PHARMA INDUSTRIES Global Scenario

The developed countries of US, Western Europe and Japan are the biggest markets. Higher purchasing power and a well-developed health insurance and reimbursement system implies that the value of drugs sold is much higher there. Growth in these markets is also higher as new blockbuster drugs drive growth.

Global Pharmaceutical Market Country

US Europe Japan Latin America South East Asia and China

Sales-2005 ($bn)
265.70 169.50 60.30 24.00 46.40

% Share
47.00 30.00 10.70 8.20 4.20

% Growth
5.20 7.10 6.80 11.00 18.50

The global pharmaceutical industry has been one of the most outstanding with doubledigit growth rates. The global pharmaceutical industry, presently valued at Us$ 602 billion is slated to grow at eight percent compound average annual rate during the next three years to $ 732 billion, predicts IMS Health. Though the markets of the US, Japan and Western Europe would continue to remain major markets, the fastest growths are expected to be Southeast Asia, including China at 11%, the Middle East by 10% and North America by 9%. Japan and Western Europe pharmaceutical markets are expected to grow at rates slower than the global average. The lifestyle disease clearly dominates the world therapeutics market. The develop countries which account for the majority of the world pharma sales are in the grip of these diseases. Most of the drugs in this category apart from being costly have to be taken for a long time, a most of these diseases are lifelong. These are the fastest growing categories for the Indian markets.

Internationally the companies are facing short term as well as long-term pressures. To live auto the past growth rates they are truing to different things. Strengthening of Research marketing seams to be the focus : Top companies are merging.

Divesting non-core healthcare businesses.

Spending more on research to bring NCEs faster.

Partnering with genomic and drug discovery companies.

Increasing sales forces.

Indian Scenario
The Indian Pharmaceutical Industry today is in the front rank of Indias sciencebased industries with wide ranging capabilities in the complex field of drug manufacture and technology. A highly organized sector, the Indian Pharma Industry is estimated to be worth $ 4.5 billion, growing at about 8 to 9 percent annually. It ranks very high in the third world, in terms of technology, quality and range of medicines manufactured. From simple headache pills to sophisticated antibiotics and complex cardiac compounds, almost every type of medicine is now made indigenously. Playing a key role in promoting and sustaining development in the vital field of medicines, Indian Pharma Industry boasts of quality producers and many units approved by regulatory authorities in USA and UK. International companies associated with this sector have stimulated, assisted and spearheaded this dynamic development in the past 53 years and helped to put India on the pharmaceutical map of the world. The Indian Pharmaceutical sector is highly fragmented with more than 20,000 registered units. It has expanded drastically in the last two decades. The leading 250 pharmaceutical companies control 70% of the market with market leader holding nearly 7% of the market share. It is an extremely fragmented market with severe price competition and government price control.

The pharmaceutical industry in India meets around 70% of the country's demand for bulk drugs, drug intermediates, pharmaceutical formulations, chemicals, tablets, capsules, orals and injectibles. There are about 250 large units and about 8000 Small Scale Units, which form the core of the pharmaceutical industry in India (including 5 Central Public Sector Units). These units produce the complete range of pharmaceutical formulations, i.e., medicines ready for consumption by patients and about 350 bulk drugs, i.e., chemicals having therapeutic value and used for production of pharmaceutical formulations. Following the de-licensing of the pharmaceutical industry, industrial licensing for

most of the drugs and pharmaceutical products has been done away with. Manufacturers are free to produce any drug duly approved by the Drug Control Authority. Technologically strong and totally self-reliant, the pharmaceutical industry in India has low costs of production, low R&D costs, innovative scientific manpower, strength of national laboratories and an increasing balance of trade. The Pharmaceutical Industry, with its rich scientific talents and research capabilities, supported by Intellectual Property Protection regime is well set to take on the international market.

ADVANTAGE INDIA
Competent workforce: India has a pool of personnel with high managerial and technical competence as also skilled workforce. It has an educated work force and English is commonly used. Professional services are easily available. Cost-effective chemical synthesis: Its track record of development, particularly in the area of improved cost-beneficial chemical synthesis for various drug molecules is excellent. It provides a wide variety of bulk drugs and exports sophisticated bulk drugs. Legal & Financial Framework: India has a 53 year old democracyand hence has a solid legal framework and strong financial markets. There is already an established international industry and business community. Information & Technology: It has a good network of world-class educational institutions and established strengths in Information Technology. Globalisation: The country is committed to a free market economy and globalization. Above all, it has a 70 million middle class market, which is continuously growing. Consolidation: For the first time in many years, the international pharmaceutical industry is finding great opportunities in India. The process of consolidation, which has become a generalized phenomenon in the world pharmaceutical industry, has started taking place in India.

THE GROWTH SCENARIO

India's US$ 3.1 billion pharmaceutical industry is growing at the rate of 14 percent per year. It is one of the largest and most advanced among the developing countries.

