INDIAN PHARMACEUTICAL INDUSTRY;CHANGING DYNAMICS_Essay by DHANALAKSHMI M


  1. India’s cost of production is nearly 33 per cent lower than that of the US
  2. Labour costs are 50–55 per cent cheaper than in Western countries. The cost of setting up a production plant in India is 40 per cent lower than in Western countries
  3. Cost-efficiency continues to create opportunities for Indian companies in emerging markets & Africa
  4. India has a skilled workforce as well as high managerial & technical competence in comparison to its peers in Asia
  5. India has the 2nd largest number of USFDA-approved manufacturing plants outside the US
  6. India has 2,633 FDA-approved drug products. India has over 546 USFDA-approved company sites, the highest number outside the US

The divisions in the Indian Pharmaceutical Industry are as follows:
 A. API Manufacturers / Traders ( Bulk Drugs)
 B. Formulation Manufacturers
C. Contract Research and Manufacturing Services Companies
 D. Biotechnology Companies
 Bulk drug exports, constituting 80-90% of total bulk drugs production, accounted for about 33% of total sales in the pharmaceutical industry in 2013-14. The share of bulk drugs is higher in India as compared with developed countries, where bulk drugs are primarily manufactured for domestic consumption.

API Manufacturers / Traders (Bulk Drugs)
The Bulk drug exports : 2008-09 :CAGR of about 18% between
                                     2013-14 :to USD 11.9 billion
Of this, exports to regulated markets, which had a 49% share, grew at a CAGR of about 21% over the past 5 years. In exports to regulated markets, exports of on-patent drugs are estimated to have surged at a 29% CAGR (on a low base), while that of off-patent drugs maintained a growth rate of 15% over the past 5 years upto 2013-14.

API manufacturing to cut costs.
             Major global innovators will not only extend existing deals with Indian players but will also look to increase sourcing of bulk drugs from Indian companies. Indian bulk drug exports have shifted in favour of regulated markets. This is evident from the increase in the share of these markets to about 49% in 2013-14 from about 43% in 2008-09.
            The share of regulated markets in Indian bulk drug exports to rise to about 51% by 2018-19, driven by Indian manufacturers' better process chemistry skills, low manufacturing costs, a higher number of drug master filings (DMFs), the expected expansion of key generic markets and cost reduction initiatives by large global companies.

Formulation Manufacturers
            The slowdown was mainly on account of import alerts on Indian companies, slowdown of growth in Europe and increased competition during the year. In the overall regulated markets, exports to the US grew at about 11% to USD 3.4 billion, lower than the close to 22% growth seen last year. On the other hand, exports to the European Union grew by just about 6% during the year to USD 1.5 billion in exports. This was another consecutive year of slow growth, with 10% growth ~ seen in 2012-13. Region-wise, the European Union market recorded an almost-flat growth in the leading markets of the UK, Germany, the Netherlands, Belgium and Spain during the year. Exports to semi-regulated markets grew steadily by an estimated 12% y-o-y in 2013-14 led by exports to the African and Asian continent during the year. Exports to Asia and Africa grew by almost 17% to reach close to USD 4.5 billion in 2013-14 (about 78% of the total semi-regulated market exports), mainly led by growth in exports to the top 30 destinations out of the roughly 124 export destinations in these two continents put together.

Contract Research and Manufacturing Services (CRAMS)
            Contract Research and Manufacturing Services (CRAMS) is one of the fastest growing segments in the pharmaceutical and biotechnology industry. It pertains to outsourcing research services/ manufacturing products to low-cost providers with world class standards, in line with international regulatory norms such as USFDA, Australian-TGA, UKMHRA, and EMEA. Pharmaceutical multinationals have traditionally been outsourcing manufacture of intermediates, API's and formulations.
             Indian CRAMS companies are the most preferred players for global pharmaceutical companies due to their product mix being skewed towards high-end research services, biologics and complex technology services, at low cost. India offers an abundant pool of professionals in the area of drug development and research chemistry with large number of pharmacists and chemistry post graduates qualifying every year. According to the Indian Government, by 2020, India would be one of the top five pharmaceutical innovation hubs with one out of every five to ten drugs discovered in India. CRAMS as a segment constitutes of Contract Research Organization (CRO) & Contract Manufacturing Organization (CMO), of which CMO constitutes a major portion (>60%) of the overall business. A Contract Research Organization (CRO) is an organization that provides support to the Pharmaceutical Industry, Biotechnology and Medical Device Industries in the form of Research Services Outsourcing on a contract basis.
 A CRO may provide such services as biopharmaceutical development, biologic assay development, commercialization, pre-clinical development, clinical research, clinical trials management, and Pharma co-vigilance. CROs specifically provide clinical-study and clinical-trial support for drugs and/or medical devices. CROs range from large, international full-service organizations to small, niche specialty groups. CROs that specialize in clinical trials services can offer their clients the expertise of moving a new drug or device from its conception to Food and Drug Administration/European Medicines Agency marketing approval, without the drug sponsor having to maintain a staff for these services.

