The pharmaceutical industry is responsible for developing through invention ; bring forthing through preparations ( such as tablets, capsules, injections, picks, lotions, etc. ) and marketing drugs that are used as medicines to handle assorted diseases. The pharmaceutical industry is one of the most complex concerns in the planetary economic system. As there is a battalion of factors involved in the pharmaceutical industry, it is besides one of the most regulated industries in the universe. The chief focal point of the pharmaceutical industry is to come up with drugs that are first-class in footings of quality, safety and efficaciousness.
HISTORY OF DRUG REGULATION: During the passage stage from 19th to twentieth century, pharmaceutics was a scientific discipline still in its juvenile phases. The most common method of fabricating drugs was by treating them with custodies in the local pharmaceutics units. It was really hard to guarantee consistence in design and composing of the drugs because progress engineerings and equipment to determine and measure the uniformity of content were non-existent. The most of import challenge faced by the 19th and twentieth century pharmaceutical patterns was to supply a concrete definition for DRUG was and to specify acceptable criterions of composing, pureness, and strength. The most of import development in this way was marked by the creative activity of the US Pharmacopoeia ( USP ) in 1820 ( FDAReview.org, 2008 ) .
Two chief events led to strategic enterprises in the field of modulating drugs. These were the Sulphanilamide catastrophe and the Thalidomide calamity. The first one i.e. Sulphanilamide catastrophe occurred in 1937 in the US. The chief cause was an elixir of the medical specialty sulfanilamide that was non prepared decently and the ingestion of which led to mass toxic condition in the US doing a loss of more than 100 lives. This mishappening prompted the USA Food, Drug and Cosmetic Act in 1938, which required pre-approval before distribution of a new drug. The Food, Drug and Cosmetic Act, besides introduced the New Drug Application ( NDA ) although at that clip there was no demand for cogent evidence of safety, merely efficaciousness needed to be demonstrated. This jurisprudence continued until the following milepost i.e. the Thalidomide calamity which occurred in the early sixtiess. Thalidomide was a drug that was introduced as a depressant ( narcotic tranquillizer ) drug in the late fiftiess. In 1961, it was withdrawn from the market owing to widespread terrible birth defects reported in newborn babes due to the ingestion of this drug by pregnant adult females. This calamity is still termed as “ one of the biggest medical calamities of modern times ” with the figure of distorted babes runing from 10,000 to 20,000 ( Anon, 2010 ) . This was a peculiarly sensational event and led to a much stricter and strict testing government for drugs before they could be marketed to the general populace. The US Food & A ; Drug Administration ( FDA ) foremost introduced Good Manufacturing Practice Regulations in 1948, but it was non until 1962 that explicit statutory power was given to these ordinances. Since those yearss, the demands for the industry and testing of medicative merchandises, and merchandise licence applications have changed drastically.
Pharmaceutical COMPANIES: Most of the pharmaceutical companies came into consequence in the 19th and the early twentieth century but the field still remained little graduated table in range. The major development and enlargement work in the field of pharmaceuticals started merely after 1970. Few cardinal mileposts in the history of pharmaceuticals occurred during the 1920s and 1930s when cardinal drug finds in footings of insulin and penicillin were made. These were the first drugs that were manufactured on a big graduated table and distributed. During this period, the European states developed peculiarly strong pharmaceutical industries and this is the chief ground why most of the pharmaceutical giants are headquartered in the European states. In the 1940s, authorities ordinances were released to label drugs as prescription medical specialties ( available merely with a physician prescription ) and non-prescription drugs ( available as over the counter drugs ) . 1950s saw a drastic development in the biotechnology sphere of the scientific attacks such as researches on human biological science and DNA. In 1970s, there were several enterprises to get down a mass enlargement in the field of pharmaceuticals. During this epoch, the pharmaceutical industry witnessed patents coming in to coerce in most states. Mid-1980s were marked by little biotechnology houses coming in to existence but these were still non a dominant force.
