Clinical trials of biosimilars should focus on how they differ from the drugs they copy rather than on creating a whole new safety or efficacy study, the World Health Organization says.
The group says it’s considering new standards for biosimilars because the industry has exploded since it last updated its rules nearly a decade ago.
WHO, in proposed guidelines posted on its website last week, suggests that “clinical development can be abbreviated” as long as sponsors can prove a biosimilar drug’s molecular structure and effect on patients mimic that of the original product.
Comparing the molecular structures and patient immune responses may allow sponsors to skip separate safety or efficacy trials and extrapolate results for regulators. But more complex products, such as monoclonal antibodies (made by identical immune cells that are clones of a unique parent cell), might require more extensive analysis before any data can be generalized, WHO says.
Some countries strictly control the biosimilar industry while others have little to no oversight. So the health agency says it’s also time to revisit the rules to come up with a uniform set of regulations. It notes, for instance, that the FDA has tougher standards for approval of biosimilars than the European Union, which lacks the authority to determine whether a biosimilar is interchangeable with the drug it’s patterned after.
The global patchwork — especially in developing countries — has allowed many biosimilars that “do not now meet current WHO regulatory expectations” to come to market, the 36-page draft guidance warns. “Very little is known about the safety and efficacy of these individual products.”
WHO regulations already require sponsors to test new biotherapies to make sure patient immune systems won’t reject them in clinical trials. The proposed guidelines say the same rules should apply to biosimilars. That means sponsors would have to show that their knockoffs’ molecular makeup or amino acid sequences are almost identical to those of the originals.
The group also recommends testing trial participants for anti-drug antibodies triggered by the original and copied versions — and investigating any differences even if the biosimilar stokes fewer anti-drug antibodies.
An FDA spokesperson said the agency is reviewing the proposals and would provide feedback. But the U.S. already has similar regs in place so the most likely scenario is that these guidelines would help force the rest of the world to play catch up.
The FDA has approved 17 biosimilars over the past decade, five of them last year.
