Shri I A Modi features in “Power 100: Eminent Personalities of Gujarat”.

3. Indian Pharmaceutical Association (IPA) confers Ramanbhai Patel Foundation

Lifetime Achievement Award to Shri I A Modi.

4. Cadila Pharmaceuticals with StemCyte Inc. USA and Apollo Hospitals Group

forms a Joint Venture, StemCyte India, for Umbilical Cord Blood Stem Cells

Banking and Research.

5. Dholka manufacturing plant facilities receive renewal of regulatory

accreditation from MCC in South Africa.

6. Cadila Pharmaceuticals Ltd. receives financial assistance from New

Millennium Indian Technology Leadership Initiative (NMITLI) to develop a

novel treatment for Sepsis management.

2009-

1. Cadila Pharmaceuticals Ltd. features as one of the “Most Trusted Companies

of 2008” by Sara Media and Zee Business.

2. Cadila Pharmaceuticals unveils Ltd. world’s first Polycap, which reduces the

risk of heart diseases by 68% and stroke by 48%.

3. Cadila Pharmaceuticals Ltd. acquires a significant stake in Novavax Inc. based

in USA which is basically a clinical-stage biopharmaceutical company.

4. Announces CPL Biologicals, a joint venture with Novavax Inc. USA, to

develop and produce the vaccines based on virus-like-particle (VLP)

technology.

5. TIPS, The Indian Polycap Study becomes the first Indian publication to

feature in The Lancet (Medical Journal).

6. Cadila Pharmaceuticals unveils POLYCAP, the combination drug for the

prevention of Cardiovasculardiseases.

7. Unveils the revolutionary Risorine, the world’s first anti TB- drug with

bioenhancer which is an outcome of Public Private Partnership (PPP) between

RRL Jammu and Cadila Pharmaceuticals Ltd.

8. Dholka manufacturing facility gets regulatory accreditation from INVIMA in

Columbia.

9. To strengthen the business ties between the two countries, Dr Rajiv Modi

addressed industrial delegation from Gujarat to Japan as part of VGGIS.

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10. Dr Rajiv Modi becomes youngest Fellow of National Associates of Engineers.

2010-

1. “State-of-the-art” Vaccine manufacturing facility of CPL Biologicals comes

up at Dholka near Ahmedabad in Gujarat.

2. Cadila Pharmaceuticals Ltd. receives prestigious Wellcome Trust Award

under the new R & D for Affordable Healthcare in India initiative to support a

phase III clinical trial of Polycap.

3. Cadila Pharmaceuticals receives financial assistance from New Millennium

Indian Technology Leadership Initiative (NMITLI) to develop novel treatment

for diabetes drug.

2011-

1. Ethiopia production facility receives WHO-cGMP certification, which is the

only facility in the region.

2. Dholka production facility receives Pre-Qualification approval from WHO in

Geneva.

3. Dr Rajiv Modi shared a view on the topic “Challenges Relevant to Vaccine

Virus Selection - Emerging Market Perspective” at 2nd WHO Informal

Consultation for enhancing Influenza Vaccine Virus Selection in Geneva.

2012-

1. Cadila Pharmaceuticals Ltd. announces a strategic alliance with Swedish

Bactiguard, who are world-leaders in medically proven solutions for

preventing hospital-acquired infections.

2. CPL Biologicals and the International Centre for Genetic Engineering and

Biotechnology enters into a new JV to develop novel multi-stage Malaria

Vaccine in India which is based on proprietary VPL vaccine technology of

Novavax.

3. Cadila Pharmaceuticals Ltd. completes TIPS II for Cardiovascular Diseases.

4. Dr Rajiv Modi elected as Vice Chairman by CII Gujarat State Council.

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5. Cadila Pharmaceuticals Ltd. starts multinational TIPS III for treatment of

Cardiovascular diseases maping twelve countries.

6. Cadila Pharmaceuticals Ltd. submits tenth ANDA with USFDA, where first

being submitted in 2009.

7. Dholka production facility receives regulatory approval from UK, MHRA and

TGA, Australia.

2013

1. Dr Rajiv Modiis elected as Chairman by CII Gujarat State Council.

2. Cadila Pharmaceuticals Ltd. enters into a strategic JV with Pergamum AB in

Sweden, to generate a novel treatment of infections with a unique targeting

mechanism which is clearly distinguished from classical antibiotics.

3. Dholka formulation manufacturing facility gets USFDA certification.

4. Dholka manufacturing facility gets regulatory approval from EU GMP-Latvia.

5. Cadila Pharmaceuticals Ltd. files 38th USDMFs where first being filed in

2007.

6. Cadila Pharmaceuticals Ltd. files 22nd API EDMF (EUDMF) for European

markets.

2.2. Diversifications

• Hospital Disposables which includes Fiberglass Casting Tape

• Diagnostics

• Laboratory Chemicals

• Machineries for P’cal Manufacturing

• Animal Health Formulations & Supplements for Feed

• Agro Business includes Plant Tissue Culture (PTC) and Bio-fertilizers

• Strategic Business Alliances (SBA) with world-leaders

Cadila Pharmaceuticals Ltd. is all set to create new records and scale a greater

heights. By the time, It has created new world-class production and R&D facilities,

focusing on new process innovations leading to patents, research and meeting global

standards. The CPL always places the common man at its core, who should be able to

get and afford their medicines anywhere in the world.

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2.3.Champion Brands:

ENVAS

Cadila Pharmaceuticals Ltd. makes India's No.1 ACE inhibitor “Envas”,

Which has been listed among the country's top 50 Pharmaceuticals Brands, across all

categories.

Aciloc and Haem-Up are other CPL brands in top 300 brands of Indian

Pharmaceutical Industry.

ACILOC

Aciloc, A Ranitidine preparation is one of India's best-selling brands in this

category.

LMX, SYMBIOTIK, CLAX

Antibiotics with live Lactobacilli combination are the first brands of its kind in

India, for which Cadila Pharmaceuticals Ltd. has applied for a worldwide patent.

This revolutionary innovation has already been approved in Indian, UK and US,

Eurasian & Sri Lankan patents.

RABELOC, ZASO, ACILOC RD, MONTELAST, MIXULIN AND NODON

They are some of the best-selling brands of this category.

Cadila Pharmaceuticals Ltd. is the first company in India to introduce

RABEPRAZOLE and FOSINOPRIL formulations.

2.3.1. Patents

The Formulation Development department in CPL initiates innovative processes

for a number of products. The Cadila Pharmaceuticals Ltd. has filed a host of

patent applications and several more are in a queue. Meanwhile a few patents

have already come CPL’s way:

• Lactobacillus + Antibiotic combinations (Patents granted in USA, Eurasia,

UK, Kenya, ARIPO, India, Sri Lanka).

• Topical beta blockers with improved efficacy in ophthalmology (Patent

granted in India).

