From our perspective: Biosimilar product labeling

Leah Christl, Ph.D., Associate Director for Therapeutic Biologics and lead of the Therapeutic Biologics and Biosimilars Staff in the Office of New Drugs, discusses FDA’s approach to biosimilar product labeling.

Therapeutic biological products

The principal components of therapeutic biological products are large, complex molecules like monoclonal antibodies and cell signaling proteins. The nature of biological products creates unique challenges that generally do not exist with small molecule drugs. For instance, unlike small molecule drugs made through chemical synthesis, biological products are produced in living systems, such as microorganisms, plant cells or animal cells.

Introducing biosimilars to the U.S. market

Until recently, most biological products had to seek FDA approval as if they were an entirely new entity, submitting a full complement of product-specific data, including animal and clinical study data. However, in 2010, the President signed legislation that created an abbreviated approval pathway for biological products to promote development and create competition, with the goals of increasing treatment options and reducing healthcare costs. Approved biosimilar products have been determined to be highly similar to an FDA-approved reference product and demonstrated that they have no clinically meaningful differences from the reference product in terms of safety, purity and potency.

Demonstrating biosimilarity

Biosimilar development programs generate an array of data comparing a proposed product to the FDA-approved reference product in order to demonstrate biosimilarity. The comparative data are generated and evaluated in step-wise fashion that begins with a foundation of detailed structural and functional characterization of the products, moving on to animal studies, if necessary, and then to comparative clinical studies.

The goal of a biosimilar development program is to demonstrate biosimilarity between the proposed product and the reference product, not to independently establish the safety and effectiveness of the proposed product. Consequently, a biosimilar product that is shown to be highly similar to an FDA-approved reference product may rely on our previous determination of the reference product’s safety and effectiveness, rather than generate a full profile of product-specific nonclinical and clinical data.

With this in mind, we are recommending an approach to biosimilar prescribing information, or “labeling,” that also relies largely on the safety and effectiveness information from labeling for the corresponding reference product.

Prescription drug labeling

Before I delve further into our approach to biosimilar labeling, let me take a step back to first explain the value of labeling. Prescription drug product labeling is the vehicle that communicates the product’s safety and effectiveness information to health care providers. Labeling summarizes key scientific information that health care providers need to assess a therapeutic product’s risk-benefit profile and decide if the product is appropriate for use by their particular patient.

In early 2006, FDA finalized its regulations on the content and format of labeling for prescription drug products, including biological products. The final labeling regulations, commonly known as the Physician Labeling Rule or PLR, are designed to ensure that health care providers have clear and concise information in prescription drug labeling, and to make it easier for health care providers to use labeling to make their prescribing decisions. Labeling includes three sections: Highlights of Prescribing Information, a Table of Contents, and the Full Prescribing Information.

In 2014, FDA updated its regulations on labeling information geared toward pregnant women, lactating women and individuals of reproductive potential through the Pregnancy and Lactation Labeling Rule. All newly approved prescription drug products, including biosimilars, must follow these labeling regulations.

Biosimilar labeling specifics

To address biosimilar labeling in particular, we have issued detailed recommendations to industry in the “Labeling for Biosimilar Products” draft guidance. One of the first items health care professionals may notice in the Highlights section is the addition of a “Biosimilarity Statement” describing the biosimilar product’s relationship to its reference product.

For the Full Prescribing Information, we recommend that biosimilar product labeling incorporates relevant data and information from the FDA-approved labeling for the reference product, along with any appropriate modifications specific to the biosimilar product. Note that a biosimilar product is not required to have the same labeling as its reference product, and so biosimilar product labeling may differ from the reference product labeling for a variety of reasons. For example, a biosimilar applicant may seek licensure for fewer than all of the indications for which the reference product is approved, and this difference would be reflected in product labeling.

Utility of comparative data

While we recommend that biosimilar labeling include biosimilar product-specific data necessary to inform safe and effective use of the product, we generally do not recommend that comparative data supporting the demonstration of biosimilarity be included in biosimilar product labeling. We’ve taken this approach to avoid potential confusion or misinterpretation of the comparative data.

As I mentioned, rather than essentially repeat the reference product’s demonstration of safety or effectiveness, comparative clinical studies are intended to demonstrate that there are no clinically meaningful differences between the proposed biosimilar product and the reference product. Indeed, comparative clinical studies in a biosimilar development program may use endpoints or study populations that are different from those used to support approval of the reference product.

Due to the potential for differences in clinical study parameters, we think that including comparative clinical data in biosimilar product labeling would be confusing or even potentially misleading to health care providers. Ultimately, the comparative data are useful for the FDA to make a decision about biosimilarity, but are not likely to be relevant to a health care provider’s prescribing considerations.

However, I want to point out that these comparative data generally will be available to the public. Health care providers and others who want to delve more deeply into the product-specific data supporting a demonstration of biosimilarity, including the comparative clinical data, may find this information in FDA’s product reviews, on our Drugs@FDA website.

Next steps for biosimilars

We think that our approach to biosimilar labeling will be truly beneficial to health care providers as they consider prescribing options and the risk-benefit decisions for their patients. The biosimilar labeling guidance has been issued in draft to provide an opportunity for public comment and we hope to hear from the various stakeholder communities - industry, health care providers, and patients. We will review and consider all of the comments received as we work to finalize guidance on this topic.

Biosimilars are relatively new products in FDA’s landscape, so there is still a lot of work to do. For example, we are currently reviewing the comments received on our draft guidance on nonproprietary naming of biosimilar products, and we are committed to finalizing the naming and labeling guidances. FDA will continue to build upon its experience in reviewing and approving biosimilar products to ensure that new, safe and effective health care options become available for patients.

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Dr. Christl is the Associate Director for Therapeutic Biologics in the Office of New Drugs (OND) in the FDA's Center for Drug Evaluation and Research. Dr. Christl leads the Therapeutic Biologics and Biosimilars Staff (TBBS) in OND. TBBS is responsible for ensuring consistency in the scientific and regulatory approach and advice to sponsors regarding development programs for proposed biosimilar products and related issues regarding development programs for therapeutic biologics. Prior to joining the FDA, Dr. Christl received her Ph.D. in Molecular and Cellular Biology and Pathobiology – Marine Biomedicine and Environmental Science from the Medical University of South Carolina in Charleston. She also spent 2 years at the University of South Carolina as an Associate Research Professor.