Over 20,000 registered pharmaceutical manufacturers exist in the country. The domestic pharmaceuticals industry output is expected to exceed Rs.260 billion in the financial year 2006, which accounts for merely 1.3% of the global pharmaceutical sector. Of this, bulk drugs will account for Rs. 54 bn (21%) and formulations, the remaining Rs. 210 bn (79%). In financial year 2005, imports were Rs. 20 bn while exports were Rs.87 bn.

STEPS TO STRENGTHEN THE INDUSTRY

Indian companies need to attain the right product-mix for sustained future growth. Core competencies will play an important role in determining the future of many Indian pharmaceutical companies in the post product-patent regime after 2005. Indian companies, in an effort to consolidate their position, will have to increasingly look at merger and acquisition options of either companies or products. This would help them to offset loss of new product options, improve their R&D efforts and improve distribution to penetrate markets. Research and development has always taken the back seat amongst Indian pharmaceutical companies. In order to stay competitive in the future, Indian companies will have to refocus and invest heavily in R&D.

The Indian pharmaceutical industry also needs to take advantage of the recent advances in biotechnology and information technology. The future of the industry will be determined by how well it markets its products to several regions and distributes risks, its forward and backward integration capabilities, its R&D, its consolidation through mergers and acquisitions, co-marketing and licensing agreements.

The Indian pharmaceutical industry is highly regulated. The Government controls prices of a large number of bulk drugs and formulations. Profit margins of players vary widely in both domestic and export sales due to many factors. Over 20,000-registered pharmaceutical manufacturer exist in the country. The market share of MNCs has fallen from 75% in 1971 to around 35% in the Indian Pharmaceuticals market, while the share of India companies has increased from 20% in 1971 to nearly 65%. The domestic pharmaceuticals industry output is expected to exceed Rs. 247 billion in FY 2006, which account for merely 15.6 % of the global pharmaceutical sector. Out of the bulk drugs will account for Rs. 54bn (21%) and formulations the remaining Rs. 210bn (79%). In 2005, imports were Rs. 20bn while exports were Rs. 87bn. The Indian Pharmaceutical sector has increased drastically in the last two decades. The leading 250 pharmaceutical companies control 70% of the market with market leader having nearly 7% of the market share. It is an extremely fragmented market with severe price competition and government price control.

External Trade:
Indias pharmaceutical exports are to the tune of Rs. 87 bn, of which formulations contribute nearly 55% and the rest 45% comes from the bulk drugs. In FY 2005 exports grew by 21%. Indias pharmaceuticals imports were to the tune of Rs. 20.3bn in FY 2006. Imports have registered a CAGR of only 2% in the past 5 years. Imports of bulk drugs have slowed down in the past 2-3 years. The Indian pharmaceutical industry is highly regulated. The Government controls prices of a large number of bulk drugs and formulations. Profit margins of players vary widely in both domestic and export sales due to many factors.

Future Prospects:
As per WTO, from the year 2005, India will grant product patent recognition to all New Chemical Entities (NCEs) i.e. bulk drugs develop then onwards. This leaves another 3 years of MNCs research output open to process piracy. But, long-term prospects for MNCs are good.

Strategies of Domestic players:

Most of the domestic companies are expanding the therapeutic reach through new product launches in high margin segments, thus enhancing the product portfolio (proper basket of products helps in convincing the medical fraternity) and increasing the critical mass. The long-term objective will be to enter into a higher platform of biotechnology and drug delivery systems.

CADILA PHARMACEUTICALS
THE INDIAN PHENOMENON The Indian pharmaceutical industry is a success story providing employment for millions and ensuring that essential drugs at affordable prices are available to the vast population of this sub-continent. Richard Gerster
The pharmaceutical scenario in India consists of a host of varied companies. All compromising of a wide mix of organizational structures, climates and cultures. Running the gamut from the deeply traditional to the radically modern. Each advocating its special parameters for corporate success factors that differentiates between the merely good and the truly exceptional. And every once in a while, there comes along one, which is just that, truly exceptional. An organization that takes its work dead seriously and its word even more so. A work that stands for its deep-rooted commitment to its end-users, An organization like CADILA PHARMA markets, employees and associates. CEUTICALS LIMITED (CPL). A company that came into being shortly after independence, (1951) when India wasnt considered capable of handling something as crucial as health care and as critical as life saving drugs. It wasnt long before the detractors were proven wrong. Within a year, CADILA became the first pharmaceutical company in the world to provide Vitamin B1, B6 and B12 together, in a compatible form. Climbing steadily, from one triumph to another, crossing milestones in rapid succession, CADILA PHARMACEUTICALS LTD., over the years has established itself as a major pharma player. Having emerged successfully with largest range of therapeutic groups, spanning 45 segments, with offices in four countries, exports to 90 nations and a wide range of products registered oversees, CADILA PHARMACEUTICALS is a top 20 ranking Indian Pharmaceuticals Group. Backed by world-class R&D and manufacturing facilities, CADILA PHARMACEUTICALS covers the largest range of therapeutic groups, in the Indian Pharmaceuticals Industry.

