Biosimilar basics

A biosimilar product is a biologic product that is approved based on demonstrating that it is highly similar to an FDA-approved biologic product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

A medication produced in living cells via a multistep process. Biologics encompass a number of broad categories, including vaccines, blood and blood components, somatic cells, gene therapy, tissues, and genetically engineered therapeutic proteins. Since their introduction, biologics have been used to treat many life-threatening and chronic conditions in areas such as nephrology, diabetes, cancer, inflammation, immunology, and respiratory, hematologic, gastrointestinal, lysosomal, and cardiovascular diseases.

A biosimilar is a biologic product and a generic is a small-molecule product. While identical generic versions of small molecules can be chemically synthesized, it is not possible to create identical versions of reference biologic medicines due to their complexity. Therefore, the processes used to develop generic medicines cannot be applied to development of biosimilar medicines.

Immunogenicity is evaluated in the biosimlar development process. Immunogenicity refers to the tendency of a biologic to induce the formation of antidrug antibodies. Antidrug antibody profile of the biosimilar must not result in clinically meaningful differences. Potential clinical consequences of antidrug antibodies are loss of efficacy, general immune effects (allergy; serum sickness; anaphylaxis) and cross-neutralization of endogenous protein and biologic drug.

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Approved biosimilar medicines are required to have no clinically meaningful differences in terms of safety, efficacy, purity, or potency from the relevant reference product and are based on the totality of evidence from analytical, nonclinical, pharmacokinetic, and clinical studies.

Extrapolation is a scientific and regulatory principle that refers to the approval of a biosimilar for use in an indication held by the reference product but not directly studied in a comparative clinical trial with a biosimilar. Extrapolation of efficacy and safety data from one indication to another may be considered if biosimilarity to the reference product has been shown by a comprehensive comparability program including safety, efficacy, and immunogenicity, and there is sufficient scientific justification for extrapolation. Extrapolation is not automatic and is considered only after biosimilarity is established based on the totality of evidence.

Interchangeability is defined by statute in the United States to mean that the product may be substituted for the reference product without the intervention of the physician who prescribed the reference product. The legal standard for interchangeability is an additional standard beyond demonstration of biosimilarity.

To be deemed interchangeable, a biological product must be biosimilar to an FDA-approved reference product and meet additional standards for interchangeability set forth by the Biologics Price Competition and Innovation Act (BPCIA). By statute, in order for the FDA to deem a biological product interchangeable, the information submitted in the application (or a supplement to such an application) must be sufficient to show that: the biological product is biosimilar to the reference product; and can be expected to produce the same clinical result as the reference product in any given patient; and for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch. In the US, although federal law gives the FDA the authority to license biological products as interchangeable, it is individual state laws that govern the substitution of biologics and pharmaceuticals.

Interchangeability is defined by statute in the United States to mean that the product may be substituted for the reference product without the intervention of the physician who prescribed the reference product. Switching is a decision made by a physician to change a patient's treatment - to another course of therapy, from a reference product to a biosimilar, or potentially among biosimilar products. Neither the Biologics Price Competition and Innovation Act nor any other provision of law suggests or requires that a biosimilar meet the statutory definition of interchangeability as a prerequisite for a physician to switch (or transition) a patient from a reference biologic to a biosimilar (or other therapy).


Biosimilar development requires significant expertise to ensure that it is “highly similar” to the originator biologic with no clinically meaningful differences in safety, efficacy, or potency. State-of-the-art analytical tools and nonclinical and comparative clinical studies are used to compare the biosimilar to the originator biologic.

Benefits of biosimilars

By potentially reducing costs while retaining safety, efficacy, and quality standards, biosimilars may be able to unlock resources that can be reinvested in things like improving patient care. Biosimilars may also help broaden treatment options for prescribers and patients to potentially improve overall health outcomes.

Biosimilars may improve access to biologics. Biosimilars have the potential to make a positive impact on patients by offering additional treatment choices to patients, physicians, and payers at a lower cost to the healthcare system. These savings to the healthcare system may enable more patients to have access to biologics, which could result in improved health outcomes for patients.

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Pfizer experience

Pfizer has nearly 12 years of experience with biosimilars and over 30 years of experience manufacturing biologics.

With 4 biosimilars marketed outside the United States, 3 in market in the United States, 2 in late-stage development, and 2 under review with the FDA, Pfizer is firmly committed to the future of biosimilars. Pfizer Biosimilars will help continue Pfizer’s commitment to providing innovative inflammation and oncology treatments that impact the lives of patients worldwide.

Transitioning to value-based care? Learn How Biosimilars may help

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