Biosimilars PDF Resource Summary
Pathways to Biosimilars: Development and Implementation
A Self-Directed Learning Experience
Welcome to “Pathways to Biosimilars: Development and Implementation”
Through this self-directed learning experience, you will:
Recognize that biosimilars were introduced to lower costs to the health care system1,2
Understand the rigorous development and FDA approval processes for biosimilars3
Gain ideas for adopting biosimilars in your health care system or practice
Ready to begin?
Continue to Why Biosimilars Matter
FDA, US Food and Drug Administration
References: 1. Biosimilars Action Plan. Balancing Innovation and Competition. US Food and Drug Administration. July 2018. Accessed March 22, 2023. https://www.fda.gov/media/114574/download 2. Mulcahy AW, Hlávka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. Rand Health Quarterly. 2018 Mar;7(4). Accessed March 22, 2023. https://www.rand.org/content/dam/rand/pubs/perspectives/PE200/PE264/RAND_PE264.pdf 3. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. US Food and Drug Administration. April 2015. Updated April 24, 2020. Accessed March 22, 2023. https://www.fda.gov/media/82647/download
Why Do We Need Biosimilars?
Biologic products have had a profound impact on the treatment of many serious and life-threatening conditions.1,2 However, their high cost can place a difficult burden on the health care system.3
From 2015 through 2020, 77 biologics received FDA approval4
Drug spending on biologics has risen, reaching $211 billion in 2019. That year, biologics comprised 43% of total medicine spending in the United States5
The goal of biosimilars is to create competitive pricing for biologics, to help reduce health care system costs, and increase access to biologic drugs.1,2
The Blueprint for Biosimilars
To understand how biosimilars may achieve their goal of reducing health care system costs, consider this analogy:
A biosimilar is to a reference biologic as a generic drug is to a small molecule drug.
Unlike generics which are often molecular copies of a small molecule drug, biologics and biosimilars are derived from a living source—making them highly complex molecules.6,7
A biosimilar is a biologic product that is highly similar to and has no clinically meaningful differences in terms of safety, purity, and potency from an existing FDA-approved reference biologic.7
Savings Snapshot: Generics and Biosimilars
Generics-based competition helps facilitate savings to the health care system.8
$313 billion in savings
from generic drugs in the United States in 20199
Biosimilars and generics were introduced with the same goal:
to increase access to medicines and reduce health care system costs.1
As more biosimilars are approved and utilized, the potential for savings and access across the health care system can grow.2
How are biosimilars created?
Continue to Development and Approval
FDA, US Food and Drug Administration
References: 1. Biosimilars Action Plan. Balancing Innovation and Competition. US Food and Drug Administration. July 2018. Accessed March 22, 2023. https://www.fda.gov/media/114574/download 2. Mulcahy AW, Hlávka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. Rand Health Quarterly. 2018 Mar;7(4). Accessed March 22, 2023. https://www.rand.org/content/dam/rand/pubs/perspectives/PE200/PE264/RAND_PE264.pdf 3. Atzinger CB, Guo JJ. Biologic disease-modifying antirheumatic drugs in a national, privately insured population: utilization, expenditures, and price trends. Am Health Drug Benefits. 2017;70(7):27-36. 4. Center for Drug Evaluation and Research. List of licensed biological products with (1) reference product exclusivity and (2) biosimilarity or interchangeability evaluations to date. September 9, 2014. Updated August 3, 2020. Accessed March 2, 2023. https://www.fda.gov/media/89589/download 5. Aitken M, Kleinrock M, Munoz E. Biosimilars in the United States 2020-2024: competition, savings, and sustainability. IQVIA Institute for Human Data Science. September 29, 2020. Accessed March 22, 2023. https://www.iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2020-2024 6. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. US Food and Drug Administration. April 2015. Updated April 24, 2020. Accessed March 22, 2023. https://www.fda.gov/media/82647/download 7. Purple Book database of licensed biological products. US Food and Drug Administration. October 2020. Updated August 20, 2017. Accessed March 22, 2023. https://www.fda.gov/files/drugs/published/Biological-Product-Definitions.pdf 8. Association for Accessible Medicines 2020 Report: Generic Drug and Biosimilars Access and Savings in the U.S. using data from IQVIA, found online. Published December 2020. Accessed March 22, 2023. https://accessiblemeds.org/sites/default/files/2020-09/AAM-2020-Generics-Biosimilars-Access-Savings-Report-US-Web.pdf 9. Lim S. Overview of the regulatory framework and FDA's guidance for the development and approval of biosimilar and interchangeable products in the US. US Food and Drug Administration. Accessed March 22, 2023. https://www.fda.gov/media/113820/download
The Rigorous Phases of
Biosimilar Development and Approval
To demonstrate that a biosimilar is highly similar to its reference biologic, the biosimilar must go through a rigorous development and approval process1
Analysis
Critical Quality Attributes (CQAs) are defined through a multifactorial analysis of the reference biologic. They serve as a blueprint for developing the biosimilar.1,2
Development
From a pool of thousands of living cell lines, the living cell line that reliably generates a biosimilar molecule with the established CQAs is identified.3,4
Testing
Extensive in vitro and in vivo assessments of the biosimilar’s CQAs are performed to support biosimilarity through structural, functional, and clinical evidence.1
FDA Approval
The FDA bases its approval on a comprehensive analysis of all structural, functional, and clinical data.1
Approval of a biosimilar indicates that there are no clinically meaningful differences between the biosimilar and its reference biologic in terms of safety, purity, and potency.1
Analysis and Development of Biosimilars
Biosimilar development begins with analyzing the reference biologic to build a “fingerprint” that helps define the structure and function of the reference biologic, which the biosimilar will match.1
- Identify critical quality attributes (CQAs), such as amino acid sequence, binding activity, protein structure, and MOA (mechanism of action) , through a multifactorial analysis of the reference biologic.1,2
- Develop a pool of thousands of living cell lines that generate a comparable molecule to the reference biologic.3,4
- Select the optimal cell line for biosimilar production.3,4
The biosimilar is continuously validated against the reference biologic’s CQAs throughout development and during manufacturing post-approval.1
Testing and Approval of Biosimilars
Testing includes extensive in vitro and in vivo assessments of CQAs and other attributes of the proposed biosimilar against the reference biologic.1 To support that there are no clinically meaningful differences between a biosimilar and its reference biologic, 3 types of tests are performed1:
Structural
- Amino acid sequence
- Protein structure
Functional
- Target binding activity
- Mechanism of action
Clinical
- PK/PD
- Immunogenicity
- Additional comparative safety and efficacy clinical studies are performed
The FDA bases its approval on a stepwise analysis of all structural, functional, and clinical data collected by a biosimilar manufacturer. FDA may request additional comparative clinical studies be performed to demonstrate similar efficacy, safety, and immunogenicity to the reference biologic.1
FDA approval of a biosimilar indicates that there are no clinically meaningful differences in safety, purity, and potency between the biosimilar and its reference biologic.1
Biosimilars videos
Structural testing video
One-minute video describing the important steps during the structural testing phase of the rigorous biosimilar approval process.
