How Biologics Manufacturing Transparency Could Bolster Biosimilar Market
By Anna Rose Welch, Editorial & Community Director, Advancing RNA
How Biologics Manufacturing Transparency Could Bolster Biosimilar Market
The recently resolved (ish) Amgen v. Sandoz case can be summarized by two big questions: how should the reference product sponsor (RPS) and the biosimilar maker define the words “shall” and “may?” And, can a biosimilar maker’s decisions to not share the application, the manufacturing processes, and any other information the RPS requests be a violation of the Biologics Price Competition and Innovation Act (BPCIA)? At face value, “shall” and “may” are simple words. In the context of this recent case, however, these words became indicative of an even bigger question: How much should pharma companies be required to share with each other? A lack of transparency is customary to the pharma industry as a whole and has been a contentious issue lately, particularly in the clinical space. But this issue was thrown into the manufacturing space as well when the Federal Circuit (FC) determined it is not a violation of the BPCIA for a biosimilar company to keep its application and manufacturing information from the RPS.
Even though a biosimilar is considered a “copy,” it is still the result of a complicated reverse engineering manufacturing process. As Craig Wheeler, CEO of Momenta Pharmaceuticals, told me in a recent interview, those making biosimilars need to maintain stricter control over their manufacturing processes — even more control than those making a novel biologic. The FC’s final ruling on Amgen v. Sandoz has given biosimilar makers the freedom to keep these processes close — a frustrating move for RPSs and one that will encourage long periods of legal wrangling. But I recently stumbled across a paper that led me to wonder why the biosimilar maker has to be the only one that gives it all away? What if it were actually the biologics makers that had to share with biosimilar manufacturers?
In his column in The New York Times, Austin Frakt addresses some of the barriers standing in the way of biosimilars entering the market. In his discussion, Frakt turns to a paper published in the Iowa Law Review by two law professors, W. Nicholson Price and Arti Rai. In their paper, “Manufacturing Barriers to Biologics Competition and Innovation,” Price and Rai identify one of the primary problems behind high healthcare costs as “one of information.” There are simply not enough incentives in place to encourage an RPS to record, let alone share, information on the manufacturing process of a biologic — a step which could lead to a more competitive and cost-effective market.
Price and Rai home in on the need for policy interventions that would encourage originator firms to generate and disclose more information, especially surrounding the manufacturing process — specifically the characteristics of the vector and cell line, cell line growth conditions, and purification processes. The authors write, “In some cases, reverse-engineering [the manufacturing process of the reference product] is impossible. Even in those cases where it is possible, it is very expensive. Moreover the biosimilar may direct its work towards duplicating idiosyncratic choices made by the reference sponsor. This path-dependence restricts the development of biosimilars for reasons unconnected with the safety and efficacy of the biologic.”
Rai and Price highlight the current value placed on trade secrecy, which is demonstrated through the current biologics patenting process. While many biologics makers file biological composition-of-matter patents, the processes outlined in the patents are rarely detailed. Price and Rai offer several options to bolster more “robust biologic disclosure.” For instance, while an RPS might garner broad patent protection to start, the patent would only remain valid so long as the firm provided a supplement containing “whatever information was necessary to ensure that competitors could actually make a biosimilar once the patent expired.” Doing so would not only ensure more transparency and ease for biosimilar makers, but would also require the RPS to choose between a patent for their product or trade secrecy over production methods.
Price and Rai also pose what they consider to be the most feasible possibility: that the FDA make public disclosure of “precise and enabling” manufacturing methods (as found in the Chemistry Manufacturing Controls [CMC] section of the Biologic License Application [BLA]) a mandatory part of the approval process. As the whole point of filing a BLA is to see the product on the market, the RPS would need to provide the appropriate amount of information to bolster future competition in order to gain access to and remain on the market. However, the authors remain uncertain as to when the appropriate time would be for disclosure of this information. Some exclusivity of this information is necessary in countries that have short to no mandatory biologics exclusivity periods. (Though the resolution of the Trans-Pacific Partnership Agreement [TPP] could make this less of an issue). But for the info to be beneficial for follow-on makers, it would need to be released prior to patent expiration, as well.
Now that the FC has given biosimilar makers the choice of whether to release their own data, an originator company would, no doubt, be more than reticent about having to provide information that could accelerate and aid competitors’ future development strategies. This wouldn’t be a free exchange, however, as Price and Rai suggest that additional exclusivity or, better yet, accelerated approval from the FDA would be an incentive that could sweeten the deal. “Given discount rates and technological advancement, some industry analysts argue that reducing time to market may be more important than regulatory exclusivity many years in the future,” the authors write.
Over the next few years post-Amgen v. Sandoz, the biologics and biosimilar sectors of the industry will no doubt be locking horns over patent infringements as more biosimilars are added to the FDA’s approval pipeline. However, I think this case, alongside Price’s and Rai’s article, opened up an interesting discussion on the role transparency could play in the increasingly high costs of biologics. While there have been many loud outcries for biologics companies to lower prices (without any real solution to do so), a lot of the burden of lowering costs has been placed on biosimilars, which will be a slow-growing market for the next few years. The notion that some of this responsibility could be placed on the makers of the originator molecule was, frankly, refreshing.