Module 1b
OVERVIEW OF THE PHARMACEUTICAL INDUSTRY
Pharmaceutical Industry Trends - Global Scenario
The global pharmaceutical market is forecast to be worth over US$1,250 billion by 2018. The established markets,
including the US, UK, and Japan, together account for 30% of the global demand for pharmaceutical excipients.
Global pharmaceutical sales are expected to grow at a compound annual growth rate (CAGR) of 3% - 6% during
the period 2011-15, despite the impending loss in revenue expected from the expiry of patents. This gain will
largely be driven by robust growth in emerging markets. It is anticipated that such markets will account for
approximately 28% of total sales worldwide in 2015, up from only 18% in 2010. This growth is in sharp contrast
to the expected CAGR of only 1% - 4% for the primary drug markets of North America and Europe.
Pharmaceutical companies face many challenges and uncertainties, including heightened competition from makers
of generic drugs, unprecedented pressure on pricing from payers (such as insurance companies), constraints on
public sector budgets and declining R&D productivity. The pressure to reorganize R&D, provide affordable price
and marketing overhauls is intense. According to IMS Health, the big pharmaceutical companies (those with large
capitalizations) are struggling to grow, with generic firms outperforming them.
However, there are improvements in early-stage product pipelines in the pharmaceutical industry – particularly in
the fields of cancer and diabetes – which offer long-term promise. In addition, an aging population and new
products are likely to create a robust future for the industry.
Asia Pacific Pharmaceutical Market
The pharma market world over will experience significant shifts. Asia-Pacific region will emerge as the fastest
growing pharmaceutical market over the recent past. The reason for this positive shift can be attributed to the low
costs and favorable regulatory environment. This region has experienced important developments regarding
contract manufacturing, especially in generics and APIs. Increased R&D activities in the region has helped Asia-
Pacific pharmaceutical industry to achieve an estimated market size of around US$ 187 Billion in 2009. Here, the
pharmaceutical industry is expected to grow at a CAGR of around 12.6% during 2010-2012. It can, in fact,
become the global API production hub in next few years.
pharmaceutical sales are growing at a fast rate in India, China, Malaysia, South Korea and Indonesia due to the
rising disposable income, several health insurance schemes (that ensures the sales of branded drugs), and intense
competition among top pharmaceutical companies in the region (that has boosted the availability of low cost
drugs). China’s pharmaceutical market will continue to grow at a 20+ % annually, and will contribute 21% of
overall global growth through 2013. India - 3rd Largest Producer of Pharmaceuticals across the World- is already
a US$ 8.2 Billion pharmaceutical market. The Indian pharmaceutical industry is further expected to grow by 10%
in the year 2010.
Middle East Pharmaceutical Market
The Middle East combined with the African Pharmaceutical market is projected to grow at a CAGR of around
11% during 2010-2012. The development of infrastructure and rapidly changing regulations in this region are
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being seen as the cause of its growth. Also there is a high prevalence of diseases and huge population base that
increases the overall pharmaceutical sales in this part of the world. Presently South Africa, Saudi Arabia and Israel
dominate the region's pharmaceutical industry due to their better infrastructure and regulatory environment.
However, The Middle East pharma market depends on imported pharmaceutical drugs and therapeutics. The
governments of countries in this region are taking measures to raise their domestic production through heavy
investments in the pharmaceutical industry. How far they are successful in the attempt of becoming considerable
pharma production center remains to be seen.
Pharmaceutical Drugs Trends
Anti-Diabetic Drugs and those for cardiovascular diseases are expected to see the fastest growth.
The global cardiovascular market recorded sales of $170bn in 2010 and is set to grow to $187bn in 2016 at a
CAGR of 1.6%. The US continued to be the largest market, with a share of 40% of the overall market. However,
the growth rates will be limited by continued patent expiries for major products and due to the lack of novel
therapies. The anti-hypertensives drugs will dominate the global cardiovascular market with a market share of
nearly 50%.