Sphere of Activities

Research &Development Human Branded

Travel & Tea Estate Pharmaceutical

Hospital Disposables

Formulations
Generics Veterinary

Machinery Mfg.

Critical Care
Specialty Chemicals &

Herbal Ago Business Bulk Drugs International Business

Lab care

SPHERE OF ACTIVITIES

10

CADILA PHARMACEUTICALS Strategic Business Units International Business Human Branded Formulations Formulations & Development Research & Development

OTHER BUSINESSES

CASIL HEALTH PRODUCTS LTD. (CHPL)

Tea Estate Travel Pharmaceutical Machinery Manufacturing

Hospital Division Critical Care Division Diagnostics Division Chemicals Division Dietary Supplement Division

State-of-the-art Formulations Manufacturing Facility Marketing Consistently Creating Brand Equity CADILA Pharma Le sante' IRM Pharma Newgen Sante' Vision Imaging Division

Generics & ONCOCARE Animal Health & Natural Products Bulk Actives & Laboratory Chemicals

11

COMPANY PROFILE
Name of the concern Constitution Date of Incorporation Business Group Cadila Pharmaceuticals Limited Public Limited Company February 28, 1991 Cadila Pharmaceuticals (Modi Group) Cadila Pharmaceuticals Ltd. Casil Health Products Ltd. Karnavati Engineering Ltd. Green Channel Travel ServicesLtd. IRM Labs Ltd.

List of companies under Same management

12

Corporate office

Cadila Pharmaceuticals Limited "Cadila Corporate Campus"

Sarkhej-Dholka Road, Bhat, Ahmedabad-382 210, INDIA. Phone : +91-2718-225001 (15 Lines) Fax :+91-2718-225039 e-mail : [email protected]

Situated in the close vicinity of Ahmadabad, yet away from the hustle and bustle of the city life, is a serene location called Bhat. And their new Corporate Complex at Bhat has already sensationalized the location! Spread over 15 Acres piece of verdant, lush green land free from any kind of pollution, CADILA PHARMACEUTICALS New Corporate Complex is setting an example, in the corporate history of India.

Cadila vision

13

Our aim, to be a global player, will lead to the establishment of operations in the key markets of the world, including the developed countries. We shall seek joint ventures with partners who are major players in their country or region. We aspire to enrich our people - our driving force to become highly competent professionals and technology based. By the turn of this decade, we shall be amongst the most admired companies in India."

Cadila mission
14

"We strive for a happier, healthier tomorrow. We shall provide total customer satisfaction and achieve leadership in chosen markets, products and services across the globe, through excellence in technology, based on world-class Research and Development. We are responsible to the society. We shall be good corporate citizens and will be driven by high Ethical standards in our practices."

Our human resources will continue to be the most valuable asset in this pursuit of leadership and the prime driving force for our growth.

15

CADILA PHARMACEUTICALS

A True Life Sciences Company

CADILA

PHARMACEUTICALS,

Ahmedabad,

India

is

top

ranking

pharmaceuticals group with an annual turnover of Rs. 5500 million. In tune with its corporate objectives, CADILA PHARMACEUTICALS is rapidly expanding its global presence. CADILA PHARMACEUTICALS envisages a sharp focus on product segments for growth, coupled with strategic alliances in key areas. CADILA PHARMACEUTICALS is an integrated healthcare solutions provider comprising Strategic Business Units: Human Branded Formulations, Generic & Ontological Products, Animal Health & Natural Products, Biotech, Bulk Actives and International Business. The Company aims to take its exports turnover. Last year, in an effort to tape the North and South American markets, the company set up a US subsidiary; CPL Inc. Besides the company has already applied for 40 patents in the US to grow into new categories.

16

CPL has been awarded by Chemexcil (Basic Chemicals, Pharmaceuticals & Cosmetics Export promotion council by the ministry of commerce, Government of India) for an outstanding export performance for the year 2000-2001.

The company has state-of-the art formulation facility confirming to the most stringent international cGMP norms viz. WHO GMP, WHO, Geneva (GDF site for Anti- TB), TGA Australia (PIC/S), USFDA, UK- MHRA, MCC-South Africa, ISO 9001 and ISO 14001 norms is on stream up at Dholka, near Ahmedabad. It is no wood, no asbestos plant. The facility has been divided into various zones of cleanliness as specified in EU-GMP guidelines 1997 in total compliance of Federal Standards 209E of USFDA. The plant has already won many laurels including the stringent MCC South Africa and TGA Australian approvals.

