Unfortunate events have catalysed the development of medicines regulation more than the evolution of a knowledge base. In 1937 the death of over 100 people in the United States by using a Sulfanilamide elixir is one such event.
In the 1930s, Sulfanilamide, a drug used to treat streptococcal infections, had been shown to have dramatic curative effects used as a tablet and powder form. As a result there was a demand for the drug in a liquid form.
In 1937, S.E. Massengil Company created a liquid preparation after experiments showed that sulfanilamide would dissolve in diethylene glycol. The company control lab tested the mixture for flavour, appearance, and fragrance and found it satisfactory, and the product was marketed as “Elixir of Sulfanilamide”. Therefore, the elixir was manufactured in large quantity and distributed across the country.
Within one month, a number of deaths related to the sulphanilamide elixir were reported to the American Medical Association (AMA). The AMA tested the compound and found the excipient, diethylene glycol, as the toxic ingredient.
FDA was notified and they then set out to retrieve the entire drug from across the country. However, by that time 353 patients had received the “Elixir” during a 4-week period resulting in more than 100 deaths (including children), about a 30% fatality rate.
It was found that Diethylene Glycol, a chemical used as antifreeze, is a deadly poison.
GCP Principles violated:
Although there were no GCP guidelines or federal regulations demanding safety testing for drugs in 1937, the sulfanilamide elixir case violated a number of GCP principles.
• The first GCP principle requires ethical conduct of a clinical trial, which have their origin in the Declaration of Helsinki. When applied to the Sulfanilamide case, one wonders if the basic ethical principle of beneficence was considered, which states harm should never outweigh benefit. Principle of “Beneficence” called for the company to explore all risks related to their drug formulation.
• The risk benefit balance was not considered therefore no clinical trial was done. In fact, if it were considered based on other testing, a clinical trial would not even have been required and the tragedy averted.
• The use of the excipient, Diethylene Glycol, was not based on adequate knowledge about its chemical properties. So according to GCP principles, its use was unjustified scientifically in humans without assessing the risks related to its use. The drug company just found it easy to use and went ahead with the preparation of the elixir.
• The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial. Though in the above case, no clinical trial was conducted, Diethylene Glycol was used as a solvent without conducting any non-clinical pharmacological or toxicological studies.
• Moreover, no literature review was done to check what was already known about...