The table below lists the Top 25 pharmaceutical companies by global sales:
Growth
# Company 2014 ($m) 2013 ($m) Growth ($m)
(%)
1 Novartis 47101 47468 -367 -1
2 Pfizer 45708 47878 -2170 -5
3 Roche 39120 39163 -43 0
4 Sanofi 36437 37124 -687 -2
5 Merck & Co. 36042 37437 -1395 -4
6 Johnson & Johnson 32313 28125 4188 15
7 GlaxoSmithKline 29580 33330 -3750 -11
8 AstraZeneca 26095 25711 384 1
9 Gilead Sciences 24474 10804 13670 127
10 Takeda 20446 19158 1288 7
11 AbbVie 20207 18790 1417 8
12 Amgen 19327 18192 1135 6
13 Teva 18374 18308 66 0
14 Lilly 17266 20962 -3696 -18
15 Bristol-Myers Squibb 15879 16385 -506 -3
16 Bayer 15486 14854 632 4
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Growth
# Company 2014 ($m) 2013 ($m) Growth ($m)
(%)
17 Novo Nordisk 15329 14877 452 3
18 Astellas 14099 13508 591 4
19 Boehringer Ingelheim 13830 15789 -1959 -12
20 Actavis 13062 8678 4384 51
21 Otsuka 11308 11226 82 1
22 Daiichi Sankyo 10430 12067 -1637 -14
23 Biogen Idec 9398 6668 2730 41
24 Baxter 8831 8347 484 6
25 Merck KGaA 7678 8399 -721 -9
THE MODERN PHARMACEUTICAL INDUSTRY
The World Health Organization (WHO) defines a drug or pharmaceutical preparation as:
“Any substance or mixture of substances manufactured, sold, offered for sale, or represented for use in
the diagnosis, treatment, mitigation, or prevention of disease, abnormal physical state or the symptoms
thereof in man or animal; [and for use in] . . . restoring, correcting, or modifying organic functions in
man or animal”.
The same organization defines a pharmaceutical specialty as:
"A simple or compound drug ready for use and placed on the market under a special name or in a
characteristic form."
The modern pharmaceutical industry began in the 19th century with the discovery of highly active
medicinal compounds that could most efficiently be manufactured on a large scale. As these compounds
replaced herbal medicines of earlier times, the occurrence and severity of such diseases as pernicious
anemia, rheumatic fever, typhoid fever, lobar pneumonia, poliomyelitis, syphilis, and tuberculosis were
greatly reduced.
Pharmaceutical industry research has greatly aided medical progress; of the 66 most valuable drugs
introduced since aspirin in 1899, 57 were discovered and then produced in industrial laboratories.
Classification of pharmaceutical products
Drugs may be classified in one of three ways:
1. By chemical group (e.g., alkaloids);
2. Pharmacologically (i.e., by the way they work in the body); and
3. According to their therapeutic uses.
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Pharmacological and therapeutic classifications show considerable divergence, as drugs that act upon the
body in different ways may bring about the same desired therapeutic result. Furthermore, classification
by therapeutic usage is complicated by the fact that a drug may be used to combat more than one ailment.
The antimalarial compound primaquine, for example, may also be employed to relieve arthritis.
Some familiar drugs classified by therapeutic use include aspirin, an analgesic, or painkiller; benzocaine,
a local anaesthetic; magnesium carbonate, an antacid; charcoal, an antiflatulent; penicillin, used against
syphilis; calcium lactate, a calcium supplement; hexachlorophene, a deodorant; phenolphthalein, a
laxative; laevulose, a nutrient; cascara sagrada, a purgative; Phenobarbital, a sedative; and thiamine
hydrochloride, a vitamin.
History
The earliest records of medicinal plants and minerals are those of the ancient Chinese, Hindu, and Mediterranean
civilizations. In 2735 BC the Chinese emperor Shen Nung wrote a herbal in which he described the antifever
capabilities of a substance known as Ch'ang Shang, since shown to contain antimalarial alkaloids.