17

Manufacturing Excellence

Pursuant to its corporate philosophy of striving for continuous improvement and betterment, the Company has re-located its manufacturing operations at the state-ofthe-art plant at Dholka, located 50 km from Ahmedabad, the commercial capital of Gujarat. Spread over 44 acres of verdant, picturesque surroundings, amidst lush green lawns and thick foliage, the new locale is the most envied pharmaceutical installation in the Asian sub-continent.

Truly unique in every sense of the term, the Plants standards and facilities can match any other, worldwide. Seven zones of cleanliness have been defined and adhered to, as per the 1997 GMP guidelines of the European Union. Some of the salient features of the design concepts:

No wood or asbestos component. Each zone has separate AHUs (Air Handling Units), dehumidification unit and dust extraction systems.

Segregation of every critical processing activity in each zone, to avoid crosscontamination.

Adherence to stringent specifications of USFDA, MCA(UK), MCC(South Africa) and TGA(Australia).

18

Respective zones, areas and even uniforms marked with specific colours of the rainbow (Indradhanush in the vernacular), to ensure total segregation.

Air environment conditioned 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; viz. 100, 1,000, 10,000, 100,000 with respect to room air changes, pressure, particle count, flow direction etc.

Duo Pass Reverse Osmosis (RO) water system, multi-stage distillation plant, self-sanitizing, sanitary SS 31 6L loops water, water for injection with online monitoring of pH, temperature, conductivity and TOC requirements as per USP XXIV.

Zero-discharge Effluent Treatment Plant constructed using technology from Advent Integrated System, USA.

Environment-friendly VAHP chillers. Rigvent heat extraction devices and Natural Skylit system in raw material, packing material and finished good stores.

Isolated and dedicated production facilities for B-Lactum and Cephalosporin dosage forms

19

SOFT GELATIN MANUFACTURING

Cadila Pharmaceuticals has also commissioned a modern, sophisticated

manufacturing facility for Soft Gelatin Capsules at its Kadi Complex. Designed to meet the most stringent international standards, all operations in this plant from encapsulation to packaging, are carried out under class 100,000. All systems are validated to meet International FDA standards, and the present capacity of one million capsules per day can be doubled with marginal investments

OTHER MANUFACTURING LOCATIONS

Surgical Supplies, Halol Plant Tissue Culture, Hirapur Casil Health Products Ltd., Pharma Machinery Manufacturing Facilities at Kadi Speciality Chemicals & Soft Gelatin Capsules Manufacturing Facilities at Kadi Active Pharmaceutical Ingredients (APIs), Ankleshwar

New Facility in J & K

Cadila Pharmaceuticals Ltd will commission its manufacturing facility for formulations in Jammu and Kashmir, by December this year. The Rs.600 Crore
20

Pharma company is investing Rs.45 Crore in bringing up this new facility at Samba to take advantage of the excise and income tax benefits being doled out by the Centre to promote investments in Jammu and Kashmir. This will not only help the company in fulfilling its corporate objective of making available quality medicines at affordable prices but also help in providing ample employment opportunities to the local population in Jammu, said Shri I. A. Modi, Cadila Pharmaceuticals Ltd. The unit will have a capacity to manufacture 1, 019.4 million tablets per annum, 1329 million tablets and capsule packing (strips and blisters), 150 million capsules, 1500 kiloliters liquid formulations and 14.4 million bottles. Several pharma companies from Gujarat have set up manufacturing facilities in taxfree zones such as Baddi in Himachal Pradesh, Uttaranchal and J&K. The facility will have a linear manufacturing structure with six manufacturing lines. Four lines will be for tablets, one for capsules manufacturing and sixth for liquid formulations. A company spokesman said that the total value of production from this unit is likely to be close to Rs.350 Crore per year. It would solely cater to the domestic market. The Jammu unit will also help us boost exports from the present facility at Dholka, near Ahmedabad, the spokesman said. The centre has exempted the payment of excise duty on the goods produced in Jammu and Kashmir for 10 years. They have also provided for income tax exemption for 10 years from the year of commercial production, besides several other financial benefits. Samba is situated on the National highway and CPL's factory is only 1.5 km away from the national highway.

Distribution Network

21

The company has more than 1,10,000 retailers, 2200 stockiest, 25 C & F agents and 36 full-fledged divisional agencies to keep the company in touch with the people in almost each and every part of the country. The countrywide distribution network is so strong that any new product launched by the company is available across the country within 72 hours.

22

RESEARCH METHOD
DEFINE THE RESEARCH PROBLEM

DESIGN THE RESEARCH PROCESS

CONDUCT THE PILOT SURVEY

ANALYSIS & MODIFICATION

CONDUCT THE MAIN SURVEY

COLLECT PRIMARY DATA FROM CUISTOMER

ANALYSIS & TABULATE THE DATA

INTERPRETE & REPORT THE FINDING

23

RESEARCH METHODOLOGY
The research was conducted in the following stages. 1. To define the research problem and identify the research objectives.
A molecule which is new in the market and presence of other substitute antibiotics makes competition high, it is necessary to understand the Drs choices of treating infection. Hence the objective of the project was decided as Potential Of Linezolid In ICU / Hospital

2. Design a research process. Research approach

Personal interviews with a structured questionnaire with doctors was decided as the medium to collect data which would be first hand and unbiased, directly from the customer.

