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197-681: Pfizer Inc. ( / ˈ f aɪ z ər / FY -zər ) is an American multinational pharmaceutical and biotechnology corporation headquartered at The Spiral in Manhattan, New York City . The company was established in 1849, in New York by two German entrepreneurs, Charles Pfizer (1824–1906) and his cousin Charles F. Erhart (1821–1891). Pfizer develops and produces medicines and vaccines for immunology , oncology , cardiology , endocrinology , and neurology . The company's largest products by sales are

394-500: A joint venture owned 68% by GlaxoSmithKline and 32% by Pfizer, with plans to make it a public company . The transaction built on a 2018 transaction where GlaxoSmithKline acquired Novartis ' stake in the GSK-Novartis consumer healthcare joint business. The transaction followed negotiations with other companies including Reckitt Benckiser , Sanofi , Johnson & Johnson , and Procter & Gamble . In September 2019, Pfizer initiated

591-596: A multi-national enterprise ( MNE ), trans-national enterprise ( TNE ), trans-national corporation ( TNC ), international corporation , or state less corporation , ) is a corporate organization that owns and controls the production of goods or services in at least one country other than its home country. Control is considered an important aspect of an MNC to distinguish it from international portfolio investment organizations , such as some international mutual funds that invest in corporations abroad solely to diversify financial risks. Black's Law Dictionary suggests that

788-457: A "demand pull" strategy, whereby products or services determined by the customer are provided exclusively on a "one customer / one supplier" basis. The products are mainly used as building blocks for proprietary products. The hardware of the top tier fine chemical companies has become almost identical. The design, lay-out and equipment of the plants and laboratories have become practically the same globally. Most chemical reactions performed go back to

985-531: A "low-tech" image but still widely used), carried-out in standard multipurpose equipment or by various types of chromatographical separation , such as standard column, simulated moving-bed (SMB) or supercritical fluid (SCF) techniques. For peptides three main types of methods are used, namely chemical synthesis, extraction from natural substances, and biosynthesis. Chemical synthesis is used for smaller peptides made of up to 30–40 amino acids. One distinguishes between "liquid phase" and "solid phase" synthesis. In

1182-766: A basis in a national ethos , being ultimate without a specific nationhood, and that this lack of an ethos appears in their ways of operating as they enter into contracts with countries that have low human rights or environmental standards . In the world economy facilitated by multinational corporations, capital will increasingly be able to play workers, communities, and nations off against one another as they demand tax, regulation and wage concessions while threatening to move. In other words, increased mobility of multinational corporations benefits capital while workers and communities lose. Some negative outcomes generated by multinational corporations include increased inequality , unemployment , and wage stagnation . Raymond Vernon presents

1379-542: A cancer medication which was approved for human use by the FDA in January 2006. A related compound, SU11654 ( Toceranib ), was also approved for cancer in dogs , and the ALK inhibitor Crizotinib also grew out of a SUGEN program. In October 2006, the company announced it would acquire PowerMed. On October 15, 2009, Pfizer acquired Wyeth for $ 68   billion in cash and stock, including

1576-515: A company or group should be considered a multi-national corporation "if it derives 25% or more of its revenue from out-of-home-country operations". Most of the current largest and most influential companies are publicly traded multinational corporations, including Forbes Global 2000 companies. The history of multinational corporations began with the history of colonialism . The first multi-national corporations were founded to set up colonial "factories" or port cities. The two main examples were

1773-586: A complaint to the US Food and Drug Administration (FDA). Ventavia fired her later the same day. The European Medicines Agency (EMA) stated in a response to the European Parliament , that "the deficiencies identified do not jeopardize the quality and integrity of the data from the main Comirnaty trial and have no impact on the benefit-risk assessment or on the conclusions on the safety, effectiveness and quality of

1970-550: A coordinated research strategy for prioritizing and speeding up development of COVID-19 vaccines and pharmaceutical products. Pfizer joined the partnership as an industry "leadership organization", and participated as a collaborator in ACTIV-led clinical trials. CEO Albert Bourla attended the GAVI COVAX AMC 2021 Investment Opportunity Launch Event, otherwise named One World Protected, on April 15, 2021. In Canada, Pfizer endorsed

2167-498: A corporation invests in a country in which it is not domiciled, it is called foreign direct investment (FDI). Countries may place restrictions on direct investment; for example, China has historically required partnerships with local firms or special approval for certain types of investments by foreigners, although some of these restrictions were eased in 2019. Similarly, the United States Committee on Foreign Investment in

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2364-434: A crude state. Since the late 1970s, fine chemicals have become an important part of the chemical industry. Their global total production value of $ 85 billion is split about 60-40 between in-house production in the life-science industry—the products' main consumers—and companies producing them for sale. The latter pursue both a "supply push" strategy, whereby standard products are developed in-house and offered ubiquitously, and

2561-399: A distinct competitive advantage. Most reactions can be carried out in standard multipurpose plants. Reaction-specific equipment, such as ozone or phosgene generators, is readily available. The installation generally is not a critical path on the overall project for developing an industrial-scale process of a new molecule. Whereas the overall demand for outsourced pharmaceutical fine chemicals

2758-466: A distinct competitive advantage. Most reactions can be carried out in standard multipurpose plants. The very versatile organometallic reactions (e.g., conversions with lithium aluminum hydride, boronic acids) may require temperatures as low as -100 °C, which can be achieved only in special cryogenic reaction units, either by using liquefied nitrogen as coolant or by installing a low-temperature unit. Other reaction-specific equipment, such as filters for

2955-564: A few selected fine chemical companies, (see section 3.2.2), the technology toolboxes of all these companies are similar. This means that they can carry out practically all types of chemical reactions. They differentiate on the basis of the breadth and quality of the service offering. Contract research organizations (CROs) provide services to the life science industries along product development. There are more than 2000 CROs operating worldwide, representing revenues of more than $ 20 billion. One distinguishes between "Product" and "Patient" CROs. Whereas

3152-560: A fine chemical company in cell culture technology are listed below: Pros: Cons: The inherent risks of the mammalian cell technology led several companies to opt out of mammalian cell technology or to substantially reduce their stake. Examples are Cambrex and Dowpharma in the US, Avecia , DSM and Siegfried in Europe and WuXi App Tech in China. In conclusion, biocatalysis should be, or become, part of

3349-414: A five-carbon sugar (either ribose or desoxyribose ), a nitrogenous base (either a pyrimidine or a purine) and 1–3 phosphate groups. The best known representative of a nucleotide is the coenzyme ATP (= Adenosine triphosphate ), MW 507.2. Oligonucleotides are chemically synthesized from protected phosphoramidites of natural or chemically modified nucleosides. The oligonucleotide chain assembly proceeds in

3546-484: A five-day course of Paxlovid. The FDA responded by announcing they had performed additional analyses of the drug's clinical trial data, and decided against changing its recommendations. U.S. President Joe Biden and Dr. Anthony Fauci were both reported to experience this rebound syndrome in the months that followed, while continuing to recommend the drug for those who may benefit from it. Multinational corporation A multi-national corporation ( MNC ; also called

3743-429: A free market system where there is little government interference. As a result, international wealth is maximized with free exchange of goods and services. To many economic liberals, multinational corporations are the vanguard of the liberal order. They are the embodiment par excellence of the liberal ideal of an interdependent world economy. They have taken the integration of national economies beyond trade and money to

3940-506: A large scale. Some important antibiotics besides penicillin are cephalosporins , azithromycin , bacitracin , gentamicin , rifamycin , streptomycin , tetracycline , and vancomycin . Cell Cultures Animal or plant cells, removed from tissues, will continue to grow if cultivated under the appropriate nutrients and conditions. When carried out outside the natural habitat, the process is called cell culture. Mammalian cell culture fermentation, also known as recombinant DNA technology ,

4137-438: A later date. On November 9, 2020, Pfizer announced that BioNTech's COVID-19 vaccine, tested on 43,500 people, was found to be 90% effective at preventing symptomatic COVID-19. The efficacy was updated to 95% a week later. Akiko Iwasaki, an immunologist interviewed by The New York Times , described the efficacy figure as "really a spectacular number." The announcement made Pfizer and BioNTech the first companies to develop and test

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4334-403: A meaningful assessment of single projects and project portfolios. Examples are attractiveness, strategic fit, innovation, gross/net present value, expected profits, R&D expenditures, development stage, probability of success, technology fit, potential conflicts with other activities of the company and realization time. Most of these parameters cannot be determined quantitatively, at least during

4531-487: A million troops to help, and by February 1991, Iraqi forces were expelled from Kuwait. Due to the oil boycott from Kuwait and Iran, oil prices rose and quickly recovered. Saudi Arabia once again led OPEC, and thanks to assistance in defending Kuwait, new relations emerged between the USA and OPEC. Operation "Desert Storm" brought mutual dependence among the main oil producers. OPEC continued to influence global oil prices but recognized

4728-433: A more straightforward fermentative process with 2-ketogluconic acid as pivotal intermediate. After the discovery of penicillin in 1928 by Sir Alexander Fleming from colonies of the bacterium Staphylococcus aureus , it took more than a decade before a powdery form of the medicine was developed. Since then, many more antibiotics and other secondary metabolites have been isolated and manufactured by microbial fermentation on

4925-465: A new chemical process has been introduced successfully on an industrial scale, process optimization is called upon to improve the economics. As a rule of thumb it should be attempted to reduce the costs of goods sold (COGS) by 10-20%, every time the yearly production quantity has doubled. The task extends from fine tuning the currently used synthetic method all the way to the search for an entirely different second generation process. Specific provisions are

5122-445: A prescription anti-inflammatory medication that became Pfizer's first product to reach $ 1   billion in revenue. In 1965, John Powers, Jr. became chief executive officer of the company, succeeding John McKeen. As the area surrounding its Brooklyn, NY plant fell into decline in the 1970s and 1980s, the company formed a public-private partnership with New York City that encompassed the construction of low- and middle-income housing,

