Kellie Zeichner, RN, BSN, OCN, discusses the production of biosimilars, their approval and naming processes, and why immunogenicity is important when discussing these agents.
As biosimilars continue to be approved for cancer-specific agents, the role of the oncology nurse in implementing and educating patients about their use becomes more pronounced, according to Kellie Zeichner, RN, BSN, OCN.
“[The Biologics Price Competition and Innovation Act of 2009] generated a licensure pathway for biologic products which [have been] proven to be biosimilar to or interchangeable with FDA[-approved] biologic products,” Zeichner, an oncology nurse with the Rutgers Cancer Institute of New Jersey who has experience working with biosimilars, said in an interview with Oncology Nursing News®.1
Frequently used agents in oncology care—trastuzumab (Herceptin), rituximab (Rituxan), and pegfilgrastim—all have approved interchangeable products. Most recently, bevacizumab (Avastin) added a third FDA-approval biosimilar, bevacizumab-maly (Alymsys) in April 2022.2
In the discussion, Zeichner highlighted the vital components of the development of biosimilars and interchangeable products that oncology nurses need to know.
Oncology Nursing News®: Please contextualize how biosimilars compare with their reference products.
[Biosimilars] are large, complex molecules made from living sources that are not identical but very similar to approved reference or brand drugs [with slight alterations and inactive components]. There are no clinically meaningful variants in safety, purity, or strength.
Biosimilars differ from generic drugs in their complexity and the manner [in] which they are manufactured. The cell lines that are processed [for reference products] are proprietary for biologics; therefore, the original product can never be duplicated precisely, and an exact copy of a biologic cannot be made. This is different from a small molecule drug, which can be copied with insignificant or no variable change from the original. The process of biosimilar manufacturing is rigorous [and is conducted] in a highly controlled environment.
The products are tested on several levels, which include preclinical, structural, and operational levels for safety, efficacy, and immunogenicity. [The biosimilars] must meet FDA standards—they have to be manufactured in an FDA-licensed facility, and they must be tracked as part of post marketing surveillance to ensure continued safety, which is of the utmost importance.
What is the approval process for a biosimilar?
Following the approval of [an] original brand drug, there is a period of market protection. For [approximately] 10 years there is an order to safeguard the reimbursement of research and developmental costs—which are quite high—for [the reference] biological agents.
Once this period has expired, biosimilars are legally allowed to be created. At this point, submission can be placed for a licensed application of biosimilar or an interchangeable [biosimilar product]. Then, through analytical data, animal testing, and clinical studies, an applicant must prove that there is no clinically meaningful difference in safety, purity, and strength between the biosimilar and the reference drug. Biosimilars can be approved as interchangeable either at initial approval, or at supplemental approval, if switching studies are conducted.
Please expand on the differences of an interchangeable biosimilar.
What is an interchangeable? This is a biosimilar product that can be substituted for a brand product without the intervention of the health care provider who prescribed it.3 To demonstrate interchangeability, [the FDA] requires that the biosimilar will produce the same clinical result as a brand product for any given patient and that it presents no additional risk to the patient if a switch between a product had occurred.
What is process of naming a biosimilar?
All biosimilars have a nonproprietary name and a suffix that is attached to the [reference product name], [this] always has a hyphen at the end [followed by 4 lowercase letters, of which 3 are distinct. They don’t carry any meaning at all, [but are there to ensure] that the biosimilar cannot be capable of being mistaken for the name of a current drug that is marketed already.
The intent for this is 2-fold. [One purpose] is patient safety, [specifically] to prevent patients from receiving medication that was not the intended biologic product prescribed and to avoid switching [to] biologics that are not deemed interchangeable. [The hyphen also serves] for tracking. It allows manufacturers specific tracking and most importantly, the remediation of adverse events should one occur.
Why is immunogenicity important when discussing a biosimilar?
Immunogenicity is an immune response [triggered by] a host against the therapeutic protein or the drug. It is an important concern regarding the efficacy and safety of biologics.
Biologics are more structurally complex than chemical drugs, and even a small variation in their manufacturing can cause undetected changes in [the] biologic composition of the product. These minor differences between a biosimilar and a reference biologic product could lead to the development of an anti-drug antibody.
At least 1 comparative parallel arm clinical trial must be done to assess the potential difference in immune response between the reference product and the biosimilar. Most importantly, the biosimilar approval process should prove that the biosimilar does not present a greater risk than the [reference] or the brand drug does. This is done through a highly complex and fully validated approach for detecting anti-drug antibodies and a head-to-head comparison of immunogenicity testing between the biosimilar and the reference product.