Two chief countries where all pharmaceutical companies delve into are the Core Pharmaceutical Business that involves patented molecules and new chemical entities and Biotechnology based Pharmaceutical Products that involve drugs and molecules that are biotechnology derived merchandises. Biotechnology derived merchandises is an umbrella term used for a aggregation of merchandises that have been prepared by a big figure of specialised engineerings and processes that involve the usage of life beings or their units to fix and develop merchandises that have an added-value and are pharmacologically feasible i.e. they can bring forth a coveted medicative consequence in the human existences or animate beings and can be used as medical specialties for the improvement of the human race. Pharmaceutical companies that utilize these procedures and techniques extensively on the industrial and commercial graduated table are referred to as biotechnology based companies.
PHARMACEUTICAL & A ; BIOTECHNOLOGY INDUSTRY: GLOBAL Scenario
Gross saless AND Gross: Global market scenario for the pharmaceutical companies can be predicted on the footing of the company ‘s one-year and quarterly study, overall market and economic province of personal businesss. In 2006, planetary pharmaceutical gross revenues totaled US $ 643 billion with a growing of 7 % from the old twelvemonth ( IMS Health, Feb 2007 ) . Strongest growing in pharmaceutical gross revenues since 1998 was reported by North America ( 12.6 % per twelvemonth ) compared to 9.3 % in Europe and 2.9 % in Japan ( Office of Fair Trading [ UK ] , Feb 2007 ) . The three major markets i.e. North America, Europe ( including the UK ) and Australia represent 45 % , 23 % and 1 % of entire planetary gross revenues ( IMS Health MIDAS, 2007 ) .
However, anticipations of high growing for the late introduced merchandises or gross revenues loss could non be predicted ever with absolute certainty due to frequent challenges encountered in the pharmaceutical industry viz. patent termination, generic entry, labeling limitations or black box warnings etc. For illustration best marketer drugs of 2008 like Risperdal, Fosamax, Prevacid, Protonix, Norvasc and Nexium faced farther loss of gross revenues due to patent termination. Regulative action by FDA ( black box warning, restricted usage and labelling alterations ) A resulted in loss of gross revenues for Avandia every bit good as Aranesp and other erythropoietin trade names.
Based on the IMS wellness Projections ( Feb 2007 ) , the planetary pharmaceutical market was $ 815 billion in 2009 and biotechnology drugs/biologics accounted for $ 130 billion and genericsA for $ 90 billion of the planetary market. The major curative countries with immense gross revenues were CNS, Cardiovascular, and Cancer holding gross revenues $ 125 billion, $ 110 billion and $ 75 billion severally.
Although the major pharmaceuticals are, now, engaged in carry oning research for new biopharmaceuticals ( active ingredients ) , biopharmaceuticals is now an indispensible and extremely focussed country, with successful merchandises in assorted curative countries like Neurology, Infectious Diseases, Cardiovascular, Oncology etc. Biopharmaceutical merchandises comprise of Monoclonal Antibodies, Biotech Vaccines, Erythropoietin, Granulocyte-Colony Stimulating Factor, Recombinant Human Insulin, Interferons, Human Growth Hormones and Others. Exceed 3 classs in biotech merchandises were monoclonal antibodies ( $ 40 billion ) , vaccines ( $ 25 billion ) and TNF inhibitors ( $ 22 billion ) gross revenues in 2009. In footings of market gross, out of entire pharmaceutical market, biopharmaceutical merchandises accounted for approximately 10 % in 2006 and are projected to account for approximately 15 % by 2015.
However, Lipitor still remains the universe best selling drug ( $ 12.4 billion projected gross revenues ) followed by Plavix ( gross revenues of $ 9 billion ) and Enbrel.A There were five biologics in the top 10 best selling list andA eight biologics in the top 20 lists in 2009. TamifluA the most talked about antiviral of 2009 with gross revenues of $ 3.1 billion failed to do the best merchandising list.A Eleven trade names had blockbuster gross revenues of more than $ 5 billion and all drugs listed in the 20 top drug lists class experienced gross revenues of more than $ 4 billion in the twelvemonth 2009 ( Knol Beta, 2010 ) .
The planetary market for biopharmaceuticals is projected to make US $ 182.5 billion by 2015, registering a CAGR of 12.4 % during the period 2006-2015 ( Piribo projections ) .