5319-407: A profit contributor. The offerings of Patient CROs (Clinical CROs) comprise more than 30 tasks addressing the clinical part of pharmaceutical development at the interface between drugs, physicians, hospitals, and patients, such as the clinical development and selection of lead new drug compounds. As clinical trials represent the largest expense in pharmaceutical research, the market for patient CROs

5516-584: A rare type of leukemia and a blood and bone marrow disease that affects primarily older adults. In November 2012, Pfizer received approval from the Food and Drug Administration for Xeljanz, a tofacitinib , for rheumatoid arthritis and ulcerative colitis . The drug had sales of $ 1.77   billion in 2018, and in January 2019, it was the top drug in the United States for direct-to-consumer advertising , passing adalimumab (Humira). On February 1, 2013, Zoetis ,

5713-404: A result. These skills were applied to the deep-submergence mass production of penicillin , an antibiotic , during World War II in response to the need to treat injured Allied soldiers. The company also embarked on a global soil collection program related to improving production yields of penicillin which ultimately resulted in 135,000 samples. On June 2, 1942, the company incorporated under

5910-431: A shortage of calcium citrate . Pfizer imported the compound from Italy for the manufacture of citric acid, and due to the disruption in supply, the company began a search for an alternative. They found this in the form of a fungus capable of fermenting sugar to citric acid. By 1919, the company was able to commercialize production of citric acid from this source. The company developed expertise in fermentation technology as

6107-421: A spokesperson for the drug. The patents for Viagra expired in 2020. In 1991, William C. Steere, Jr. became chief executive officers of the company, succeeding Edmund T. Pratt Jr. In 1991 Pfizer also began marketing Zoloft ( sertraline ), an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class developed nine years earlier by Pfizer chemists Kenneth Koe and Willard Welch. Sertraline

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6304-568: A strong demand for advanced organic chemicals used in their manufacture. As the in-house production capacities of the originators, the pharmaceutical companies Smith, Kline, & French and Glaxo, could not keep pace with the rapidly increasing requirements, both companies (now merged as GlaxoSmithKline ) outsourced part of the manufacturing to chemical companies experienced in producing relatively sophisticated organic molecules. Lonza , Switzerland, which already had supplied an early intermediate, methyl acetoacetate, during drug development, soon became

6501-671: A study with the CDC Foundation to investigate the tracking of healthcare-associated infections , scheduled to run through to June 2023. In December 2019, Pfizer awarded the CDC Foundation a further $ 1,948,482 to continue its cryptococcal disease screening and treatment research in nine African countries. In March 2020, Pfizer joined the COVID-19 Therapeutics Accelerator funding vehicle to expedite development of treatments against COVID-19 . The $ 125 million initiative

6698-530: A technological point of view, MRT, a.k.a. continuous flow reactors, represents the first breakthrough development in reactor design since the introduction of the stirred-tank reactor, which was used by Perkin & Sons , when they established a factory on the banks of what was then the Grand Junction Canal in London in 1857 to produce mauveïne, the first-ever synthetic purple dye. For a comprehensive coverage of

6895-532: A total business in the range of $ 1.5-$ 2 billion. Their tasks are described in Chapter 5, Examples of are: The business of CROs is usually done through a "pay for service" arrangement. Contrary to manufacturing companies, invoicing of CROs is not based on unit product price, but on full-time equivalents (FTEs), that is, the cost of a scientist working one year on a given customer assignment. Companies offering both contract research and manufacturing services (CRAMS) combine

7092-423: A very high enantiomeric excess (ee). An example is AstraZeneca 's blockbuster drug Crestor (rosuvastatin), see Chemical / Enzymatic Synthesis of Crestor. Further examples of modern drugs, where enzymes are used in the synthesis, are Pfizer 's Lipitor (atorvastatin), where the pivotal intermediate R-3-Hydroxy-4-cyanobutyrate is now made with a nitrilase , and Merck & Co.'s Singulair (montelukast), where

7289-509: A working vaccine for COVID-19. Over the following month and a half, regulators in various countries approved Pfizer's vaccine for emergency use. In February 2021, after a year long investigation relying on unnamed officials, Pfizer was accused by The Bureau of Investigative Journalism (TBIJ) of employing "high-level bullying" against at least two Latin American countries during negotiations to acquire COVID-19 vaccines, including requesting that

7486-480: Is a big step forward regarding administration of peptide and protein drugs. The method offers the two-fold advantage of substituting injection by oral administration and reducing the dosage, and therefore the cost of the treatment. The pioneer company in this field is Prolong Pharmaceuticals which has developed a PEGylated erythropoietin (PEG-EPO). Oligonucleotides are a third category of big molecules. They are oligomers of nucleotides , which in turn are composed of

7683-403: Is a much more demanding operation than conventional biocatalysis and –synthesis. The bioreactor batch requires more stringent controls of operating parameters, since mammalian cells are heat and shear sensitive. In addition, the growth rate of mammalian cells is very slow, lasting from days to several months. While there are substantial differences between microbial and mammalian technologies (e.g.,

7880-635: Is about 1500 kilograms and sales approach $ 500 million on the active pharmaceutical (API) level and $ 10 billion on the finished drug level, respectively. The bulk of the production of peptide drugs, which comprise also the first generation anti-AIDS drugs, the "...navirs", is outsourced to a few specialized contract manufacturers, such as Bachem , Switzerland; Chengu GT Biochem, China; Chinese Peptide Company, China; Lonza, Switzerland, and Polypeptide , Denmark. Proteins are "very high-molecular-weight" (MW > 100,000) organic compounds, consisting of amino acid sequences linked by peptide bonds. They are essential to

8077-731: Is available for each step of the synthesis of a fine chemical. The reactions have been developed on laboratory scale by academia over the last two centuries and subsequently adapted to industrial scale, for instance for the manufacture of dyestuffs & pigments. The most comprehensive handbook describing organic synthetic methods is Methods of Molecular Transformations . About 10% of the 26,000 synthetic methods described therein are currently used on an industrial scale for fine chemicals production. Amination , condensation , esterification , Friedel–Crafts , Grignard , halogenation (esp. chlorination), and hydrogenation , respectively reduction (both catalytic and chemical) are most frequently mentioned on

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8274-466: Is expected to increase moderately ( see Chapter 8), the estimated annual growth rates for the above-mentioned niche technologies are much higher. Microreactors and the SMB separation technology are expected to grow at a rate of even 50–100% per year. The total size of the accessible market typically does not exceed a few hundred tons per year at best. Industrial biotechnology, also called " white biotechnology ",

8471-524: Is increasingly impacting the chemical industry, enabling both the conversion of renewable resources , such as sugar or vegetable oils, and the more efficient transformation of conventional raw materials into a wide range of commodities (e.g., cellulose , ethanol and succinic acid ), fine chemicals (e.g. 6-aminopenicillanic acid), and specialties (e.g., food and feed additives). As opposed to green and red biotechnology, which relate to agriculture and medicine, respectively, white biotechnology seeks to improve

8668-493: Is involved. The most important regulatory authorities are the (US) Food and Drug Administration (FDA) and (Chinese) State Food & Drug Administration (SFDA) , respectively. Their main responsibilities comprise formulating comprehensive supervision policies (" Good Manufacturing Practice ") and control the implementation, to be in charge of drug registration, draw up criteria for marketing authorization and formulate national essential medicines lists. The European correspondent

8865-596: Is larger than for their product counterparts. Thus, the sales of the top tier firms, Charles River Laboratories , Fortrea , Parexel , PPD , Quintiles Transnational , all USA, and TCG Lifescience , India; are in the $ 1–$ 2 billion range, whereas the largest product CROs have revenues of a few 100 million dollars. The overall emphasis of fine chemical R&D is more on development than on research. The main tasks are (1) designing, respectively duplicating and adapting in case of custom manufacture, and developing laboratory procedures for new products or processes; (2) transferring

9062-410: Is often handled through international arbitration . The actions of multinational corporations are strongly supported by economic liberalism and free market system in a globalized international society. According to the economic realist view, individuals act in rational ways to maximize their self-interest and therefore, when individuals act rationally, markets are created and they function best in

9259-406: Is particularly the case in the synthesis of molecules with chiral centres. Here, it is possible to substitute the formation of a salt with a chiral compound, e.g., (+)-α-phenylethylamine , crystallization, salt breaking and recycling of the chiral auxiliary, resulting in a theoretical yield of not more than 50%, with a one step, high yield reaction under mild conditions and resulting in a product with

9456-454: Is practically no lower limit. New fine chemical plants have come on-stream mostly in Far East countries over the past few years. Their annual turnover rate rarely exceeds $ 25 million. All big and medium-size fine chemical companies have cGMP-compliant plants that are suitable for the production of pharmaceutical fine chemicals. With the exception of biopharmaceuticals, which are manufactured by only

9653-477: Is primarily prescribed for major depressive disorder in adult outpatients as well as obsessive-compulsive disorder , panic disorder , and social anxiety disorder in both adults and children. In 2005, the year before it became a generic drug, sales were over $ 3   billion and over 100   million people had been treated with the drug. The patent for Zoloft expired in the summer of 2006. In 1996, Eisai , in partnership with Pfizer, received approval from

9850-579: Is the European Medicines Agency (EMEA) , which is manly responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union. The role of REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) is self-explanatory. The U.S. Pharmacopeia codifies quality standards for Active Pharmaceutical Ingredients. As these standards are observed worldwide, they contribute also to

10047-462: Is the leader in modifying enzymes to specific chemical reactions. The highest-volume chemicals made by biocatalysis are bio-ethanol (70 million metric tons), high-fructose corn syrup (2 million metric tons); acrylamide , 6-aminopenicillanic acid (APA), L-lysine and other amino acids, citric acid and niacinamide (all more than 10,000 metric tons). Biosynthesis i.e. the conversion of organic materials into fine chemicals by microorganisms,