The school of alchemy that flourished in Alexandria in the 2nd century BC could prepare white lead (lead
carbonate) from litharge, arsenic from realgar (arsenic disulfide), and mercury by roasting cinnabar (mercuric
sulphide) in a current of air. It is recorded in De materia medica, a book of the 1st century BC, that verdigris (basic
cupric acetate) and cupric sulfate were prescribed as medicinal agents.
Remarkably, cupric sulphate is still used in medicine today. Many crude drugs still used now, such as ipecacuanha
root (ipecac), were known and employed by the ancients. The Egyptians treated constipation with senna pods and
castor oil and employed caraway and peppermint to relieve indigestion. The Greek physician Galen (c. AD 130-c.
200) included hyoscyamus, opium, squill (a plant drug used as an expectorant, cardiac stimulant, and diuretic), and
viper toxin among other drugs in his apothecary shop. He also insisted on purity in drugs--i.e. the right variety and
age of the botanical specimens.
Pharmaceutical practice improved markedly in the 16th and 17th centuries. In 1546 the first pharmacopoeia, or
collected list of drugs and medicinal chemicals with directions for making preparations from them, appeared in
Nuremberg (Nürnberg, West Germany). Previous to this time, medical preparations had varied in concentration
and even in constituents. Other pharmacopoeias followed, in Basel (1561), Augsburg (1564), and London (1618).
Despite its name, the London Pharmacopoeia was mandatory for the whole of England and thus was the first
example of a national pharmacopoeia. In 1617 the Society of Apothecaries, London, was founded, marking the
emergence of pharmacy as a distinct profession. The separation of apothecaries from grocers was authorized by
King James I; only a member of the society could keep an apothecary's shop and make or sell pharmaceutical
preparations.
In 1841 the Pharmaceutical Society of Great Britain, London, was founded, placing the education and training of
the pharmacist on a proper scientific basis. Today, pharmaceutical practice and education are carefully supervised
throughout the world.
Known as "Hoffman's drops", ether was first employed as an anaesthetic in 1842; chloroform followed soon
afterward in 1847. Alkaloid compounds were also isolated from plant sources during this period. Narcotine was
obtained from opium by a French pharmacist in 1803 and was followed by morphine in 1806, emetine and
strychnine (about 1817), brucine and piperine (1819), colchicine and quinine (1820), nicotine (1828), atropine
(1833), cocaine (1860), and physostigmine (1867).
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Isolation of these potent compounds was a milestone in pharmaceutical progress for three reasons. First, accurate
doses could now be administered; this had been impossible previously with crude drugs of unknown and variable
composition. Second, toxic effects due to impurities in crude drugs could now be eliminated if pure compounds
were used; and third, knowledge of the chemical structure of these drugs led to attempts at laboratory synthesis,
which led in turn to discovery of valuable related compounds.
Joseph Lister, in England, opened the modern era of antiseptic surgery in 1865 when he used phenol (carbolic
acid) to prevent infections. In 1869 the soporific properties of chloral hydrate, the first synthetic hypnotic (sleep-
producing drug), were discovered. In 1874 it was found that organic nitrites relax the blood vessels, and, in 1875,
salts of salicylic acid were introduced as remedies for fever. The year 1879 witnessed the introduction of
saccharin, still in use today as a sweetening agent for diabetic patients. The simple compound acetanilide,
introduced in 1886, was one of the first analgesic-antipyretic drugs (i.e., reducing both pain and fever) to be used
but was later replaced by the less toxic phenacetin in 1887, by aspirin in 1899, and all of these to some extent by
acetaminophen (paracetamol) in 1956.
The hypnotic sulfonal (sulfonmethane) was discovered about 1888, followed a few years later by barbital; this
later led to a whole series of barbiturates, of which Phenobarbital is the best known. Cocaine was the only known
potent local anaesthetic until about 1900, when the much simpler compound benzocaine was introduced. The
closely related local anaesthetic procaine followed early in the 20th century.
