Dear Colleagues!  This is Asrar Qureshi’s Blog Post #794 for Pharma Veterans. Pharma Veterans welcome sharing of knowledge and wisdom by Veterans for the benefit of Community at large. Pharma Veterans Blog is published by Asrar Qureshi on WordPress, the top blog site. Please email to for publishing your contributions here.

Several posts shall be published under this topic, but each post shall be complete in itself.

Product Safety Cases

Product development is the starting point from where the industry starts business because they must have a product to sell. In trade, the formulations and recipes are kept secret, and that is how pharmaceuticals started. They did not divulge what the product contained but made big claims about it. Some vintage posters gleaned from internet show clearly the type of hyped claims that were made.

Product development at that time was completely unregulated all over the world. Anyone could make any concoction and start selling it. There was no consideration for safety or efficacy; the only consideration was profit. And I am referring to the US and Europe. LMICs –  Low and Middle Income Countries were decades behind.

The US had a Food, Drug, and Cosmetics Act of 1938 in place, however, the passage of Kefauver Harris amendment of 1962 mandated that pharmaceutical companies shall demonstrate the safety and efficacy of new drugs not just in animals, but also in humans. Similar laws were passed in various countries of Western Europe. The companies were required to conduct proper clinical trials and submit results to the health authorities.

The case of thalidomide in early 1960s really jolted the whole world at large and the medical community in particular. The drug was widely prescribed to pregnant women in Europe and the US and caused the birth of scores of limbless children. In the wake of this huge tragedy, governments, health authorities, and social circles became united to demand that the safety of drugs must be proven through large scale human trials, before these are made available.

Thalidomide was especially shocking due to its scale of damage, but there are several other cases where drugs were withdrawn after several years of use and appearance of side effects.

Phenformin was a drug similar to metformin which was prescribed to type 2 diabetes patients for glucose control. It was developed in late 1950s and remained available until its withdrawal in 1978 due to many cases of severe lactic acidosis which was fatal in 50% cases. Europe and other countries did not follow suit and phenformin in still available in Italy and few other countries.

Terfenadine was launched as the first non-sedating antiallergic in 1985 and it became evident that it caused cardiac arrythmias leading to some deaths. The deaths kept piling up till late 1990s when terfenadine was finally withdrawn. In fact, the company got fexofenadine registered simultaneously while terfenadine was withdrawn.

Another serious case was that of Vioxx (rofecoxib), Merck drug for pain and inflammation for arthritis patients. Vioxx was introduced in 1999 and remained on the market for five years only when it was withdrawn in 2004. Vioxx became hugely popular, and it was worth over three billion dollars in sales at the time of its withdrawal. One FDA analyst estimated that based upon his mathematical model, Vioxx may have caused between 88,000 and 139,000 heart attacks, 30 to 40 percent of which were probably fatal, during those five years. The tragedy was that Merck knew about this side effect but chose not to share that information with regulators and physicians.

The most bizarre case of drug safety was that of antidepressants. The clinical trials showed that antidepressants could cause suicidal tendencies, especially among children and teenagers. The USFDA instructed companies to withhold information about studies suggesting that antidepressants were ineffective and that their use may be linked with suicidal tendencies. When the news of suppression of facts under the instruction of a government agency which was required to safeguard interests of patients, not the companies, were surfaced, it led to a serious debate. After the uproar, FDA announced it would require a prominent ‘blackbox’ warning label about the suicidal risk among children.

Product research takes place in the US and Europe, mostly in US. Due to regulatory restrictions, drug development cost had been constantly increasing and currently stands around one billion US$ to develop and commercialize one product. It is quite high and only pharma companies with enough resources can afford to do that.

Situation in Pakistan and other LMICs is the same. New molecules are not researched here. Our pharma companies manufacture generic products but fortunately for us, the local pharma industry has grown big enough to fulfill domestic requirement and do a little export also. Many companies have spare capacity which they can utilize as their business increases.

Generic product development in Pakistan does not follow the same route as in the developed countries. Until recently, any pharma company could formulate any combination and get it registered disregarding whether it was approved internationally or not. India was much ahead of us and had such irrational combinations of drugs available in their own market which no one would endorse in a developed country. There was no need for any trial of any kind on animals or humans. The pharma companies would put up a few pages of information in the registration dossier and apply for registration. Since the availability of internet, it became much easier to download loads of information from internet and make a decent looking dossier.

Some credit is certainly due to the Ministry of Health and later DRAP. They objected to the irrational combinations and gradually tightened the drug registration process despite protracted resistance from the industry. Presently, the pharma companies are required to do some original work by way of testing the drug and incorporating real data in the registration dossier. We are still far from doing clinical work on generic products on the premise that we are a poor country and compelled to sell drugs at low prices. We cannot afford to do costly clinical trials because that cost would not be recovered.

So here we are vis-à-vis product safety. Over 80% consumption is of generic drugs in Pakistan, and the safety and efficacy of none of these has been documented, before or after the marketing. We rely on the safety data of the original research product which is applicable to a large extent. However, while major side effects are related to the molecule, several other issues are related to formulation. Efficacy also varies due to formulation which is another subject.


Disclaimer: Most pictures in these blogs are taken from Google Images and Pexels. Credit is given where known; some do not show copyright ownership. However, if a claim is lodged at any stage, we shall either mention the ownership clearly, or remove the picture with suitable regrets.


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