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10244-489: Is used for the production of both small molecules (using enzymes in whole cell systems) and less complex, non-glycosylated big molecules, including peptides and simpler proteins. The technology has been used for 10,000 years to produce food products, like alcoholic beverages, cheese, yogurt, and vinegar. In contrast to biocatalysis, a biosynthetic process does not depend on chemicals as starting materials, but only on cheap natural feedstock, such as glucose, to serve as nutrient for

10441-569: Is used mainly for the production of complex big molecule therapeutic proteins, a.k.a. biopharmaceuticals. The first products made were interferon (discovered in 1957), insulin , and somatropin . Commonly used cell lines are Chinese hamster ovary (CHO) cells or plant cell cultures. The production volumes are very small. They exceed 100 kg per year for only three products: Rituxan ( Roche-Genentech ), Enbrel ( Amgen and Merck & Co . [formerly Wyeth]), and Remicade ( Johnson & Johnson ). Fine chemical production by mammalian cell culture

10638-865: Is usually a large corporation incorporated in one country that produces or sells goods or services in various countries. Two common characteristics shared by MNCs are their large size and centrally controlled worldwide activities. MNCs may gain from their global presence in a variety of ways. First of all, MNCs can benefit from the economy of scale by spreading R&D expenditures and advertising costs over their global sales, pooling global purchasing power over suppliers, and utilizing their technological and managerial experience globally with minimal additional costs. Furthermore, MNCs can use their global presence to take advantage of underpriced labor services available in certain developing countries and gain access to special R&D capabilities residing in advanced foreign countries. The problem of moral and legal constraints upon

10835-462: Is very fragmented. 2000 – 3000 fine chemical companies exist globally, extending from small, "garage-type" outfits in China making just one product, all the way to the big, diversified enterprises, resp. units. The main reason for the fragmentation is the lack of economy of scale (see below). The industry is subject to a high degree of regulation even more so than the chemical industry as a whole, particularly if pharmaceutical fine chemical production

11032-930: The British East India Company founded in 1600 and the Dutch East India Company (VOC) founded in 1602. In addition to carrying on trade between Great Britain and its colonies, the British East India Company became a quasi-government in its own right, with local government officials and its own army in India. Other examples include the Swedish Africa Company founded in 1649 and the Hudson's Bay Company founded in 1670. These early corporations engaged in international trade and exploration and set up trading posts. The Dutch government took over

11229-515: The Delaware General Corporation Law . Due to price declines for penicillin , Pfizer searched for new antibiotics with greater profit potential. Pfizer discovered oxytetracycline in 1950, and this changed the company from a manufacturer of fine chemicals to a research-based pharmaceutical company. Pfizer developed a drug discovery program focused on in vitro synthesis to augment its research in fermentation technology. In 1959,

11426-604: The FDA . The company began Phase   II-III testing on 30,000 people in the last week of July 2020 and was slated to be paid $ 1.95   billion for 100   million doses of the vaccine by the US government. In September 2020, Pfizer and BioNTech announced that they had completed talks with the European Commission to provide an initial 200   million vaccine doses to the EU, with the option to supply another 100   million doses at

11623-470: The Food and Drug Administration approved enzalutamide , developed by Pfizer and Astellas Pharma for patients with castration -resistant prostate cancer . In August 2018, Pfizer signed an agreement with BioNTech to conduct joint research and development activities regarding mRNA -based influenza vaccines . In October 2018, effective January 1, 2019, Albert Bourla was promoted to chief executive officer , succeeding Ian Read , his mentor. In July 2019,

11820-444: The Food and Drug Administration for donepezil under the brand Aricept for treatment of Alzheimer's disease ; Pfizer also received approval for Norvasc ( amlodipine ), an antihypertensive drug of the dihydropyridine calcium channel blocker class. In 1997, the company entered into a co-marketing agreement with Warner–Lambert for Lipitor ( atorvastatin ), a statin for the treatment of hypercholesterolemia . Although atorvastatin

12017-473: The Pfizer–BioNTech COVID-19 vaccine ($ 11 billion in 2023 revenues), apixaban ($ 6 billion in 2023 revenues), a pneumococcal conjugate vaccine ($ 6 billion in 2023 revenues), palbociclib ($ 4 billion in 2023 revenues), and tafamidis ($ 3 billion in 2023 revenues). In 2023, 46% of the company's revenues came from the United States, 6% came from Japan, and 48% came from other countries. As of 2024,

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12214-478: The Phase III trial of Tanezumab . In May 2015, Pfizer and a Bar-Ilan University laboratory announced a partnership based on the development of medical DNA nanotechnology . In June 2015, the company acquired Nimenrix and Mencevax, meningococcal vaccines , from GlaxoSmithKline for around $ 130   million. In September 2015, Pfizer acquired Hospira for $ 17   billion, including the assumption of debt. Hospira

12411-428: The life science industry plays a big role; however, a significant portion of the fine chemicals total production volume is manufactured in-house by large users. The industry is fragmented and extends from small, privately owned companies to divisions of big, diversified chemical enterprises. The term "fine chemicals" is used in distinction to "heavy chemicals", which are produced and handled in large lots and are often in

12608-506: The pain and inflammation in osteoarthritis , acute pain in adults, rheumatoid arthritis , ankylosing spondylitis , painful menstruation , and juvenile rheumatoid arthritis . SUGEN , a company focused on protein kinase inhibitors, had pioneered the use of ATP-mimetic small molecules to block signal transduction . The SUGEN facility was shut down in 2003 by Pfizer, with the loss of more than 300 jobs, and several programs were transferred to Pfizer. These included sunitinib (Sutent),

12805-518: The "-pril" cardiovascular drugs , such as Alapril (lisinopril), Captoril (captopril), Novolac (imidapril) and Renitec (enalapril). Also the artificial sweetener Aspartame (N-L-α-Aspartyl-L-phenylalanine 1-methyl ester) is a dipeptide. At the high end there is the anticoagulant hirudin , MW ≈ 7000, which is composed of 65 amino acids. Apart from pharmaceuticals, peptides are also used for diagnostics and vaccines. The total production volume (excl. Aspartame) of chemically synthesized, pure peptides

13002-428: The "bottom-up" approach is the method of choice. The researcher converts a commercially available starting material and sequentially adds more reagents until the target molecule is synthesized. For more complex molecules, a "top-down" approach, also known as retro synthesis , or de-construction, is chosen. Key fragments of the target molecule are first identified, then synthesized individually, and finally combined to form

13199-601: The 19th century, such as the Rio Tinto company founded in 1873, which started with the purchase of sulfur and copper mines from the Spanish government. Rio Tinto, now based in London and Melbourne , Australia, has made many acquisitions and expanded globally to mine aluminum , iron ore , copper , uranium , and diamonds . European mines in South Africa began opening in the late 19th century, producing gold and other minerals for

13396-585: The Agriculture Division of Pfizer and later Pfizer Animal Health, became a public company via an initial public offering , raising $ 2.2   billion. Later in 2013, Pfizer completed the corporate spin-off of its remaining stake in Zoetis . In September 2014, the company acquired Innopharma for $ 225   million, plus up to $ 135   million in milestone payments, in a deal that expanded Pfizer's range of generic and injectable drugs. On January 5, 2015,

13593-546: The English language. Senior officials, although mostly still Swedish, all learned English and all major internal documents were in English, the lingua franca of multinational corporations. After the war, the number of businesses having at least one foreign country operation rose drastically from a few thousand to 78,411 in 2007. Meanwhile, 74% of parent companies are located in economically advanced countries. Developing and former communist countries such as China, India, and Brazil are

13790-557: The International Energy Agency (IEA), enabling states to coordinate policy, gather data, and monitor global oil reserves. In the 1970s, OPEC gradually nationalized the Seven Sisters. The Kingdom of Saudi Arabia, as the only largest world oil producer, could leverage this. However, Saudi Arabia opted for the correct approach and maintained consistent oil prices throughout the 1970s. In 1979, the "second oil shock" came from

13987-505: The Netherlands has become a popular choice, as its company laws have fewer requirements for meetings, compensation, and audit committees, and Great Britain had advantages due to laws on withholding dividends and a double-taxation treaty with the United States. Corporations can legally engage in tax avoidance through their choice of jurisdiction but must be careful to avoid illegal tax evasion . Corporations that are broadly active across

14184-545: The OLI framework. The other theoretical dimension of the role of multinational corporations concerns the relationship between the globalization of economic engagement and the culture of national and local responses. This has a history of self-conscious cultural management going back at least to the 60s. For example: Ernest Dichter, architect, of Exxon's international campaign, writing in the Harvard Business Review in 1963,

14381-519: The Pfizer CEO Albert Bourla confirmed that the trial results of a fourth dose were pending until March 2022. He said that the firm was setting up a collaboration to develop an anti-COVID pill treatment along with a French company, Novasep . He also said the COVID vaccine was "safe and efficient" for children. In May 2022, reports emerged of patients experiencing "rebound" symptoms after completing

14578-458: The Third World colonies. That changed dramatically after 1945 as investors turned to industrialized countries and invested in manufacturing (especially high-tech electronics, chemicals, drugs, and vehicles) as well as trade. Sweden's leading manufacturing concern was SKF , a leading maker of bearings for machinery. In order to expand its international business, it decided in 1966 it needed to use

14775-636: The U.S. applies its corporate taxation "extraterritorially", which has motivated tax inversions to change the home state. By 2019, most OECD nations, with the notable exception of the U.S., had moved to territorial tax in which only revenue inside the border was taxed; however, these nations typically scrutinize foreign income with controlled foreign corporation (CFC) rules to avoid base erosion and profit shifting . In practice, even under an extraterritorial system, taxes may be deferred until remittance, with possible repatriation tax holidays , and subject to foreign tax credits . Countries generally cannot tax

