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In a public hearing held May 11, 2012, the U.S. Food and Drug Administration (FDA) gathered stakeholders to gain feedback on the first drafts of the FDA guidance

documents outlining future product development for generic biologics. The panel consisted of representatives from the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Office of Special Health Issues, and Office of the Chief Counsel. The hearing was chaired by Dr. Rachel Sherman, MD, MPH, Associate Director for Medical Policy at CDER. The audience consisted of representatives from patient-advocacy groups, trade organizations, and pharmaceutical, biotech, and generics manufacturers.

Biologics and BiosimilarsBiologics are complex therapeutic products primarily synthesized within living organisms, as opposed to most drugs which are chemically synthesized. Biologics include a range of products, including vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Highly complex generic versions of biologic therapies are often referred to as biosimilars. The FDA’s draft guidance on biosimilars was mandated as part of the Patient Protection and Affordable Care Act signed on March 23, 2010 by President Obama. This act will serve as an abbreviated licensure pathway for biologic products that are highly similar to or interchangeable with approved reference products.

Biosimilarity and InterchangeabilityMany patient advocacy groups discussed the importance of formulating a firm plan for establishing interchangeability between biosimilars. The current FDA draft guidance document states that “the FDA is continuing to consider the type of information sufficient to enable the FDA to determine that a biological product is interchangeable with the reference product”. Many of the presenters gave rationale and pointed assessments of the current FDA draft guidance documents. Many also described the current language as vague, allowing for broad interpretations which could lead to tragic consequences for patients.

Several panelists stressed the importance of drafting clear and expedient guidances for the benefit of patients. By drafting separate guidances on interchangeability patients with debilitating diseases would have low-cost alternatives for treatment. Representative Kristin Bass, Senior Vice President for Policy and Federal Affairs of the Pharmaceutical Care Management Association (PCMA) highlighted the need for accelerated development of guidances for interchangeability so that development of biosimilars can be advanced, resulting in increased competition. This move would benefit patients and decrease overall cost. Bass cited a recent study that reported that generics for small molecules have resulted in a savings of $931 billion from 2001-2010, with $150 billion of this in 2010 alone. Dr. Amy M. Belton is a Research Associate at Johns Hopkins University

in Baltimore, Maryland. Dr. Belton is interested in biosimilars and their promise for both patients and the U.S. economy. Dr. Belton is also a guest

blogger for the Institute for International Research Future BioPharma.

“The tracking and tracing of biosimilars is an issue

of great concern to many stakeholders who feel that

biologics and biosimilars should be distinguishable

and have no overlap...”

BIOSIMILARS

July 2012

by Amy Belton, PhD

The high standards of biosimilars were discussed by Dr. Richard Dolinar, Chairman of the Alliance for Safe Biologic Medicines, who stated the importance of maintaining the “patient-doctor relationship” with respect to interchangeability. He feels that a physician’s decision to prescribe a patient a specific therapy should not be superseded by a third party, such as a pharmacist or insurer, due to cost or convenience. Dolinar later added that a physician must also be assured of a biosimilar’s safety and efficacy by stressing that a foreign-sourced reference product should be developed and/or manufactured by a U.S. manufacturer to assure acceptable standards. These high standards would require foreign-sourced reference products to have clinical studies, immunogenicity studies using analytical testing, and clinical trials in order to gain FDA approval.

The issue of “drifting” was also addressed by the panel. A drift is a variation in molecular structure and function that can occur during manufacturing, packaging or substitutions of inert compounds. Drift can cause a biosimilar to become unstable, which can negatively affect patient health. Panelists felt the need to develop methods to monitor drift between the reference product and the biosimilar.

These issues of interchangeability will undoubtedly need to be addressed in an additional set of FDA draft guidances for biosimilars.

Biosimilar Labeling and TrackingThe tracking and tracing of biosimilars is an issue of great concern to many stakeholders who feel that biologics and biosimilars should be distinguishable and have no overlap. As a result, there is the substantial need for a section in the guidance documents to address the naming and tracking of biosimilars. Joseph Miletich, Senior Vice President of Research and Development at Amgen, stated the advancement of biologics depend on a few key elements: manufacturer accountability, FDA communication, and supply-chain stability.

He felt that supply-chain stability should also be outlined in FDA guidance documents. His sentiments echoed many speakers who voiced the need for transparent and straightforward communication with both biologics and biosimilar manufacturers.

Establishing BiosimilarityThe precise method for establishing biosimilarity is still unclear. One presenter, Sumant Ramavchandra, Senior Vice President, Research and Development, Medical and Regulatory Affairs and Chief Scientific Officer of Hospira, recommended allowing for broader analytical testing methods to ensure the most appropriate testing is done in order to establish biosimilairty. In addition, he called for more clarity in the definition of acceptable methods for determining similarity and acceptance ranges

for biosimilarity. Marcia Boyle, from the Immune Deficiency Foundation, stressed that immunoglobulins should be exempt from the biosimilars pathways due to the uncertainty of the current analytical methods for establishing similarity. She also emphasized the importance of clinical-trial testing and post-marketing surveillance of biosimilars. These are critical areas for ensuring the safety and effectiveness of biosimilars.

In summary, the FDA and stakeholder community are poised to begin the process of biosimilar development for the treatment of life-threatening diseases. The FDA’s public hearing dealing with biosimilarity and interchangeability will contribute to how the FDA will address these issues in the final draft guidances and direct the future of this industry.

Public Hearing on FDA Draft

Guidance Documents

for Biosimilar Development

PuBlic HeArinG on FDA DrAFt GuiDAnce Documents For BiosimilAr DeveloPment - BiosimilArs