Pharmaceutical Industry

I

Introduction

Pharmaceutical Industry, that section of industry which manufactures medicinal chemicals and prepares them for use in the prevention or treatment of disease. Some companies engaged in this business manufacture pharmaceutical chemicals in bulk (primary manufacture), but all of them prepare them for medical use by methods known collectively as secondary manufacture. These highly automated processes include the production of drugs in single-dose forms, such as tablets, capsules, or sachets for oral administration, solutions for injection, and pessaries and suppositories for insertion into the vagina or rectum respectively.

Other preparations include liquids such as linctuses and syrups to be taken by mouth, inhalations in metered-dose aerosol sprays, drops for the nose, ears, or eyes, and creams, ointments, lotions, and so on for application to the skin. Some companies make anaesthetics, or contrast media used for visualizing body structures by X-ray or nuclear magnetic resonance imaging (NMR).

Many pharmaceutical companies engage in research and development aimed at introducing new and improved treatments. In some countries, each stage of the trial of new medicines involving domestic, farm, or laboratory animals, or human beings, is subject to approval by national licensing authorities. If finally approved, a licence for a new medicine's use in stated conditions will be issued. In some other countries permission to market may be granted on sight of the licence from the country of origin.

Patent coverage for recently developed or modified medicines is usually granted by most countries for periods averaging 15 years from the licence date. Companies give their innovations brand names, which remain their unique property. Each new drug is also given an official generic name, which remains common property. After patent expiry products may be made and sold under these generic names by any company that can meet the licensing body's standards.

Most pharmaceutical companies operate internationally and own subsidiaries of various sizes in many countries. The old companies originated from, and have their headquarters in, either the United States, Switzerland, or a member country of the European Union. This technologically advanced industry employs many graduates, including biologists, biochemists, chemists, engineers, microbiologists, nurses, pharmacologists, doctors, physicists, and veterinary surgeons. They are employed in research and development (R & D), manufacturing, quality control, marketing, medical representation, public affairs, or general administration.

II

The Development of the Industry

The pharmaceutical industry grew from a number of different activities that provided sources of substances used in medicine. During the early 19th century, apothecaries, chemists, druggists, and herbalists obtained dried parts of various plants, either harvested locally or from overseas. The latter were purchased from spicers, who mainly imported spices but also, as a sideline, medicines, including opium from Persia, and ipecacuanha and cinchona bark from South America. Simple chemicals and minerals were similarly purchased from dry-salters (traders in such goods as gums, oils, pickles, and so on).

Apothecaries, chemists, and druggists made various preparations from these items, including extracts, tinctures, mixtures, lotions, ointments, and pills. Certain practitioners made more of these than required for their own use and sold them, in bulk, to their colleagues.

Some medicines, such as those prepared from cinchona bark, deadly nightshade, foxglove (digitalis), ergot of rye (Claviceps purpurea), and opium (dried latex from Papeverum somniferum), had real value, but their activity often varied considerably. In 1820 the French chemist Joseph Pelletier, prepared the active alkaloid of cinchona bark and called it quinine. He followed this success by isolating several other alkaloids, including atropine from belladonna and strychnine from nux vomica.

His work and that of others made possible the standardization of many medicines and the subsequent commercial extraction of their active principles. One of the first firms to extract pure alkaloids in commercial quantities was the Edinburgh pharmacy of T. H. Smith Ltd. Details of chemical assays were soon included in pharmacopoeias, compelling manufacturers to set up their own laboratories.

III

The First Synthetic Medicines

Chemicals extracted from plants or animals were known as “organic” as opposed to “inorganic” compounds made from other sources. It was believed that the former could be made “only by God”. But in 1836 the German chemist Friedrich Wöhler heated an inorganic chemical, ammonium cyanate, and produced urea, previously isolated only from urine.

This pioneering synthesis let to attempts to synthesize other carbon-based chemicals hitherto derived only from living organisms. Most important for the future pharmaceutical industry was the accidental discovery in 1856 of the first synthetic dyestuff, “mauvine”, by a young English chemistry student, William Henry Perkin. This discovery encouraged dye makers in Germany and Switzerland to develop new synthetic colours and thus gain a knowledge of the new chemistry. Perkin, aged 21, borrowed family money to set up his own dyestuffs company; much later it was to merge with other United Kingdom chemical makers to form Imperial Chemical Industries (ICI).

Synthetic dyestuffs had an enormous impact on medical progress. They considerably increased the range of biological stains and thus accelerated the progress of bacteriology and histology. The search for new colours stimulated the study of organic chemistry and, in turn, the search for new medicines. The first synthetic medicine was acetophenetidine, marketed in 1885 as a pain-killer by Bayer at Leverkusen, Germany, under their brand name, Phenacetin. Today's household remedy paracetamol was derived from it.

The second important synthetic drug, marketed in 1897, was acetylsalicylic acid. Invented by Dr Felix Hoffmann, working in Bayer's research laboratory, it was sold worldwide under the Bayer trade name, aspirin, to provide a new and useful treatment for “rheumatic pains”. From these early beginnings Bayer grew to become the giant company IG Farbenindustrie.

IV

The First Anti-Infective Drugs

The first drug to cure an often fatal infectious disease was the “magic bullet” of the German bacteriologist Paul Ehrlich. Convinced that arsenic provided the clue to a cure for the venereal disease syphilis, Ehrlich synthesized hundreds of organic arsenical compounds. These he injected into mice previously infected with the causative organism, Spirochaete pallidum. Some of the 605 compounds tested showed some promise of success but too many mice died. In 1910 Ehrlich made and tested compound number 606, arsphenamine. It cured his infected mice and, more importantly, left them in good health.

Ehrlich now had the problem of making his compound in quantity, suitably packaged for injection, and distributing it for use. He sought the help of the Frankfurt chemical company Hoechst AG. They marketed the substance in glass ampoules, each containing a single dose of arsphenamine in powder form, to be dissolved in sterile water prior to injection. Exported worldwide, it was given the trade name Salvarsan. This process of discovery, commercial production, and distribution has remained a pattern for the pharmaceutical industry to the present day.

In 1916 Bayer's scientists invented an effective drug to treat the tropical disease trypanosomiasis, or sleeping sickness. Affecting both human beings and cattle, it is caused by micro-organisms called trypanosomes, carried by tsetse flies. World War I cut off supplies of both German and (effectively) Swiss chemicals, in Britain and the United States, thus stimulating further research and development.