14972-527: The United States sanctions against Iran ; European companies faced with the possibility of losing access to the U.S. market by trading with Iran. International investment agreements also facilitate direct investment between two countries, such as the North American Free Trade Agreement and most favored nation status. Raymond Vernon reported in 1977 that of the largest multinationals focused on manufacturing, 250 were headquartered in

15169-506: The United States scrutinizes foreign investments. In addition, corporations may be prohibited from various business transactions by international sanctions or domestic laws. For example, Chinese domestic corporations or citizens have limitations on their ability to make foreign investments outside China, in part to reduce capital outflow . Countries can impose extraterritorial sanctions on foreign corporations even for doing business with other foreign corporations, which occurred in 2019 with

15366-609: The United States as the largest consumer and guarantor of the existing oil security order. Since the Iraq War, OPEC has had only a minor influence on oil prices, but it has expanded to 11 members, accounting for about 40 percent of total global oil production, although this is a decline from nearly 50 percent in 1974. Oil has practically become a common commodity, leading to much more volatile prices. Most OPEC members are wealthy, and most remain dependent on oil revenues, which has serious consequences, such as when OPEC members were pressured by

15563-461: The United States from 2010. The USA became the leading oil producer, creating tension with OPEC. In 2014, Saudi Arabia increased production to push new American producers out of the market, leading to lower prices. OPEC then reduced production in 2016 to raise prices, further worsening relations with the United States. By 2012, only 7% of the world's known oil reserves were in countries that allowed private international companies free rein; 65% were in

15760-561: The United States, 115 in Western Europe, 70 in Japan, and 20 in the rest of the world. The multinationals in banking numbered 20 headquartered in the United States, 13 in Europe, nine in Japan and three in Canada. Today multinationals can select from a variety of jurisdictions for various subsidiaries, but the ultimate parent company can select a single legal domicile ; The Economist suggests that

15957-410: The United States. Pfizer introduced an improved version of the vaccine in 2010, for which it was granted a patent in India in 2017. Prevnar 13 provides coverage of 13 bacterial variants, expanding beyond the original 7-valent version. By 2012, the rate of invasive infections among children under age   5 had been reduced by an additional 50%. In 2010, Ian Read was named chief executive officer of

16154-738: The VOC in 1799, and during the 19th century, other governments increasingly took over private companies, most notably in British India. During the process of decolonization , the European colonial charter companies were disbanded, with the final colonial corporation, the Mozambique Company , dissolving in 1972. Mining of gold, silver, copper, and oil was a major activity early on and remains so today. International mining companies became prominent in Britain in

16351-533: The Ventavia Research Group. Ventavia was hired by Pfizer as a research subcontractor. A regional director (whistleblower) who was employed at Ventavia Research Group has told The BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer's pivotal phase III trial . The regional director, Brook Jackson, emailed

16548-498: The West to the post-colonial South and invest either in foreign expenditures or ostentatious economic development projects. After 1974, most of the money from OPEC members ceased as payments for goods and services or investments in Western industry. In February 1974, the first Washington Energy Conference was convened. The most significant contribution of this conference was the establishment of

16745-418: The ability to synthesize chiral molecules has become an important competency. Two types of processes are used, namely the physical separation of the enantiomers and the stereo specific synthesis, using chiral catalysts. Among the latter, enzymes and synthetic BINAP (2,2'–Bis(diphenylphosphino)–1,1'–binaphthyl) types are used most frequently. Large volume (> 103 mtpa) processes using chiral catalysts include

16942-475: The activities of CROs and CMOs. Their history is either a forward integration of a CRO, which adds industrial scale capabilities or backwards integration of a CMO. As there are only limited synergies (e.g. > 90% of the projects end at the sample preparation stage). It is questionable, though, whether one-stop shops really fulfil a need. Actually, the large fine chemical companies consider the preparation of samples more as marketing tool (and expense ...) rather than

17139-488: The advent of biopharmaceuticals had a major impact on the demand for fine chemicals and the evolution of the fine chemical industry as a distinct entity. For many years, the life science industry continued considering captive production of the active ingredients of their drugs and agrochemicals as a core competency. Outsourcing was used only in exceptional cases, such as capacity shortfalls, processes requiring hazardous chemistry or new products, where uncertainties existed about

17336-449: The amount of taxes they pay). In June 2016, the company acquired Anacor Pharmaceuticals for $ 5.2   billion, expanding its portfolio in both inflammation and immunology drugs areas. In August 2016, the company made a $ 40   million bid for the assets of BIND Therapeutics, which was in bankruptcy . The same month, the company acquired Bamboo Therapeutics for $ 645   million, expanding its gene therapy offerings. In September 2016,

17533-542: The antiulcerants Tagamet (cimetidine. see above) and Nexium (omeprazole), the antimycotics Daktarin (miconazole), Fungarest (ketoconazole) and Travogen ( isoconazole ). Tetrazoles and tetrazolidines are pivotal parts of the " sartan " class of hypertensives , e.g. Candesartan cilexetil (candesartan), Avapro (irbesartan), Cozaar (losartan) and Diovan (valsartan). A vast array of pharmaceuticals and agrochemicals are based on pyrimidines , such as Vitamin B1 (thiamine),

17730-533: The assumption of debt, making Pfizer the largest pharmaceutical company in the world. The acquisition of Wyeth provided Pfizer with a pneumococcal conjugate vaccine , trademarked Prevnar 13 ; this is used for the prevention of invasive pneumococcal infections. The introduction of the original, 7-valent version of the vaccine, developed by Wyeth in February 2000, led to a 75% reduction in the incidence of invasive pneumococcal infections among children under age   5 in

17927-462: The behavior of multinational corporations, given that they are effectively "stateless" actors, is one of several urgent global socioeconomic problems that has emerged during the late twentieth century. Potentially, the best concept for analyzing society's governance limitations over modern corporations is the concept of "stateless corporations". Coined at least as early as 1991 in Business Week ,

18124-554: The bench-scale laboratory or pilot plant. Furthermore, it has to be adapted to the specific characteristics of available production trains. Bench-scale Laboratory , kg-lab and Pilot Plant Development . Depending on the volume requirements, three different types of equipment are used for process research, development and optimization, namely bench-scale laboratories for gram to 100 gram, kilo-labs for kg to 10 kg and pilot plants for 100 kg to ton quantities. Particularities of laboratory processes that have to be eliminated include

18321-493: The cancer cells. The first commercialized ADCs were Isis 's Fomivirsen and, more recently, Pfizer's (formerly Wyeth) Mylotarg (gemtuzumab ozogamicin). Examples of ADCs in phase III of development are Abbott 's / Isis's Alicaforsen and Eli Lilly 's Aprinocarsen . Several key technologies are used for the production of fine chemicals, including Chemical synthesis and biotechnology are most frequently used; sometimes also in combination. A large toolbox of chemical reactions

18518-450: The cells. The enzyme systems triggered in the particular microorganism strain lead to the excretion of the desired product into the medium, or, in the case of HMW peptides and proteins, to the accumulation within so-called inclusion bodies in the cells. The key elements of fermentation development are strain selection and optimization, as well as media and process development. Dedicated plants are used for large-scale industrial production. As

18715-400: The cells; (2) Fermentation, i.e. the actual production of the protein, typically in 10,000 Liter, or multiples, bioreactors; (3) Purification, i.e. separation of the cells from the culture medium and purification, mostly by chromatography, (4) Formulation, i.e. conversion of the sensitive proteins to a stable form. All steps are fully automated. The low productivity of the animal culture makes

18912-471: The chance of a successful launch. In terms of molecular structure, one distinguishes first between low-molecular-weight (LMW) and high-molecular-weight (HMW) products. The generally accepted threshold between LMW and HMW is a molecular weight of about 700. LMW fine chemicals, also designated as small molecules, are produced by traditional chemical synthesis, by microorganisms ( fermentation or biotransformation ), or by extraction from plants and animals. In

19109-728: The collapse of the Shah's regime in Iran. Iran became a regional power due to oil money and American weapons. The Shah eventually abdicated and fled the country. This prompted a strike by thousands of Iranian oil workers, significantly reducing oil production in Iran. Saudi Arabia tried to cope with the crisis by increasing production, but oil prices still soared, leading to the "second oil shock." Saudi Arabia significantly reduced oil production, losing most of its revenues. In 1986, Riyadh changed course, and oil production in Saudi Arabia sharply increased, flooding

19306-502: The commodities industry. They represent around 5–10% versus 2–5% of sales. On the business side, product innovation must proceed at a more rapid pace, because life cycles of fine chemicals are shorter than those of commodities. Therefore, there is an ongoing need for substitution of obsolete products. On the technical side, the higher complexity of the products and the more stringent regulatory requirements absorb more resources. Many economic and technical parameters have been proposed to enable

19503-650: The companies. This occurred in 1960. Prior to the 1973 oil crisis , the Seven Sisters controlled around 85 percent of the world's petroleum reserves . In the 1970s, most countries with large reserves nationalized their reserves that had been owned by major oil companies. Since then, industry dominance has shifted to the OPEC cartel and state-owned oil and gas companies, such as Saudi Aramco , Gazprom (Russia), China National Petroleum Corporation , National Iranian Oil Company , PDVSA (Venezuela), Petrobras (Brazil), and Petronas (Malaysia). A unilateral increase in oil prices

19700-484: The company acquired Therachon for up to $ 810   million, expanding its rare disease portfolio through Therachon's recombinant human fibroblast growth factor receptor 3 compound, aimed at treating conditions such as achondroplasia . Also in July, Pfizer acquired Array Biopharma for $ 10.6   billion, boosting its oncology pipeline. In August 2019, Pfizer merged its consumer health business with that of GlaxoSmithKline, into

19897-765: The company acquired cancer drug-maker Medivation for $ 14   billion. In October 2016, the company licensed the anti- CTLA4 monoclonal antibody, ONC-392, from OncoImmune. In November 2016, Pfizer funded a $ 3,435,600 study with the CDC Foundation to research "screen-and-treat" strategies for cryptococcal disease in Botswana . In December 2016, Pfizer acquired AstraZeneca 's small-molecule antibiotics business for $ 1.575 billion. In January 2018, Pfizer announced that it would end its work on research into treatments for Alzheimer's disease and Parkinsonism (a symptom of Parkinson's disease and other conditions). The company said about 300 researchers would lose their jobs. In July 2018,

