What does clinically meaningful mean? US lawyer predicts biosimilar battles

The prediction was made by Dave Rosen, a partner at law firm Foley & Lardner LLC, who suggested the lack of defintion of key terms in the US Biologics Price Competition and Innovation Act (BPCI), which was signed into law in 2009, would be a source disagreement between biopharmas and the agency.

"So what is a biosimilar product? It is one that is highly similar to an already approved biological product, notwithstanding minor diferences in clinically inactive components parts and there are no clinically significant differences between the biosimilar and the approved product in terms of saftey, purity and potency.​"

This imprecise wording is the problem according to Rosen, who predicted that: "Each one of those terms is going to get litigated at some point in time.​

"There is not a lot of guidance on what is 'highly similar,' what consititues minor differences and what are not clinically meaningful differences. Those are inexact terms and so the onus is going to be on the companies that are going in to FDA to demonstrate that their product does not have any clinically meaningful differences​."

"So it is going to be tought sledding to say the least​" he predicted, suggesting that likely points of diagreement between filers and the FDA will related to whether or not differences in [protein confirmation], differences in impurities and degredants, cross linking will be defined as clinically meaningful.

Cost concerns​

According to FDA data, as of Septmber 18 2013, there have been 41 initial meeting between biopharma firms interesting in filing biosimilar products under BPCI and 17 formal review applications seeking approval for 12 such products have been submitted.

Meeting and filing with the FDA is an expensive business according to Rosen, who framed the high cost in the context of the legal disputes he expects to happen.

"If you want to hold one of these meetings it costs $216,000 just to get the meeting so that's a pretty big barrier to entry​" he said adding that "to actually file an application it is $2,169,000 if you include clinical data or $1.84m if you dont include clinical data​."

"So those are very large amounts of money for companies, especially if they are not well capitalised​."

Bioequivalence questions​

The other potential legal issue Rosen flagged was interchangability and how sponsors should go about proving their drugs can be switched with reference products or indeed whether they even need to.

Rosen said that under BPCI a biosimilar can be either similar to a reference product or similar and interchangable, explaining that: "so it [the biosimilar] doesnt have to be interchangable in order to get approval and that is a big deal because the issues associated with establishing bioequivalence with a biosimilar product has raised a lot of questions​."