The Kennedy-Eshoo Amendment to the Health Care Legislation Proposes Significant Changes to the Marketing of Biologics

By: Seth A. Mailhot

Much of the debate concerning the proposed health care reform legislation has centered on the impact to the health insurance industry and the specter of a public option. Given this focus, it is easy to overlook what will be one of the most significant changes to the premarket review process for biologics[1] by the U.S. Food and Drug Administration (FDA) in some time. Contained within the over 1,000 pages of text is a proposal to establish a generic, or “similar,” approval pathway for biologics. This legislation will have a profound impact on the biologics market in much the same way that the Hatch-Waxman Act (formally named “The Drug Price Competition and Patent Term Restoration Act of 1984”) has had on the pharmaceutical market.

A biologic is defined as “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.”[2] Given the therapeutic nature of biologics, they also qualify as “drugs” under the Federal Food, Drug and Cosmetic Act.[3] Currently, any applicant is permitted to market a biologic similar to a currently marketed innovative biologic (called a “biosimilar”), under certain conditions. Specifically, the innovative biologic can not be protected by a valid patent and the applicant must provide complete information on the safety and efficacy of the biosimilar. The safety and efficacy information required in an application includes clinical and non-clinical data developed to establish the safety and efficacy of the product. Under the Kennedy-Eshoo amendment to the House and Senate bills, a biosimilar application would be able to rely on the safety and efficacy data developed by the innovator in exchange for twelve (12) years of “data exclusivity.” Data exclusivity is a phrase that has been coined to describe the ownership protections afforded to innovators who develop safety and efficacy data. During a period of data exclusivity, the FDA would not be permitted to accept an application for a biosimilar that references clinical or non-clinical data that had been previously submitted by another company without a right of reference to that data. This data exclusivity would run concurrently with any patent protections. This is similar to the type of arrangement found in the Hatch-Waxman Act.

While the House and Senate have come to an agreement on biosimilars, there has been some disagreement between Congress and the White House on the length of data exclusivity to be granted innovators. Compared to the Kennedy-Eshoo amendment, which applies a twelve (12) year period, the White House sought to limit the data exclusivity to seven (7) years. Limiting the data exclusivity period is generally seen as a means to bring down the prices of biologics, while extending the data exclusivity period is viewed as a way to foster innovation.

Beyond the length of data exclusivity afforded innovators, there are significant regulatory science questions that need to be adequately resolved before biosimilars can be approved. A fundamental issue that vexes regulatory authorities is the question of immunogenicity. Immunogenicity is the capacity of a drug to trigger an immune response, which may cause allergic or anaphylactic reactions, reduction in efficacy, or induction of autoimmunity. The more complex the drug, the greater the chance for that drug, or some closely-related variant, to trigger an immune response.

This leads us to the fundamental reason why it has taken Congress so long to develop legislation for biosimilars, despite the fact that effective generic drug legislation has existed since 1984. Unlike most drugs, the chemical structure or makeup of a biologic can not easily be confirmed through traditional analytical methods because of their complexity. Due to this complexity, biologics manufacturers are highly dependent on maintaining a consistent manufacturing process to ensure that their biologic is consistent from lot to lot.

The complexity of biologics and biologic manufacturers’ dependence on the manufacturing process to ensure consistency are the two key reasons why many eschew the term “generic” to describe a biosimilar. A biosimilar manufacturer may never be capable of exactly duplicating an innovator’s process, and would generally be prevented from ever learning it. Thus, biosimilar manufacturers would never be able to produce a biologic under the same process as used by the innovator. This potential for variation in the finished product compared to the innovative biologic would only make the two products “similar,” and not completely interchangeable, as can be achieved by many generic drugs.

Regardless of the terminology used to describe biosimilars, there have been complex drugs that present issues of immunogenicity, despite falling outside of the definition of a biologic. At least some abbreviated new drug application (or, ANDA) applicants have been informed by the FDA that their applications do “not adequately address the potential for immunogenicity of the drug product.”[4]

As the Kennedy-Eshoo amended health care legislation winds its way through the legislative process, the ways in which the FDA addresses existing issues of immunogenicity will help to determine how the FDA will implement a biosimilar approval pathway. This will present innovators and biosimilar manufacturers the opportunity to engage the FDA on these issues once biosimilar legislation is signed into law.