20094-468: The company announced it would acquire a controlling interest in Redvax, expanding its vaccine portfolio targeting human cytomegalovirus . In February 2015, the company received approval from the Food and Drug Administration for palbociclib (Ibrance) for treatment of certain types of breast cancer . In March 2015, the company announced it would restart its collaboration with Eli Lilly and Company surrounding

20291-659: The company established an animal health division with a 700-acre (2.8 km) farm and research facility in Terre Haute, Indiana . By the 1950s, Pfizer had established offices in Belgium, Brazil, Canada, Cuba, Mexico, Panama, Puerto Rico, and the United Kingdom. In 1960, the company moved its medical research laboratory operations out of New York City to a new facility in Groton, Connecticut. In 1980, Pfizer launched Feldene ( piroxicam ),

20488-509: The company had not evaluated their COVID-19 vaccine for its ability to reduce transmission of the SARS-CoV-2 virus prior to its release to the general public. Dutch MEP Rob Roos described the admission as "scandalous". CEO Albert Bourla was slated to attend, but withdrew. Roos' statements in turn have been described as "misleading". In November 2021, Pfizer launched a new COVID-19 oral antivirus treatment known as Paxlovid . In January 2022,

20685-513: The company ranks 69th on the Fortune 500 . Pfizer was founded in 1849 as "Charles Pfizer & Company" by Charles Pfizer and Charles F. Erhart , two cousins who had immigrated to the United States from Ludwigsburg, Germany . The business produced chemical compounds, and was headquartered on Bartlett Street in Williamsburgh, New York where they produced an antiparasitic called santonin . This

20882-435: The company received approval for Lyrica ( pregabalin ), an anticonvulsant and anxiolytic medication used to treat epilepsy , neuropathic pain , fibromyalgia , restless leg syndrome , and generalized anxiety disorder . The United States patent on Lyrica was challenged by generic manufacturers and was upheld in 2014, extending the expiration date to 2018. In July 2006, Jeff Kindler was named chief executive officer of

21079-454: The company, replacing Henry McKinnell . On December 3, 2006, Pfizer ceased development of torcetrapib , a drug that increases production of HDL , which reduces LDL thought to be correlated to heart disease. During a Phase III clinical trial involving 15,000 patients, more deaths than expected occurred in the group that took the medicine, and the mortality rate of patients taking the combination of torcetrapib and Lipitor (82 deaths during

21276-553: The company. In February 2011, Pfizer announced the closure of its UK research and development facility (formerly also a manufacturing plant) in Sandwich, Kent , which at the time employed 2,400 people. In March 2011, Pfizer acquired King Pharmaceuticals for $ 3.6   billion in cash. King produced emergency injectables such as the EpiPen . On September 4, 2012, the FDA approved bosutinib (Bosulif) for chronic myelogenous leukemia (CML),

21473-744: The comparison of fine chemicals, commodities and specialties). The class of fine chemicals is subdivided either on the basis of the added value (building blocks, advanced intermediates or active ingredients ), or the type of business transaction, namely standard or exclusive products. Fine chemicals are produced in limited volumes (< 1000 tons/year) and at relatively high prices (> $ 10/kg) according to exacting specifications, mainly by traditional organic synthesis in multipurpose chemical plants . Biotechnical processes are gaining ground. Fine chemicals are used as starting materials for specialty chemicals , particularly pharmaceuticals , biopharmaceuticals and agrochemicals . Custom manufacturing for

21670-510: The conception was theoretically clarified in 1993: that an empirical strategy for defining a stateless corporation is with analytical tools at the intersection between demographic analysis and transportation research. This intersection is known as logistics management , and it describes the importance of rapidly increasing global mobility of resources. In a long history of analysis of multinational corporations, we are some quarter-century into an era of stateless corporations—corporations that meet

21867-451: The countries put sovereign assets as collateral for payments. According to TBIJ, these negotiation tactics resulted in a months long delay in Pfizer reaching a vaccine agreement with one country and a complete failure to reach agreements with two other countries, including Argentina and Brazil. In November 2021, TBMJ published an article after obtaining information from a whistleblower from

22064-475: The cradle of the fine chemical industry. This is e.g. the case for the world's #1 company, Lonza, headquartered in Basel. Switzerland. Custom manufacturing prevails in northern Europe; the manufacture of active substances for generics, in southern Europe. The second largest geographic area is Asia, housing 7 of the top 20. With 4 large companies, the US rank last. Whereas the European and U.S. pharma industry constitutes

22261-643: The creation of a "world customer". The idea of a global corporate village entailed the management and reconstitution of parochial attachments to one's nation. It involved not a denial of the naturalness of national attachments, but an internationalization of the way a nation defines itself. "Multinational enterprise" (MNE) is the term used by international economist and similarly defined with the multinational corporation (MNC) as an enterprise that controls and manages production establishments, known as plants located in at least two countries. The multinational enterprise (MNE) will engage in foreign direct investment (FDI) as

22458-441: The days of the dyestuff industry. Numerous regulations determine the way labs and plants must be operated, thereby contributing to the uniformity. The term "fine chemicals" was in use as early as 1908. The emergence of the fine chemical industry as a distinct entity dates to the late 1970s, when the overwhelming success of the histamine H 2 receptor antagonists Tagamet (cimetidine) and Zantac (ranitidine hydrochloride) created

22655-553: The debate from a neo-liberal perspective in Storm over the Multinationals (1977). Fine chemical In chemistry , fine chemicals are complex, single, pure chemical substances , produced in limited quantities in multipurpose plants by multistep batch chemical or biotechnological processes. They are described by exacting specifications, used for further processing within the chemical industry and sold for more than $ 10/kg (see

22852-582: The decision maker— and they can better leverage their purchasing power. The third tier includes thousands of small independents with sales below $ 100 million per year. Most of them are located in Asia. They often specialize in niche technologies. The minimum economical size of a fine chemical company depends on the availability of infrastructure. If a company is located in an industrial park, where analytical services; utilities, safety, health, and environmental (SHE) services, and warehousing are readily available, there

23049-421: The desired molecule through convergent synthesis. Process Development focuses on the design of new, efficient, stable, safe, and scalable synthetic routes to a target fine chemical. It represents an essential link between process research and commercial production. The resulting " base process " description provides the necessary data for the determination of preliminary raw material and product specifications ,

23246-442: The direction from 3'- to 5'-terminus by following a procedure referred to as a " synthetic cycle ". Completion of a single synthetic cycle results in the addition of one nucleotide residue to the growing chain. The maximum length of synthetic oligonucleotides hardly exceeds 200 nucleotide components. From its current range of applications in basic research as well as in drug target validation, drug discovery, and therapeutic development,

23443-435: The early phases of a project. The best way to take advantage of a project portfolio is to develop and use it in an iterative way. By comparing the entries at regular intervals, for instance, every 3 months, the directions that the projects take can be visualized. If a negative trend persists with one particular project, the project should be put on the watch list. R&D has to manage the following functions in order to deliver

23640-721: The economic and sustainable production of existing products, and provide access to new products, especially biopharmaceuticals. It is expected that revenues from white biotechnology will account for 10%, or $ 250 billion, of the global chemical market of $ 2,500 billion by 2013. In ten to 15 years it is expected that most amino acids and vitamins and many specialty chemicals will be produced by means of biotechnology. Three very different process technologies -biocatalysis, biosynthesis (microbial fermentation), and cell cultures- are used. Biocatalysis , a.k.a. biotransformation and bioconversion , makes use of natural or modified isolated enzymes , enzyme extracts, or whole-cell systems for enhancing

23837-583: The emergence of a uniform worldwide set-up of the top tier fine chemical companies. In terms of size, resources, and complexity of the chemical process technologies mastered, the fine chemical companies can be broadly divided into three segments, each of them accounting for approximately the same turnover, namely about $ 10 billion. The top tier, about twenty, has sales in excess of $ 250 million per year (see Table 3). Most are not pure players but divisions or b.u.'s of large, multinational companies. Their share varies between one percent or less for BASF and Pfizer , all

24034-421: The expected large-volume requirements. Both equipment and plant layout of the pilot plant reflect those of an industrial multipurpose plant, except for the size of reaction vessels (bench-scale laboratory ~10–60 liters; pilot plant ~100–2500 liters) and the degree of process automation. Before the process is ready for transfer to the industrial-scale plant, the following activities have to be completed: Adaptation of

24231-481: The firm makes direct investments in host country plants for equity ownership and managerial control to avoid some transaction costs . Sanjaya Lall in 1974 proposed a spectrum of scholarly analysis of multinational corporations, from the political right to the left. He put the business school how-to-do-it writers at the extreme right, followed by the liberal laissez-faire economists, and the neoliberals (they remain right of center but do allow for occasional mistakes of

24428-416: The hands of state-owned companies that operated in one country and sold oil to multinationals such as BP, Shell, ExxonMobil and Chevron. Down through the 1930s, about 80% of the international investments by multinational corporations were concentrated in the primary sector, especially mining (especially oil) and agriculture (rubber, tobacco, sugar, palm oil , coffee, cocoa, and tropical fruits). Most went to

24625-461: The inherent safety, environmental, and economic risks. In development, the viability of the process on a semi commercial scale has to be demonstrated. Trial quantities of the new fine chemical have to be manufactured for market development, clinical tests, and other requirements. The necessary data have to be generated to enable the engineering department to plan the modifications of the industrial-scale plant and in order to calculate production costs for

