One in four biologically derived medicinal products such as insulin and antibodies approved in the U.S. and Europe since 1995 have been the subject of a safety warning, a new study has found.

As the name suggests, "biologicals" are produced or extracted from a biological source — such as antibodies, enzymes and hormones — and then bioengineered into treatments. Biologicals are an important and growing medical therapy, and more than 250 have been approved since 1982, the study authors say.

'My message to patients is that these biological products often can treat very difficult to treat diseases but may have very substantial risks, and that you need to take extra care to educate yourself as to what those risks might be.'— Thomas Moore

The arthritis drugs Humira and Remicade, and the cancer drugs Rituxan and Erbitux, were among those biologicals flagged for safety issues after approval.

In Wednesday's issue of the Journal of the American Medical Association, Thijs Giezen of the Utrecht Institute for Pharmaceutical Sciences in the Netherlands and his colleagues looked at how many safety-related warnings were issued for the 174 biological products approved in the U.S. and the European Union between January 1995 and June 2007.

"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 study's authors say.

Biologicals, a relatively new kind of medicines, carry specific risks, since they often work by stimulating an immune response, the researchers say.

New side-effects arise

The approach may result in side-effects often not seen in traditional medicines, such as major infections and cancer, said Dr. Charles Bennett, a drug safety expert at Northwestern University in Chicago who was not involved in the research.

During the study period, 82 safety-related regulatory actions were issued for 41 of the 174 biologicals, or 24 per cent.

These included 46 warnings of health hazards sent to health care professionals in the U.S., 17 in the EU and 19 black box warnings for serious health hazards. No biologicals were withdrawn for safety reasons.

Most of the warnings, nearly 27 per cent, involved problems at the system or organ level or problems where the biologicals were given, such as an injection in the arm. Most biologicals are given intravenously or by injection.

"A more in-depth evaluation of the mode of action of biologicals might have predicted some safety problems during the developmental phase," the researchers say.

Since most of the issues cropped up within a few years, the potential for widespread harm was minimized, Giezen said.

Consider value and risks, patients told

Infections and infestations accounted for 22 per cent of the warnings, immune system disorders 16 per cent, and benign, malignant or unspecified growths rounded out the list at 12 per cent.

The findings show how the drug approval process and the surveillance system after drugs are marketed needs to the improved, because the regulatory process "is at best an inexact and incomplete science," editors Dr. Catherine DeAngelis and Dr. Phil Fontanarosa write in journal editorial accompanying the study.

"Just as with other consumer products that cause harms, consumers (i.e., patients) who are injured by defective medical devices or by pharmaceutical products with inadequate warnings of potential harms may have to resort to legal action as recourse for their injuries," DeAngelis and Fontanarosa write.

Many biologicals have advantages over conventional medicines, but patients should also consider the risk, said Thomas Moore of the Pennsylvania-based Institute for Safe Medication Practices

"My message to patients is that these biological products often can treat very difficult to treat diseases but may have very substantial risks, and that you need to take extra care to educate yourself as to what those risks might be," Moore said.

With files from the Associated Press