In an effort to break the regulatory impasse over biosimilar medicines in the US, Representative Henry Waxman and two other Democrats have introduced a bill laying out an abbreviated approval route for generic versions of biotechnology products.

Unlike the historic 1984 legislation co-authored by Waxman and Republican Senator Orrin Hatch, however, the Access to Life-Saving Medicine Act (HR 6257) does not temper its pro-generic provisions with compensatory protections for the research-based industry. This suggests a tough battle ahead when the bill comes under full scrutiny in the 110th Congress next year.

So far, and despite persistent lobbying from the generics industry and its supporters, the Food and Drug Administration has approved only one ‘follow-on protein’, Sandoz’ Omnitrope (somatropin). It did so reluctantly and under legal pressure, using the Section 505 (b) (2) provisions of the Federal Food, Drug and Cosmetic Act.

The FDA has made clear, though, that Omnitrope does not set a precedent for approval of other biosimilars. Moreover, most biotechnology products in the US are regulated under the Public Health Service (PHS) Act, which does not expressly include an abbreviated pathway for follow-on biologics.

Waxman and his co-sponsors, Senators Charles Schumer and Hillary Clinton, have tackled this deadlock by proposing amendments to the PHS Act that would introduce a two-tiered system of abbreviated approvals for biosimilars.

Generic contenders could position their products as “comparable” to or “interchangeable” with the reference biological product. HR 6257 defines comparability as no clinically meaningful differences between the biosimilar and the reference product in terms of safety, purity and potency, based on non-clinical studies or clinical trials if deemed necessary. The FDA, which has resisted a blanket approval process for biosimilars, could determine on a case-by-case basis the studies needed to establish comparability.

Applicants would also have to show that the follow-on product shared the “principal molecular structural features” of the reference biological as well as the same mechanism(s) of action, if known.

An ‘interchangeable’ product could be “expected to produce the same clinical result(s) as the reference product in any given patient”. Product labelling would indicate interchangeability with the reference drug for the approved conditions of use, qualifying the follow-on product for generic substitution by pharmacists.

The bill recognises this approval pathway would be significantly more expensive and problematic than establishing comparability. Studies demonstrating interchangeability would be eligible for tax credits and the first successful applicant by this route would gain a market exclusivity period in line with the Hatch-Waxman provisions (180 days from launch or alternative arrangements depending on whether there was a claim of patent infringement).

HR 6257 would also prohibit the launch of a ‘rebranded interchangeable product’ (i.e., authorised generic) with the consent of the originator during the exclusivity period. Other perceived abuses of Hatch-Waxman are addressed through tight deadlines for processing comparable biological applications and restrictions on “frivolous” citizen petitions aimed at delaying their approval. Last-minute patent lawsuits would also be discouraged – for example, by barring enforcement of patents not disclosed in response to requests from generic challengers.

While the bill’s determinedly pro-generic stance drew enthusiastic support from the Generic Pharmaceutical Association (GPhA) and other interested parties such as the Consumer Federation of America, the research-based industry dug its heels in.

Stressing that any discussion of an approval pathway for follow-on biologicals must include “how to maintain incentives that spur continued innovation, including strong protections for intellectual property rights and access to capital”, the Biotechnology Industry Assocation stated: “It is imperative that the US FDA continue to require a full complement of data, including clinical evidence, to demonstrate safety and effectiveness for all biotechnology products.”

The emphasis on IP protection will sit well with Orrin Hatch, who recognises the need for abbreviated approvals to stem the ballooning cost of new biotech products but is unlikely to endorse HR 6257 unless it incorporates checks and balances for the research-based sector.