Switching from a Reference Biologic to a Biosimilar
Switching from a reference biologic to a biosimilar is important because:
It maximizes cost-savings to the healthcare system.
It determines the initial market for a biosimilar. If a biosimilar manufacturer is blocked from the larger share of the market, it is disadvantaged in contracting with payers, being on formularies, and offering value.
Single switch of reference biologic (RB) to a biosimilar (The FDA uses the term “transition” for a one-time (single) switch from reference biologic to a biosimilar).
Multiple switches between a reference biologic and its biosimilar, such as RB→ biosimilar → RB → biosimilar → RB → biosimilar.
Physicians always have the ability to prescribe whichever medicine they believe is most appropriate for their patients. This includes switching patients from reference biologics to biosimilars.
Pharmacists must dispense the biosimilar specified by the prescriber, unless the FDA has designated a given biosimilar as interchangeable. "Interchangeability" is a regulatory category unique to the US,1 which permits a pharmacist to substitute a biosimilar in place of its reference product without first obtaining permission from the prescriber.2,3 This only applies to products dispensed in a retail or specialty pharmacy setting. This is a regulatory designation only and not a quality designation.2
At Sandoz, we believe the interchangeability category is not based on science and hinders patients’ ability to access more affordable biologic treatment options. It is our position that an approved biosimilar should be considered interchangeable with its reference medicine, meaning that a patient can expect an equivalent treatment outcome with regard to safety and efficacy.
To date, no company has sought an interchangeability designation.2,4
Two large reviews of reference biologic to biosimilar provide persuasive data on this topic:3,4
One review included 90 such studies that collectively enrolled 14,225 patients with 7 different biologics used to treat 14 different diseases.3
Another review published two years later identified 178 such studies with 10 different biologics.4
Both reviews included randomized clinical trials and observational studies conducted in a real-world setting.
These studies concluded that:
There are no differences in safety, efficacy, or immunogenicity after a single switch event compared to patients that were not switched.
The act of switching from a reference biologic to a biosimilar is not inherently dangerous, and one that patients, healthcare professionals and the public should not assume is problematic.
The results provide reassurance to healthcare professionals and the public that the risk of immunogenicity-related safety concerns or diminished efficacy is unchanged after switching from a reference biologic to a biosimilar medicine.
The results of these large reviews have been corroborated by multiple other literature reviews.5-8
1. US Food and Drug Administration. Public Workshop: FDA/FTC Workshop on a Competitive Marketplace for Biosimilars. March 9. 2020. https://www.fda.gov/drugs/news-events-human-drugs/public-workshop-fdaftc.... Accessed May 21, 2020. 2. Mirazol F. Biosimilars Tackle Interchangeability Standards Demonstrating interchangeability can ensure biosimilar substitutability at the pharmacy level. Biopharm International. 2020; 33(4), 28–32. 3. Cohen HP, Beydoun D, Chien D, et al. Awareness, Knowledge, and Perceptions of Biosimilars Among Specialty Physicians. Adv Ther 33, 2160–2172 (2016). https://doi.org/10.1007/s12325-016-0431-5. 4. US Department of Health and Human Services. Considerations in Demonstrating Interchangeability With a Reference Product: guidance for industry. May 2019. https://www.fda.gov/media/124907/download. Accessed October 7, 2020. 5. Cohen HP et al. Switching reference medicines to biosimilars: A systematic literature review of clinical outcomes. Drugs (2018) 78:463-478 6. Barbier et al. The efficacy, safety and immunogenicity of switching between reference bio-pharmaceuticals and biosimilars: a systematic review. Clinical Pharmacol Pharmacotherapy (2020) doi: 10.1002/CPT.1836 7. Ebbers et al. The safety of switching between therapeutic proteins. Expert Opinion Biol Therapy (2012) 12:1473-1485 8. Gisbert and Chaparro. Switching from an originator anti-TNF to a biosimilar in patients with inflammatory bowel disease: Can it be recommended? A systematic review. Gastroenterol Hepatol. (2018) https://doi.org/10.1016/j.gastrohep.2018.04.005 9. Moots et al. Switching between reference biologics and biosimilars for thetreatment of rheumatology, gastroenterology, and dermatology inflammatory conditions: Considerations for the clinician. Curr Rheum Rep (2017) 19:37-53 10. McKinnon et al. Biosimilarity and interchangeability: Principles and Evidence: A systematic review. BioDrugs (2018) 32:27-53