FDA, Back In The Day

The Food and Drug Administration was basically founded by Dr. Harvey W. Wiley, as a successor to the Department of Agriculture’s Bureau of Chemistry. I was recruited out of college as a chemist. In many ways, the 1960’s were the golden age of federal government. I was well trained; although the pay wasn’t great, I was given really good scientific equipment and a wide variety of stuff to work on. I was hired into the New York office. The mission involved examining foods and drugs, as the name implies, to ensure they met labeling requirements (for example, was the stuff in the drug store really aspirin, was its strength what the label said it was, were there any dangerous impurities present).

The same year they hired me, they also hired Dr. Frances Kelsey at FDA HQ, to evaluate NDA’s (new drug applications). Dr. Kelsey’s first assignment involved a drug called Thalidomide, a sleeping pill and tranquilizer in wide use in Europe. The manufacturer wanted to market the drug in the U.S. Dr. Kelsey carefully studied the data presented in the NDA, and found a number of red flags. Despite considerable pressure from the manufacturer, Dr.Kelsey refused to allow thalidomide to be marketed. Eventually, reports began to circulate of really terrible birth defects of numerous children of pregnant mothers who had taken the drug in Britain and West Germany. The babies were born lacking arms and legs. I shudder to think of pressure which might be brought to bear in this age of Twitter and the Internet (even Dr. Anthony Fauci receives death threats these days). By saving uncounted numbers of children from this “side effect” of this otherwise useful drug, the nation owed Dr. Kelsey big time, to say the least.

In my own career, I was included with several others in an attempt to straighten out a troubled drug manufacturer. I don’t know whether the outfit is still in business. However, we had looked into complaints from consumers who had taken the manufacturer’s eyedrops containing epinephrine. In order to prevent stinging pain in the eyes of users, the stuff was formulated to keep the pH (acidity level) between 4.0 and 7.0.

Without going into the somewhat complicated chemistry, pH of aqueous solutions (water based) ranges from 1-14. pH 1 would be strongly acid, while pH 14 is strongly alkaline. Distilled water’s pH is about 7 (usually said to be “neutral”). Any formulation for use in the eye needs to be close to “neutral” ; the specification for pH between 4 and 7 is established in the United States Pharmacopeia (USP) monograph for the preparation.

Epinephrine,unfortunately, combines with oxygen and turns brown in water solutions. Nobody wants to add brown liquid into eyes. The formulation needs to be combined with a chemical which acts as an oxygen scavenger, so to speak, to prevent it from turning brown. Once the product has been formulated, it undergoes quality control testing in the firm’s lab. Initially, pH specs were within limits; however, pH levels of samples tested a few days later were measured at about 1.2, strongly acidic. Talk about stinging! Instead of recalling batches such as these, the company sold them, based on the initial pH levels, and did nothing to correct or modify procedures to stabilize them.

I brought samples back to our lab. The oxygen scavenger they were using was sodium bisulfite, which, unfortunately, reacts with oxygen dissolved in water to form sodium bisulfate, which is strongly acidic. Turns out the reaction could be stopped if the water used was de-oxygenated by simply bubbling nitrogen into it for a few minutes. Who knew? We were able to show that formulations made with nitrogen saturated water retained correct pH levels almost indefinitely.

No big deal, compared with the prevention of thousands of birth defects. Civil servants do stuff like this almost every day, even if nobody knows. The FDA’s independence from politics is being threatened these days (we need to have a Covid-19 vaccination by November or else!). People like Dr.Kelsey are obstructionists! We need them, and in this current climate, they are becoming harder to recruit.

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