In 1909 arsphenamine, highly effective against syphilis, was introduced. Since arsphenamine is both insoluble in
water and unstable, further work led to neoarsphenamine in 1912, a soluble derivative. Many other synthetic drugs
followed, among which was the hormone progesterone, synthesized in 1934. Some thousands of similar
compounds have since been prepared, some of which are used as oral contraceptives. In 1935 it was discovered
that sulphanilamide (Prontosil) stopped the growth of bacteria. Over 6,000 derivatives of sulphanilamide--the
sulphonamides, or sulfa drugs--were prepared and tested for their antibacterial properties. Today, the
sulphonamides have partially been superseded by antibiotics, of which the first was penicillin, first isolated in
1941.
In 1959, 6-aminopenicillanic acid was isolated for the first time; this led to production of many semi synthetic
penicillin such as ampicillin, carbenicillin, cloxacillin, methicillin, oxacillin, and phenethicillin. Also used as
antibiotics are compounds known as cephalosporins, the first of which was isolated in 1961.
Pay, Profits and Spending by Drug Companies
The industry pursued two new approaches--vertical partnering and regionalization--to the problem of adapting to a
customer base that showed ever-greater power and complexity. Rather than acting merely as suppliers of
medicines, companies offered managed-care organizations (MCOs) additional services and collaborations,
including evidence of their products' cost-effectiveness, educational programs for patients and professionals, and
risk-sharing contracts that compensated companies on a per-patient basis. To get closer to their customers, large
companies created regional or strategic business units. Companies such as Bayer of Germany also began to apply
the U.S. model to their global operations.
Some companies encountered problems over their mergers with pharmacy benefits management organizations
(PBMs) and over other vertical initiatives. Medco settled with 17 states that sued the PBM for favoring products of
its owner, Merck. MCOs also remained skeptical of new "disease-management" programs offered by
pharmaceutical companies or by separate entities such as Lilly's Integrated Disease Management subsidiary.
Zeneca went beyond offering such programs into actual care with its $195 million purchase of oncology company
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Salick Health Care, Inc.
Backed by a weak dollar, European acquisitions of U.S. companies led industry consolidations. Germany's
Hoechst AG bought Marion Merrell Dow for $7 billion, and Switzerland's Roche Holding AG completed its
absorption of Syntex Corp. Upjohn and Pharmacia formed a $7 billion transatlantic merger. Marrying two British
companies, Glaxo purchased Welcome for about $15 billion. Companies also made many smaller investments to
capture new technologies and markets. Sandoz AG entered a host of alliances in gene therapy, and Bayer
repurchased its U.S. aspirin line and extended an alliance with the generics company Schein.
Pharmaceutical research, in schools of pharmacy, and in the laboratories of the pharmaceutical manufacturing
houses, embraces the organic chemical synthesis of new chemical agents for use as drugs and is also concerned
with the isolation and purification of plant constituents that might be useful as drugs. Research in pharmacy also
includes formulation of dosage forms of medicaments and study of their stability, methods of assay, and
standardization.
Another facet of pharmaceutical research that has attracted wide medical attention is the "availability" to the body
(bioavailability) of various dosage forms of drugs. Exact methods of determining levels of drugs in blood and
organs have revealed that slight changes in the mode of manufacture or the incorporation of a small amount of
inert ingredient in a tablet may diminish or completely prevent its absorption from the gastrointestinal tract, thus
nullifying the action of the drug. Ingenious methods have been devised to test the bioavailability of dosage forms.
Although such in vitro, or test-tube, methods are useful and indicative, the ultimate test of bioavailability is the
patient's response to the dosage form of the drug.
Licensing systems for new medicinal products in Europe and North America demand extensive and increasingly
costly investigation and testing in the laboratory and in clinical trials to establish the efficacy and safety of new
products in relation to the claims to be made for their use. Proprietary rights for innovation by the grant of patents
and by the registration of trademarks have become increasingly important in the growth of the pharmaceutical
industry and its development internationally.
Competitive and technological changes in the pharmaceutical industry
Competitive and technological changes in the pharmaceutical industry-from powerful new drug chemistries to
innovative partnerships and marketing plans-are reshaping the business strategies of many pharmaceutical and
biotechnology companies. According to new research on the Pharmaceutical Industry, many companies today are
searching for ways to increase productivity, decrease costs, and develop new treatment modalities that will
enhance profitability. The strategies seem to be working best for successful pharmaceutical and biotech companies
when it comes to the productivity of drug discovery and the time it takes to develop new drugs are investment in
research and development (R&D) projects; manufacturing processes; and OTC (over the counter) switching.