2.4. Marketing Divisions

Following is an brief introduction to different divisions under Branded Strategic

Business Unit (SBU):

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Magna

Magna is a multi-specialty division. It includes consulting physicians, general

practitioners, cardiologists, surgeons, gastroenterologists, paediatricians,

gynaecologists and nephrologists. Magna's portfolio mainly covers cardiology,

gastroenterology, gynaecology and others. Magna's major brands are 'Rabeloc',

'Aciloc', 'Cadilose', 'Losium', 'Envas', 'Caditor', 'Calcirol', 'LMX', 'Haemup', 'LMX

forte', ‘Levocide’, and 'Fludac'.

Maxima

Maxima is also a multispecialty division. Its portfolio includes respiratory

inclusive of ENT, dentistry, chest (anti tuberculosis), anti-infectives and orthopaedic

therapies. Maxima targets ENT specialists, dentists, paediatricians, chest physicians,

orthopaedicians and surgeons. Major brands of this division are 'Lorfast', 'Vasograin',

'Mycobutol', 'Symbiotik', 'P-Zide', 'Emvit Plus', 'Amdepin', 'Cuga', and 'Immuvac'.

'Immuvac' is a revolutionary immuno-modulator that has various applications

including reduced duration of therapy for treatment of multi drug resistant

tuberculosis and multibacillary leprosy. This division also has certain superspecialty

brands like 'Halonix' for orthopaedics.

A special task crew for ophthalmology 'OTF' works as a sub-unit of this

division focusing on opthalmologists with brands like 'Scat', 'Loptame', 'Gatt', and

'Visial' among others.

Volta

Volta is a super-specialty division. Its portfolio includes diabetology,

cardiology, endocrinology, nephrology, gastroenterology and critical care. This

division adopts 3 therapeutic approaches which are diabetic therapy, cardiac therapy

and critical therapy. Major brands of this division are 'STPase', 'Nodon', 'Teli',

'Glyloc', 'Envas IV', 'Glista', 'Humstard', 'Caditor'.

Oncocare

Oncocare division markets products that manages and treats the cancers and

tumours. Oncocare is penetrating in haematology segment to evolve as a complete

division providing medicines for treatment of the solid tumour and the

haematological malignancies. Oncocare's major brands are 'Caditrex', 'Cadigran',

'Karplat', 'Posid', 'Paclicad', 'Kinaplat', 'Docecad', 'Cadria L', 'Filcad', 'Recovarin' and

'Platin'.

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Magna XL

Magna XL division’s objective is to widen the reach and penetration in the rural

market. Magna XL works for the aim to make available quality medicines at

affordable price for the people living in interior towns and villages. Magna XL's

portfolio includes consulting physicians, general practitioners, gynaecologists and

pediatricians. Magna XL's champion brands are 'Haem up', 'Nuflam', 'Tummy Ease',

'Lactoceff', 'Happytizer', 'Anstisept', 'LMX', 'Hepasave', 'Fleximuv' and 'Wormin A'.

Generic

Generic is the wing of pharma business. The wing covers almost all the

therapeutic segments. Generic directly deals with the stockists primarily, and

dispensing doctors’ and retailers secondarily through super distributors. A major part

of business and promotion concerntrates mainly on the stockists. Generic has 3 sub

divisions namely, 'Genvista', 'Genstar' and 'Generic'. Generic's major brands are

'DPhesic', 'Ciprodac', 'Dexasone', 'Demisone', 'Famonext', 'Campicillin', 'Mokcan',

'Oritaxim Inj.' and 'Cotrimoxazole DS'.

Vetnova

Vetnova is animal healthcare division. At present, Vetnova is to be one of the

fastest growing enterpises harnessing the opportunities across the market. A team

consists of more than 100 people take a wide range of CPL’s brands pertaining to

poultry, canine and cattle into the remotest corners of India. While some of Vetnova's

brands like 'Onfeed', 'Cal D Min' and 'Cal D Plus DS' are household names, other

brands like 'Endotrin (Ecbolic)' and 'Nolapse' (for pre-lapse) are innovative offerings

of Vetnova.

2.5. Manufacturing Excellence

With regard to its corporate philosophy of striving for continuous betterment and

improvement, the Company has re-located its production operations at the “state-of-

the-art” plant at Dholka, located 50 km away from Ahmedabad which happens to be

the commercial capital of Gujarat. Spreading over 44 acres of land and amidst lush

green lawns is a begrudged pharmaceutical installation in the Asian sub-continent.

Truly revolutionary in every sense of the term, the Plant’s standards and

facilities can match any other specifications, worldwide. 7 ‘zones of cleanliness’

have been defined and adhered to as per the 1997 GMP guidelines of the European

Union. Few of the salient features of the design concepts:

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No wood or asbestos component in plant.

Each zone has its separate AHUs (Air Handling Units), dehumidification unit

and dust extraction systems (DESs).

To avoid cross-contamination, Segregation of every critical processing

activity in each zone.

Adherence to stringent standards of USFDA, MCA (UK), MCC (South

Africa) and TGA (Australia).

Respective zones, areas and even uniforms marked with specific colours of

the rainbow, to ensure total segregation.

Air conditioned environments in each area with respect to temperature,

humidity, filtration, particle counts, etc.

Conformation of each processing stage with US Federal Standard 209E class

of cleanliness which are 100, 1,000, 10,000, 100,000 with respect to pressure,

room air changes, flow direction, particle count etc.

Duo Pass Reverse Osmosis (DPRO) water system, multi-stage distillation

plant, self-sanitizing, water for injection with online monitoring of

temperature, sanitary SS 31 6L loops water, pH, TOC and conductivity

requirements as per USP XXIV.

Zero-discharge Effluent Treatment Plant built using technology from Advent

Integrated System, in USA.

Environment-friendly VAHP chillers.

Natural Skylit system and Rigvent heat extraction devices in raw material,

packing material and finished goods stores.

Isolated production facilities for Antibiotics B-Lactum and Cephalosporin

dosage forms.

The complex also has its own full-fledged R&D center; set up at an expense of

Rs. 200 million.

The Plant is having modern high-speed machines and integrated packaging

lines to be cost effective. Excessive use of non-fill devices, collators, FFS machines,

Brevetti visual inspection machines, multi-station tablet presses, high speed

vial/ampoule filler/sealers are some of the examples of it.

21

The plant- with high capacities and scope for future expansion- is capable of

manufacturing all dosage forms viz. Capsules, Tablets, Liquid Orals, Aseptic Liquid

and Solid preparations, Dry Syrups, Sachets etc.

2.5.1. Contract Manufacturing

Generic Formulations

“State-of-the art facilities”, which stick to stringent specifications of

cGMP, TGA-Australia, and MCC-South Africa.

Production capacity of Tablets is 3900 million / year, Capsules 150

million / year, Liquids 6000 kilo-liters / year, Ampoules + Vials 168

million / year.

