Pharmaceutical industry
The pharmaceutical industry is a medical industry that discovers, develops, produces, and markets pharmaceutical goods such as medications. Medications are then administered to patients for curing or preventing disease or for alleviating symptoms of illness or injury.
Generic drugs are typically not protected by patents, whereas branded drugs are covered by patents. The industry's various subdivisions include distinct areas, such as manufacturing biologics and total synthesis. The industry is subject to a variety of laws and regulations that govern the patenting, efficacy testing, safety evaluation, and marketing of these drugs.
The global pharmaceutical market was valued at approximately US$1.48 trillion in 2022, reflecting steady growth from 2020 and continuing expansion despite the impacts of the COVID-19 pandemic. The sector showed a compound annual growth rate of 1.8% in 2021, including the effects of the COVID-19 pandemic.
In historical terms, the pharmaceutical industry, as an intellectual concept, arose in the middle to late 1800s in nation-states with developed economies such as Germany, Switzerland, and the United States. Some businesses engaging in synthetic organic chemistry, such as several firms generating dyestuffs derived from coal tar on a large scale, were seeking out new applications for their artificial materials in terms of human health. This trend of increased capital investment occurred in tandem with the scholarly study of pathology as a field advancing significantly, and a variety of businesses set up cooperative relationships with academic laboratories evaluating human injury and disease. Examples of industrial companies with a pharmaceutical focus that have endured to this day after such distant beginnings include Bayer and Pfizer.
The pharmaceutical industry has faced extensive criticism for its marketing practices, including undue influence on physicians through pharmaceutical sales representatives, biased continuing medical education, and disease mongering to expand markets. Pharmaceutical lobbying has made it one of the most powerful influences on health policy, particularly in the United States. There are documented cases of pharmaceutical fraud, including off-label promotion and kickbacks, resulting in multi-billion dollar settlements. Drug pricing continues to be a major issue, with many unable to afford essential prescription drugs. Regulatory agencies like the FDA have been accused of being too lenient due to revolving doors with industry. During the COVID-19 pandemic, major pharmaceutical companies received public funding while retaining intellectual property rights, prompting calls for greater transparency and access.
History
Mid-1800s–1945
The modern era of the pharmaceutical industry began with local apothecaries that expanded their traditional role of distributing botanical drugs such as morphine and quinine to wholesale manufacture in the mid-1800s. Intentional drug discovery from plants began with the extraction of morphine – an analgesic and sleep-inducing agent – from opium by the German apothecary assistant Friedrich Sertürner somewhere between 1803 and 1805. Sertürner later named this compound after the Greek god of dreams, Morpheus. Multinational corporations including Merck, Hoffman-La Roche, Burroughs-Wellcome, Abbott Laboratories, Eli Lilly, and Upjohn began as local apothecary shops in the mid-1800s. By the late 1880s, German dye manufacturers had perfected the purification of individual organic compounds from tar and other mineral sources and had also established rudimentary methods in organic chemical synthesis. The development of synthetic chemical methods allowed scientists to systematically vary the structure of chemical substances, and growth in the emerging science of pharmacology expanded their ability to evaluate the biological effects of these structural changes.Epinephrine, norepinephrine, and amphetamine
By the 1890s, the profound effect of adrenal extracts on many different tissue types had been discovered, setting off a search both for the mechanism of chemical signaling and efforts to exploit these observations for the development of new drugs. The blood pressure raising and vasoconstrictive effects of adrenal extracts were of particular interest to surgeons as hemostatic agents and as a treatment for shock, and several companies developed products based on adrenal extracts containing varying purities of the active substance. In 1897, John Abel at the Johns Hopkins University identified the active substance as epinephrine, which he isolated in an impure state as the sulfate salt. Industrial chemist Jōkichi Takamine later developed a method for obtaining epinephrine in a pure state and licensed the technology to Parke-Davis. Parke-Davis marketed epinephrine under the trade name Adrenalin. Injected epinephrine proved to be especially efficacious for the acute treatment of asthma attacks, and an inhaled version is sold over the counter in the United States.. By 1929 epinephrine had been formulated into an inhaler for use in the treatment of nasal congestion.While highly effective, the requirement for injection limited the use of epinephrine and orally active derivatives were sought. A structurally similar compound, ephedrine, was identified by Japanese chemists in the Ma Huang plant and marketed by Eli Lilly as an oral treatment for asthma. Following the work of Henry Dale and George Barger at Burroughs-Wellcome, academic chemist Gordon Alles synthesized amphetamine and tested it in asthma patients in 1929. The drug proved to have only modest anti-asthma effects but produced sensations of exhilaration and palpitations. Amphetamine was developed by Smith, Kline and French as a nasal decongestant under the trade name Benzedrine Inhaler. Amphetamine was eventually developed for the treatment of narcolepsy, post-encephalitic parkinsonism, and mood elevation in depression and other psychiatric indications. It received approval as a New and Nonofficial Remedy from the American Medical Association for these uses in 1937, and remained in common use for depression until the development of tricyclic antidepressants in the 1960s.