The Future
Pharmaceuticals will have an increasingly prominent role in the health care of the future. The health of our citizens
depends on the availability of safe, effective and affordable medicines. In the future, pharmaceutical
manufacturing will need to employ innovation, cutting edge scientific and engineering knowledge, and the best
principles of quality management to respond to the challenges of new discoveries and ways of doing business such
as individualized therapies or genetically tailored treatments.
Regulation of the future will also need to meet these challenges, by incorporating new scientific information into
regulatory standards and policies. Both industry and regulatory practices will need to be informed by the best
techniques of risk assessment and management. "Pharmaceutical current Good Manufacturing Process (cGMPs)
for the 21st Century" is intended to jump-start progress into this future.
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Pharmaceutical manufacturing is evolving from an art form to one that is now science and engineering based.
Effectively using this knowledge in regulatory decisions in establishing specifications and evaluating
manufacturing processes can substantially improve the efficiency of both manufacturing and regulatory processes.
It is clear that there must be change in the pharmaceutical industry. Declining R&D (research and development)
productivity, reduced effectiveness of the blockbuster drug model, and new drug discovery technologies mean that
the industry must adapt.
According to the futurologists, several changes will take place. The new pharmaceutical industry model must:
1. Shift from chemical-based small molecules to biological-based large molecules (proteins, antibodies)
2. Put clear emphasis on early validation of targets
3. Provide better disease segmentation to understand differences among patients resulting in developing drugs
targeting sub-populations with specific disease states
4. Create drugs with disease modifying rather than symptom modifying impact
5. Shift to a more holistic service; rather than drugs only, providing diagnosis, treatment, monitoring and patient
support.
There is clear evidence that we are heading this way. Over 30% of drugs in development are biological-based. In
the area of diagnostics integration, cholesterol testing helped Merck achieve blockbuster status with Mevacor and
diagnostics are integral to the product offering of Roche's Herceptin.
When a number of players in the pharmaceutical industry have been polled, including executives at
pharmaceutical and biotech companies, analysts and investors, this change was imperative and broadly agreed
with the direction described by the futurologists. However, they indicated that the timescale for making the
transition to the new model would be much larger than predicted (from ten to twenty years).
Success in the short to medium term: Back to Basics
Over the next five to fifteen years, the successful companies will be those who manage the transition effectively
while running two business models in parallel, namely the chemical-based blockbuster model (pharmaceuticals
that generate $500 million or more in annual sales), and the biological-based individualized therapy model.
Winners will successfully meet six challenges:
1. Instituting effective portfolio management
2. Reconciling agility and size
3. Meeting short term investor expectations
4. Increasing transparency
5. Motivating the organization
6. Embracing creative collaborations
1. Instituting effective portfolio management
A portfolio is simply the collection of new products and products in development, that have the potential to make
money. In the case of pharmaceutical companies this means all drugs and devices that have either been approved
for marketing and are actively being marketed, as well as those that are undergoing clinical development. It is this
portfolio that determines the value of a publicly traded company on the stock market. Value is determined through
a number of factors including:
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Past Successes
Current products on the market and their performance
The diversity and number of products in development
How far along products are in the clinical trials/regulatory process
Effective portfolio management, then, means that a company has developed effective management techniques for
regular review of the portfolio in order to:
Withdraw marketing funds for products at the end of their life cycle
Drop drugs in development that do not match the performance criteria of the Target Project Profile so that
research funds will be conserved.
Monitoring sources of potential drug candidates and continuously adding compounds with promising drug
properties to the research & development program
Diversifying the portfolio to produce an eclectic mix of products. This not only helps to protect the firm
through periods of poor economic performance, but also increases the chances of discovering new drug
candidates.
The better a pharmaceutical company is at controlling its portfolio, the better it will perform. This results in higher
market value and stock that is sought after by investors.