Capacity to produce dosage forms in general and sterile, including all

therapeutic segments along with lyophilization facility.

Dedicated and isolated production facilities for Cephalosporin, Beta-

Lactam, Rifampicin dosage form and Insulin.

Qualified and experienced technical team in the areas of production,

quality assurance, quality control, research and development (R&D) for

all range of products.

Highly qualified management and staff and Experienced professionals,

with SAP ERP and Supply Chain Management in place.

Active Pharmaceutical Ingredients (APIs)

Inspected & got approval by USFDA for Ethambutol and Fluoxetine.

US COS filed / DMF / EDMF / under process for about 20 products.

ISO 9002 / ISO 14000 certified Bulk Actives manufacturing facilities,

offering ease for the "Contract Manufacturing".

Products’ range: Anti-allergic, Active Pharmaceutical Ingredients,

Cardiovascular, Disinfectants, Anti-diabetic, CNS, Anti-TB, NSAIDs,

Gastrointestinal, Anti-histamines.

Economic Value of Strategic Alliance

Reliable supply of quality products - Validated and approved processes

and in compliance with the registration file.

Minimize the investments in capital-intensive facilities.

Improve net earnings and cash flow.

22

Divert the resources to focus on their core competencies which are R&D

and marketing.

All products are analysed and released by their Quality Control (QC)

staff before shipment.

Track and optimize the timeliness of their delivery and keep it up to

CPL’s customer's full satisfaction.

Business Opportunities And Strategic Alliance With Cadila Pharmaceuticals

Ltd.

CPL offer contract manufacturing of all dosage forms.

According on your needs, CPL’s services include purchasing of the

production, raw materials, packaging and quality control.

Through this flexible approach, CPL is able to integrate perfectly into

your supply chain for solid dosage forms.

Looking forward to partnering or JV for a mutually beneficial / Profitable

working relationship and strategic alliance.

2.5.2. International Business

In line with Cadila Pharmaceuticals Ltd.’s vision to be significant global

player by 2015 A.D., Cadila Pharmaceuticals Ltd. is fast emerging as a true

Indian multinational.

As part of Cadila Pharmaceuticals Ltd.’s strategy, they have wholly or

partially owned joint ventures, subsidiaries, strategic alliances, own marketing

offices, contract manufacturing in four countries and have remarkable presence

in over 45 countries across the globe. Cadila Pharmaceuticals Ltd.’s business

revolves around the exports of bulk actives, formulations, Veterinary

formulations, hospital disposables, and p’cal machineries manufacturing.

Apart from a significant presence in the CIS Countries, Americas, Africa,

Oceanic Countries, Central and South-East Asia, Middle East, Europe and Japan,

The company has offices in Japan, USA, Kenya, Russia, Nigeria, Ukraine and

Kazakhstan. The International Strategic Business Unit plans to expand its

operations to more than 100 countries by 2015.

The main focus is on building the brands in the following therapeutic segments:

Gastrointestinal

Anti-infective

23

Analgesic/Anti-inflammatory

Respiratory

Cardiovascular

Ophthalmology

Bio-technical Products

Bonds exist with regional majors in the form of Joint ventures,

International Marketing and Contract manufacturing. Many more such

collaborations/JVs are under progress to expand their supply chain network and

make available extensive market coverage. An ultra-modern formulations

production facility conforming to the standards of USFDA, WHO-GMP,

MHRA-UK, TGA-Australia, MCC-South Africa, ANVISA- Brazil, ISO 9002,

EU GMP and Japanese GMP is a value-addition to their International Strategic

Business Unit in flexing its energy in the overseas arena. This Strategic Business

Unit has been honoured with the “Chemexcil Award”, 2000-01 and “Niryat

Shree Award” from FIEO, for the year 2001-02.

With its basic corporate philosophy of giving the best formulations to the

world at an affordable price, Cadila Pharmaceuticals Ltd. continues to make a

difference in the lives of millions of people, while carving a niche market for

Indian Pharmaceuticals exports, globally.

2.6. Production Capacity

Main Pharma Production Capacity

2 Shift / day basis

Tablets : 3900 million/year

Capsules : 150 million/year

Liquids : 6000 kiloliters/year

Sterile vials : 84 million/year

Ampoules : 84 million/year

Granules : 15.6 Tones/year

2 Shift / day basis

Beta Lactum / Cephalosporin

Dry Sterile vials : 48 million/year

Dry Syrup bottles : 27 million/year

Capsules : 630 million/year

24

Tablets : 510 million/year

2.6.1. Soft Gelatin Manufacturing Facility

Cadila Pharmaceuticals also licensed a modern, sophisticated production facility

for Soft Gelatin Capsules at its Jammu Plant which is Designed to meet the most

stringent international standards (IS), all operations in this plant from

encapsulation to packaging are carried out under class 1,00,000 area. Each

system is validated to meet International FDA standards, and the present

capacity of 10,00,000 capsules per day can be doubled with marginal

investments.

2.6.2. Other Manufacturing Locations

Plant Tissue Culture (PTC) , Hirapur

Casil Industries Ltd., Pharma Machineries, Speciality Chemicals & Soft

Gelatin Capsules Production Facilities, Jammu

Active Pharmaceutical Ingredients (APIs), Ankleshwar

2.7. Quality Control

Quality personify the spirit of the CPL. Quality is an apparent right from the moment

you step into premises of CPL, in the numerous aspects instilles and internalised into

the CPL’s ethos.

The slogan “Cadila for Quality” was deeply engraved into all logos of the

CPL and subsequently into the minds of millions, is bind to with utmost dedication as

it was years ago. A separate Quality Management division leading the concept of

Total Quality Management, an integration of all of the functions with built-in quality.

2.8. Group Companies

2.8.1. Casil Industries Ltd. (CIL)

Casil Industries Limited (CIL) is one of the market leaders in hospital products.

The concerntration of the company is on important allied segments such as

Orthopaedic, Surgical, Wound care, Critical Care, Disinfection, patient care

systems and Diagnostic. The company now has four major divisions:

2.8.1.1. Hospicon

This wide range covers Duralite, a fibre glass-based synthetic cast bandage;

Orthoset, a leading Plaster of Paris bandage; Glotex examination gloves

and Surgitex surgical gloves, both made of high-grade double-centrifuged

latex;Dermapore hypoallergic tapes, Opstic adhesive tapes, Castinet gauze

25

bandages and Dermasilk wound dressing. Other speciality products include

Softcrepe and cotton crepe bandages; Cadi-V infusion sets and Bioflon I.V.

Cannula. Apart from these, the CPL has entered into an agreement to

launch the modern wound care products which includes Hydrogel. Few of

these plants have the approval of Statutory bodies, including the DGQA

and have been awarded ISO 9002 certification.

