October 21, 2008
A study in the October 22/29 issue of the Journal of the American Medical Association (JAMA) finds that roughly 25
percent of biological medicinal products--things like antibodies,
enzymes and insulin--approved since 1995 in the U.S. and Europe have
had at least one safety-related regulatory action issued for them 10
years after their approval, including about 11 percent receiving a
"black box" warning.
Biologicals are preparations in which the active substance is produced by or extracted from a biological source, such as antibodies, enzymes and hormones. They represent an important and growing part of medical therapies, with more than 250 biologicals having been approved since 1982.
"Between 2003 and 2006, biologicals represented 24 percent and 22 percent of all new chemical entities approved by the U.S. and EU regulatory authorities, respectively," the authors write. "Biologicals are a relatively new class of medicines that carry specific risks. However, limited information is available on the nature and timing of safety problems with their use that were identified after approval."
The researchers from the Utrecht University, Utrecht, the Netherlands examined the nature and probability of safety-related regulatory actions issued for biologicals approved in the United States and/or the European Union between January 1995 and June 2007. Vaccines, allergenic products (a substance capable of causing an allergic reaction), and products for further manufacture and transfusion purposes were excluded.
A total of 174 biological medicinal products were approved during the study period, including 136 biologicals in the U.S. and 105 in the European Union, of which 67 obtained approval in both regions during this time.
The researchers found that between January 1995 and June 2008, 82 safety-related regulatory actions were issued for 41 of the 174 biologicals. These included 46 written communications to health care professionals in the U.S., 17 in the European Union, and 19 black box warnings. None were withdrawn due to safety reasons.
The average time to a safety-related regulatory action was 3.7 years and 70.7 percent of the safety-related regulatory actions were issued within five years after approval. The probability of a biological requiring its first safety-related regulatory action was 14 percent three years after approval and 29 percent ten years after approval.
Biologicals that were the first to be approved in their chemical, pharmacological, and therapeutic subgroup had a significantly higher risk for the occurrence of its first safety-related regulatory action compared with later approved products.
"Health care 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," the authors write.