Research instrument
A sample of questions first made and than after consulting with person in-charge relevant questions were filtered out for pilot survey.

Sampling plan
The nature of research necessitated the use of doctors with sample size of 60 in Ahmedabad. Main hospitals of Ahmedabad were surveyed.

Pilot survey
Twenty-five doctors from Ahmedabad was visited to check the efficacy of the research questionnaire

3. Analysis and modification.

The finding of the pilot survey suggested no change in the questionnaire, so as to obtain maximum possible information from the customer. No change were require in the research approach.

24

4. Main survey
Some potential doctors were also surveyed from the private clinics and ICU in-charge in hospitals with the total sample size of 60 doctors.

5. Data analysis
The data was analyzed systematically to give the following information. No of doctors which are normally using particular antibiotics in ICU/critical care setting. Preference of culture sensitivity test in percentage. Percentage of resistance gram(+)ve infection and resistance gram(-)ve infection. Top five choice of treatment for resistance gram(+)ve infection and resistance gram(-)ve infection. Effectiveness of different drugs in doctors point of view. Attributes for their prefrence. Brand that is in the top of doctors mind. Average no. of prescription given by doctors in a month.

6. Present the major findings.

The major findings of the survey have been highlighted. Certain suggestions and recommendation have been given to improve the sales.

25

ABOUT LINEZOLID
Linezolid is the leading agent in a new chemical class of antibiotics, the oxazolidinones, which have a novel structure. Oxazolidinones are protein synthesis inhibitors that prevent the formation of the bacterial 705 ribosomal initiation complex. Linezolid's unique targeting of the protein synthesis machinery has no pre-existing resistance mechanism in nature. During evaluation, there were no bacteria found that were resistant to linezolid. Thus, linezolid can be used as an empirical therapy when there is a known resistance to other classes of drugs. Oxazolidinones are active against Gram-positive bacteria, including antibiotic-resistant strains, such as methi-cillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PR5P), and vanco-mycin-resistant f nferococeus faecium (VREF). Linezolid is particularly useful in treating nosocomial infections that are resistant to other antibiotics. Linezolid is available in oral formulations, tablets, or oral suspensions, and is injectable. This gives linezolid an advantage over vancomycin, which can only be given by the intravenous (IV) route. Patients may be discharged from hospital early following IV linezolid therapy and continue oral therapy at home with no loss of efficacy. When administered to patients, a single 600 mg oral dose of linezolid results in a plasma concentration of up to 18 mg/L, which is higher than the minimal concentration required to inhibit the growth of S. aureus (4 g/L) for about 16 hours.3 This pharmacokinetic profile illustrates the effectiveness of linezolid in treating Gram-positive infections in humans.

26

DRUG FOCUS
Glycopeptlde-resistant enterococci The enterococci are normal commensals of the bowel with only moderate virulence in normals. They cause infections of the urinary and biliary tracts, sometime* wounds, and occasionally more serious and invasive disease in the compromised. They are becoming more common, probably because they are increasingly antibiotic resistant, especially to the cephulosporins. quinolones and aminoglycosidcs used against Gram-negative infections." Among the enterococci. Enterococcus fatcalis is the most common human pathogen; however, Enterococcta faecium, which is more inherently resistant, is being seen with increasing frequency. Furthermore, since the mid-1980s, VRE or ORE have appeared. This glycopeptide resistance is most commonly seen in K. faecium and usually occurs in renal, hepatic or haematological transplant patients. Some enterococci are thus now resistant to all commonly available antibiotics. GRE are most common in the US, where the percentage of enterococci resistant to vancomycin causing nosocomial infection increased from 0.4% to more than 10% between 1989 and 1995." GRE infections are less common in Europe, where, however, these organisms arc said to colonise the bowels of normal people in low numbers." This may be because, until recently, farm animals in many European countries were fed the growth-promoting glycopeptide avoparcin, which encourages colonisation with GRE and subsequent contamination of meat products." In the UK, GRE are being isolated from hospital patients in increasing numbers and several hospital outbreaks have besn seen. The most important and commonest type of glycopeptide resistance is called Van A, which is high-level resistance to both vancomycin and teicoplanin which can transfer between enterococci on plasmids and transposons. This resistance has been transferred in the laboratory to several other Gram-positive bacteria, including S. aureus." It is probably inevitable this will eventually happen in nature and the resulting high-level glycopeptide resistance in MRSA will be a much more serious problem than the present low-level resistance seen in sporadic isolates of VISA. Since we have become so dependent on the glycopeptides as the treatment of last resort for MAR Gram-positives, the transfer of high level Van A resistance from GRE to pneumococci and staphylococci could produce potentially untreatable and lethal infections.