2.8.1.2. Kemicon

Today, CIL is the leading supplier of Tetramethylene Sulfone (Sulfolane)

for most of all the refineries in India. Newer approaches are constantly

developing to expand the market for the products, which is now widely

used in the synthesis of Cephalosporins. Tetramethylene Sulfone

(Sulfolane) is also exported to other countries.

2.8.1.3. Sofgel

CIL has “state-of-the-art” set up to produce Soft Gelatin Capsule mainly to

serve the dietary supplements market, including minerals, hematinics and

vitamins. ISO 9002 approved plant has been consult with the Quality

Award by the Indian Drug Manufacturers' Association (IDMA) and also

carries WHO-GMP certification by the Government of India. Casil

products have been approved by other p’cal organizations and are exported

to the Far-East, African markets and SAARC. CPL is in the process of

expanding its capacities to double the production.

2.8.1.4. Diacon

Casil is the alone distributor for PanBio, Australia’s dengue detection kits.

It is the only product of its kind in the country. After the success of

Accuplan and Accutest HCG, ovulation and pregnancy tests, respectively;

CHPL is going to launch dry chemistry rapid test kits for malaria, hepatites

and other infectious diseases. These unique kits will greatly reduce the time

taken for diagnosis.

2.8.1.4.1. Product list

Clinical chemistry

• Liquid Ready-for-Use Reagents

• Enzymes

• Substrates

• Electrolytes

26

• Proteins

Coagulation – Immunoturbitimetry

Rheumatology

Lipid Diagnostics

Plasma Proteins

Rapid screening

Pregnancy (Medtek Asia P Ltd., Mysore )

Urinalysis (Medtek Asia P Ltd., Mysore )

HIV (Cadila Pharmaceuticals Ltd.)

Tropical Disease ( Panbio Ltd., Australia )

ELISA

Hormones

Infectious Diseases

Tropical Diseases ( Panbio Ltd., Australia )

HIV (Cadila Pharmaceuticals Ltd.)

HCV (Cadila Pharmaceuticals Ltd.)

Makers

2.8.2. IRM Ltd.

2.8.2.1. Green channel Travel Services

With the increasing view of the world as a 'Global Village', and

elimination of a large number of boundaries and barriers, traveling has

turned easier than ever before - both international and domestic. CPL

recognized the trend years ago, when it has launched its IATA accredited

agency first in Ahmedabad, “GREEN CHANNEL TRAVEL SERVICES”,

with the aim of catering to traveling and traveling related needs of

individual, families and different companies.

From 1997, the agency has been nominated with the best agency for

domestic booking by Indian Airlines. Green Channel has also been

conferred with :

The 'Lufthansa Award for Excellence', for topping sales during

1998-99.

27

The 'Outstanding Performance Award' by Jet Airways for highest

ticket sales during 1998-99.

For Highest Sales in 2000-01, 'Singapore Airlines' Award.

'Indian Airlines' Awards for Highest Sales Performance in 2000-01.

'KLM Airlines' Awards for maximum sales in 2000-01.

Besides being the alone representative of American Express Travel

Related Services in Ahmedabad, GREEN CHANNEL also stocks Amex

and Thomas Cook travellers' cheques, outbound tours, deals in car rentals,

corporate incentive tours and money-changing business, authorized by the

Reserve Bank of India (RBI).

2.8.2.2. Rousdonmullai Tea Estates

Cashing in on the lucrative prospects in the agro business sector, CPL

has added a new dimension by acquiring a tea plantation in Tamil Nadu.

Spreaded over 900 acres of blue mountains and set amidst lush green

gardens, Rousdonmullai Tea Estates is located in Devala, in the Nilgiris,

Tamil Nadu.

With mainly focus on tea planting and processing, unadulterated tea

garden from Rousdonmullai, is being supplied to regions like Hyderabad,

Mumbai, Cochin, Coimbatore and Gujarat.

Apart from growing tea gardens, a bunch of agro-based projects are

also being intended by the company in the estate.

2.8.2.3. Karnavati Engineering Ltd.

The engineering arm of Cadila Pharmaceuticals Ltd. group, Karnavati

Engineering Ltd. (KEL) is a well-established manufacturer of precision

machinery and component for pharmaceutical and its allied industries.

Following its come out with the all-purpose Kalweka for pharmaceutical

research in academic institutions, research and development (R&D)

centers, p’cals and associated industries; KEL has been developing a set of

innovative products in production, packaging and research.

The company's has a wide range of equipments which includes

Colloid Mill, tablet compression machines of various outputs,

Communiting Mill, Automatic Blister Packing Machine, Unik Press and

others.

28

KEL has been leader in technology revolution in the field of pharma

machinery for a decade and has emerged as synonymous with tablet press

machines worldwide. The latest introduction is the UNIK-II PC, an

engineering marvel which moils out 7,75,000 tablets/hr.

On packaging front, KEL's Blister Packaging machine is already a

landmark product. The KEL also has other supporting equipment, like table

cleaning system, punches & dies, dust extraction unit, inspection &

maintenance kit etc.

KEL invests almost 20% of its turnover in R&D. The company take

part in various exhibitions and propose trial runs on its machines at its

factory and have won the appreciation of technocrats and their end-users

worldwide. The products have gained wide acceptance in domestic and

international markets, and are exported to UK, USA, CIS countries,

Belgium, Italy, South Africa, Indonesia, Columbia, Syria, Malaysia etc.

Today, it ranks No. 1 in the country in exporting pharma machinery

to the US and is all collected for a quantum leap in the precision equipment

manufacturing sector.

2.9. Cadila Pharmaceuticals Ltd. has two joint ventures:

2.9.1. Cadila Pharmaceuticals (Ethiopia) PLC

The company has established a Joint Venture Company in Ethiopia with a

local partner and put up a “state-of-art manufacturing” plant there for the

production of tablets, capsules, liquid, injectables etc. The Joint Ventured

Company (JVC) is named as “Cadila Pharmaceuticals (Ethiopia) PLC”, wherein

Cadila Pharmaceuticals Ltd. Is having 60% equity and the local partner holds

40% equity. The plant is working since last more than six years and is expected

to achieve a turnover of approx Rs. 300 million for the year 2012.

2.9.2. CPL Biologicals Private Ltd.

The company has also established a JVC (Joint Venture Company) in India

namely CPL Biologicals Pvt. Ltd. in partnership with The M/s. Novavax Inc.

USA (a NASDAC which is one of the US stock exchange listed company), with

Cadila Pharmaceuticals Ltd. havinng 80% equity and Novavax 20%. The JVC is

working in the area of development and Production of biological therapeutics,

therapeutic and prophylactic vaccines and diagnostics in India. This joint venture

company represents an important strategic alliance for vaccine development and

29

production in India and uses revolutionary vaccine technologies. JVC’s vision is

to be a leading provider of high quality, affordable biological therapeutics,

vaccines and diagnostics through world-class research and innovation in

production to target current and future global health challenges.

The JVC is now in the process of developing novel vaccines based on “Virus

Like Particles” (VLP) using cutting edge technology.

