Chapter 1

Overview of pharmaceutical industry

1. OVERVIEW OF PHARMACEUTICAL INDUSTRY:

1.1 An Introduction The Indian pharma industry currently tops the graph amongst India's sciencebased industries with wide ranging capabilities in the field of drug technology and manufacture. A well-organized sector, the Indian pcal 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 McKinseys report, India Pharma 2015 - Unlocking the potential of Indian Pharmaceuticals market. Dr Reddy's Lab has launched a new Finasteride tablets which is a bioequivalent 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:

Year 2007-08 2008-09 2009-10 2010-11

Value of import of Medicinal and Pharmaceutical products (Rs. In bn.) 67.34 86.49 99.59 109.37 Table No. 1.1

Growth (%) 14.79 28.43 15.15 9.82

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.) 2007-08 2008-09 2009-10 2010-11 1.4 293.54 398.21 424.56 475.51 Table No. 1.2 Major Pharmaceutical Companies in India Some of the Indian pharmaceutical player by their sales volume in INR Billion: Company Name Cipla Ranbaxy lab Dr Reddys lab Sun pharma Lupin Ltd. Aurobindo Pharma Jubilant Life Cadila Health Ipca Lab Wockhardt Sales in INR Billion 69.77 76.86 66.86 40.15 53.64 42.84 26.41 31.52 23.52 26.50
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Growth (%) 14.37 35.66 6.62 12.00

Table No 1.3

1.5

Government Initiatives and Investments 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, HIVAIDS 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.

1.5.1 Government Initiatives

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.

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.

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 1.7 Effects of new products patent Drug price control over (DPCO) Regulatory reforms affair Infrastructure development Quality management and Conformance to the global standards.

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.

Chapter 2

INTRODUCTION to Organisation

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 CPLs 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.Milestones
1951

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 Worlds First IMMUVAC, an unique Immunomodulator. 2001

Cadila Pharmaceuticals Ltd. launches NEVA HIV, Which is world's First whole blood Rapid HIV detection kit.

20021. 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.

20041. 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. 200512

1. KELs 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). 20061. 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. 20071. 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. 20081. 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. 20091. Cadila Pharmaceuticals Ltd. features as one of the Most Trusted Companies of 2008 by Sara Media and Zee Business. 2. Cadila Pharmaceuticals unveils Ltd. worlds 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 worlds 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. 20101. 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. 20111. 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. 20121. 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 Pcal 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 CPLs 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 divisions 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 CPLs 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-ofthe-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 Plants 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.

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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, BetaLactam, 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.
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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 CPLs 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, CPLs 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 pcal 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
22

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 : Capsules : Liquids : Ampoules : Granules : 3900 million/year 150 million/year 6000 kiloliters/year 84 million/year 15.6 Tones/year

Sterile vials : 84 million/year

2 Shift / day basis Beta Lactum / Cephalosporin Dry Sterile vials : Dry Syrup bottles : Capsules : 48 million/year 27 million/year

630 million/year
23

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 CPLs 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
24

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 pcal 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, Australias 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 Liquid Ready-for-Use Reagents Enzymes Substrates Electrolytes
25

Clinical chemistry

Proteins Rheumatology Lipid Diagnostics Plasma Proteins Pregnancy (Medtek Asia P Ltd., Mysore ) Urinalysis (Medtek Asia P Ltd., Mysore ) HIV (Cadila Pharmaceuticals Ltd.) Tropical Disease ( Panbio Ltd., Australia )

Coagulation Immunoturbitimetry

Rapid screening

ELISA 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. Hormones Infectious Diseases Tropical Diseases ( Panbio Ltd., Australia ) HIV (Cadila Pharmaceuticals Ltd.) HCV (Cadila Pharmaceuticals Ltd.) Makers

26

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, pcals 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 others.
27

Mill,

tablet

compression

machines

of

various

outputs,

Communiting Mill, Automatic Blister Packing Machine, Unik Press and

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
28

production in India and uses revolutionary vaccine technologies. JVCs 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.

