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Understanding the abbreviated licensure pathway: Q&A with FDA's Leah Christl
To clarify some of the procedural details and concerns surrounding the abbreviated licensure pathway for biosimilars, Healio spoke with Leah Christl, PhD, associate director for therapeutic biologics at FDA.
[Editor’s Note: This Q&A was conducted on November 10, 2016 prior to the publication of the FDA’s Considerations in Demonstrating Interchangeability With a Reference Product: Guidance for Industry.]
Are there estimates of the potential cost savings and increased patient access to biologics that will result from the abbreviated development pathway for biosimilars?
The Biologicals Price Competition and Innovation Act (BCPI) of 2009 was signed into law through The Patient Protection and Affordable Care Act (Affordable Care Act) on March 23, 2010. The BCPI Act created an abbreviated licensure pathway for biological products that are demonstrated to be “biosimilar” to or “interchangeable” with an FDA-licensed (approved) biological product. One intention of the BPCI Act was to create more competition in the marketplace for expensive and life-saving biological products, which can lead to less expensive alternatives to reference biological products, enhancing patient access and lowering costs to consumers. There are varying estimates about savings, however FDA does not have the authority to regulate the pricing or reimbursement for biological products.
In the stepwise development approach, how does the FDA determine whether comparative data elements are unnecessary based on data established in a previous step?
Because there is no one-size-fits-all approach, the scientific framework for biosimilars uses a stepwise approach to generate data in support of a demonstration of biosimilarity and reduce residual uncertainty at each step. This means that at each step of the process FDA will review and evaluate the data submitted and if any residual uncertainty remains, FDA may require additional data to support a demonstration of biosimilarity.
FDA also uses a totality-of-the-evidence approach when reviewing a marketing application for a proposed biosimilar product. This approach considers all available data and information submitted by the sponsor including, as appropriate, analytical data, animal data, human pharmacokinetics (PK) and pharmacodynamics (PD), clinical immunogenicity, and clinical safety and effectiveness data. There is no one “pivotal” study that demonstrates biosimilarity, but instead a step-wise approach is applied to data generation and the evaluation of residual uncertainty. Therefore, the totality of the data and information needed to support a demonstration of biosimilarity may be dependent upon and influenced by multiple factors, including specific product-dependent factors such as product complexity and its impact on comparative structural and functional characterization of the molecule. Approval of a proposed biosimilar product is based on the integration of various information and the totality of the evidence submitted by the biosimilar sponsor to provide an overall assessment that the proposed product is biosimilar to the reference product.
During the advisory committee hearing on ABP 501 (now approved and known as Amjevita [adalimumab- atto , Amgen]) , several committee members expressed concerns about using analytical data to justify extrapolation to clinical indications, due to possible unknown mechanisms of action. Is this a legitimate concern, and should postmarketing studies therefore be mandated as some have advised?
When the FDA approves a biosimilar product, it has determined the product meets the statutory requirements for approval and is safe and effective for all indications for which the biosimilar product is approved, including any approved indications that were supported by extrapolation. Comparative clinical safety and effectiveness data with Humira (adalimumab, AbbVie) and Amjevita was obtained from studies in rheumatoid arthritis and plaque psoriasis patients. In addition, Amgen submitted extensive data and sufficient justification to address the scientific considerations for extrapolation of data to support biosimilarity to other conditions of use for which the reference product, Humira, is licensed (approved) and for which Amgen sought licensure of Amjevita. Therefore, based on the totality of evidence submitted in the biologics license application, Amjevita was approved for the following indications: moderately to severely active rheumatoid arthritis; active psoriatic arthritis; active ankylosing spondylitis (an arthritis that affects the spine); moderately to severely active Crohn’s disease in adults; moderately to severely active ulcerative colitis in adults; and, moderate to severe plaque psoriasis. Amjevita is also indicated for moderately to severely active polyarticular juvenile idiopathic arthritis in patients aged 4 years and older. It is important to remember that extrapolation in this context is from the reference product to the proposed biosimilar product, not from one clinical indication to another, based on all available data and information, not just analytical data.
Robust postmarketing safety monitoring is an important component in ensuring the safety and effectiveness of all biological products, including biosimilar products. There are many factors that influence postmarketing safety monitoring considerations, including but not limited to, any particular safety or effectiveness concerns associated with the use of the reference product and other products in the class, data on the proposed product obtained during its development and clinical use (if marketed outside the United States), and the specific condition(s) of use and patient population(s). When FDA approves a biosimilar product, it has determined that the product meets the Agency’s standard for approval and has been demonstrated to have no clinically meaningful differences from the reference product in terms of safety, purity, and potency for the labeled uses, including any indications that were supported by extrapolation.
Committee members at that hearing also expressed concerns about nonmedical switching of originator products with biosimilars. Is the FDA still deliberating on its interchangeability policy, and if so, are there any updates on this front?
Under the Biologics Price Competition and Innovation Act of 2009 Act (BPCI Act) a biological product may be approved as biosimilar to or interchangeable with an FDA-approved reference product. The BPCI Act provides that an interchangeable product “may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.”
However, pharmacy practices related to substitution are generally governed by state law, and the specific laws for substitution of interchangeable products may vary from state to state. To contain drug costs, some states have adopted laws and/or regulations that encourage the substitution of drug products, including biosimilar and interchangeable products.
The FDA’s high standard for approval of biosimilar and interchangeable products means that patients and health care professionals can be confident of the safety and effectiveness of a biosimilar or interchangeable product for its approved indications, just as they would for the reference product.
The draft guidance Considerations in Demonstrating Interchangeability to a Reference Product remains on the 2016 CDER guidance agenda and FDA continues to work toward the intention of issuing the draft guidance in 2016; however, the guidance agenda is not a commitment.
Disclosures : Christl reports no relevant financial disclosures.