CPL Biologicals has established Production facilities in India to produce,

develop and sell products such as an influenza vaccine and other novel vaccines

based on VLP technology. The initial estimated investment for this is expected

to rise around Rs. 100 crores.

30

Chapter 3

Research

methodology

31

3. RESEARCH METHODOLOGY:3.1. Problem Statement

Objective of the study is to know the perception of the doctors’ towards

Bromelain + Trypsin + Rutoside combination drug and for which indication they

would prefer this drug.

3.2. Objective

To find out Doctors’ Perception regarding drug prescription when come to

Inflammation or Inflammatory Pain or Inflammatory oedema.

To find drug’s low acceptance by Doctors.

Try to know this drug’s competitive advantage over other competitor drugs.

To study how competitor manufacturers of same drug promote their product.

To Study doctors’ perception regarding different drug’s safety

3.3. Scope of Study

I took Doctors and Pharmacists (Chemists and Druggists) as my respondents. I made

Doctors to fill up my questionnaire and with Pharmacists I talked verbally and tried

to get competitive advantage of this drug over other competitive molecules.

3.4. Research Type

The Research which I conducted was Exploratory kind of a research. To get my

objective fulfilled, I prepared a questionnaire for doctors and for druggist I interacted

verbally.

3.5. Sample

3.5.1. Sample Size

Total 80 (30 Doctors + 50 Drug stores)

3.5.2. Sampling Method

Quota Sampling Method

3.6. Place of Study

I conducted this research in Godhra which is in Panchmahal district, Gujarat, India. I

almost went to 30 doctors who are eligible for my research sample and take into

accounts those doctors’ response who are prescribing this medicine. I also met

nearby medical stores for furthermore feedback about this drug.

32

Chapter 4

INTRODUCTION to pain,

inflammation and

oedema

33

4. INTRODUCTION TO PAIN, INFLAMMATION & OEDEMA:4.1. Pain

Pain is a feeling directly triggered in the nervous system. Pain may also be

sharp or dull. It may also come and go, or it may be constant for some time. You may

feel pain in one area of your body, such as your back, head, abdomen or chest or you

may feel pain all over, such as when your muscles ache from the flu.

Pain can also be helpful in diagnosing a problem. You might seriously hurt

yourself without knowing it, or you might not realize you have a medical problem

that needs treatment. When you take care of the problem, pain generally flew away.

Though, sometimes pain continues for weeks, months or even years on. It is also

called as chronic pain. However, sometimes chronic pain is due to continuing cause,

such as arthritis or cancer. Sometimes may be the cause is unknown.

Now a day, there are many ways to treat pain. Treatments may vary depending

on the cause of pain. Acupuncture, Painkillers and Sometimes surgery are helpful.

4.2. Inflammation

The word inflammation comes from the Latin "inflammo", meaning "I set

alight, I ignite".

Inflammation is the body's attempt to self-protection; the aim is to remove

harmful stimuli including damaged cells, irritants, or pathogens - and begin the

healing process.

When something which is harmful or irritating affects a part of body, there is

initiation of biological response to try to remove it. The signs and symptoms of acute

inflammation show that the body healing itself by this mechanism. Inflammation

does not mean infection, though an infection causes inflammation. Infection may be

caused by a virus, fungus or bacterium; while inflammation is the body's immune

response to it.

Inflammation is part of the body's immune response. At first, it is beneficial

when your knee sustains a blow and tissues need a care and protection. However, in

some cases inflammation can cause further inflammation, which can turn in to self-

perpetuating. Furthermore inflammation is developed in response to the existing

inflammation.

34

4.3. Oedema

Oedema is fluid retention, which is also called as “Dropsy”. Oedema can be

most easily seen round the ankles after you have been standing (peripheral oedema)

or lying down. After lying down for some time, your eyes may look like puffy and

swollen. Oedema can also collect in your lungs and make you short of breath in

severe cases.

Mild oedema is common and usually harmless to body. It may be due to

allergies, more serious underlying disease or medication.

It is important to seek medical attention if you have oedema history. Most often

no particular cause is to be found out.

Oedema is basically a collection of fluid in the spaces between cells of the

human body. Fluid simply leaks out of damaged cells. This fluid cannot be simply

just drained with a needle and may or may not improve if you take 'water pills'

(diuretics).

4.3.1. Types Of Oedema include:

Idiopathic - no known cause.

Localised - fluid retention in a particular part of the body. It is generally

due to an allergic reaction or injury.

Generalised - affects the whole human body. It generally causes puffy

ankles after standing and puffy reddish eyes after lying down for some

time. This may happen be due to an underlying heart condition.

Cerebral oedema - fluid on the brain, generally due to infection

(meningitis) or serious brain disease (stroke or brain tumour).

Pulmonary oedema - fluid on the lungs, usually due to heart disease.

Lymphoedema - a build-up of lymph fluid when lymph channels are

damaged - eg, after breast cancer surgery.

Women are more prone than men to oedema. Female hormones

(progesterone and estrogen) tend to cause fluid retention so some women

notice puffy ankles just before period of time. Oedema may occur for the

first time at any age if you become anaemic or suffer an allergic reaction.

Old people can acquire oedema rapidly, as they sit for longer periods of time.

35

Older people are also more prone to heart or kidney conditions that may

cause oedema.

4.3.2. Problems which cause Oedema

This list may or may not include all the possible causes of oedema but lists

some of the more common causes.

4.3.2.1. No known cause (idiopathic)

In Idiopathic oedema fluid retention happens which it not caused by a

known medical condition. It is most general in women and can sometimes

its get worsen as you get older and older. Though there is no absolute cure

for idiopathic oedema, but having a healthy diet which contains low salt

can make a real difference. Most people with idiopathic oedema are

overweight and losing weight can make a huge difference to cure the

oedema. A gradual weight loss, rather than fasting and bingeing are

recommended. Regular exercise and Support stockings are also beneficial

in this condition. Avoiding long periods of standing and lying can also

help.

4.3.2.2. Heart Failure

Pulmonary oedema, which means an excess collection of watery fluid

in the lungs, is most often caused by heart failure. The fluid collected in the

air sacs of the lung make it difficult to breathe. When a heart is not able to

pump blood to the whole body effectively, the amount of blood remaining

in the veins, that takes blood through the lungs to the left side of the heart

increases. When the pressure in these veins increases, fluid is pushed into

the air sacs (alveoli) in the lungs. This fluid retention reduces normal

oxygen movement through the lungs, which leads to shortness of breath.

4.3.2.3. Angio-oedema

Angio-oedema is a medical condition in where in swelling of the

deeper layers of the skin. This also includes the dermis and subcutaneous

tissues. It affects the tissues just underneath the lining of the airways,

mouth and gut - that is, called the sub-mucosal tissues.

