Defining Key Terms Associated With Biosimilars

EP: 1.What are Biologics and Biosimilars, and How Are They Devolved?

EP: 2.Difference Between Biosimilars and Reference Product

EP: 3.Differences Between Biosimilars and Generic Drugs

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EP: 4.Defining Key Terms Associated With Biosimilars

EP: 5.Defining Extrapolation

EP: 6.Defining Interchangeability Status

EP: 7.Unmet Needs With Biosimilars

EP: 8.Impact of Biosimilars on Payers, Health Care System, and Patients

EP: 9.Role of Biosimilars and Assessing Clinical Impact

EP: 10.How to Switch Patients to Biosimilars

EP: 11.Challenges With Biosimilars Being Approved in the US

EP: 12.Clinician Confidence in Biosimilars

EP: 13.Addressing Patients' Concerns With Biosimilars

Roy M. Fleischmann, MD: There are some terms that have been introduced with the concept of the biosimilar, including extrapolation. Extrapolation means that if an adalimumab biosimilar is approved, should it be allowed to be used in all of the indications for the reference, the branded adalimumab? The answer is: why not? If it’s similar, why not? But then there’s another term: interchangeability. That’s different. Let’s talk about that for a second.

The FDA guidance document states that to show interchangeability, which means the ability of someone to use the biosimilar rather than the reference product, and then go back to the reference product. In order to do that, the company must analyze and identify that the biosimilar has critical quality attributes, including showing the analytical differences between the reference product and the proposed interchangeable product.

They have to show an analysis to potential clinical impact of the differences. They have to show analysis of the mechanism or mechanisms of action in each condition of use for which the reference product is licensed, including the target receptor or receptors for each relevant activity or function of the product; the binding, dose concentration response, and pattern of molecular signaling upon engagement of target receptor or receptors; the relationship between product structure and target receptor interactions; and the location and expression of target receptor or receptors.

They have to show an analysis of any differences in the expected pharmacokinetics and biodistribution of the product in different patient populations for which the reference product is licensed; an analysis of any differences in the expected immunogenicity risk of the product in different patient populations for which the reference product is licensed; an analysis of any differences in expected toxicities of the product in each condition of use and patient population—including whether the expected toxicities are related to the pharmacological activity of the product or to off-target activities—for which the reference product is licensed.

Further, for biologics administered more than once to a patient, the information in the application must be sufficient to show that the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product isn’t greater than the risk of using the reference product without alteration or switch. The FDA expects that applications generally include data from a switching study or studies in 1 or more appropriate conditions of use. The FDA uses the data from a switching study to assess the risk in terms of safety and diminished efficacy of alternating or switching between the products. This is a very complex process that a company with a biosimilar has to go through to obtain interchangeability.

Transcript Edited for Clarity