Table 1 shows the list of 12 largest pharmaceutical and biotechnology companies besides called as the BIG PHARMA ranked by health care grosss in 2009. As is apparent from the tabular array, of the 12 large drug company by grosss, 6 companies are US based and another 6 are UK based. The tabular array clearly depicts the laterality of the US and the UK in the pharmaceutical sector.
In general footings a DRUG is a substance which when absorbed into the organic structure of a life being, alters normal bodily map in some manner. In pharmacological context, a drug is “ a chemical substance used in the intervention, remedy, bar, or diagnosing of disease or used to otherwise heighten physical or mental wellbeing. ” ( Dictionary.com, 2010 ) . AN ACTIVE PHARMACEUTICAL INGREDIENT ( API ) is any biologically active substance nowadays in a pharmaceutical drug. It is sometimes besides referred to as active substance, active entity or mediety. A FORMULATION besides called as a DOSAGE FORM or DRUG PRODUCT of a drug has two chief ingredients. These are, the API which is the active portion of the drug itself doing the coveted pharmacological consequence and an excipient that is pharmaceutically and pharmacologically inert and is added to the API in order to equilibrate the API and besides in order to maintain the concluding dose signifier integral.
All medicative substances that have pharmacological belongingss are called pharmaceutical substances and these can be classified within a figure of nomenclatures as described under.
New CHEMICAL ENTITIES or SMALL MOLECULE DRUGS: A new chemical entity ( NCE ) or new molecular entity ( NME ) is defined as a new compound with new chemical construction, different interaction with biological marks and say a better curative response when compared to already present merchandises / preparations. In other words this is a molecule or a pharmacologically active mediety that has non been antecedently approved by drug regulative governments for medicative usage in general populace. An NCE is produced during the drug find stage and can later on undergo clinical tests after which it will be approved for marketing in worlds. The company that produces the NCE is known as the pioneer company.
Generic: A drug with the same active ingredients and equality as the original small-molecule pharmaceutical ( API ) produced by utilizing chemical synthesis. A generic must incorporate the same active ingredients as the original preparation. Generic drugs should be indistinguishable or within an acceptable scope to the branded merchandise ( innovator merchandise ) with regard to the pharmacological consequence produced. Generics are besides expected to be indistinguishable in dosage, strength, path of disposal, safety, efficaciousness, and intended usage with the pioneer merchandise.
BIOPHARMACEUTICALS ( Accenture research, 2009 ) is a general term referred to merchandises that are biotechnology-derived pharmaceuticals or merchandises that are produced by utilizing procedures and techniques specific to the field of biotechnology. Biopharmaceuticals is a wide term that covers several sub-terms such as biological, biosimilars, biogenerics. BIOLOGICAL PRODUCTS or BIOLOGICALS are defined by the US FDA as “ pharmaceuticals that include a wide scope of merchandises such as vaccinums, blood and blood constituents, allergenic merchandises, bodily cells, cistron therapy, tissues, and recombinant curative proteins by and large composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be populating entities such as cells and tissues ” . Biologicals can be isolated from a broad scope of natural beginnings such as homo, animate being, or micro-organism or possibly produced utilizing assorted other engineerings such as gene-based and cellular techniques. When compared to the conventional little molecules or APIs, biological are really different. This is due to the fact that that biological have a immense complex construction against little molecules whose construction is relatively simple and really good known. Due to this ground, biological can non be easy identified and isolated. Besides because these merchandises are heat labile and can be easy infected by micro-organisms, it is comparatively hard to fix these merchandises and hence there are fewer companies that are extensively biotech based in the universe.
BIOSIMILARS ( European EMEA ) or FOLLOW-ON BIOLOGICS ( US FDA ) are approved drugs, produced by utilizing biotechnology, citing an conceiver biologic. These are follow-on or transcripts or different versions of the already approved and manufactured biotech merchandises. There is ever trouble in set uping similarity amongst these merchandises because it is about impossible to compare one protein with another protein and hence at that place safety and efficaciousness can non be easy established with already approved opposite numbers. Therefore, unlike we have generics for the little molecules or APIs it is really hard for any company to hold a biogeneric for a generic merchandise. Hence, these merchandises are normally called as Biosimilars. BIOGENERICS is a term used to mention to interchangeable Biosimilars which are really hard to calculate out.