In most of the cases there is no known cause and it is not clear about

why it occurs. This is also called idiopathic angio-oedema. Though the

cause is not clear, in up to 50 pecent of the cases there is a link to an

36

autoimmune disorder. This includes chronic systemic lupus erythematosus

(SLE), thyroiditis (hypothyroidism) or urticarial. In some of the cases there

are known triggers that cause the release of histamine, which triggers to

tissue swelling of angio-oedema. These also include allergic reactions and

non-allergic reactions to the medicines.

4.3.2.4. Other possible causes of oedema may also include some kidney

diseases, anaemia and pregnancy. Blood clot in a leg can lead to sweeling

of leg.

The doctor wants to know when you noticed the oedema, how long it’s

been there for and whether do you have any other symptoms of oedema. It

is very important to mention ifever you've started any new medication. You

will be under a physical examination of your blood pressure, lungs and

blood as well as the part which is puffy (swell). You may be asked for a

urine sample and a blood test. You may probably asked for further tests on

your heart and a chest X-ray.

4.3.3. Treatments:

Treatment will depend on the cause of oedema. In most of the cases, it is

managed by your GP but you may be asked for further investigation and

treatment at the hospital. Treatment includes:

Regular exercise such as gyming or walking or swimming.

Losing of weight if you are overweight.

Raising both legs on a footstool when possible.

'Water pills' (diuretics) - only if it is prescribed.

Treatment of the underlying condition - eg, heart failure, kidney failure

etc.

4.3.4. To be done

You should call a medical help / an ambulance if you are experiencing severe

shortness of breath or chest pain or vertigo. Mild puffiness / swelling of your

ankles that gets better whenever you lie down for a few hours, may not need any

treatment. In almost all cases, you should see your GP to find out if there is an

underlying cause.

37

4.3.5. How can I avoid Oedema?

You will need to find underlying cause and try to cure it if it is possible.

Idiopathic oedema has no specific cause and is common. The best treatment is to

walk regularly, avoid becoming overweight and put feet raised on a footstool

when resting.

4.3.6. Prognosis:

This depends on the underlying cause but is generally very good. Most of the

oedema is because of standing too long on the hot day, specifically if you are

overweight. Any of the increased risk depends on the underlying cause.

4.4. Drugs Used Fore It

4.4.1. Drugs used to relieve Pain:

Diclofenac

Ibuprofen

Hydroxyzine

Celecoxib

Meperidine

Ampitryptyline

Hydromorphone

Acetaminophen

Tapentadol

Oxymorphone

Oxycodone

Ketorolac

Tramadol

Diclofenac

Alfentanil

Naproxen

Aspirin

Lidocaine

Flubiprofen

38

4.4.2. Drugs used to heal Inflammation

Aspirin

Naproxen

Hydroxychloroquine

Plaquenil

Oxyphenbutazone

Tandearil

Butazolidine

Phenylbutazone

Pediapred

Prednisolone

Prelone

Deltasone

Meticorten

Orasone

Prednisone

Decadron

Dexamethasone

Dexone

Hexadrol

Oradexone

Ibuprofen

Acetaminophen

Integrin

Glucocorticoids

4.4.3. Drugs used to heal Oedema

Hydrochlorothiazide

Chlorthiazide

Bumetanide

Torsemide

Acetazolamide

39

Triameterene

Ethacrynic acid

Methychlothiazide

Furosemide

Indapamide

Amiloride

Metolazone

40

Chapter 5

INTRODUCTION to

product

41

5. INTRODUCTION TO BROMELAIN, TRYPSIN & RUTOSIDE:5.1. Bromelain

It is an extract which is derived from the stems of pineapple, although it

presents in all parts of the fresh fruit and plant. This extract has a history of folk and

modern medicinal usage. As a supplement it is supposed to have anti-inflammatory

effects. It also contains chemicals which might interfere with the growth of tumour

cells and slower down blood clotting. As a culinary ingredient it is used mainly for

tenderizer.

The term “Bromelain” may refer to either of two protease enzymes refer to a

combination of those enzymes along with other compounds produced in an extract or

it may refer to enzymes extracted from the plants of the family, Bromeliaceae.

5.2. Trypsin

Trypsin is basically a serine protease found in the digestive system of many

vertebrates, where it hydrolyses the proteins into peptides. Trypsin is produced in the

pancreas as the inactive pro-enzyme Trypsinogen. Trypsin mainly cleaves peptide

chains at the carboxyl side of the amino-acids lysine or arginine, except when either

of is followed by proline. It is generally used for numerous biotechnological

processes. This process is usually referred to as trypsinisation or trypsin proteolysis

and Proteins that have been treated / digested with trypsin are said to have been

trypsinized.

5.3. Rutoside

Rutin (also called rutoside / quercetin-3-O-rutinoside and sophorin) is the

glycoside between the flavonol quercetin and the disaccharide rutinose (α-L-

rhamnopyranosyl-(1→6))-β-D-glucopyranose). In the fava d'anta tree, the synthesis

is done via a rutin synthase activity.

Rutin is one of the phenolic compounds mostly found in the invasive plant

species Carpobrotus edulis and contributes to the antibacterial and antioxidant

properties of the plant.

Its name comes from the name of “Ruta graveolens”, a plant that also contains

rutin.

It can combine with cations supplying nutrients from the soil to the cells in

plants. In humans, it attaches to the iron ion Fe2+, preventing it from binding to

42

hydrogen peroxide, which would otherwise create a highly reactive free radical that

may damage cells. It is also an antioxidant.

Furthermore, it has been shown to inhibit vascular endothelial growth factor in

subtoxic concentrations, so it acts as an inhibitor of angiogenesis. The finding may

have potential relevance for the control of some cancers.

5.4. Studies on this Drugs

In a recent blinded study from Germany, researchers divided 90 patients with

painful osteoarthritis of the hip into two groups: one half receiving an oral enzyme

preparation containing bromelain for six weeks, while the other half received the

anti-inflammatory drug diclofenac. They found out that the bromelain preparation

was as effective as diclofenac in standard scales of pain, stiffness and physical

function, and have better tolerance than the drug comparator. The researchers

concluded, “The bromelain preparation may well be recommended for the treatment

of patients with osteoarthritis of the hip with signs of inflammation as indicated by a

high pain level.”

Another study comparing a standardized commercial enzyme preparation

containing bromelain with diclofenac reached the same conclusion. The study

reported that the supplement containing bromelain (90 mg, three times daily) to be as

effective as diclofenac (50 mg, twice daily) in improving the symptoms of

osteoarthritis of the knee. Patients reported comparable reductions in joint

tenderness, pain and swelling, and improvement in range of motion at the end of the

study. The investigators found bromelain to be as good as diclofenac on a standard

pain assessment scale and to be better than the drug in reducing pain at rest (by 41%

for bromelain versus 23% for the drug), improving restricted function (by 10% for

bromelain versus 0% for the drug), being rated by more patients in improving

symptoms (24% for bromelain versus 19% for the drug), and being evaluated by

more physicians as having good efficacy (51% for bromelain versus 37% for the

drug). In summary, the investigators determined bromelain to be an effective and

safe alternative to NSAIDs such as diclofenac for painful osteoarthritis.Together,

these findings reveal that bromelain may provide safe, effective relief from acute and

chronic joint pain caused by arthritis and other conditions.

