UNVEILING MEDICINAL ADULTERATIONS: PHARMACOVIGILANCE DÉJÀ VU

The regulation of medicines and medical practitioners is of considerable antiquity. The Babylonian Code of Hammurabi, 1700 BC, whilst covering all aspects of life in Mesopotamia also had a section devoted to professional men, and gave gruesome descriptions of the fate that might befall errant surgeons. For those who can decipher ancient Mesopotamian scripts, the stone tablet or stele that contains these laws can be seen in the Louvre Museum. Moving on two thousand years or so to Arabia Abu Bakr Mohammad Ibn Zakariya Al-Razi (more commonly and not unsurprisingly referred to as Rhazes) was a Persian physician who made the Arabian authorities appoint a Muhtasib with the power to supervise drug makers, and the authority to inspect without warning, day or night. Further countries followed with similar laws but most were concerned with the quality of medicines rather than their safety, and concentrated principally on the regulation of apothecaries.

In the early 20th century the situation was little different. The FDA, which had been launched in 1906 as the Bureau of Chemistry, existed primarily to monitor claims made about food and drug ingredients and at that time no formal government approval was required to market new drugs. As so often in the history of regulation, it was a tragedy that led to significant changes in the law.

In 1937 a small company in Tennessee decided to formulate a liquid preparation of the antibacterial Sulfanilamide to compete with the various solid dose forms available from some of the larger companies. This formulation contained 72% diethylene glycol which gave a slightly sweet taste to the product and was approved by the company's internal laboratory for “appearance, taste and fragrance”. To be fair, the addition of raspberry extract and saccharin probably helped with those. Branded as Elixir Sulfanilamide, large quantities were distributed but there were soon reports of deaths associated with the elixir and in all, over 100 patients died, mostly of renal failure and of whom 34 were children. It soon became apparent that the cause of these deaths was the diethylene glycol. Amazingly to us now, the company had not contravened the existing regulations, as subsequent analysis showed that their description of the ingredients was accurate. The agency was however able to seize the stock on the grounds that the term Elixir could only be applied to products containing ethanol. The disaster and the subsequent public outcry led to the passage of the 1938 Food, Drug and Cosmetic Act which gave the FDA the power to monitor new drugs for safety.

So why am I bringing up this historical tragedy now? Because, despite all our regulations, it continues to be an issue. Some manufacturers, in an attempt to save costs are replacing pharmaceutical grade propylene glycol with cheaper alternative which might even include diethylene glycol, the culprit in the 1937 Sulfanilamide problem.

The World Health Organisation first learned of contaminated medicines after the Gambian medical authorities saw a noticeable increase in cases of acute kidney injury in children under the age of five last year. They reported last month that dozens of children in their country had died as a result. Further reports have been received from around the world and, in response, the agency issued another alert for seven India-made syrups linked to over 300 deaths across the globe. This does not mean that the agency has taken direct action against the manufacturers involved as it lacks such power, but it does serve as a warning to all stakeholders in the process to take action to avoid any recurrences.

The Indian authorities have reacted swiftly, and it is now compulsory to test all syrups prior to export. However, it is sad that things we learnt all those years ago can still resurface today -whether through avarice and incompetence and further emphasises the role of pharmacovigilance in the early detection of such issues.