Discovery and development of the barbiturates
In 1903, Hermann Emil Fischer and Joseph von Mering disclosed their discovery that diethylbarbituric acid, formed from the reaction of acid, phosphorus oxychloride and urea, induces sleep in dogs. The discovery was patented and licensed to Bayer pharmaceuticals, which marketed the compound under the trade name Veronal as a sleep aid beginning in 1904. Systematic investigations of the effect of structural changes on potency and duration of action led to the discovery of phenobarbital at Bayer in 1911 and the discovery of its potent anti-epileptic activity in 1912. Phenobarbital was among the most widely used drugs for the treatment of epilepsy through the 1970s, and as of 2023, it remains on the World Health Organization's List of Essential Medicines.Restrictions in use of amphetamines and barbiturates
The 1950s and 1960s saw increased awareness of the addictive properties and abuse potential of barbiturates and amphetamines and led to increasing restrictions on their use and growing government oversight of prescribers. Today, amphetamine is largely restricted to use in the treatment of attention deficit disorder and phenobarbital in the treatment of epilepsy.Benzodiazepines
In 1958, Leo Sternbach discovered the first benzodiazepine, chlordiazepoxide. Dozens of other benzodiazepines have been developed and are in use, some of the more popular drugs being diazepam, alprazolam, clonazepam, and lorazepam. Due to their far superior safety and therapeutic properties, benzodiazepines have largely replaced the use of barbiturates in medicine, except in certain special cases. When it was later discovered that benzodiazepines, like barbiturates, significantly lose their effectiveness and can have serious side effects when taken long-term, Heather Ashton researched benzodiazepine dependence and developed a protocol to discontinue their use.Insulin
A series of experiments performed from the late 1800s to the early 1900s revealed that diabetes is caused by the absence of a substance normally produced by the pancreas. In 1869, Oskar Minkowski and Joseph von Mering found that diabetes could be induced in dogs by surgical removal of the pancreas. In 1921, Canadian professor Frederick Banting and his student Charles Best repeated this study and found that injections of pancreatic extract reversed the symptoms produced by pancreas removal. Soon, the extract was demonstrated to work in humans, but the development of insulin therapy as a routine medical procedure was delayed by difficulties in producing the material in sufficient quantity and with reproducible purity. The researchers sought assistance from industrial collaborators at Eli Lilly and Co. based on the company's experience with large-scale purification of biological materials. Chemist George B. Walden of Eli Lilly and Company found that careful adjustment of the pH of the extract allowed a relatively pure grade of insulin to be produced. Under pressure from Toronto University and a potential patent challenge by academic scientists who had independently developed a similar purification method, an agreement was reached for the non-exclusive production of insulin by multiple companies. Before the discovery and widespread availability of insulin therapy, the life expectancy of diabetics was only a few months.Early anti-infective research: salvarsan, prontosil, penicillin and vaccines
The development of drugs for the treatment of infectious diseases was a major focus of early research and development efforts; in 1900, pneumonia, tuberculosis, and diarrhea were the three leading causes of death in the United States and mortality in the first year of life exceeded 10%.In 1911 arsphenamine, the first synthetic anti-infective drug, was developed by Paul Ehrlich and chemist Alfred Bertheim of the Institute of Experimental Therapy in Berlin. The drug was given the commercial name Salvarsan. Ehrlich, noting both the general toxicity of arsenic and the selective absorption of certain dyes by bacteria, hypothesized that an arsenic-containing dye with similar selective absorption properties could be used to treat bacterial infections. Arsphenamine was prepared as part of a campaign to synthesize a series of such compounds and exhibited partially selective toxicity. Arsphenamine proved to be the first effective treatment for syphilis, a disease that until then had been incurable and led inexorably to severe skin ulceration, neurological damage, and death.
Ehrlich's approach of systematically varying the chemical structure of synthetic compounds and measuring the effects of these changes on biological activity was pursued broadly by industrial scientists, including Bayer scientists Josef Klarer, Fritz Mietzsch, and Gerhard Domagk. This work, also based on the testing of compounds available from the German dye industry, led to the development of Prontosil, the first representative of the sulfonamide class of antibiotics. Compared to arsphenamine, the sulfonamides had a broader spectrum of activity and were far less toxic, rendering them useful for infections caused by pathogens such as streptococci. In 1939, Domagk received the Nobel Prize in Medicine for this discovery. Nonetheless, the dramatic decrease in deaths from infectious diseases that occurred before World War II was primarily the result of improved public health measures such as clean water and less crowded housing, and the impact of anti-infective drugs and vaccines was significant mainly after World War II.
In 1928, Alexander Fleming discovered the antibacterial effects of penicillin, but its exploitation for the treatment of human disease awaited the development of methods for its large-scale production and purification. These were developed by a U.S. and British government-led consortium of pharmaceutical companies during World War II.
There was early progress toward the development of vaccines throughout this period, primarily in the form of academic and government-funded basic research directed toward the identification of the pathogens responsible for common communicable diseases. In 1885, Louis Pasteur and Pierre Paul Émile Roux created the first rabies vaccine. The first diphtheria vaccines were produced in 1914 from a mixture of diphtheria toxin and antitoxin, but the safety of the inoculation was marginal and it was not widely used. The United States recorded 206,000 cases of diphtheria in 1921, resulting in 15,520 deaths. In 1923, parallel efforts by Gaston Ramon at the Pasteur Institute and Alexander Glenny at the Wellcome Research Laboratories led to the discovery that a safer vaccine could be produced by treating diphtheria toxin with formaldehyde. In 1944, Maurice Hilleman of Squibb Pharmaceuticals developed the first vaccine against Japanese Encephalitis. Hilleman later moved to Merck, where he played a key role in the development of vaccines against measles, mumps, chickenpox, rubella, hepatitis A, hepatitis B, and meningitis.