Growing evidence of the cardiovascular and gastrointestinal risks associated

with non-steroidal anti-inflammatory (NSAID) drugs has left many people

seeking safe, effective strategies for relieving pain and inflammation.

43

Derived from the pineapple plant, the protein-digesting enzyme bromelain

demonstrates powerful effects in alleviating pain, swelling, and inflammation.

In clinical trials, bromelain-based formulations were more effective than an

NSAID drug in relieving arthritis pain. Supplementing with bromelain-based

formulations after injury or surgery also speeds healing and reduces pain.

Bromelain hastens the resolution of sinusitis, and shows promise in fighting

inflammatory bowel disorders. Preliminary studies suggest that bromelain

may even help fight cancer.

Experts suggest consuming bromelain between meals to capture its anti-

inflammatory benefits. To promote healthy digestive function, take bromelain

with meals.

Bromelain may offer important support for healing and pain relief after surgery.

Investigators administered a combination of bromelain, trypsin, and rutoside (rutin)

to patients for two weeks following surgery to fix fractured long bones. Compared

with surgical patients who did not receive the supplement, the bromelain-treated

group showed a remarkable reduction in postoperative swelling. Additionally, the

supplemented individuals required less pain medication during their recovery period,

indicating a significant analgesic effect and more rapid and comfortable recovery.

44

5.5. Competitor Companies who make this Drug

Bromelaine + Trypsine + Rutoside

Brand Name Manufacturer Price(Rs.)Xymoheal Corona remedies Pvt Ltd 115

Invilin Synokem Pharmaceuticals Ltd 149

Invillin Forte Synokem Pharmaceuticals Ltd 300

Allanz Wallace Pharmaceuticals Ltd 150

Enractin Molekule Ind Pvt Ltd 150

Enractin Plus Molekule Ind Pvt Ltd 499

Enzoheal Healthguard Pvt Ltd 156

Enzomac Plus maleods Pharmaceuticals Ltd 160

Proenza Dewcare Concept 190

Enzody Malody 160

Triobest Bestochem NA

Activin-R Waves biotech NA

Rutoheal Mankind 130

45

Chapter 6

Analysis of survey

response

46

6. ANALYSIS OF SURVEY RESPONSES6.1. How many Patients do you see in a week suffering from Inflammation or

Inflammatory pain or Inflammatory oedema?

6.2. What therapy do you initiate for these patients?

Diclo + PCM diclo

Ibuprofen

Analgesics + antibiotics

INJ Aceclofenac + Serratio

Xymoheal

Trypsin + Chymotrypsin

Diclo + PCM + Serratio

Antibiotics

PCM

Diaminic DA

PCM

NSAIDS + REST

No. of patients Responded docs %

0–30 7 22%

31–60 18 56%

61-90 7 22%

Other 0 0%

Table No 6.1

Graph No 6.1

47

Enzyme prepn

Indomethacin

Anti-inflammatory

Find etiology and prescribe accordingly

6.3. For which type of indication you would suggest Bromelain + Trypsin + Rutoside

combination:

6.4. Which strength do you prescribe and in which indications?

Strength Response %

Bromelain 90mg + Trypsin 48mg +

Rutoside 100 mg

64 58

Bromelain 180mg + Trypsin 96mg +

Rutoside 200 mg

46 42

Indication response %

Pain 2 1%

Inflammation 30 21%

Inflammatory Pain 46 32%

Inflammatory Oedema 62 44%

Other 2 1%

Graph No 6.2

Table No 6.2

Table No 6.3

48

6.5. Duration Of therapy for this combination:

6.6. What dosage would you prefer for this combination?

6.7. You use this medication as:

Duration Response %

5 38 59

6 24 38

7 2 3

Dosage Response %

Twice a day 14 22

Thrice a day 50 78

Use as Response %

Single medication 8 13

Combination with other medicines 56 87

Graph No 6.3

Table No 6.4

Graph No 6.4

Table No 6.5

Table No 6.6

49

6.8. Which other Molecule you prefer in this indication?

6.9. Your Preference for this combination Drug:

Molecule Response %

Diclofenac 64 29%

Paracetamol 52 24%

Paracetamol (IR+SR) 58 26%

Serratiopeptidase 20 9%

Ibuprofen 26 12%

Other 0 0%

Preference Response %

Starting with higher and moving

on to lower dosage

2 3

Starting with lower and moving on

to higher dosage

2 3

Combination medication 60 94

Graph No 6.5

Table No 6.7

Graph No 6.6

Table No 6.8

50

6.10. Diclofenac [Patients' safety level:]

6.11. Paracetamol [Patients' safety level:]

Safety level Response %

Safest 2 3%

Safer 52 81%

Neutral 10 16%

Unsafe 0 0%

Extremely Unsafe 0 0%

Safety level Response %

Safest 22 39%

Safer 28 50%

Neutral 3 11%

Unsafe 0 0%

Extremely Unsafe 0 0%

Graph No 6.7

Table No 6.9

Graph No 6.8

Table No 6.10

51

6.12. Paracetamol (SR+IR) [Patients' safety level:]

6.13. Serratiopeptidase [Patients' safety level:]

Safety level Response %

Safest 22 73%

Safer 30 23%

Neutral 2 3%

Unsafe 0 0%

Extremely Unsafe 0 0%

Safety level Response %

Safest 24 63%

Safer 12 32%

Neutral 0 0%

Unsafe 2 3%

Extremely Unsafe 0 0%

Graph No 6.9

Graph No 6.10

Table No 6.11

Table No 6.12

52

6.14. Ibuprofen [Patients' safety level:]

6.15. What is your Clinical Experience with this combination drug?

Safety level Response %

Safest 2 6%

Safer 6 18%

Neutral 18 53%

Unsafe 8 24%

Extremely Unsafe 0 0%

Experience Response %

Good 44 69

Neutral 14 22

Bad 6 9

Graph No 6.11

Graph No 6.12

Table No 6.13

Table No 6.14

53

6.16. Diclofenac [Considering all factors into consideration, Give your

opinion:]

6.17. Paracetamol [Considering all factors into consideration, Give your

opinion:]

Experience Response %

Excellent 50 78%

Good 14 22%

Fair 0 0%

Poor 0 0%

Very Poor 0 0%

Experience Response %

Excellent 46 79%

Good 10 17%

Fair 2 3%

Poor 0 0%

Very Poor 0 0%

Table No 6.15

Graph No 6.13

Graph No 6.14

Table No 6.16

54

6.18. Paracetamol (SR+IR) [Considering all factors into consideration, Give

your opinion:]