Functional testing video
One-minute video describing the important steps during the functional testing phase of the rigorous biosimilar approval process.
Clinical testing video
One-minute video describing the important steps during the clinical testing phase of the rigorous biosimilar approval process.
What is your role in
the biosimilars story?
Continue to a Biosimilars Action Plan
FDA, US Food and Drug Administration; PD, pharmacodynamics; PK, pharmacokinetics.
References: 1. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. US Food and Drug Administration. April 2015. Updated April 24, 2020. Accessed March 22, 2023. https://www.fda.gov/media/82647/download 2. Guidance for industry: Q8(R2) pharmaceutical development. US Food and Drug Administration. Accessed March 22, 2023. https://www.fda.gov/media/77535/download 3. Monoclonal antibody production. National Academy of Sciences. Accessed March 22, 2023. http://www.nap.edu/catalog/9450.html 4. Dranitsaris G, Amir E, Dorward K. Biosimilars of biological drug therapies: regulatory, clinical and commercial considerations. Drugs. 2011;71(12):1527-1536. doi:10.2165/11593730-000000000-00000.
How Can You Successfully Adopt Biosimilars Into Your Health Care Practice or Organization?
The potential for savings to the health care system may depend on how biosimilars are utilized moving forward.
As competition increases from biosimilar adoptions, the potential for significant savings to the health care system can increase as well.1
Deciding to Adopt a Biosimilar:
- Building knowledge about the product
- Assessing the payer landscape
- Building a consensus among key stakeholders in your organization
Implementing a Biosimilar:
- Updating systems
- Addressing payer landscape and reimbursement
- Educating and communicating key information
- Becoming available to patients and stakeholders
Monitoring Biosimilar Use and Experience:
- Measuring and confirming success
For biosimilars to fulfill their potential to increase access and reduce costs across the health care system, it will take the collective efforts of all stakeholders throughout the biosimilars adoption process.1,2
Additional Biosimilars Resources
Download a comprehensive roadmap for adopting biosimilars.
Biosimilars roadmap—for institutions
Roadmap for health care professionals for considering, implementing, and monitoring biosimilar adoption in an institution.
Review and wrap up
Continue to Summary and References
Based on the experience at a major health care institution. The adoption process and roles may vary by institution. Organon does not guarantee that your use of this information will help you achieve your biosimilars goals. This information was prepared in consultation with, and with the permission of, a health care administrator at a major health care institution who had successfully implemented a biosimilars switch within their organization.
References: 1. Mulcahy AW, Hlavka JP, Case SR Biosimilar cost savings in the United States: initial experience and future potential. Accessed March 22, 2023. https://www.rand.org/content/dam/rand/pubs/perspectives/PE200/PE264/RAND_PE264.pdf 2. Biosimilars Action Plan. Balancing Innovation and Competition. US Food and Drug Administration. July 2018. Accessed March 22, 2023. https://www.fda.gov/media/114574/download
Key Takeaways
The 3 key points to remember are:
Biosimilars are projected to have the potential to save the health care system $104 billion from 2020 to 20241
Biosimilars are FDA approved as having no clinically meaningful differences in safety, purity, and potency from their reference biologic, as demonstrated by a rigorous development process2
Adopting biosimilars requires the collective efforts of all stakeholders in your organization. A guide is available to help you get your adoption journey started.
As the health care landscape continues to change, consider whether adopting biosimilars presents an opportunity for your organization.
References: 1. Aitken M, Kleinrock M, Munoz E. Biosimilars in the United States 2020-2024: competition, savings, and sustainability. IQVIA Institute for Human Data Science. September 29, 2020. Accessed March 22, 2023. https://www.iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2020-2024 2. Scientific considerations in demonstrating biosimilarity to a reference product. Guidance for industry. US Food and Drug Administration. April 2015. Updated April 24, 2020. Accessed March 22, 2023. https://www.fda.gov/media/82647/download