Now that the United States’ acceptance of biosimilars matches that in the European Union, developers should be encouraging changes to testing regulations to increase biosimilar accessibility, according to Sarfaraz K. Niazi, PhD, in his recent perspective paper.
Now that the United States has over 10 years of experience with biosimilars and the European Union has nearly 20 years, developers need to be doing more to increase biosimilar accessibility, according to Sarfaraz K. Niazi, PhD, in his recent perspective paper.
Niazi, an adjunct professor of biopharmaceutical sciences at the University of Illinois and the University of Houston, had the peer-reviewed piece published in Biologics. He is also the founder of the biosimilars companies Karyo Biologics and Adello Biologics, and he is a member of The Center for Biosimilars®' Advisory Board.
Niazi listed several lessons learned from the previous 17 years of biosimilar development and marketing around the world, including which forms of clinical and preclinical testing are necessary to prove a biosimilar's effectiveness and safety compared with its reference product and which forms should be considered redundant or misleading.
Overall, there have been 84 approvals in the European Union and 35 in the United States as of April 2022. Although acceptance of biosimilars in the United States has increased to levels similar to those in Europe, biosimilars costs in the European Union are much lower and are often interchangeable with reference products without requiring a separate designation and additional testing as is the case in the United States.
Niazi suggested that developers could play a role in encouraging changes to testing requirements, arguing that reducing the number of time-consuming and expensive testing could increase biosimilar accessibility. “Making biosimilars accessible means reducing their cost of development, which is currently at around US$100 to US200 million, keeping small and medium-size companies out of play and leaving most current biosimilars in the hands of big pharma.”
After submitting several citizen petitions and conducting meetings with biosimilar advocates and experts as well as the FDA, Niazi predicted that animal testing, clinical efficacy testing, and clinical pharmacology testing will either be eliminated or reduced greatly as regulatory agencies continue to gain more confidence in the safety and efficacy of biosimilars.
According to Niazi, animal toxicology data are not as relevant as other data because biologic drugs do not consistently show pharmacologic responses in animal species. Additionally, high doses of the drug are required to produce a toxic response in animal subjects, making it difficult to differentiate between products that are being compared with one another and are supposed to be clinically similar. Niazi stated that testing drugs in animal species could lead to misguidance if safety is based on animal testing, putting human patients at risk.
Although clinical pharmacology comparisons can produce the most relevant results, the required number of volunteers for testing is higher than what is needed to establish biosimilarity. Niazi argued that data acceptance policies could be changed so that a smaller population is required for these studies.
“This suggestion reduces the risk of study failure without compromising the purpose of these studies: to compare how the body sees the molecule and how the molecule sees the body,” Niazi wrote.
Thus far, no biosimilars have been rejected for approval on the basis of clinical efficacy and safety testing if they passed all other tests, suggesting that either the biosimilar or the testing was too insensitive to detect differences. Niazi pointed out that comparative clinical trials are viewed as “sloppy techniques” for assessing similarity between biologic agents.
Niazi also contended that if clinical efficacy testing was truly vital to establishing biosimilarity, extrapolation of indications wouldn’t be allowed. “If there are any doubts about the safety or efficacy, then they should be tested in all indications, not just one selected by the developer, even where the modes of action are the same,” he said.
“Biosimilars have come of age; now it is the turn of the developers to grow up, and one way to show this is to challenge the current regulatory guidelines but only on scientific grounds to seek more concessions, for which both the FDA and European Medicines Agency are ready,” Niazi wrote.
Niazi SK. The coming of age of biosimilars: a personal perspective. Biologics. 2022;2:107-127. doi:10.3390/ biologics2020009