6.19. Serratiopeptidase [Considering all factors into consideration, Give your

opinion:]

Experience Response %

Excellent 56 93%

Good 2 3%

Fair 2 3%

Poor 0 0%

Very Poor 0 0%

Eexperience Response %

Excellent 30 83%

Good 6 17%

Fair 0 0%

Poor 0 0%

Very Poor 0 0%

Table No 6.17

Graph No 6.15

Graph No 6.16

Table No 6.18

55

6.20. Ibuprofen [Considering all factors into consideration, Give your opinion:]

6.21. What shoud be Price band for 10 tablet strip of this combination drug?

Price shoud be Rs.80-90 per 10 tablet strip (Got this price by taking mean of 32

doctors and pharmacists)

6.22. What could be advantage of these drugs over other competitior drugs?

Reduce oedema easrlier than serratiopeptidase

Comparatively less side effect

Almost nill side effect

Safe drug as it is enzyme preparation

Experience Response %

Excellent 8 24%

Good 12 35%

Fair 14 41%

Poor 0 0%

Very Poor 0 0%

Graph No 6.17

Table No 6.19

56

Chapter 7

findings

57

7. FINDINGS

Doctors in general use (Bromelain 90mg + Trypsin 48mg + Rutoside

100 mg) combination but in severe cases they also prefer (Bromelain

180mg + Trypsin 96mg + Rutoside 200 mg).

59% of the doctors use this medicine as 5 days therapy duration &

38% of doctors use this medicine as 7 days duration.

78% of doctors prescribe this medicine thrice a day & 22% of doctors

prescribe this medicine twice a day.

87% of doctors use this medicine combination with other medicines.

Most of the doctors use Diclofenac, PCM, PCM (SR+IR) or

serratiopepdidase combination to initiate therapy.

81% of the doctors rated Diclofenac as safer drug, 73% Doctors rated

PCM (SR+IR) as safest drug 63% doctors rated Serratiopeptidase as

safest drug & 77% doctors don’t prefer Ibuprofen when comes to

safety level.

When comes to clinical symptoms reduce, doctors feel PCM, PCM

(IR+SR), Serratiopeptidase and diclofenac as Excellent drug and not

ibuprofen.

According to doctors, price should be within the range of Rs.80-90 per

10 tablet strip.

BTR combination has almost nill side effect and reduce oedema

earlier than serrationpeptidase as per doctor’s opinion.

58

Chapter 8

suggestion

59

8. SUGGESTIONS

This drug should be marketed with regards to its Safety measure as it has very

strong competitiveness to its safety parameter.

It should be recommended to the doctors for inflammatory oedema as 76%

doctors believe that it reduces inflammatory oedema rapidly than any other drugs.

As we know, we can’t reduce its price drastically because other competitiors will

also get involve in price war and it will affect the other drugs’ portfolio.

According to my research, Most of the doctors don’t know about this drug and if

know, they don’t know when to prescribe and its competitive advantage so we

should first concentrate on increasing Awareness amongst doctors.

I recommend to name this drug as “BTR” as it would be easy for the doctors to

memorise and recollect the API by its name’s first alphabate.

I would also like to drag your attention towards its price which is main weakness

of this drug. To overcome this first we have make doctors trust this drug and for

that we have to distribute free sample so that doctors can give to patients and

check their satisfaction level at initial stage.

60

Chapter 9

bIBLIOGRAPHY

61

9. BIBLIOGRAPHY http://www.cadilapharma.com/

http://www.medguideindia.com/find_brand_bygeneric.php?gen_mask=,1618,2176,29

08,

http://www.medschat.com/topics/use-of-trypsin-bromelain-rutoside-trihydrate-tab/

http://www.seacoast.com/topic.php?health=trypsin+and+bromelain+rutoside+mode+

of+action

http://www.patient.co.uk/health/oedema-swelling

http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Medications_non-

steroidal_anti-inflammatory_drugs

http://www.thefreedictionary.com/anti-inflammatory+drug

http://www.rxlist.com/script/main/art.asp?articlekey=104699

http://www.drugs.com/condition/pain.html

en.wikipedia.org/wiki/Rutoside

http://en.wikipedia.org/wiki/Trypsin

http://en.wikipedia.org/wiki/Bromelain

http://en.wikipedia.org/wiki/Pharmaceutical_industry_in_India

http://www.mims.com/India

62

Chapter 10

APPENDIX

63

10.APPENDIX

Questionnaire:

Personal Profile

Name: Dr. __________________________________________________________

Qualification: ___________________________

Address: __________________________________________________________________

___________________________________________________________________

___________________________________________________________________

DOB: ____________________________

Marriage Anniversary: _________________

Contact Details:

Mobile No.: __________________________

Phone (O): ___________________________

Email ID: ______________________________________________________________

64

1. How many Patients do you see in a week suffering from pain, inflammation and

oedema? ( )

2. What therapy do you initiate for these patients?

a. _______________________________________________________

b. _______________________________________________________

3. For which type of indications you would suggest Bromelain + Trypsin + Rutoside

combination:

a. Pain

b. Inflamation

c. Inflammatory oedema

d. Inflamation with Pain

e. Others Please Specify: ______________________________________

4. Which Strength you prescribe:

Bromelain 90mg + Trypsin 48mg + Rutoside 100mg

(If yes, In which indication:_______________________________________ )

Bromelain 180mg + Trypsin 96mg + Rutoside 200mg

(If yes, In which indication:_______________________________________ )

5. Duration of therapy: ( ) days

6. What dosage would you prefer for this combination?

Twice a day

Thrice a day

Other:______________

7. You use this medication as

Single medication Combination with other medication

8. Which other molecules you prefer in this indication?

Diclofenac

Paracetamol

Paracetamol (IR+SR)

Serratiopeptidase

Ibuprofen

Other:_______________________________________

65

9. Your preference for this combination

Starting with higher dosage and moving on to the lower dosage

Starting with lower dosage and moving on to the higher dosage

Combination with other medicines

Others: ______________________________________

10. What is your Clinical experience with this combination, If any?__________________

_____________________________________________________________________

11. Patients’ safety level:

Safest Safer Neutral Unsafe Extremely unsafe

Diclofenac

Serratiopeptidase

Ibuprofen

Paracetamol

Paracetamol (SR+IR)

Other:___________________

12. Considering all the factors give rating to these molecules:

Excellent Good Fair Poor Very poor

Diclofenac

Paracetamol

Paracetamol (SR+IR)

Serratiopeptidase

Ibuprofen

Other:_________________

13. What should be the price band per 10 tablet strip of this combination drug? ( )

14. What could be advantage of this drug over other competitor drugs?_______________

_____________________________________________________________________

_____________________________________________________________________

_____________________________________________________________________

We are pleased to have your valuable part in our survey. We really appreciate

your help.

Thanking you sir.