DRUGS & A ; MECHANISM OF ACTION
Pharmacology is a subdivision of scientific discipline covering with the survey of drug action. It surveies the interactions that occur in beings when a chemical substance ( in this instance the drug substance ) interacts with the biochemical maps of the organic structure. Pharmacology encompasses the survey of specific facets related to pharmaceuticals such as the drug belongingss determined by its composing, drug-body and drug-drug interactions, toxicology, curative efficaciousness, and medicative benefits accomplished.
Whenever a drug substance is administered to a patient it initiates a specific biochemical interaction in the organic structure to bring forth its pharmacological consequence. In pharmacological medicine, this dynamic action – reaction is called as the Mechanism of Action ( MOA ) . Generally, a mechanism of action includes one or the other molecular marks or selectivity site to which the drug binds to bring forth an consequence. When the drug binds to the receptor or the mark ( such as an enzyme ) it produces an irreversible alteration to the receptor originating farther biochemical reactions in the cell. These reactions are responsible for the targeted pharmacological consequence desired.
Figure 3 demonstrates the MOA of assorted antiplatelet drugs that are a group of powerful medicines that prevent the formation of blood coagulums. Whenever a individual gets wounded, thrombocytes arrive and aggregate on the site of lesion and nine together to organize a coagulum that stops the hemorrhage. Normally this is a really utile phenomenon and helps our organic structure to forestall inordinate blood loss. Problem occurs when these thrombocytes start aggregating inside an injured blood vas in diseases such as coronary artery disease and forestall the smooth blood flow through the blood vas. Antiplatelet medicines are the drugs administered to forestall this procedure from happening. The most common antiplatelet drug is Aspirin, others being Plavix (clopidogrel bisulfate) and Ticlid ( ticlopidine hydrochloride ) ( Cleveland Clinic, 2009 ) .
As is clear from the diagram, the assorted manners of actions of antiplatelet drugs ( that do non let thrombocytes to aggregate ) can be described as:
- Aspirin inhibits the enzyme cyclo-oxygenase 1 and in bend inhibits platelet activation. This prevents the synthesis of thromboxane A2 that causes thrombocyte collection
- Clopidogrel prevents adenosine diphosphate from adhering to a thrombocyte receptor and in bend inhibits the activation of the glycoprotein IIb/IIIa composite. This inhibits thrombocyte collection.
- Dipyridamole inhibits thrombocyte collection by increasing the production of prostacyclin that causes thrombocyte collection
- Therefore, it is clear from this treatment that assorted drug molecules act on assorted sites in the same cell with assorted mechanisms of actions to bring forth similar pharmacological effects.
The planetary pharmaceutical market stood at $ 810 billion in 2009 but was faced by hard market kineticss, recession and compelling force per unit area from the generics market with many blockbusters going off patented. Of the entire gross revenues quoted above the entire biotechnology portion was $ 130A billion and that of the generic market was deserving $ 90 billion.
GENERICS OF SMALL MOLECULES
Generic drugs as discussed in the debut chapter come into being when patents for the blockbusters expire and the new bioequivalent preparations are launched in the market. These “ Me Too ” drugs are known as generics. Generic drugs are lower in monetary value when compared to the branded merchandises because during the fabrication of generic merchandises, companies tend to salvage a batch of money that is spent by pioneer companies in research and development. There are a figure of interest holders that benefit from generics. These are described in the undermentioned paragraphs.
GENERIC DRUG COMPANIES: Many companies that dabble in fabricating low cost generics tend to be the highest gainers from this concern. In fact many companies in the emerging markets are entirely generic makers and are universe leaders in this field. These include large and profitable companies such as the India based Ranbaxy that was late acquired by Daichi-Sankyo and the Israel based pharmaceutical company Teva Pharmaceutical Industries. These companies save a batch in footings of money spent in the initial find and development stage of new molecules particularly clinical tests. These nest eggs are in the melody of $ 800 million and therefore the lower cost of generics.