27

NEW ANTIMICROBIALS FOR RESISTANT GRAM-POSITIVE INFECTIONS

The problem of increasing antibiotic resistance is now recognised as a global emergency and has been recently addressed in the UK by the reports of the House of Lords Science and Technology Committee (1998) and the Standing Medical Advisory Committee (1998).14 The problem can be partly resolved by improvements in the control of hospital cross-infection and the reduction of unnecessary antibiotic usage, but it is also essential to have new agents to treat MAR staphylococci, streptococci and enterococci.

Figure 1. The structure of linezolid

28

Several new drugs for resistant Gram-positive infections are in development, including new derivatives of macrolidex, kctolidcs. sireptogramins, quinolones and glycopeptides. The new intravenous streptogramin combination quinupristin plus dalfopristin (Synercid) was licensed for clinical use in Europe in 1999. Synercid is active against MAR pneumococci, staphylococci and enlerococci, but not E.faecalis. Fortunately, E.faecalis usually remains susceptible to ampicillin. All these agents are developments or derivatives of older drugs. To these can now be added the oxazolidinoncs. the first new class of antibacterial compounds to be developed in more than two decades.

LINEZOLID, THE FIRST OF THE OXAZOLIDONONES

The oxazolidinones are entirely artificial compounds that were first discovered by the DuPont Company in the 1970s. Some early oxazolidinones had in vitro activity against Gram-positive bacteria, but they were not developed for human use because of serious animal toxicity. The Upjohn Company (now Pharmacia & Upjohn) revived oxidolidinone research in the 1990s and discovered new derivatives that retained good antibacterial activity but without animal toxicity. The first of these to be developed for clinical use is linezolid (Zyvox) (formerly U-100766), a synthetic 3-(fluoropbenyl)-2-oxazolidiiione that has a morpholin-1-yl group substitution (Figure 1). Linezolid was licensed for clinical use in the US in March 2000, but much of the information on linezolid has not yet been published in peer reviewed journals and is held on file by Pharmacia & Upjohn. However, a document produced by the manufacturers for the Anti-Infective Drug Products Advisory Committee meeting of the Food and Drug Administration (FDA) last March contains much of the relevant information.

Antimicrobial activity, mechanism of action and development of resistance

Linezolid is active against most clinically important Gram-positive cocci, including penicillin-resistant pneumococci, MRSA and GRE, with minimum inhibitory concentrations (MICs) ranging from 0.25 to 4 mg/1 and usually falling between 1 and 2

29

mg/1" . Breakpoints of 2-4 mg/l" have been suggested ( isolates with in vitro linezolid MICs of =<2 mg/1 or =<4 mgfl are susceptible).

DATA ANALYSIS
1) In ICU/critical care setting which antibiotics do you use and why ?
__________________________________________________________________________________ __________________________________________________________________________________

Finding :
Top Five Choices of antibiotics Sr.no 1 2 3 4 5 Name Cephalosporin Aminoglycocide Augmentin ceftazidine Amoxicillin No. of Doctor 22 12 10 7 3

30

No.of Doctor

19% 22% 13% 6% 1 Cephalosporin 2 Aminoglycocide 3 Augmentin 4 ceftazidine 5 Amoxicillin

40%

Interpretation:
In I.C.U./critical care setting majority of Drs. are cephalosporin. Preferring

Reason :
Cephalosporin good result (Cefotexin +Amikacin+metrogyl) combination. Cover all bacterial infections. Aminoglycocide good response from patients.

31

Mainly ceftazidine for good result & both gram +ve and gram ve coverage.

2) How many cases of infections do you investigate for culture sensitivity?

(a) upto 25% (b) (c) upto 75% (b) upto 50% (d) upto 100%

Finding:

32

Sr .no 1 2 3 4

Option (a)up to 25% (b)up to 50% (c)up to 75% (d)up to 100%

No.of Drs 17 11 13 19

32%

28% 25% 50% 75% 22% 18% 100%

Interpretation:

All doctors preferring culture sensitivity test.

33

(3) From these what are % of resistant gram (+)ve and gram (-)ve infections? ___________________________________________________________ ___________________________________________________________ Finding:
Average 80% 60% 40% 20% 0% Gram +ve Gram -ve 37%

63% Average

Interpretation:

Cases of gram (+)ve infection is comparative low than gram (-)ve infection.

34

(4) Your choice of treatment for gram (+)ve infection.

(a)_______________________________________________________. (b)_______________________________________________________. (c)_______________________________________________________. (d)_______________________________________________________.