Significance of CRAMS
With an increasing focus on managing costs and shortening time to market, many pharmaceutical companies now outsource their clinical trials to CROs. CROs are hired by pharmaceuticals companies and medical-device makers to provide research services such as overseeing discovery, preclinical and clinical testing.
            

Biotechnology refers to the application of scientific techniques using living organisms or their parts to make or modify plants, animals, micro organisms or environment to enhance their performance and values. In the recent years biotechnology has emerged as a major focal point for the developed as well as the developing nations. It has a greater vision to sectors such as human health, agriculture and environmental science for the future. The Biotech Industry comprising Bio-Pharmaceuticals, Bio-Services, Bio- Agriculture, Bio-Industrial and BioInformatics is among the country's rising sector and is growing at CAGR of 20%.            

            The market size of this sector was estimated at around USD 4 billion in 2013-14. India is among the top 12 biotech destinations in the world and ranks second in Asia, after China. The Indian biotechnology industry has evolved over the last three decades and the sector's revenue has rapidly increased from USD 300 million in 2002-03 to USD 4 billion in 2013-14. The Indian Biotechnology sector is presently divided into five segments based on the products and services offered. These segments are Bio-Pharmaceuticals, Bio-Services, Bio- Agriculture, Bio-Industrial and BioInformatics.
             Bio-Pharma is the largest sector contributing to 62% of the total revenue followed by BioServices, Bio-Agri and Bio-Industrial sectors which contribute 18%, 15% and 4% respectively. Bio-Informatics is still at a nascent stage contributing to only 1% of the total revenue. Bio-Pharmaceuticals This constitutes the largest segment of the Indian biotech industry both in terms of domestic and export revenues. In 2013-14, bio-pharma generated revenues of USD 2.5 billion comprising approximately 62% of the domestic biotech industry. The Bio-Pharma sector includes vaccines, therapeutics and diagnostics. The highest growth was witnessed in the year 2003-04 when the growth crossed the 50% mark. The growth rate dwindled thereafter reaching a low of 12% in 2009-10. However in 2013-14, the growth saw positive signs and again increased to 18%.

Bio-Services
            Bioservices is the second largest sector of the Indian Biotechnology industry with revenues amounting to USD 600 million. The growth rate of this segment could be attributed to the fact that India has become a popular destination for clinical trial, contract research and manufacturing activities. The sector witnessed a growth of 16% in 2013-14. The highest growth of 104% was witnessed in the year 2003-04.

Indian Biotechnology
            The global biotechnology industry is undergoing a transformation, thereby creating enabling factors that can lead to the growth of the Indian Biotech Industry. Increasing cost of bringing a new drug to the market: India can play a key role in reducing cost and time to market for new drug development through outsourcing of various components of the drug ü development process Top pharma companies spend a large part of their research for in licensing new modules: There is an opportunity for R&D focused Indian biotech companies to enter into such alliances through collaborative development projects Inflammatory & Infectious disease segment high on agenda: In the Indian context these are the two of the strongest disease segments with a huge domestic market Early stage deals are more common compared to the middle and late stage deals: Indian companies with limited financial resources can optimize business models by partnering with larger companies for product development and licensing at an early stage

Regulatory Environment in India
            The Pharmaceutical Industry is characterized by maintenance of high quality standards as it concerns the lives of people. Regulatory bodies impose regulations to ensure that drugs meet the safety and quality standards. Regulatory bodies not only ensure that pharmaceutical companies meet the set quality standards, but also ensure that the pharmaceutical companies do not charge unreasonable prices from consumers. The stringency of regulatory procedures varies across countries. On the basis of established regulations and patent laws, the global pharmaceutical industry can be broadly classified into regulated and semi-regulated markets.