Insurance Company: In many states, particularly in the developed states, the health care disbursals are covered by either the province or the insurance bureaus. Many good known participants in this field such as the UnitedHealth Group ( UNH ) , WellPoint Health Networks ( WLP ) , and AFLAC ( AFL ) have invariably motivated their clients to travel for generic merchandises. These merchandises as discussed above are every bit efficacious as the patented molecules and besides much cheaper. Hence the usage of these merchandises is good both to the insurance company every bit good as the clients.
Pharmacy: As generic drugs are cheaper hence the pharmaceuticss get a better portion of border on the sweeping monetary values of these drugs. Some portion of this net income is passed on to the clients in footings of lesser costs and the remainder is relished by the pharmaceuticss.
Table 1 clearly shows informations from 3 good known pharmaceutics ironss in the USA that sell generics ( Costco, Walgreens and CVS ) . The tabular array provides the comparing between the monetary value of generics versus patented merchandises. The branded drugs are given in bold followed by generics in unbold.
GENERICS MARKET TILL PRESENT
Table 2 shows the list and features of a few top merchandising drugs in the sphere of generics in 2008. Therefore, the tabular array clearly depicts that if the current gross revenues are any word pictures so generics will shortly catch their patented opposite numbers.
The first Biotechnology Company was started by Robert Swanson and Herbert Boyer in 1976 with the exclusive purpose of utilizing familial engineering to do commercially feasible curative proteins. The initial success narratives of the biotechnology companies were molecules such as human insulin, human growing endocrine and erythropoietin approved by FDA in 1982, 1985 and 1989, severally ) . Today, biopharmaceuticals account for 10 % to 15 % of the universe pharmaceutical market, with gross revenues in the USA entirely making around $ 30 billion ( Sargent, M.G. , 2005 ) .
As per latest trends the market for biopharmaceutical has reached a astonishing $ 40 billion USD and includes vaccinums, anti-cancer agents, and arthritis and psoriasis drugs. These sections are besides the fastest turning sections in the pharmaceutical industry. Of the 10,000 drugs present in the planetary pharmaceutical market, about 250 drugs are biopharmaceutical based.
THE FIRST BIOSIMILAR – OMNITROPE
In 2006, EMEA and the FDA approved a biosimilar called Omnitrope for the branded drug Genotropin. This determination proved to be a first of its type in the pharmaceutical industry as this was the first “ Me Too ” merchandise for a biotechnology based merchandise or drug. Omnitrope developed and marketed by Sandoz is a intervention for growing upset in kids and grownups. The regulative governments stressed that Omnitrope was similar to Genotropin but non tantamount to the trade name drug, therefore the name biosimilar ( EMEA – and non biogeneric ) or follow on proteins ( US FDA ) . It was ever a challenge to bring forth Omnitrope as the follow on proteins are big molecules synthesized in life cells and are really hard to double or retroflex when compared to the little molecule drugs that have a particular and good characterized construction. Omnitrope was really good to the patients as it was marketed at a monetary value that was 25 % less than the Pfizer drug, Genotropin ( thePharmaLetter, 2006 ) .
CURRENT TRENDS IN THE BIOSIMILAR MARKET
In the 2010 budget presented to the US Congress by President Barack Obama, particular commissariats have been laid down for the expedite blessing of biosimilars with the exclusive purpose of cutting wellness costs and take downing down the monetary values for the branded biological. If USA was able to O.K. biosimilars rapidly it would assist the authorities to cut down on branded drugs by $ 25 billion from 2009 to 2018 ( Nature News, 2009 ) .
Therefore, if we analyze the latest market trends it becomes apparent that the biosimilars have a immense market and can take to gain maximization for the pharmaceutical companies. After the new statute law coming up in the USA and EU, the biosimilar market is set to spread out by another $ 5A billion.
FUTURE TRENDS IN THE BIOSIMILAR MARKET
Therefore a big figure of profitable biological will go off patent by 2010 ( deserving $ 10 billion ) . This estimation is bound to lift by another $ 10 billion biotechnology based merchandises coming off patent by 2015 ( Insmed, 2008 ) . By 2010 biotechnology based merchandises will represent more than 15 % of the planetary pharmaceutical market with every bit high as $ 18 billion merchandises expected to travel off patent by 2011 ( Pharma Focus Asia, 2008 ) .
