As a nurse and advanced practice provider, I am always looking for ways to provide the best possible care for my patients. One of the most important considerations when it comes to providing quality care is ensuring that the treatments we use are safe and effective. Recently, there has been much discussion around the use of biosimilars, which are similar, but not identical, versions of biologic drugs. One of the key components of biosimilars is interchangeability, or the ability to substitute one medication for another without changing the therapeutic effect. In this blog post, we will discuss the role of interchangeability in a biosimilar and how it affects patient care.
- What is the difference between a biosimilar and a biologic?
A biosimilar is an FDA-approved biologic product that is approved based on the demonstration of a high degree of similarity to an FDA approved reference biologic product; biosimilars must also show no clinically meaningful difference to the reference product in terms of safety and effectiveness.
- What is interchangeability?
When applied to biological drugs, the term “interchangeable” or “interchangeability,” means that a biosimilar drug may be substituted at the pharmacy counter by a pharmacist for the reference product without first getting permission from the health care provider – typically a physician or nurse practitioner – who wrote the prescription. Interchangeability is different from substitution that is initiated by the health care provider that occurs when a healthcare provider writes a prescription for one drug in place of another. Physicians always have the freedom to prescribe whatever drug they believe is appropriate for their patients.
According to U.S. law, an interchangeable biologic is a distinct regulatory category of biosimilar and is not a different product. To obtain an FDA designation of “interchangeability,” the sponsor of a biosimilar typically must conduct an additional clinical study with multiple switches back and forth between the biosimilar and reference product. This clinical study must prove that for a product administered to an individual more than once, the risk in terms of safety or diminished efficacy of switching back and forth between the interchangeable biologic and its reference product is not greater than the risk of using the reference product by itself, without switching.
- What does the first interchangeable exclusivity date indicate?
From the FDA: The date a first interchangeable product’s period of exclusivity ends, which is the date that FDA may make a determination that a second or subsequent biological product is interchangeable with the reference product against which the first interchangeable biological product was evaluated for any condition of use. The presence of “Date TBD” in the Purple Book (the FDA’s “Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations”) indicates that FDA has determined that the listed biological product is eligible for first interchangeable exclusivity, but FDA has not yet determined the applicable period of exclusivity under section 351(k)(6) of the PHS Act. The absence of a first interchangeable exclusivity expiration date in the Purple Book does not mean that a biological product on the list is not, or was not, eligible for the periods of exclusivity described in section 351(k)(6) of the PHS Act.
- How many interchangeable biosimilars are on the market?
As of February 2023, there are four biosimilars with the approval of interchangeability.
- Should a nurse or APP be concerned if his/her patient receives an interchangeable product in place of the prescribed reference product?
Prescribers and patients can expect that the interchangeable product will have the same clinical result as the reference product. Prescribers and their patients can be assured that an FDA-approved interchangeable product has been thoroughly tested and has met FDA’s high standards for approval. Meeting these standards means that health care professionals and patients can be assured of the safety and effectiveness of an interchangeable product, just as they would be for a reference product.
- Can an interchangeable product be used in patients who have previously been treated with the reference product?
Yes, interchangeable products can be used in patients who have previously been treated with the reference product (treatment-experienced), as well as in patients who have not previously received the reference product (treatment-naïve). As part of the approval process for interchangeable products given more than once, manufacturers must show that patients can be switched back and forth between the reference product and the proposed interchangeable product without an increased risk in terms of safety or diminished efficacy.
- Where can you find more information about interchangeable products?
FDA’s “Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations,” known as the “Purple Book,” is an online resource for health care professionals and patients to locate information about approved biological products. The Purple Book provides information about whether a biological product is a reference product, biosimilar, or interchangeable product. Product-specific information, including a summary of FDA’s review of the data that were used to support approval of a biological product, can be found at the Drugs@FDA website. You can also visit https://www.fda.gov/biosimilars
- What additional data must a biosimilar have for FDA approval to be interchangeable?
Biosimilar manufacturers must demonstrate that no clinically meaningful differences exist between the biosimilar product and reference product by providing comparative clinical pharmacology data (i.e., pharmacokinetics, and where applicable, pharmacodynamics), and if needed, additional clinical studies.
Source: FDA PowerPoint: Biosimilars and Interchangeable Biosimilars
- Why does this matter to me as a nurse or Advanced Practice Provider?
One of the biggest impacts I foresee is that this adds another level of options for a patient. A pharmacist will be able to dispense an interchangeable without involving the provider. This will hopefully increase access to these powerful, disease altering medications without unnecessary delays due to denials or back and forth between the providers, insurance and pharmacy. – Karen McKerihan, MSN, NP-C
- How does interchangeability impact my patients?
Interchangeability increases patient access to treatment as well as reduces the cost without changing the potentially life saving effect of the treatment option.
Summary: The benefits of interchangeability
Interchangeability is a critical aspect of biosimilars. It is a designation granted by the FDA that allows for the switching of a biosimilar from the reference product without the need to notify the prescribing healthcare provider.
The approval pathway for interchangeability involves clinical studies and other data to demonstrate that there are no clinically meaningful differences between the biosimilar and the reference product in terms of safety, efficacy, and quality. This process helps ensure that patients can benefit from the same therapeutic effects with the interchangeable biosimilar as they would with the reference product.
Interchangeability also has the potential to increase access to treatments and lower costs of biologics. By providing a lower cost alternative, more patients have the opportunity to access these treatments. This could have a significant impact in both developed and developing countries where access to biologics may be limited due to cost or availability.
In addition, interchangeability provides an assurance to both healthcare providers and patients that switching between the reference product and an interchangeable biosimilar does not compromise safety or efficacy of the treatment. This can help reduce anxiety and uncertainty when considering a switch.
Overall, interchangeability is an important consideration for healthcare providers and patients when determining if a biosimilar is an appropriate treatment option. It ensures that treatment remains consistent and effective, while also providing cost savings and increased access to biologic medications.
This content sponsored by Boehringer Ingelheim
More Resources on Biosimilars:
Biologics Prescribers Collaborative
PurpleBook FDA FAQs
Biologics Prescribers Collaborative – Biologics & Biosimilars in Rheumatology
Biosimilars: Non-Medical Switching and Transitioning
Biologics, Biosimilars, Interchangeability – BPC One Sheet
Biosimilar Review and Approval
Prescribing Interchangeable Products
Karen McKerihan, MSN, NP-C, President-Elect
Karen McKerihan currently resides in Charleston, South Carolina where she works as the Director of Infusion Services at Articularis Healthcare. She studied at the University of Tennessee, Walden University, and graduated Magna Cum Laude . She began her nursing career in 1987 and worked as an RN in women’s care and pain management until 2016. Since then she has worked as an FNP in rheumatology and is currently the Director of Infusion Services for Articularis Healthcare. She is a member of the AANP, ARP, INS, and the RNS. As the daughter of educators, she grew up in India, speaks Hindi, and in her spare time plays the bagpipes for the Charleston Pipe Band.