2. Reconciling agility and size
This refers to the age old problems associated with managing any large organization. It is a truism that that larger
an organization becomes, the more bureaucratic processes it adopts. Alternatively smaller organizations are
generally able to respond to a situation quickly because communication is good. The advent of a larger
organization translates to problems in internal communication that ultimately cause a loss of control by the senior
management of the organization. This is particularly observable in governments which, to a large extent, are not
subject to market forces and the need to survive. An organization, pharmaceutical or otherwise, that does not
address this problem will ultimately fail.
The nature of the pharmaceutical industry directly contributes to this problem within itself through the large
corporations that are formed when larger companies merge and/or buy out smaller firms in an effort to diversify. It
is critical that proper communication takes place to ensure that new organizational components are brought into
the internal corporate environment in a manner that will ensure total integration and realize efficiencies. In the past
10 years, computerized information systems, e-mail and databases have significantly reduced many of these
communication problems. However, much more work will be needed in this area for pharmaceutical companies to
effectively take advantage of all resources gained through mergers and buy-outs.
3. Meeting short term investor expectations
A major problem in attracting investors in the pharmaceutical industry is the length of time and cost of bringing a
new drug to market. This is quite different from what occurs naturally in the marketplace when there are no
regulatory restrictions placed upon a product. Short-term (this is a relative term) investors usually expect to see
some return on their investment on an annual basis through dividends or natural increases in the market value of
the stock. When investment take place in a pharmaceutical venture there is often a time period of years 4where
there is no return followed by dramatic increase in stock value if and when the drug is approved. If the drug is not
approved then there is likely to be a decrease in stock value.
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This makes it very hard to attract investors and is one other reason that companies diversify: more products
coming to market on a regular basis will result in a steady strong stock value with regular dividends, thus making
it more attractive to the traditional market investor.
4. Increasing transparency
Increasing transparency is important from two perspectives:
1. The public at large has become very suspicious of pharmaceutical companies as they have been vilified by
the media and certain activist groups. This places pressure on the government to further regulate, thus
putting more of a burden on an already over-regulated industry. In order to counteract this perception and
break this cycle, pharmaceutical companies must be approachable, open and honest. This means providing
a Public Relation function that will interact with the media and special interest groups to provide
information on drug safety and efficacy, in a variety of forms including release of clinical study results
and known side effects.
2. Transparency is also important when attracting investors. It is expected that a pharmaceutical company
will seek to protect its market share and protect its research and development programs. However, too
much secrecy on the product development will cause investors to shy away. It will also lead to a public
perception that the firm has something to hide. In order for investors to feel confident about investing
capital, they need to know a certain amount about probable efficacy, pharmacology and side effects of
products within a company’s portfolio so that they may invest wisely. Marketing departments must walk a
fine line between promoting their products and protecting the company’s patents, and there is continuous
pressure from the media, public and government to reveal more about their products.
5. Motivating the organization
This is another area that has been impacted by the advent of large multinational pharmaceutical companies. With
communication problems come problems of low morale and motivation. When a smaller company is absorbed into
a much larger one, as is often the case, one of the first things to be impacted is the collegial attitude that often
exists in smaller firms. When this is combined with projects that are many years in length, with potentially no
outcome, employees become de-focused on the immediate tasks at hand. This, in turn causes projects to lag behind
with significant cost to the organization. Traditionally, high salaries and good compensation packages have been a
successful motivator within the industry. More recently innovations such as more vacation time, internal
performance competitions with rewards such as package vacations or conference travel and paternity leave for
men have been introduced.
6. Embracing creative collaborations
The high speed at which technology is advancing both in terms of biotechnology and computerization demand that
creative collaborations between companies take place in order to effectively compete in today’s pharmaceutical
market. It generally several years from the time that a technology is discovered to the time it becomes part of
academic curriculums. In order that knowledge be taken advantage of and turned into profit, collaborations and
information exchange takes place where all contributing parties (there may be more than 2) benefit and profit. This
represents a large challenge in an industry that has traditionally been quite secretive.
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