29

Chapter 3

Research methodology

30

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 drugs low acceptance by Doctors. Try to know this drugs competitive advantage over other competitor drugs. To study how competitor manufacturers of same drug promote their product. To Study doctors perception regarding different drugs 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.

31

Chapter 4

INTRODUCTION to pain, inflammation and oedema

32

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 selfperpetuating. Furthermore inflammation is developed in response to the existing inflammation.

33

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.

34

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
35

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 its 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.

36

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

37

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
38

Triameterene Ethacrynic acid Methychlothiazide Furosemide Indapamide Amiloride Metolazone

39

Chapter 5

INTRODUCTION to product

40

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 (-Lrhamnopyranosyl-(16))--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

41

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.
42

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 antiinflammatory 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.

43

5.5. Competitor Companies who make this Drug

Bromelaine + Trypsine + Rutoside

Brand Name
Xymoheal Invilin Invillin Forte Allanz Enractin Enractin Plus Enzoheal Enzomac Plus Proenza Enzody Triobest Activin-R Rutoheal

Manufacturer
Corona remedies Pvt Ltd Synokem Pharmaceuticals Ltd Synokem Pharmaceuticals Ltd Wallace Pharmaceuticals Ltd Molekule Ind Pvt Ltd Molekule Ind Pvt Ltd Healthguard Pvt Ltd maleods Pharmaceuticals Ltd Dewcare Concept Malody Bestochem Waves biotech Mankind

Price(Rs.)
115 149 300 150 150 499 156 160 190 160 NA NA 130

44

Chapter 6

Analysis of survey response

45

6. ANALYSIS OF SURVEY RESPONSES

6.1. How many Patients do you see in a week suffering from Inflammation or Inflammatory pain or Inflammatory oedema?

No. of patients 030 3160 61-90 Other

Responded docs 7 18 7 0

% 22% 56% 22% 0% Table No 6.1

Graph No 6.1

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
46

Enzyme prepn Indomethacin Anti-inflammatory Find etiology and prescribe accordingly

6.3. For which type of indication you would suggest Bromelain + Trypsin + Rutoside combination: Indication Pain Inflammation Inflammatory Pain Inflammatory Oedema Other response 2 30 46 62 2 % 1% 21% 32% 44% 1% Table No 6.2

Graph No 6.2

6.4. Which strength do you prescribe and in which indications? Strength Bromelain 90mg + Trypsin 48mg + Rutoside 100 mg Bromelain 180mg + Trypsin 96mg + Rutoside 200 mg Table No 6.3
47

Response 64 46

% 58 42

Graph No 6.3

6.5. Duration Of therapy for this combination:

Duration 5 6 7

Response 38 24 2

% 59 38 3 Table No 6.4

6.6. What dosage would you prefer for this combination?

Dosage Twice a day Thrice a day

Response 14 50

% 22 78 Table No 6.5

Graph No 6.4

6.7. You use this medication as: Use as Single medication Combination with other medicines Response 8 56 % 13 87

Table No 6.6

48

Graph No 6.5

6.8. Which other Molecule you prefer in this indication?

Molecule Diclofenac Paracetamol Paracetamol (IR+SR) Serratiopeptidase Ibuprofen Other

Response 64 52 58 20 26 0

% 29% 24% 26% 9% 12% 0% Table No 6.7

Graph No 6.6

6.9. Your Preference for this combination Drug: Preference on to lower dosage Starting with lower and moving on 2 to higher dosage Combination medication 60 94 3 Response % 3 Table No 6.8

Starting with higher and moving 2

49

Graph No 6.7

6.10.

Diclofenac [Patients' safety level:] Safety level Safest Safer Neutral Unsafe Extremely Unsafe Response 2 52 10 0 0 % 3% 81% 16% 0% 0% Table No 6.9

Graph No 6.8

6.11.