Finding:
Top Five Choice of antibiotics Sr. no Name 1 Cephalosporin 2 Augmentin 3 (Amoxicillin+clavulinic acid) 4 Linezolid 5 Vancomycin No.of Doctor 21 13 12 11 11

No.of Doctor

1 Cephalosporin 2 Augmentin

16% 31% 16% 18% 19%

3 (Amoxicillin + clavulinic acid) 4 Linezolid 5 Vancomycin

Interpretation:

35

 IIIrd or IVth Cephalosporin, (Amoxicillin + Clavulinic acid) combination, Vancomycin, Linezolid. These are the main choice of doctors while treating gram positive infections, in that Cephalosporin is most preferable.

(5) Your choice of treatment for gram (-)ve infection . (a)________________________________________________________. (b)________________________________________________________. (c)________________________________________________________. (d)___________________________________________________________. Finding:
Top Five Choice of antibiotics Sr.no Name 1 Amikacin 2 Cephalosporin 3 Aminoglycocide 4 (Piperaceline+Tazobactum) 5 Quinolone No.of Doctor 24 20 18 7 6
1 Amikacin 8% 9% 32% 2 Cephalosporin

3 Aminoglycocide 24% 4 (Piperaceline+Taz obactum) 5 Quinolone

27%

Interpretation:
36

 Aminoglycocide, (Amikacin/Tobramycin), (Piperaceline + Tazobactum) combation, IIIrd or IVth Cephalosporin. Main preference of the doctors is Aminoglycocide and (Amikacin/Tobramycin) while treating gram ve infection . (6) While treating gram (+)ve infections how do you define effectiveness of these drugs. Not Good (a) Linezolid (b)Vancomycin (c) Teicoplanin (d) Meropenam (e) __________ (any other please specify) Ok Good Excellent

37

Effectiveness
35 30 25 cases 20 15 10 5 0 1 14 10 6 0 1 0 13 14 13 12 7 2 26 23 20 15 14 9 31

Linezolid Vancomycin Teicoplanin Meropenam

Performance

Interpretation:
Vancomycin is Excellent one in case of effectiveness against gram(+)ve infection, than comes Meropenam. Linezolid and Teicoplanin are consider as a Good one.

38

(7)

In ICU/ critical care setting which antibiotic do you feel is must and why ?

____________________________________________________ ____________________________________________________

Finding :

Sr .no 1 2

Option Depend Others

No. of Drs 36 24

In Percentage 60% 40%

39

Any must antibiotics

40% 60%

Depend on culture sensitivity Others

Interpretation:
60% doctors thinking depends upon culture sensitivity. 40% doctors giving other antibiotics name. Some doctors preferring Cephalosporin for gram (+)ve infection and Aminoglycocide for gram ()ve infectionand some are preferring (Piperaceline + Tazobactum) combination.

(8)Please rank the below given criteria for Rx in terms of their importance while
treating resistant gram (+)ve infection.

(a) Cost (c) Safety

(b) Efficacy (d) Availability

Finding:

40

Ranking
60 Performance 40 20 0 18
6

53
41

33 24 00 0
2

34 26 0
0

10

First Second Third Forth

Efficacy First Second Third Forth 53 6 1 0

Safety 18 41 0 0

Cost 0 2 24 33

Availabili ty 0 0 34 26

Factors

Interpretation:
Majority of Drs. preferring EFFICACY hence they are preferring SAFETY also, but the no. 1 ranking is EFFICACY. Very few doctors concerning with price, but the availability is in-evitable.

9) Do you use Linezolid ?

Why ?

Yes

No

___________________________________________________________________ ___________________________________________________________________.

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Finding :Sr. no 1 2 Using Yes No No.of Drs 48 12

Using Linezolid
No 20% Yes No Yes 80%

Interpretation:
80% doctors are using Linezolid so, great potential of Linezolid was found.

Reasons : Good coverage. Economically and effective. To cover M.R S.A. I.V & oral available.

10) Name one brand / company of Linezolid which come first to your mind. (a) _______________________ Why ?

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(i) (ii) (iii) (iv) (v) (vi) (vii)

Efficacy Regular M. R. visit CME attended Regular information provided by company Price Discount Availability

Finding:
Sr. no 1 2 3 4 5 Name of Brand Linox Linid Lizolid Lizbid Targocid No.of Doctor 16 16 7 5 1

No.of Doctor 11% 2% 16% 35%

36%

1 Linox 2 Linid 3 Lizolid 4 Lizbid 5 Targocid

Interpretation:

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 Linox ( from Unichem) and Linid( from Cadila) both are equal positioning in the mind of doctors as shown in pie chart.

Reason :
EFFICACY and AVAILABILITY these are main reasons. Then comes the regular M.R visit.