            Regulated markets include the USA, EU and Japan that have established systems of patent laws regulated markets include countries such as China, India and South Africa, which have less stringent systems of patent laws and less sophisticated regulatory systems for drug quality control.

            The Pharmaceutical regulatory environment in India comprises of the participants as displayed in the schematic arrangement below. The Drugs and Cosmetics Act, 1940 (Drugs Act) and Drugs and Cosmetic Rules, 1945 (Drug rules) regulate the import, manufacture, distribution and sale of drugs in India. Under the provisions of these Acts, the Centre appoints the Drugs Technical Advisory Board (DTAB) to advise the Central Government and the State Governments on technical matters. Under the Drugs and Cosmetics Act, State authorities are responsible for regulating the manufacturing, sale and distribution of drugs, whereas the central authorities are responsible for approving new drugs and clinical trials, laying down the standards for drugs, controlling the quality of imported drugs, and co-ordinating the activities of State drug control organisations.

            The Drugs Controller General of India (DCGI) is the central body that co-ordinates the activities of state drug control organisations, formulates policies and ensures uniform implementation of the Drugs Act throughout India. It is also responsible for approval of licenses of specified categories of drugs, such as blood and blood products, IV Fluids, Vaccine and Sera. Indian Pharmaceuticals Industry is mainly regulated on the basis of patents, price and quality Central Government DCGI State DCO Regulatory Bodies Co-ordinating activities
 • Approval for setting up manufacturing facilities
 • License to sell and stock drugs
• Recall of sub-standard drugs
 • Licensing of drug testing laboratories State Government
• Formulating policies
• Ensure uniform policy implementation across India
 • Policy approval and standards
• Clinical trials
• New drug introduction
• Import licenses for new drugs

The India Advantage in the Life sciences Industry
             India has emerged as a pharmaceutical supplier in the international markets. This is not only because of a lowcost manufacturing, operations and research base but also a combination of additional factors such as process improvements in manufacturing API, faster recruitment for conducting clinical trials, availability of skilled manpower and developed regulatory skills. In Contract Research Business, India is also an ideal location due to availability of skilled manpower and a large patient population which results in faster recruitment of patients. With low costs, highly competitive market and only process patents till recently, Indian companies have developed expertise in process innovation.
 Low Cost Labour costs in India are about 1/7th the levels in developed countries and offer an obvious cost advantage. American or European generics companies without API capabilities almost always have to source from India or China. Strong Product Pipeline Geographical Diversification Cost Competitiveness Assured API Supply Control over front end

Biogenerics
            Biopharmaceuticals are defined as pharmaceuticals manufactured by biotechnology methods, with the products having biological sources, usually involving live organisms or their active components. Biopharmaceutical drugs (or biologics) address areas of clinical need that are unmet by conventional therapeutics (including many cancers and genetic diseases). Biosimilars/ Biogenerics are essentially generic versions of Biopharmaceuticals. The introduction of similar biological medicinal products (biosimilars) into clinical practice presents new challenges that are not ordinarily presented by small-molecule generic medicines. This is because a biosimilar can only be proven to be similar and not identical to its reference product.
            In addition, all biotechnology products, including biosimilars have a potential to cause immunogenic events that are not caused by smallmolecule products. Some countries already have widely prevalent biogenerics in their pharma markets. China, Eastern Europe, India and South America already have biogenerics marketed along with other formulation generics. Biogenerics already command high prices in many countries, especially the USA, and are expected to be potential sources of sizeable future income for the generics industry, with profit levels expected to be higher than those of traditional generics. Most biological drugs command a higher price than traditional formulations because of their difficult to make nature and high stress on quality.
             The cost of entering into the Biosimilars market is considerably higher than that of generic pharma manufacturing. Besides Dr. Reddy's, Wockhardt and Shantha Biotech, many other companies like Intas Bio, Zydus Cadila, and Emcure are developing various molecules in the biogeneric segment.
Product pipelines of Indian players such as Ranbaxy, Dr. Reddy's, Aurobindo, and Sun Pharma are comparable with that of global generics giant. Indian companies received final approval for 154 ANDAs during the year 2013 from US FDA and 38 tentative ANDAs approval during 2013. The US FDA has approved a total 400 final ANDAs during the year 2013 as against 476 in the previous year and it approved total 86 tentative ANDAs during 2013 as against 94 during 2012. Out of the total approvals, Indian companies grabbed 38.5% final approval during 2013 as against 37.4% in the previous year.
Thus, generic manufacturers are leveraging this opportunity by increasing their ANDA filings. b) Low-cost Manufacturing Base Production cost in India is about 50%-60% lower as compared with developed countries, such as US and Europe, because of lower labour cost which is 50%-55% cheaper and capital cost of setting a production plant in India is 40% lower than in western countries. As a result, outside the US, India has the second-highest number of USFDA-approved plants after China. India is home to more than 523 USFDA approved drug manufacturing facilities as on March 31, 2014.

