HITCHIN, U.K.—A half-century after Germany’s Chemie Grünenthal dubbed new drug thalidomide a “miracle pill,” which pregnant women were given for morning sickness, tragically resulting in babies with startling physical birth defects (stunted flipper-like limbs), specialist contract research organization (CRO) Quanticate has followed the European Union (EU) into an era of heightened pharmacovigilance.
Although thalidomide was banned in 1962, by then 10,000 children, mostly in Europe, had been born with thalidomide-induced birth defects. The United Kingdom vowed never again, and set stricter drug approval policies. Just recently, the EU has announced stricter regulations set to impact the pharmaceutical industry later this year.
Quanticate recently upgraded its pharmacovigilance (PV) safety database and in-house technology platform in preparation for the upcoming Article 2(3) of Directive 2010/84/EU. The European Medicines Agency (EMA) has a planned launch of Nov. 22 for an improved version of EudraVigilance, the European information system for suspected adverse events.
EU nations have until March 30, 2019, to comply with the PV regulations.
Since its introduction in the wake of the thalidomide tragedy, international pharmacovigilance systems have been evolving to meet the changing requirements for effective protection of public health, with a shift towards a more proactive approach, not only to evaluate potential safety issues, but to minimize risks and promote the safe and effective use of medicines, according to Quanticate.
“As clinical data experts, we always aim to be at the forefront of compliance, hence our proactive onboarding of the upcoming E2B(R3) requirements and our technology investment,” states Tom Nichols, senior director pharmacovigilance at Quanticate.
“It is up to sponsors, marketing authorization holders and clinical research organizations to make the transition, and we believe our pre-emptive upgrade avoids the need for pharmaceutical organizations to use cumbersome and short-term conversion tools, which simply delay the inevitable need to upgrade later to become fully compliant,” Nichols says.
“With the current uncertainty about Brexit’s effects on PV in Europe, it is a huge advantage to be ahead of the curve on E2B(R3), rather than having to manage two big changes simultaneously,” he adds.
There is also increasing public awareness and changing expectations with regard to the safety of medicines, fueled by recent high-profile safety issues and product withdrawals, as well as large costs associated with drug safety, Nichols says.
This applies both to pharmaceutical companies looking to halt the development of products with an unacceptable risk-benefit profile as early as possible, as well as to curbing the cost to public health, with an estimated 5 percent of hospital admissions in the EU thought to be due to an adverse drug reaction, he says.
In the United States, far fewer thalidomide babies were born, reportedly largely due to the diligence of Dr. Frances Oldham Kelsey, a pharmacologist who had just started working at the U.S. Food and Drug Administration. She became alarmed by what she saw in 1960 as the lack of rigorous scientific research supporting the drug’s safety. Because of Kelsey’s perseverance, the drug never received FDA approval and, in 1962, thalidomide was banned worldwide. This marked the beginning of a new era for the FDA, which mandated major regulatory reforms on the pharmaceutical industry.
Although thalidomide was never licensed for distribution in the United States, it did not escape the drug’s devastating legacy. While the pharmaceutical company was waiting for licensing approval from the FDA , approximately 2.5 million sample tablets were handed out to 1,267 U.S. doctors for “clinical trials,” says Eileen Cronin, author of memoir Mermaid.
Although it is a growing challenge for pharmaceutical companies to manage the large amounts of safety data from numerous sources, the volume is increasing with more global clinical trials and post-marketing studies intensifying to strengthen consumer reporting in the EU, making it a requirement to report adverse reactions received directly from consumers, as is already required in the U.S., according to Quanticate.
And as far as thalidomide, its chapters are still being written. In the early 1990s, researchers discovered that the same properties of the drug that restrict blood vessel growth, resulting in stunted limbs, were useful in treating a number of medical disorders, including some cancerous tumors, Crohn’s disease and multiple sclerosis. Since July 16, 1998, thalidomide, under the brand name Thalomid, has been licensed for use in the U.S. in treating complications related to leprosy. In Oct. 26, 2006, the drug was also authorized in cases of multiple myeloma.
However, the danger of thalidomide to unborn babies has recently reared its ugly head again.
Despite carrying a strict warning that thalidomide is not to be taken by pregnant women, in Brazil—where it is used extensively to treat leprosy—a group of researchers report that as many as 100 children have been disabled by thalidomide since 2005.
