One in four biologics, such as antibodies, enzymes and insulin, which have been approved since 1995 in the USA and Europe, have had at least one safety-related regulatory action issued for them 10 years after their approval.

Furthermore, 11% received a black box warning, according to a study published in the Journal of the American Medical Association. Between 2003 and 2006, biologicals represented 24% and 22% of all new chemical entities approved by the USA and the EU, respectively, the authors write, and while biologicals “are a relatively new class of medicines that carry specific risks (eg immunogenicity)”, limited information is available “on the nature and timing of safety problems with their use that were identified after approval.”

Thijs Giezen of Utrecht University in the Netherlands and colleagues noted that 174 biologicals obtained approval during the study period, and between January 1995 and June 2008, 82 safety-related regulatory actions were issued for 41 of them. These included 46 written communications to healthcare professionals in the USA, 17 in the European Union, and 19 black box warnings. However, no biologicals were withdrawn due to safety reasons.

The safety-related regulatory actions issued for biologicals mostly involved the system organ classes of general disorders and administration site conditions (26.8% of 82), infections and infestations (22%), immune system disorders (15.9%), and neoplasms benign, malignant, and unspecified (12.2%). The authors noted that the warnings can be partly explained by “the infusion reactions occurring after the parenteral [intravenously or by injection] route of administration, which is the mode of administration for most biologicals”. They add that “a more in-depth evaluation of the mode of action of biologicals might have predicted some safety problems during the developmental phase”.

The study adds that “although the limitations of preclinical trials for biologicals are acknowledged”, results from pharmacology, preclinical and clinical studies “might result in the prediction of potential risks related to the drug for which close monitoring is needed in the postapproval setting”. Giezen et al conclude that healthcare professionals “should be aware of the specific risks related to the relatively new class of biologicals to be able to provide a link between the use of the biological and the patient presenting with a clinical problem”.