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(11) Approx no of prescription given for Linezolid in a month ________________

Finding:
Sr. no 1 2 3 4 5 6 7 8 Range 2 to 3 1 to 2 4 to 5 3 to 4 7 to 10 10 to 15 5 to 6 15 to 20 No.of Doctor 12 11 7 6 6 3 2 1

Prescription in a month
1 3 2 6 6 11 7

12

2 to 3 1 to 2 4 to 5 3 to 4 7 to 10 10 to 15 5 to 6 15 to 20

Interpretation:

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 2 to 3 prescription in a month found 12 times which is highest. Than comes 1 to 2 prescription in a month found 11 times. There is also not available or none prescription found in 11 sample. We can say majority of doctors giving prescription in range of 1 to 3.

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FINDINGS
Cephalosporins is mainly use as antibiotic in critical care setting due to good coverage. All the doctors go for culture sensitivity report. There are comparatively low cases of gram(+) infection found. Cephalosporins is mainly use for treating gram(+) infection. Amikacin is mainly use for treating gram(-) infection. Vancomycin and Teicoplanin these drugs are Execellent while treating gram(+) infections. Any antibiotics is not must this is depends upon culture sensitivity. But some doctors preferring Cephalosporin for gram (+)ve infection and Aminoglycocide for gram ()ve infection and some are preferring (Piperaceline + Tazobactum) combination. 88% doctors giving the no.1 rank to Efficacy. 80% doctors are using linezolid. Reason: Good coverage. Economically and effective. to cover M.R S.A. I.V & oral available.

16 times Linox and 16 times Linezolid both are comes first in the mind of
doctor.

Reason:

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EFFICACY and AVAILABILITY these options are mainly selected , then comes the regular M.R visit options

Average 1 to 3 prescription given by doctors in 1 month.

RECOMMENDATION
The observation and finding of the survey reveals that the company should increase awarness programme of Linezolid molecule, which is as a trade name of LINID. Since it was launched before One year. It is important to mention about efficiency and effectiveness of LINID (contain linezolid). On which stage of infection or condition it is more effective. Company should go for big seminar, which cover all potential doctors as well as ICU in-charge, so company can put special image of Linid in mind of doctors. Another way to attract doctors by giving regularly exciting gifts so we can get the advantage of doctors in this competitive market The company should target not only to the big hospital but also other Potential doctors doing practice in private clinics or in small hospitals. Company can improve our antibiotic product line by introducing antibiotic for resistance gram(-)ve infection. Because scenario of resistance gram(-)infection very high in critical care setting/ICU. So we can get another advantage of getting high market share. If possible company go for that kind of antibiotics which react fast while treating resistance gram(+)ve infection.

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CONCLUSION

From the overall survey and findings it shows that the Potential of Linezolid is Good in ICU/hospitals. It is good in terms of effectiveness but from the doctors point of view vancomycin is excellent one. Now a days prescription of linezolid is increasing, so the usage of Linid for treating gram(+)ve infection is progressive.

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ANNEXURE
Name of Dr. ________________________________ Qualification / Speciality _______________________ Address ____________________________________ ____________________________________________ Ph . no ____________ email-id __________________

POTENTIAL OF LINEZOLID IN ICU / HOSPITAL

1) In ICU/critical care setting which antibiotics do you use and why ? ____________________________________________________________________ ____________________________________________________________________ __ 2) How many cases of infections do you investigate for culture sensitivity? (a) upto 25% (b) upto 50% (c) upto 75% (d) upto 100%

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(3) From these what are % of resistant gram (+)ve and gram(-)ve infections? ___________________________________________________________ ___________________________________________________________ (4) Your choice of treatment for gram (+)ve infection. (a)_______________________________________________________ (b)______________________________________________________ (c)_______________________________________________________ (d)_______________________________________________________ (5) Your choice of treatment for gram (-)ve infection . (a)___________________________________________________________ (b)__________________________________________________________ (c)___________________________________________________________ (d)___________________________________________________________ (6) While treating gram (+)ve infections how do you define effectiveness of these drugs. Not Good (b) Linezolid (b)Vancomycin (c) Teicoplanin (f) Meropenam (g) __________ Ok Good Excellent

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(any other please specify) (7) In ICU/ critical care setting which antibiotic do you feel is must and why ? ____________________________________________________ ____________________________________________________ (8) Please rank the below given criteria for Rx in terms of their importance while treating resistant gram (+)ve infection (a) Cost

(b) Efficacy

(c) Safety

(d) Availability

9)

Do you use Linezolid ? why ?

Yes

No

___________________________________________________________________ ___________________________________________________________________. 10) Name one brand / company of Linezolid which come first to your mind. (a) _______________________

why ? (i) Efficacy

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(ii) (iii) (iv) (v) (vi) (vii)

Regular M. R. visit CME attended Regular information provided by company Price Discount Availability

(11) Approx no of prescription given for Linezolid in a month _______________.

BIBLIOGRAPHY

Marketing Management by Philip kotler www.google.com www.cadilapharma.com

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