The US Food and Drug Administration’s (FDA) review of the Remicade biosimilar was originally scheduled for March. However, the meeting was postponed by the agency in February “due to information requests pending with the sponsor of the application.”
Specific details of these requests have now been made public by Liz Pollitt, Celltrion VP of Regulatory Affairs, who told delegates at the BioProcess International Summit in Dusseldorf, Germany the US regulator asked for more details of statistical analysis data used in the application.
“We have had a lot of communications with the stats unit of FDA, and we actually first asked them the question to which they eventually got back to us.” Furthermore, she added the firm is receiving “slightly contradictory requests” from the unit.
“In some cases they are asking us to unpool our data and in other cases they want us to pool it so we’re not quite certain what they are looking for there.”
Pollitt recommended that biosimilar developers have clear and constant communications with the agency on this matter, as “at the moment we still haven’t seen any sign of an FDA guideline on statistical analysis.”
The FDA also asked for more information about the microbial sampling, amino acid composition and oligosaccharide analysis methods used during the Remsima manufacturing process.
Additional studies and Interchangeability
Pollitt stressed that Celltion is continuing to work with the FDA to address the requests and explained that the firm has already provided more information than was included in the dossier filed in Europe.
She gave the example of additional three-way PK studies and biosimilarity studies, which Celltrion provided to the FDA as “an analytical bridge between EU and US Remicade” that reflects at least 35 manufacturing process changes made since the original EU submission.
Interchangability is another area of focus for the team guiding Celltion's US efforts according to Pollitt, who said “in the US we are not quite certain what the requirements are going to be around interchangeability.
"Remsima’s clinical programme wasn’t designed to show interchangeability; there was no pathway when the clinical programme was conducted.”
INN issues
Finally, for a global biosimilar maker, questions surrounding the INN (International Nonproprietary Name) of biosimilars continue to cause a problem.
In the EU and Canada, Remisima’s nonproprietary name is Infliximab, but the WHO has been discussing a biological qualifier with four random letters added as a differentiator.
“In Japan we have the nonproprietary name of the reference product, plus biosimilar, plus a number which indicates the order that we were approved in in Japan,” Pollitt said. “TGA is currently talking about a nonproprietary name, a biosimilar identifier prefix and a three-letter unique code.
“FDA is to be determined but if we look at what’s currently happening for Sandoz’ we can see it is going to have some sort of company identifier.”