MAIN PLAYERS IN THE BIOSIMILARS MARKET ( ICIS.com, 2009 )
The leader in the biosimilars market is Sandoz a concern unit of the Switzerland based pioneer company Novartis. Sandoz already has 3 approved biosimilars in the signifier of Omnitrope, Binocrit and Zarzio and is the lone company to hold a biosimilar approved in the USA ( Omnitrope ) . Teva pharmaceuticals, the taking Israel based generic company has one merchandise Tevagrastim on the European market and has acquired 2 biotech based companies in the USA – Barr Pharmaceuticals and CoGenesys to widen its biotech base. Recently Teva entered in a strategic partnership with the Switzerland based usage fabricating company Lonza to jointly develop, industry and market biosimilars. Large Drug company participants such as Eli Lilly and AstraZeneca are besides be aftering to come in strategic confederations with biotechnology based companies or get smaller such companies.
The leader amongst all the Big Pharma still remains Merck & A ; Company that has established a new division called as Merck BioVentures ( MBV ) to tackle the best from the biotech sphere. It has besides acquired merchandises in late stage clinical tests from the US-based Insmed and GlycoFi.
OPPORTUNITIES FOR EMERGING MARKETS SUCH AS INDIA ( BioSpectrum, 2010 )
In recent old ages the most figure of biosimilars will be developed for drug categories erythropoietin, filgrastim, human growing endocrine ( HGH ) and insulin. Maximum growing will be around the twelvemonth 2016 with the timeframe of 2012-19 seeing patents deserving $ 60 billion acquiring expired for the biotech drugs. The major participants from India in the biosimilar field will be Dr Reddy ‘s Labs, Ranbaxy, Biocon, Shantha Biotech and Intas Biopharmaceuticals. Harmonizing to studies, the Indian biosimilars market was deserving $ 200 million in 2008 and is heading for the $ 580 million grade by 2012. The economic sciences of graduated table that has been achieved by the Indian companies fabricating biosimilars can be estimated by the fact that Biocon has been able to sell the biosimilar version of its human insulin merchandise at a price reduction of about up to 80-85 per centum when compared to the branded biotech merchandises.
One of the premier marks for these companies is to develop biosimilars for the oncology curative section. The current market size of the domestic oncology market is about $ 19A million which may lift to $ 50 million by the terminal of 2010. In the oncology sector, Dr Reddy ‘s Labs had a large name when it launched its biosimilar Reditux, in 2003 which was manner cheaper than the branded merchandises.
Other participants that are rather active in bring forthing biosimilars in the Indian pharmaceutical sector are Biocon ( 4 merchandises – EPO, insulin, GCSF and streptokinase ) , Reliance Life Sciences ( 3A biosimilars – ReliPoietin Erythropoietin [ EPO ] , ReliGrast Granulocyte Colony Stimulating Factor [ G-CSF ] , and ReliFeron [ Interferon Alpha 2b ] launched in 2008 ) and Intas Biopharmaceuticals ( 4 biosimilars launched in India and abroad – G-CSF, EPO, Interferon Alpha Beta ( IFN- ) and Peg-GCSF ) . Other Indian companies that are concentrating on constructing their biotech competences include Glenmark ( be aftering to establish its first biotech merchandise by 2010 from its Switzerland based biological research installation ) , Ranbaxy ( anticipating to establish G-CSF with its strategic coaction with Zenotech Laboratories in Brazil, Mexico, CIS and Russia ) and Cipla ( Joint ventures called as BioMab with a Chinese company with its first merchandise to be out by 2010 ) . Similarly, Wockhardt has a figure of biosimilars at assorted phases of development that are targeted towards the US and EU markets.
Therefore, in the words of Mr. Jay Desai, Founder and CEO, Universal Consulting as quoted in BioSpectrum, 2010:
“ The current theory-in-use is that India will at some point in the not-too-distant hereafter retroflex the comparative success of its pharma generics industry in the biosimilars market worldwide. ”