The United States of America has always been at the forefront of developing the necessary regulatory guidelines for drug products, and the trend continues today. Much of the history of drug regulations therefore covers events in the US.
In the olden days, medicines were prepared mainly in the
form of elixirs, ointments, and pills, and sold by the person making them.
These medicine containers were labeled with nothing beyond the name of the
product they contained and the troubles they promised to cure. Later, as
science and technology advanced, some small family businesses began
manufacturing other products like vaccines and anti-toxins too, but there was
almost no control over these operations.
In 1902, a mishap occurred to focus attention on the dangers
of such manufacturing. Twelve children died after being administered an
antitoxin for diphtheria and it was found that the product had been
contaminated with live tetanus bacilli. In response to strong protests from the
public, the United States Congress passed the Biologics Control Act. Under this
Act, the manufacturers and sellers of such biological products had to test
their products for strength and purity and undergo regular inspections
by the health authorities.
In 1906, the US Congress passed the Pure Food and Drug Act. This made it illegal for people to sell adulterated or contaminated food or meat. Medicines were now required to have labels that stated the true facts about their contents, without any false information or promising magical cures. Out of this Act was born one of the world’s first government regulatory bodies, which we now know as the United States Food and Drug Administration (USFDA).
This body has conferred the authority to seize illegal drugs
and foods. Any dangerous ingredients in medicines now had to be labeled, and
the labeling had to be true and accurate.
In 1935, 107 people, a majority of them children, died after
consuming oral sulfanilamide elixir. An investigation showed that this product
had been made using a solvent called diethylene glycol which is a poisonous
solvent! The public was incensed and demanded stricter laws.
In response, the US Congress passed the Federal Food, Drug, and Cosmetic Act of 1938. For the first time in the history of drug manufacturing, companies had to prove that their products were safe before allowing them into the market. This Act also made factory inspections mandatory, set standards for food products, and made penalties and criminal proceedings more stringent.
In 1941, yet another tragedy occurred in which close to 300
people died. The cause was Sulfathiazole tablets had been contaminated with a
sedative Phenobarbital. This led to significant changes in the regulations
controlling manufacturing and quality control requirements for drugs. The
Public Health Services (PHS) Act which was passed in 1944 further expanded the
scope of regulations to biological products.
The process of certification of batches by the FDA began
during the time of World War II. Manufacturers of insulin, penicillin, and
other antibiotics would submit samples to the FDA from each lot they made and
get permission for the release of these products.
In 1955, days after a mass polio vaccination drive began
using the newly developed Salk polio vaccine, it had to be abandoned. The
reason was children who received the vaccine (from batches made by Cutter
Laboratories) were found to have developed the disease.
An investigation showed that the process of inactivating the live polio virus had failed, and this had gone undetected! This incident was widely discussed internationally and brought home the need for even more control over vaccine safety standards. The worst was yet to come, though.
In 1957, a pharmaceutical company in Germany called Chemie
Grunenthal GmbH developed the world’s first non-barbiturate anti-convulsant
drug called Thalidomide. It was found to also have a sedative effect and
doctors began prescribing it as a tranquilizer.
Thalidomide was sold over-the-counter based only on the
claims of its manufacturer. Laboratory studies on animals showed it was
practically impossible to reach an LD50 dose. (LD50 is the lethal dose that
causes death in 50% of the animals tested.) So the company advertised it as
totally safe even for mother and child. This “wonder drug” became hugely
popular and was marketed to 46 countries across the world.
Around 1960, an Australian obstetrician McBride noticed that
the drug also helped to reduce the morning sickness associated with pregnancy.
He began recommending it to his pregnant patients, and through word-of-mouth
reports in the medical fraternity, this practice, too spread across the world.
Only in the USA, the drug had not been approved for use by the FDA’s drug
examiner named Frances Kelsey. (Years later, she was conferred with awards for
the service she had rendered to the American public through this act.)
However, by 1961, McBride began noticing a severe birth
defect called phocomelia in babies delivered by his patients who had taken
Thalidomide. Phocomelia is the condition where a baby has no limbs, or
shortened or flipper-like limbs. A newspaper in Germany reported that close to
161 babies had been thus adversely affected by the drug, and the distribution
of Thalidomide in Germany was stopped, with other countries following suit. By
1962, after at least 10,000 cases of deformed infants had been born, Thalidomide
was finally completely banned.
This shocking tragedy was the catalyst for putting in place
a more rigorous drug approval and quality monitoring system developed by the US
FDA. Companies were now required to test both the efficacy and safety of their
drugs. Drugs had to be tested on animals before they could be tried on humans.
Clinical trial regulations became more stringent and the drug investigators
were made responsible for supervising the drugs being studied. In other words,
companies now had to obtain consent from the regulatory authorities before
testing a drug and had to prove the drug’s safety and efficacy before
manufacturing it and taking it to the market.
It was only in 1963 that the USFDA published the first-ever
set of Good Manufacturing Practices (GMP) for finished pharmaceuticals.
Today, GMP, or current Good Manufacturing Practices (cGMP),
as it is now known, is the very backbone of ensuring the quality, safety, and
efficacy of drug products. Every country has regulatory bodies to oversee the
drug development, manufacturing, and distribution process. These bodies lay
down cGMP guidelines that ensure all processes right from procuring materials
to drug manufacturing to their distribution occur under the most stringent of
controls.
Global Regulatory Bodies
|
Country |
Regulatory Body |
|
USA |
Food &
Drug Administration (FDA) |
|
Japan |
Ministry of
Health Labour and Welfare |
|
Australia |
Therapeutic
Goods Administration (TGA) |
|
UK |
Medicines and
Healthcare products Regulatory Agency (MHRA) |
|
South Africa |
Medicine
Control Council (MCC) |
|
India |
Central Drugs
Standard Control Organization (CDSCO) |
|
China |
State Food
and Drug Administration |