24822-406: The intermediate products resulting from individual synthetic steps cannot be purified, a selectivity of effectively 100% is essential for the synthesis of larger-peptide molecules. Even at a selectivity of 99% per reaction step, the purity will drop to less than 75% for a dekapeptide (30 steps). Therefore, for industrial quantities of peptides not more than 10–15 amino acid peptides can be made using

25019-566: The international oil market. Iran was unable to sell any of its oil. In August 1953, the then-prime minister was overthrown by a pro-American dictatorship led by the Shah, and in October 1954, the Iranian industry was denationalized. Worldwide oil consumption increased rapidly between 1949 and 1970, a period known as the 'golden age of oil'. This increase in consumption was caused not only by the growth of production by multinational oil companies but also by

25216-415: The internationalization of production. For the first time in history, production, marketing, and investment are being organized on a global scale rather than in terms of isolated national economies. International business is also a specialist field of academic research. Economic theories of the multinational corporation include internalization theory and the eclectic paradigm . The latter is also known as

25413-513: The laboratory process to the constraints of a pilot plant, hazard and operability (HAZOP) analysis, execution of demonstration batches . The main differences between laboratory synthesis and industrial scale production are shown in Table 4. In case of cGMP fine chemicals also a process validation is required. It consists of the three elements process design , process qualification and continued process verification . Process Optimization . Once

25610-460: The largest recipients. However, 70% of foreign direct investment went into developed countries in the form of stocks and cash flows. The rise in the number of multinational companies could be due to a stable political environment that encourages cooperation, advances in technology that enable management of faraway regions, and favorable organizational development that encourages business expansion into other countries. A multinational corporation (MNC)

25807-441: The latter, reagents are incorporated in a resin that is contained in a reactor or column. The synthesis sequence starts by attaching the first amino acid to the reactive group of the resin and then adding the remaining amino acids one after the other. In order to ascertain a full selectivity, the amino groups have to be protected in advance. Most developmental peptides are synthesized by this method, which lends itself to automation. As

26004-474: The laws and regulations of both their domicile and the additional jurisdictions where they are engaged in business. In some cases, the jurisdiction can help to avoid burdensome laws, but regulatory statutes often target the "enterprise" with statutory language around "control". As of 1992 , the United States and most OECD countries have the donot legal authority to tax a domiciled parent corporation on its worldwide revenue, including subsidiaries. As of 2019 ,

26201-458: The main customer base for most fine chemical companies, some have a significant share of products and services for the agrochemical industry. Examples are Archimica, CABB, Saltigo (all Germany), DSM (The Netherlands) and Hikal, India. Several large pharmaceutical companies market fine chemicals as subsidiary activity to their production for captive use, e.g. Abbott , USA; Bayer Schering Pharma , Boehringer-Ingelheim , Germany; Daiichi-Sankyo (after

26398-410: The main supplier of more and more advanced precursors. The signature of a first, simple supply contract is generally acknowledged as the historical document marking the beginning of the fine chemical industry. In subsequent years, the business developed and Lonza was the first fine chemical company entering in a strategic partnership with SKF. In a similar way, Fine Organics, UK became the supplier of

26595-477: The major categories. Peptides and proteins are oligomers or polycondensates of amino acids linked together by a carboxamide group. The threshold between the two is as at about 50 amino acids. Because of their unique biological functions, a significant and growing part of new drug discovery and development is focused on this class of biomolecules. Their biological functions are determined by the exact arrangement or sequence of different amino acids in their makeup. For

26792-424: The manufacture of semi commercial quantities in the pilot plant, the assessment of the ecological impact, the regulatory submissions and technology transfer to manufacture at industrial scale, and an estimate of the manufacturing costs in an industrial-scale plant. If the base process is provided by the customer as part of the technology transfer, process, research has to optimize it so that it can be transferred to

26989-462: The manufacture of the perfume ingredient l-Menthol and Syngenta's Dual (metolachlor) as well as BASF's Outlook (dimethenamid-P) herbicides. Examples of originator drugs, which apply asymmetric technology, are AstraZeneca 's Nexium (esomeprazole) and Merck & Co 's Januvia (sitagliptin). The physical separation of chiral mixtures and purification of the desired enantiomer can be achieved either by classical fractional crystallization (having

27186-488: The market with cheap oil. This caused a worldwide drop in oil prices, hence the "third oil shock" or "counter-shock." However, this shock represented something much bigger—the end of OPEC's dominance and its control over oil prices. Iraqi President Saddam Hussein decided to attack Kuwait. The invasion sparked a crisis in the Middle East, prompting Saudi Arabia to request assistance from the United States. The United States sent

27383-531: The marketplace such as externalities). Moving to the left side of the line are nationalists, who prioritize national interests over corporate profits, then the "dependencia" school in Latin America that focuses on the evils of imperialism, and on the far left the Marxists. The range is so broad that scholarly consensus is hard to discern. Anti-corporate advocates criticize multinational corporations for being without

27580-568: The narrower sense are active in process scale up, pilot plant (trial) production, industrial-scale exclusive and non-exclusive manufacture and marketing. Their product portfolios comprise exclusive products, produced by custom manufacturing, as main activity, non-exclusive products, e.g. API-for Generics, and standard products. Characteristics are high asset intensity, batch production in campaigns in multipurpose plants, above-industry-average R&D expenditures and close, multi-level and multi-functional relationships with industrial customers. The industry

27777-430: The now-demolished 295 Washington Avenue) and Erhart (at 280 Washington Avenue) established their main residences in the nearby Clinton Hill district, known for its concentration of Gilded Age wealth. In 1881, Pfizer moved its administrative headquarters to 81 Maiden Lane in Manhattan , presaging the company's expansion to Chicago, Illinois a year later. By 1906 sales exceeded $ 3   million. World War I caused

27974-399: The original six- to eight-step synthetic process starting from barbituric acid has been substituted completely by a microbial one-step process, allowing a 95% waste reduction and an approximately 50% manufacturing cost reduction. In ascorbic acid, the five-step process (yield ≈ 85%) starting from D-glucose , originally invented by Tadeus Reichstein in 1933, is being gradually substituted by

28171-466: The potential use of oligonucleotides is foreseen in gene therapy ( antisense drugs), disease prevention and agriculture. Antibody-drug conjugates (ADC) constitute a combination between small and big molecules. The small molecule parts, up to four different APIs, are highly potent cytotoxic drugs. They are linked with a monoclonal antibody, a big molecule which is of little or no therapeutic value in itself, but extremely discriminating for its targets,

28368-560: The price collapse in 1998–1999. The United States still maintains close relations with Saudi Arabia. In 2003, U.S. forces invaded Iraq with the aim of removing the dictatorship and gaining access to Iraqi oil reserves, giving the United States greater strategic importance from 2000 to 2008. During this period, there was a constant shortage of oil, but its consumption continued to rise, maintaining high prices and leading to concerns about "peak oil". From 2005 to 2012, there were advances in oil and gas extraction, leading to increased production in

28565-430: The processes from the laboratory via pilot plant to the industrial scale (the scale up factor from a 10g sample to a 1-ton batch is 100,000); and (3) to optimize existing processes. At all times during this course of action it has to be ensured that the four critical constraints, namely, economics, timing, safety, ecology and sustainability are observed . R&D expenditures in the fine chemical industry are higher than in

28762-698: The production of modern life science products, total synthesis from petrochemicals prevails. The HMW products, respectively large molecules, are obtained mainly through biotechnology processes. Within LMWs, the N-heterocyclic compounds are the most important category; within HMWs they are the peptides and proteins. As aromatic compounds have been exhausted to a large extent as building blocks for life science products, N-heterocyclic structures prevail nowadays. They are found in many natural products, such as chlorophyll, hemoglobin, and

28959-466: The production of small molecules. It has much to offer compared to traditional organic synthesis. The syntheses are shorter, less energy intensive and generate less waste, hence are both environmentally and economically more attractive. About 2/3 of chiral products produced on large industrial scale are already made using biocatalysis. In the manufacture of fine chemicals, enzymes represent the single most important technology for radical cost reductions. This

29156-685: The production sites of CMOs are multipurpose plants, allowing for the production of tens to hundreds of tons of fine chemicals, the work places of patient CROs are the test persons (volunteers) for the clinical trials and those of the product CROs are the laboratory benches. Major customers for CRO services are the large global pharmaceutical companies. Half a dozen companies ( Pfizer , GlaxoSmithKline , Sanofi-Aventis , AstraZeneca , Johnson & Johnson , and Merck & Co .) alone absorb about one third of all CRO spending. As for CMOs also for CROs, biotech start-up companies with their dichotomy between ambitious drug development programs and limited resources are

29353-546: The range of $ 100–$ 250 million per year. Their portfolios comprise both custom manufacturing and API-for-generics. They include both independents and subsidiaries of major companies. A number of these companies are privately owned and have grown mainly by reinvesting the profits. Examples are Bachem , Switzerland; Dishman, India; F.I.S. and Poli Industria Chimica , Italy; Hikal , India, and Hovione , Portugal. Customers prefer to do business with mid-sized companies, because communications are easier —they typically deal directly with

29550-434: The reaction. Conventional plant equipment can be used with no, or only modest, adaptations. The International Union of Biochemistry and Molecular Biology (IUBMB) has developed a classification for enzymes. The main categories are Oxidoreductases , Transferases , Hydrolases , Lipases (subcategory), Lyases , Isomerases and Ligases , Companies specializing in making enzymes are Novozymes , Danisco (Genencor). Codexis

29747-595: The realities of the needs of source materials on a worldwide basis and to produce and customize products for individual countries. One of the first multinational business organizations, the East India Company , was established in 1601. After the East India Company came the Dutch East India Company , founded on March 20, 1603, which would become the largest company in the world for nearly 200 years. The main characteristics of multinational companies are: When

