FDA's and GCP's roots extend back 100 years

Good clinical practice (GCP) may be a catch-phrase of the 21st century, but the concept's roots date back to the shortly after the 20th century began.

"In the context of the evolution of good clinical practice, I try to set up a regulatory framework," says Brian Bennett, BA, CCRA, CCRT, senior director of corporate communications and knowledge management at i3 of Little Rock, AR.

"It dates back to the 1906 Pure Food and Drug Act," Bennett says.

The Pure Food and Drug Act of 1906 and the Harrison Act of 1914 banned the sale of some narcotic drugs and established the first version of the FDA.

But it was the 1938 Food, Drug, and Cosmetic (FDC) Act that gave the FDA broad regulatory powers in approving pharmaceutical products before they could be marketed to the public.

The 1938 FDC Act was a response to a nationwide tragedy in 1937 in which 107 people died after ingesting a cold and cough syrup called Elixir Sulfanilamide, Bennett says.

The product existed in pill form, and there was a rush to dissolve it and put it in liquid form, Bennett explains.

A pharmaceutical company succeeded in creating the syrup after using a solvent called diethylene glycol, which is a clear, odorless liquid that is similar to antifreeze.

Once the manufacturer mixed the solution with a strong enough raspberry flavoring and put it on the market, it was quickly purchased by parents who wanted a cold and sore throat remedy for their children, Bennett says.

"It killed 107 people in the United States, and these were primarily children," Bennett says. "The tragedy got a lot of public attention and led to the 1938 establishment of the FDA."

S. E. Massengill Co. of Bristol, TN, which had distributed the lethal cough syrup, had not conducted any studies, even on animals, according to an FDA report of the event.1

The drug had been shipped early in September, and the first deaths were reported in early October by physicians who had prescribed the syrup.1

The children who took the drug were ill for 1-3 weeks, finally dying of kidney failure after suffering intense pain and experiencing severe nausea, vomiting, and convulsions.1

At that time, the law did not prohibit the sale of toxic or untested drugs, and the manufacturer's statement after the tragedy indicated that the company's owners did not feel the problem was their fault since they could not "have foreseen the unlooked-for results."1

There had been similar tragedies due to toxic drugs prior to the Elixir Sulfanilamide poisoning. These included people going blind after ingesting a new drug called dinitrophenol and liver poisoning and deaths from ingestion of cinchophen, a drug used to treat rheumatism.1

Ironically, although the use of diethylene glycol in products consumed by humans is prohibited in the United States, the deadly compound continues to show up in cough syrups, toothpaste, and other products—both sold in the United States and abroad. According to various news reports, dozens of children in Haiti died in 1996 after being given glycerine contaminated with diethylene glycol in a syrup that was traced back to China. Likewise, in May, June, and July, 2007, there were media reports of similarly contaminated toothpaste sold in Costa Rica, Spain, England, the United States, and elsewhere. These also were traced back to Chinese manufacturers who used diethylene glycol rather than a more expensive and safe compound.2-6


  1. Ballentine C. Taste of raspberries, taste of death; the 1937 Elixir Sulfanilamide incident. Available at: www.fda.gov. Accessed Aug. 29, 2007.
  2. Burros M. F.D.A. inspections lax, Congress is told. New York Times July 18, 2007.
  3. Munoz SS, Zamiska N. How safe are imported goods? Wall Street Journal July 5, 2007:B5.
  4. Bogdanich W. China prohibits poisonous industrial solvent in toothpaste. New York Times July 12, 2007.
  5. Barboza D. China steps up its safety efforts. New York Times July 7, 2007.
  6. Junod SW. Diethylene glycol deaths in Haiti. Public Health Rep 2000;115:78-86.