Paracetamol [Patients' safety level:]

Safety level Safest Safer Neutral Unsafe Extremely Unsafe

Response 22 28 3 0 0

% 39% 50% 11% 0% 0% Table No 6.10

50

Graph No 6.9

6.12.

Paracetamol (SR+IR) [Patients' safety level:] Safety level Safest Safer Neutral Unsafe Extremely Unsafe Response 22 30 2 0 0 % 73% 23% 3% 0% 0% Table No 6.11

Graph No 6.10

6.13.

Serratiopeptidase [Patients' safety level:] Safety level Safest Safer Neutral Unsafe Extremely Unsafe Response 24 12 0 2 0
51

% 63% 32% 0% 3% 0% Table No 6.12

Graph No 6.11

6.14.

Ibuprofen [Patients' safety level:] Safety level Safest Safer Neutral Unsafe Extremely Unsafe Response 2 6 18 8 0 % 6% 18% 53% 24% 0%

Table No 6.13

Graph No 6.12

6.15.

What is your Clinical Experience with this combination drug?

Experience Good Neutral Bad

Response % 44 14 6 69 22 9 Table No 6.14

52

6.16.

Diclofenac [Considering all factors into consideration, Give your

opinion:] Experience Excellent Good Fair Poor Very Poor Response 50 14 0 0 0 % 78% 22% 0% 0% 0% Table No 6.15

Graph No 6.13

6.17.

Paracetamol [Considering all factors into consideration, Give your Experience Excellent Good Fair Poor Very Poor Response 46 10 2 0 0 % 79% 17% 3% 0% 0% Table No 6.16

opinion:]

Graph No 6.14

53

6.18.

Paracetamol (SR+IR) [Considering all factors into consideration, Give Experience Excellent Good Fair Poor Very Poor Response 56 2 2 0 0 % 93% 3% 3% 0% 0% Table No 6.17

your opinion:]

Graph No 6.15

6.19.

Serratiopeptidase [Considering all factors into consideration, Give your Eexperience Excellent Good Fair Poor Very Poor Response 30 6 0 0 0 % 83% 17% 0% 0% 0% Table No 6.18

opinion:]

Graph No 6.16

54

6.20.

Ibuprofen [Considering all factors into consideration, Give your opinion:] Experience Excellent Good Fair Poor Very Poor Response 8 12 14 0 0 % 24% 35% 41% 0% 0% Table No 6.19

Graph No 6.17

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

55

Chapter 7

findings

56

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 dont 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 doctors opinion.

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Chapter 8

suggestion

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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 cant 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 dont know about this drug and if
know, they dont 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 names 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.

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Chapter 9

bIBLIOGRAPHY

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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_nonsteroidal_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

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Chapter 10

APPENDIX

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10.APPENDIX

Questionnaire:
Personal Profile
Name: Dr. __________________________________________________________

Qualification: ___________________________ Address: __________________________________________________________________ ___________________________________________________________________ ___________________________________________________________________ DOB: ____________________________

Marriage Anniversary: _________________ Contact Details: Mobile No.: __________________________ Phone (O): ___________________________ Email ID: ______________________________________________________________

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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: ( Twice a day Thrice a day Other:______________ 7. You use this medication as Single medication Combination with other medication ) days

6. What dosage would you prefer for this combination?

8. Which other molecules you prefer in this indication? Diclofenac Paracetamol Paracetamol (IR+SR) Serratiopeptidase Ibuprofen Other:_______________________________________
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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 Diclofenac Serratiopeptidase Ibuprofen Paracetamol Paracetamol (SR+IR) Other:___________________ 12. Considering all the factors give rating to these molecules: Excellent Diclofenac Paracetamol Paracetamol (SR+IR) Serratiopeptidase Ibuprofen Other:_________________ 13. What should be the price band per 10 tablet strip of this combination drug? ( ) Good Fair Poor Very poor Safer Neutral Unsafe Extremely unsafe

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.
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