Key advantages for Indian companies
Ø  process development
Ø  synthesis skills
Ø  quality
Ø  cost effective manufacturing facilities.
The product range encompasses a wide variety of therapeutics and from pharmaceutical intermediates to finished dosage forms (formulations). Contract Research Segment (CRS) is an end result of the discovery process being outsourced to cost-efficient destinations like India and China. The process is a mix of drug discovery, pre-clinical and final clinical development, leading to a new chemical entity. This being a time and capital consuming process is well aided by CROs across the globe.
Declining R&D Productivity Increasing Cost base 1,000 Compounds Screened 700,000 Screening Hits 12 Candidates 1 Product 3 2 1 50% fail in Preclinical 30% fail in Phase I 50% fail in Phase II Attrition on the R&D Process 6 Candidates Discovery Exploratory Development Full Development PhaseI PhaseII PhaseIII

Contract Research & Custom Synthesis (CRS) -
            There is a clear realization that small volume intermediaries can be economically sourced from countries like India without any compromise in quality. This opportunity is expected to grow as the product patent regime has kicked in, giving significant comfort to big pharma with respect to IP protection. Drug Discovery & Development (CRS) - As per industry estimates, the gobal outsourcing market for drug discovery services was pegged at USD 10 billion, and is expected to cross USD 15 billion by 2020. Drug discovery services include areas such as Analogue Research, Combinatorial Chemistry, Chiral Chemistry, New Drug Delivery Systems and Phyto-Medicine. Other services include combinatorial chemistry synthesis, compound purification and characterization and finally creation of different types of libraries of novel compounds. Biology Services (CRS) - These services include
 i) identifying and characterizing targets involving genomics, proteomics, structural biology, computer modeling and protein functioning technologies
 ii) screening including assay development and
iii) lead optimization for enhancing qualities of lead candidates using ADMET (absorption, distribution, metabolism, efficacy and toxicity) predictive techniques and structure activity relationship (SAR).
Clinical Research (CRS) - More than 40% of drug development costs are incurred in clinical trials, and India in addition to its vast and diverse genetic pool has a distinct cost advantage in the area. As per industry estimates, the cost of conducting clinical trials in India is between 40-60% of equivalent trials in US or Europe. Also, companies are potentially looking at undertaking quick small trials to lead to fast and cost effective go/no go decisions, especially for new indications.
The Indian Pharma industry is showing signs of healthy growth and is likely to be in the top 10 global markets by value by 2020. The major drivers of increase in revenues would be the branded generics segment and the emergence of the contract research and manufacturing services.

Cost Advantage in Clinical Research Outsourcing to India
            With adequate support from the Government, the clinical research industry would definitely witness greener pastures. The sector has significant cost advantage as compared to other geographies in the world. In addition to this, the diverse patient pool and highly skilled manpower will indeed make India into an attractive clinical research destination. India by virtue of its cost effective human resource pool and currency, offers direct operational cost advantage in the conduct of clinical trials. A large part of the cost advantages also stem from the potential time saving by undertaking concurrent trials in India - aided by large patient population, better patient accruals, a reasonably good pool of ICH GCP aware clinical investigators, amongst others.


Road Ahead:

The Indian pharmaceutical market size is expected to grow to US$ 100 billion by 2025, driven by increasing consumer spending, rapid urbanisation, and raising healthcare insurance among others. Pharma sector’s revenues are expected to grow by 9 per cent year-on-year through fiscal 2020.Going forward, better growth in domestic sales would also depend on the ability of companies to align their product portfolio towards chronic therapies for diseases such as such as cardiovascular, anti-diabetes, anti-depressants and anti-cancers that are on the rise.
The Indian government has taken many steps to reduce costs and bring down healthcare expenses. Speedy introduction of generic drugs into the market has remained in focus and is expected to benefit the Indian Pharmaceutical companies. In addition, the thrust on rural health programmes, lifesaving drugs and preventive vaccines also augurs well for the Pharmaceutical companies.

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