Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Thalidomide catastrophe: its impact on the design and assessment of toxicological experiments and its current regulatory recommendations

Sarah Safaa Essmat (Abschlußjahr: 2020)

Summary
Language: English
Thalidomide is an effective drug with unacceptable risks for malformations in newborns if administered in pregnant women. It was first marketed during the 1950s in Europe as a sedative, which was also prescribed to treat morning sickness in pregnant women. It was advertised as effective and completely safe; this led to a high rate of prescriptions, ending with one of the world's most crucial medical disasters.  More than 10,000 babies were born with extreme malformations, of which only 40% survived. It took ten years to understand that it was thalidomide that caused this teratogenicity, leading to its final ban in 1961. Years of research were needed to understand the embryo-pathic mechanism of action. Finally, in 2018 a group of scientists discovered that thalidomide induces complete degradation of SALL4 (a protein-coding gene responsible for development pathways) in humans and rabbits but not in rodents or fish. The former observations, fortified by the recently discovered mechanism were the reason for a paradigm shift in drug safety assessments, where in former times the potential for human teratogenicity was based on testing in rodents, but today also in rabbits as a non-rodent species with high human predictive power for bone malformations. In addition, even though thalidomide's teratogenicity stereotypically presents with phocomelia, a wide range of damage to other organs could also be reported. Despite its identified high toxicity, thalidomide is still used today to manage different conditions such as Leprosy and Multiple Myeloma. The new thalidomide regulations are very strict. However, between 2005 and 2013, the world experienced another thalidomide tragedy, this time in Brazil. This was in part due to late response of Brazilian regulators since the first adequate thalidomide regulation was issued in 2011. Another reason is the inadequate education, especially in the poor areas where Leprosy is endemic. In conclusion, thalidomide has the potential of severe toxicity, but when used with high awareness of risks and subsequent preventive measurements, thalidomide can still be used as a valuable drug despite its risky past. The key to preventing undesirable adverse effects in babies is through intensive education of patients and prescribing doctors, all following recommendations published by regulatory bodies. It needs to be stressed, education of medical professionals and patients is of paramount importance. The example of Brazil reveal that such educating campaigns serve to increase awareness for the risks and prevention options, patient education supports the correctness of therapeutic intervention, the open cooperation among patients, prescribing doctors, pharmacists and regulatory bodies is the best guarantee to exercise strict control of the investigated undesirable side effects of thalidomide. No doubt, a restricted availability will be beneficial.
Pages: 83
Annexes: 15, Pages: 36