Regulatory authorities are crucial for the safety and efficacy of medicines and medical devices. And yet, achieving the high level of regulation we have today has been a long road – with lives saved and lost along the way.
No one could really blame Jim, a retired milk cart horse who rose to prominence in 1901 in St Louis, USA, for contracting tetanus. At that time, an antitoxin delivered to diphtheria patients was derived from the blood of horses. Thirteen children died of tetanus as a result.
This tragedy led to a milestone in the history of health regulation, the Biologics Control Act of 1902, which gave the US government regulatory powers over biologics. It also raised awareness domestically and abroad of the need for improved regulation of medicines and biologics.
Early beginnings with pharmacopoeia
The origins of modern-day regulation of medicines can be traced back to the pharmacopoeia. Among the early collections describing known drugs and their uses and effects was the London Pharmacopoeia from 1621, which, among some highly unusual entries, included dog’s excrement. It was later removed. The Pharmacy Act in the UK became law in 1868 and was the first legislation in the UK to place restrictions on who could sell “poisons”.
FDA and the “Chamber of Horrors”
In 1906, the Food and Drugs Act was passed in the US to ban interstate commercial activity in adulterated and misbranded food, drinks and drugs. The focus was on incorrect labelling rather than drug approval. In 1930, after several name changes, the bureau overseeing this legislation was formally amended to the Food and Drug Administration (FDA), and a few years later it issued a report known informally as the “Chamber of Horrors,” focusing attention on the shortcomings of the 1906 legislation.
Proving safety and efficacy in the United States
When in 1937 a poisonous solvent in the sulfonamide antibiotic Elixir Sulfanilamide killed 107 people, calls for stricter laws were taken seriously, and a Federal Food, Drug and Cosmetic Act required proof that drugs were safe before they could be sold. It also ordered that labelling contained directions for safe use.
This ushered in a new era in drug regulation, giving, for instance, the FDA power to inspect factories, and requiring that certain drugs be administered by professionals. It also regulated medical devices and cosmetics. Other regulation and quality controls followed – some of these in response to deaths and injury due to quality lapses – in areas such as good manufacturing practices (GMP; the origins of this were in the 1938 act), prescription vs. over-the-counter medicines (Durham-Humphrey amendment of 1951), advertising, labelling and packaging (especially through the Fair Packaging and Labeling Act of 1966), and approval of generics without the need to repeat safety and efficacy research, and more.
The Kefauver-Harris Drug Amendments of 1962 meant that efficacy as well as safety now had to be proved. This was in response to the thalidomide tragedy.
Today, regulation in the US is comprehensive and the FDA protects public health by – in its own words – “assuring that foods… are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drugs, and vaccines and other biological products and medical devices intended for human use are safe and effective.”
Meanwhile in Europe…
Aware of regulatory steps in the US, many other countries introduced their own laws to regulate medicines. But arguably the most significant need for regulation both in Europe and beyond was the thalidomide tragedy in the late 1950s, when this over-the-counter drug marketed in Germany and elsewhere was found to cause birth defects when taken during pregnancy.
The FDA never approved thalidomide, thanks in large part to opposition by one woman, the reviewer Frances Oldham Kelsey and the US was spared some of the worst consequences, although about 20,000 Americans received it in clinical trials in the 1950s and 1960s.The tragedy was another wake-up call for further regulation.
Bringing the patchwork into an EU family
Prior to the creation of the European Economic Community (EEC), regulation and control of medicines in member countries was solely on a country-by-country basis, with a patchwork of rules and practices. In direct response to the thalidomide tragedy, in 1965 Directive 65/65/EEC came into force. Article 3 stipulated: “No proprietary medicinal product may be placed on the market in a Member State unless an authorization has been issued by the competent authority of that Member State.”
Streamlining regulation in Europe
In 1975 a directive created a procedure for mutual recognition within the EEC, and an advisory committee, the Committee on Proprietary Medicinal Products (CPMP) was established to assist with decisions. This so-called CPMP Procedure proved cumbersome, however, and in 1985, with the move towards a single market, plans were made for establishing the European Medicines Agency.
Past decades also saw many individual states revamp their own systems and bodies. In Germany, the Bundesgesundheitsamt (Federal Health Office) was dissolved and replaced by three offices, one of which later became today’s Bundesinstitute für Artzneimittel und Medizinprodukte ( BfArM; Federal Institute for Drugs and Medical Devices). In the UK, the thalidomide tragedy resulted in the Yellow Card Reporting scheme for adverse reactions to medicines, and this was influential for pharmacovigilance worldwide.
Furthermore, in 1971 the UK Medicines Act from 1968 came into force, which established licensing regulations and a number of committees to oversee medicine safety and other areas. With the UK joining the EEC in 1973, and the Single European Act of 1986, which set a course for a single European market, a Medicines Control Agency was founded in the late 1980s. It merged with the agency responsible for devices and together these became the Medicines and Healthcare products Regulatory Agency (MHRA) in 2003. In France, agencies also underwent restructuring.
In 1995 the European Medicines Agency (EMA; see its historical timeline) was formally established, headquartered in London. In the same year the first centrally authorized human medicine was approved, and in 2020 EMA relocated its headquarters from London to Amsterdam (due to Brexit).
Today, there are four routes and three types of approval in the EU (read more), including the centralized procedure directly via EMA. The Agency also has mutual recognition agreements (MRAs) on GMP and confidential information sharing agreements with many national regulatory bodies outside the EU.
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