29944-780: The reduction of a ketone to S-alcohol, which had required stoichiometric amounts of expensive and moisture sensitive " (-)-DIP chloride " is now replaced by a ketoreductase enzyme catalyst step. Similar rewarding switches from chemical steps to enzymatic ones have also been achieved in steroid synthesis. Thus, it has been possible to reduce the number of steps required for the synthesis of Dexamethasone from bile from 28 to 15. Enzymes differ from chemical catalysts particularly with regard to stereoselectivity , regioselectivity , and chemoselectivity . They can also be modified ("reshuffled") for specific reactions, for use in chemical synthesis. " Immobilized enzymes " are those fixed on solid supports. They can be recovered by filtration after completion of

30141-513: The refurbishment of apartment buildings for the homeless and the establishment of a charter school . In 1972, Edmund T. Pratt Jr. became chief executive officer of the company, succeeding John Powers, Jr. In 1981, the company received approval for Diflucan ( fluconazole ), the first oral treatment for severe fungal infections including candidiasis , blastomycosis , coccidiodomycosis , cryptococcosis , histoplasmosis , dermatophytosis , and pityriasis versicolor . In 1986, Pfizer acquired

30338-644: The relatively low rate of 12.5%. The deal was to constitute a reverse merger , whereby Allergan acquired Pfizer, with the new company then changing its name to "Pfizer, plc". On April 6, 2016, Pfizer and Allergan terminated the merger agreement after the Obama administration and the United States Department of the Treasury introduced new laws intended to limit corporate inversions (the extent to which companies could move their headquarters overseas in order to reduce

30535-504: The requested services: Literature and Patent Research . Provisions have to be made for a periodic examination of all acquired research results to safeguard Intellectual Property Rights (IPR) and to determine whether patent applications are indicated. Patent research is particularly important for evaluation of the feasibility of taking up R&D for new APIs-for-generics. Process Research has to design new synthetic routes and sequences. Two approaches are feasible. For simple molecules,

30732-444: The second most promising prospects. Product CROs (chemical CROs) are providing primarily sample preparation, process research and development services. An overlap between the latter and CMOs exists with regard to pilot plants (100 kg quantities), which are part of the arsenal of both types of enterprise. There are more 100 product CROs. Most of them are privately held and have revenues of $ 10–$ 20 million per year or less, adding up to

30929-462: The separation of catalysts, ozone or phosgene generators, can be purchased in many different sizes. The installation of special equipment generally is not a critical path on the overall project for developing an industrial-scale process of a new molecule. Since the mid-1990s the commercial importance of single-enantiomer fine chemicals has increased steadily. They constitute about half of both existing and developmental drug APIs. In this context,

31126-610: The services offered, there are two types of fine chemical companies. The Fine Chemical Companies are active in industrial scale production, both of standard and exclusive products. If the latter prevails, they are referred to as Fine Chemical / Custom Manufacturing Organizations (CMOs) . The main assets of the Contract Research Organizations (CROs) are their research laboratories. CRAMS ; Contract Research and Manufacturing Organizations are hybrids (see section 4.2). Fine chemical / Custom Manufacturing companies in

31323-442: The solid-phase method. For laboratory quantities, up to 40 are possible. To prepare larger peptides, individual fragments are first produced, purified, and then combined to the final molecule by liquid phase synthesis. Thus, for the production of Roche's anti-AIDS drug Fuzeon (enfuvirtide), three fragments of 10–12 amino acids are first made by solid-phase synthesis and then linked together by liquid-phase synthesis. The preparation of

31520-639: The solution efficiently and in an environmentally friendly manner under mild conditions. The final purification is often achieved by conventional chemical crystallization processes. In contrast to the isolation of small molecules, the isolation and purification of microbial proteins is tedious and often involves a number of expensive large-scale chromatographic operations. Examples of large-volume LMW products made by modern industrial microbial biosynthetic processes are monosodium glutamate (MSG), vitamin B2 (riboflavin), and vitamin C (ascorbic acid). In vitamin B2, riboflavin,

31717-495: The strong influence of the United States on the global oil market. In 1959, companies lowered the price of oil due to a surplus in the market. This reduction dealt a significant blow to the finances of producers. Saudi oil minister Abdullah Tariki and Venezuela’s Juan Perez Alfonso entered into a secret agreement (the Mahdi Pact), promising that if the price of oil was lowered a second time, they would take collective action against

31914-541: The structure and function of all living cells and viruses and are among the most actively studied molecules in biochemistry. They can be made only by advanced biotechnological processes; primarily mammalian cell cultures . Monoclonal antibodies (mAb) prevail among human-made proteins. About a dozen of them are approved as pharmaceuticals. Important modern products are EPO (Binocrit, NeoRecormon, erythropoietin), Enbrel (etanercerpt), Remicade (infliximab); MabThera/Rituxin (rituximab), and Herceptin (trastuzumab). PEGylation

32111-853: The study) was 60% higher than those taking Lipitor alone (52 deaths during the study). Lipitor alone was not implicated in the results, but Pfizer lost nearly $ 1   billion developing the failed drug and its stock price dropped 11% on the day of the announcement. Between 2007 and 2010, Pfizer spent $ 3.3   million on investigations and legal fees and recovered about $ 5.1   million, and had another $ 5   million of pending recoveries from civil lawsuits against makers of counterfeit prescription drugs. Pfizer has hired customs and narcotics experts worldwide to track down fakes and assemble evidence that can be used to pursue civil suits for trademark infringement . In July 2008, Pfizer announced 275 job cuts at its manufacturing facility in Portage, Michigan . Portage

32308-522: The subject see Micro Process Engineering . Examples for reactions that have worked in microreactors include aromatics oxidations, diazomethane conversions, Grignards , halogenations , hydrogenations , nitrations , and Suzuki couplings . According to experts in the field, 70% of all chemical reactions could be done in microreactors, however only 10-15% are economically justified. With the exception of some stereospecific reactions, particularly biotechnology, mastering these technologies does not represent

32505-924: The sulfonamide antibiotics, e.g. Madribon (sulfadimethoxime) and –half a century later– the sulfonyl urea herbicides, e.g. Eagle (amidosulfuron) and Londax (bensulfuron-methyl). Benzodiazepine derivatives are the pivotal structural elements of breakthrough CNS Drugs , such as Librium (chlordiazepoxide) and Valium (diazepam). Pyridine derivatives are found in both well-known Diquat and Chlorpyrifos herbicides, and in modern nicotinoid insecticides, such as Imidacloprid . Even modern pigments , such as diphenylpyrazolopyrazoles, quinacridones, and engineering plastics, such as polybenzimidazoles, polyimides, and triazine resins, exhibit an N-heterocyclic structure. Big molecules , also called high molecular weight (HMW) molecules, are mostly oligomers or polymers of small molecules or chains of amino acids. Thus, within pharmaceutical sciences, peptides , proteins and oligonucleotides constitute

32702-400: The synthesis of peptides, four categories of fine chemicals, commonly referred to as peptide building blocks (PBBs), are key, namely amino acids (=starting materials), protected amino acids, peptide fragments and peptides themselves. Along the way, the molecular weights increase from about 10 up to 10 and the unit prices from about $ 100 up to $ 10 per kilogram. However, only a small part of

32899-487: The takeover of Ranbaxy ), Japan; Johnson & Johnson, USA; Merck KGaA , Germany; Pfizer (formerly Upjohn), US. Large fine chemical companies, in contrast to mid-sized and small ones, are characterized by A comprehensive list of about 1400 fine chemical companies (including traders) can be found in the "event catalogue" of the CPhI exhibition. The second tier consists of several dozens of midsized companies with sales in

33096-530: The technology expensive and vulnerable to contamination. Actually, as a small number of bacteria would soon outgrow a larger population of animal cells. Its main disadvantages are low volume productivity and the animal provenance. It is conceivable that other technologies, particularly plant cell production , will gain importance in future. Given the fundamental differences between the two process technologies, plants for mammalian cell culture technologies have to be built ex novo. The pros and cons of an involvement of

33293-407: The technology toolbox of any fine chemical company. Mammalian cell culture fermentation, on the other hand, should be considered only by large fine chemical companies with a full war chest and a long-term strategic orientation. Within the chemical universe, the fine chemical industry is positioned between the commodity, their suppliers, and specialty chemical industries, their customers. Depending on

33490-663: The thioethyl-N'-methyl-2-nitro-1,1-ethenediamine moiety of ranitidine, the second H2 receptor antagonist, marketed as Zantac by Glaxo. Other pharmaceutical and agrochemical companies gradually followed suit and started outsourcing the procurement of fine chemicals. An example in case is F.I.S., Italy, which partnered with Roche , Switzerland for custom manufacturing precursors of the benzodiazepine class of tranquilizers, such as Librium (chlordiazepoxide HCl) and Valium (diazepam). The growing complexity and potency of new pharmaceuticals and agrochemicals requiring production in multipurpose, instead of dedicated plants and, more recently,

33687-433: The time, the second-largest pharmaceutical company worldwide. In 2003, Pfizer merged with Pharmacia , and in the process acquired Searle and SUGEN . Searle had developed Flagyl ( metronidazole ), a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa . Searle also developed celecoxib (Celebrex) a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID) used to treat

33884-433: The total amino acid production is used for peptide synthesis. In fact, L-glutamic acid , D, L-methionine , L-aspartic acid and L-phenylalanine are used in large quantities as food and feed additives. About 50 peptide drugs are commercialized. The number of amino acids that make up a specific peptide varies widely. At the low end are the dipeptides . The most important drugs with a dipeptide (L-alanyl-L-proline) moiety are

34081-410: The total sales, the second one to the fine chemical sales. Both are in $ million The combined revenues of the top 20 fine chemical companies amounted to $ 10 billion in 2009, representing about 30% of the figure for the whole industry. The leading companies are typically divisions of large, diversified chemical companies. In terms of geography, 9 of the top 20 are located in Europe, which is recognized as

