Patent Baristas

Representatives Waxman, Emerson, and Pallone, along with Senators Schumer and Clinton, have re-introduced H.R. 1038, the “Access to Life-Saving Medicine Act,” which will establish a process through which the FDA will be able to approve generic biologics or biopharmaceuticals. While generic drugs have been extremely successful in bringing down the high cost of prescription drugs, there is currently no FDA pathway for getting approval for biogenerics.

It is estimated that generic drugs save about $10 billion a year and many would like to see this same result with expensive biotech drugs, many of which cost tens of thousands of dollars a year, even after patent expiration. Pharmacy benefit manager Express Scripts Inc., conducted a study showing that the average biotech drug costs $71,600 a year, compared with the annual average for a traditional drug of $1,200. It said that escalating biotech drug costs, which reached $40 billion in 2005, are expected to more than double in four years to a total of $90 billion in 2009, a rate three times faster than traditional drug costs. While they predict a savings of at least $71 billion over 10 years if there was a regulatory mechanism that allowed for the marketing of biogenerics, BIO cautioned against forecasting any savings from generic biotech drugs without knowing how much testing regulators would require.

In summary, H.R. 1038 provides for the following:

Amends section 351 of the Public Health Service (PHS) Act to authorize the Secretary of HHS to approve abbreviated applications for biological products that are “comparable” to previously approved (reference) biological products.

An application for a comparable biological product must demonstrate that there are no clinically meaningful differences between the two products with respect to safety or effectiveness. The application must also show that the new product and the reference product contain highly similar “principal molecular structural features” and the same mechanism(s) of action, if known.

The Secretary has discretion on a product-by-product basis to determine what studies are necessary to establish comparability. Unlike the sharply limited studies that can be required for traditional generic drugs, the Secretary is given authority to require one or more clinical studies in an application for a comparable biological product, if necessary to establish that the new product has comparable safety, purity, and potency to the reference product.

An application for a comparable biological product will be subject to user fees.

An applicant for a comparable biological product may elect, but is not required, to establish interchangeability. The Secretary is given discretion to determine what studies are required to establish interchangeability. The bill grants the first applicant to obtain approval of an interchangeable version of a biological product a period of exclusive marketing during which no other interchangeable version of the product may be approved.

Applicants for comparable biological products may elect to ask the holder of the reference product for a list of patents on the product and may elect to notify the reference product holder and owner of one or more of the patents identified that the applicant has filed a comparable biological product application. If the applicant sends such a notice, it must contain a detailed statement explaining why the identified patent(s) is invalid, unenforceable, or not infringed. If the reference product holder fails to disclose a relevant patent, it may not enforce that patent against that applicant. If no patent infringement action is brought within 45 days of notice of a challenge, the remedy in any later action to enforce that patent against that applicant is limited to a reasonable royalty.

While the FDA has approved Novartis AG’s Omnitrope hormone, there has not been a change in the stance taken by the FDA on generic biotechnology drugs. Omnitrope was approved only after a federal judge ordered the FDA to decide after a long delay. Also, Omnitrope is considered less complicated than most other biologics.Under both the Federal Food Drug and Cosmetic Act and the Food Prescription Drug User Fee Act, the FDA is required to either approve or reject new drug applications. However, no biogenerics (or follow-on proteins) have yet been approved in the US pharmaceutical market beyond Omnitrope.

The reason for the lack of a regulatory pathway for approval of biogenerics lies in the complexity of the biological products themselves. Biologics are large, complex, heterogeneous molecules for which the manufacturing process can be a determinant of the end product. Demonstrating that a generic version of the product is as safe and effective as the brand name product would be a difficult at best since, for example, establishing that immunogenicity had not been altered and that any undetected differences in the product would not impact safety and efficacy would be problematic without conducting extensive clinical trials.

With Omnitrope, the FDA, however, went out of its way to say that Omnitrope is not a generic biologic stating that “Omnitrope is not rated as therapeutically equivalent to (and therefore substitutable for) any of the other approved human growth hormone products. Omnitrope is more appropriately characterized as a “follow-on protein product.”

The FDA indicated that the approval of Omnitrope in a 505(b)(2) application does not establish a pathway for approval of follow-on products for biological products licensed under section 351 of the Public Heath Service Act, nor does it mean that more complex and/or less well understood proteins approved as drugs under the Food, Drug, and Cosmetic Act could be approved as follow-on products.

See the full text (pdf) of the bill here.