34278-898: The use of a vaccine passport mobile app developed by CANImmunize in order to record and track status of COVID-19 vaccination. As the scale of the COVID-19 pandemic became apparent, Pfizer partnered with BioNTech to study and develop COVID-19 mRNA vaccine candidates. Unlike many of its competitors, Pfizer took no initial research funds from the United States' Operation Warp Speed vaccine development program, instead choosing to invest roughly $ 2 billion of its own funds. Pfizer CEO Albert Bourla has said that he declined money from Operation Warp Speed to avoid government intervention, stating later that "when you get money from someone that always comes with strings. They want to see how we are going to progress, what type of moves you are going to do. They want reports. And also, I wanted to keep Pfizer out of politics, by

34475-412: The use of large numbers of unit operations , dilute reaction mixtures, vast quantities of solvents for extraction, evaporation to dryness, drying of solutions with hygroscopic salts. Although modern reaction calorimeters consent to foresee the effects of these different conditions to a certain extent, a direct transfer of a process from the laboratory to the industrial scale is not recommended, because of

34672-468: The vaccine". Science-Based Medicine emphasized that Ventavia oversaw just three of the 153 clinical sites involved with Pfizer's trial and "a small fraction (~1,000 by the time the whistleblower was fired) of the trial's over ~44,000 subjects." On 10 October 2022, during a session of the European Parliament 's Special Committee on the COVID-19 Pandemic, Pfizer executive Janine Small testified that

34869-459: The vitamins biotin , folic acid , niacin (PP), pyridoxine (vitamin B 6 ), riboflavin (vitamin B 2 ), and thiamine (vitamin B 1 ). In synthetic life science products, N-heterocyclic moieties are widely used in both pharmaceuticals and agrochemicals. Thus, β-lactams are structural elements of penicillin and cephalosporin antibiotics, imidazoles are found both in modern herbicides, e.g. Arsenal (imazapyr) and pharmaceuticals, e.g.

35066-435: The volume / value relationships are 10 $ /kg and 100 tons for microbial, 1,000,000 $ /kg and 10 kilograms for mammalian technology; the cycle times are 2–4 and 10–20 days, respectively), they are even more pronounced between mammalian and synthetic chemical technology (see Table 1). The mammalian cell production process, as used for most biopharmaceuticals, is divided into the four main steps: (1) Cultivation, i.e. reproduction of

35263-409: The volume productivity is low, the bioreactors, called fermenters , are large, with volumes that can exceed 250 m3. Product isolation was previously based on large-volume extraction of the medium containing the product. Modern isolation and membrane technologies, like reverse osmosis , ultra- and nano-filtration , or affinity chromatography can help to remove salts and by-products, and to concentrate

35460-884: The way to 100% for Cambrex , USA; Divi's Laboratories , India, and F.I.S. Italy. All have extensive resources in terms of chemists and other specialists, plants, process knowledge, backwards integration, international presence, etc. part of the sales do not derive from fine chemicals, e.g., generics, catalysts, excipients Author's estimate (non figures published by the company) HMW, high molecular weight, LMW, low molecular weight fine chemicals 11.-20.: Jubilant Organosys. India,800 /470; Dr. Reddy's, India, 1370/370; Evonik-Degussa, Germany, 18,900/350 ; Johnson Matthey, UK 12,500/350; Aurobinda, India 665/340; NCPC , North China Pharmaceutical, China, 718/300 ; Divi's Laboratories, India, 250/250; Pfizer, US, 50,000/250 ; Cambrex, US, 235/235; F.I.S., Italy, 230/230 Σ11-20 ~ 2,900 million; ΣΣ1-20 ~ $ 10,000 million note: The first number refers to

35657-415: The way." In May 2020, Pfizer began testing four different COVID-19 vaccine variations using lipid nanoparticle technology provided by Canadian biotechnology company Acuitas Therapeutics . Vaccines were injected into the first human participants in the U.S. in early May. In July 2020, Pfizer and BioNTech announced that two of the partners' four mRNA vaccine candidates had won fast track designation from

35854-438: The websites of individual companies. Optically active cyanohydrins , cyclopolymerization , ionic liquids , nitrones , oligonucletides, peptide (both liquid- and solid-phase), electrochemical reactions (e.g., perfluorination) and steroid synthesis are promoted by only a limited number of companies. With the exception of some stereospecific reactions, particularly biotechnology, mastering these technologies does not represent

36051-564: The whole 35 amino acid peptide requires more than 130 individual steps. Microreactor Technology (MRT), making part of "process intensification", is a relatively new tool that is being developed at several universities, as well as leading fine chemical companies, such as Bayer Technology Services , Germany; Clariant , Switzerland; Evonik-Degussa , Germany; DSM , The Netherlands; Lonza , Switzerland; PCAS , France, and Sigma-Aldrich , US. The latter company produces about 50 fine chemicals up to multi-kilogram quantities in microreactors. From

36248-484: The world market, jobs for locals, and business and profits for companies. Cecil Rhodes (1853–1902) was one of the few businessmen in the era who became Prime Minister (of South Africa 1890–1896). His mining enterprises included the British South Africa Company and De Beers . The latter company practically controlled the global diamond market from its base in southern Africa. In 1945, the United States

36445-573: The world without a concentration in one area have been called stateless or "transnational" (although "transnational corporation" is also used synonymously with "multinational corporation" ), but as of 1992, a corporation must be legally domiciled in a particular country and engage in other countries through foreign direct investment and the creation of foreign subsidiaries. Geographic diversification can be measured across various domains, including ownership and control, workforce, sales, and regulation and taxation. Multinational corporations may be subject to

36642-503: The worldwide revenue of a foreign subsidiary, and taxation is complicated by transfer pricing arrangements with parent corporations. For small corporations, registering a foreign subsidiary can be expensive and complex, involving fees, signatures, and forms; a professional employer organization (PEO) is sometimes advertised as a cheaper and simpler alternative, but not all jurisdictions have laws accepting these types of arrangements. Disputes between corporations in different nations

36839-503: The worldwide rights to Zithromax ( azithromycin ), a macrolide antibiotic that is recommended by the Infectious Disease Society of America as a first line treatment for certain cases of community-acquired pneumonia, from Pliva . In 1989, Pfizer scientists Peter Dunn and Albert Wood created Viagra ( sildenafil ) for treating high blood pressure and angina , a chest pain associated with coronary artery disease . In 1991, it

37036-617: Was an immediate success, although it was production of citric acid that led to Pfizer's growth in the 1880s. Pfizer continued to buy property in the area (by now the Williamsburg district of the city of Brooklyn, New York and beginning in 1898, the City of Greater New York ) to expand its lab and factory, retaining offices on Flushing Avenue until the 1960s; the Brooklyn plant ultimately closed in 2009. Following their success with citric acid, Pfizer (at

37233-438: Was enabled by multinational corporations known as the 'Seven Sisters'. The "Seven Sisters" was a common term for the seven multinational companies that dominated the global petroleum industry from the mid-1940s to the mid-1970s. The nationalization of the Iranian oil industry in 1951 by Iranian Prime Minister Mohammad Mosaddegh and the subsequent boycott of Iranian oil by all companies had dramatic consequences for Iran and

37430-448: Was fully aware that the means to overcoming cultural resistance depended on an "understanding" of the countries in which a corporation operated. He observed that companies with "foresight to capitalize on international opportunities" must recognize that " cultural anthropology will be an important tool for competitive marketing". However, the projected outcome of this was not the assimilation of international firms into national cultures, but

37627-546: Was labeled as "the largest nonviolent transfer of wealth in human history." The OPEC sought immediate discussions regarding participation in national oil industries. Companies were not inclined to object as the price hike benefited both them and OPEC members. In 1980, the Seven Sisters were entirely displaced and replaced by national oil companies (NOCs). The rise in oil prices burdened developing countries with balance of payments deficits, leading to an energy crisis. OPEC members had to abandon their plan of redistributing wealth from

37824-709: Was launched by the Bill & Melinda Gates Foundation in partnership with Mastercard and Wellcome Trust , with additional funding announced shortly after from Chan Zuckerberg Initiative , UK Foreign, Commonwealth and Development Office and Madonna . The following month, the Foundation for the National Institutes of Health announced the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to develop

38021-466: Was patented in the United Kingdom as a heart medication. Early trials for the medication showed that it did not work for the treatment of heart disease, but volunteers in the clinical trials had increased erections several days after taking the drug. It was patented in the United States in 1996 and received approval by the Food and Drug Administration in March 1998. In December 1998, Pfizer hired Bob Dole as

38218-589: Was previously the world headquarters of Upjohn Company , which had been acquired as part of Pharmacia. In June 2000, Pfizer acquired Warner-Lambert outright for $ 116   billion. To satisfy conditions imposed by antitrust regulators at the Federal Trade Commission , Pfizer sold off or transferred stakes in several minor products, including RID (a shampoo for treatment of head lice , sold to Bayer ) and Warner-Lambert's antidepressant Celexa (which competes with Zoloft). The acquisition created what was, at

38415-534: Was the fifth statin to be developed, clinical trials showed that atorvastatin caused a more dramatic reduction in low-density lipoprotein pattern C (LDL-C) than the other statin drugs. Upon its patent expiration in 2011, Lipitor was the best-selling drug ever, with approximately $ 125   billion in sales over 14.5 years. In 2001, Henry McKinnell became chief executive officer of the company, replacing William C. Steere, Jr. In 2002, The Bill & Melinda Gates Foundation purchased stock in Pfizer. In 2004,

38612-491: Was the largest producer of generic injectable pharmaceuticals in the world. On November 23, 2015, Pfizer and Allergan announced a planned $ 160   billion merger, in the largest pharmaceutical deal ever and the third largest corporate merger in history. The proposed transaction contemplated that the merged company maintain Allergan's Republic of Ireland domicile, resulting in the new company being subject to corporation tax at

38809-503: Was the world's largest oil producer. However, their reserves were declining due to high demand. Therefore, the United States turned to foreign oil sources, which had a significant impact on the recovery of the West after World War II. Most of the world's oil was found in Latin America and the Middle East, particularly in the Arab states of the Persian Gulf. This increase in non-American production

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