Daller J. Biosimilars: A consideration of the regulations in the United States and European union. Regulatory Toxicology and Pharmacology. 2016 Apr 1;76:199-208.
 European Medicines Agency. Biosimilar medicines: Overview. 2022
 Gherghescu I, Delgado-Charro MB. The biosimilar landscape: an overview of regulatory approvals by the EMA and FDA. Pharmaceutics. 2020 Dec 31;13(1):48.
 Konstantinidou S, Papaspiliou A, Kokkotou E. Current and future roles of biosimilars in oncology practice. Oncology letters. 2020 Jan 1;19(1):45-51.
 Janjigian YY, Bissig M, Curigliano G, Coppola J, Latymer M. Talking to patients about biosimilars. Future Oncology. 2018 Oct;14(23):2403-14.
 Abraham I, Han L, Sun D, MacDonald K, Aapro M. Cost savings from anemia management with biosimilar epoetin alfa and increased access to targeted antineoplastic treatment: a simulation for the EU G5 countries. Future Oncology. 2014 Jul;10(9):1599-609.
 US Food and Drug Administration. Biosimilar User Fee Amendments. 2022
 European Medicines Agency. Explanatory note on general fees payable to the European Medicines Agency. 2022
 European Medicines Agency. News: Biosimilar medicines can be interchanged. 2022
Differences in the regulatory pathways for biosimilar development: EU vs USA
Regulations surrounding biosimilar development are based on how well the similarity between the proposed molecule and the reference product (RP) can be demonstrated. Indeed, there is a need for increased access to cost-effective treatment for various conditions, which drives biosimilar development. Regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have similar requirements for demonstrating biosimilarity, i.e., head-to-head comparisons across pre-clinical, clinical, pharmacokinetic (PK)/pharmacodynamic (PD) physiochemical characterization, biological activity, etc. However, EMA’s biosimilar guidelines are based on the classification of the biological molecule, where policies are available for different product classes. In contrast, the US FDA takes a more case-by-case approach .
Comparison of biosimilar approval rates
EMA’s biosimilar guidelines were established in 2005, and they approved their first biosimilar in 2006 . Meanwhile, the US FDA approved their first biosimilar in 2015 and demonstrated a faster approval rate for biosimilars during the first four years of implementing their guidelines (16 biosimilars) compared to the first four years of EMA implementing their policies (13 biosimilars) . The difference in approval rate and time for biosimilars can be attributed to differences within the respective regulatory pathways. Biosimilar commercialization cannot only widen the range of therapeutic options available at relatively lower prices but also instigate competition where prices for originator products are reduced, thereby driving the biosimilar market from the perspective of economic opportunity and consumer affordability.
Exclusivity period, assessment fees, and interchangeability
The exclusivity period for biologics is 12 years in the USA and ten years in the EU; with several biologic patents and exclusivities expiring across the globe and more that are due for expiration in the year 2023, the space for biosimilar growth in the market is wide open. However, due to the stringent requirements for biosimilars in terms of development, manufacturing, and licensing, the save on cost is not as ‘fruitful’ compared to generics; 15-30% of the price is held for biosimilars vs. 80% cost that is reserved for generics . Nevertheless, the burden on healthcare costs would still be reduced and would encourage biosimilar development.
A study revealed that switching to a rituximab biosimilar would save roughly EUR 56 billion in Europe . Another study demonstrated significant cost savings when switching to an erythropoietin biosimilar in patients with chemotherapy-induced anemia. This allowed additional treatments with trastuzumab, rituximab, and bevacizumab .
Furthermore, in terms of the payer system, the EU implements a ‘single-payer’ healthcare system, whereas the US payer system is fragmented. This leads to differences when it comes to pricing and other practices. Reduced price is a key driving point for successful biosimilar adoption. Factors such as acquisition & reimbursement costs, payer systems & contracts, pharmacy substitution, and more can influence the adoption of biosimilars in different regions.
The difference in cost for biosimilar development, application, and even for seeking scientific advice could make specific markets more favorable than others. For example, the US FDA has established fees for assessing biosimilar biological products for fiscal years 2023 to 2027. On the 30th September 2022, the FDA User Fee Reauthorization Act 2022 for biosimilars- also known as the BsUFA III- was enforced to expedite critical processes involved in biosimilar development, including biosimilar biological product application review & post-market safety surveillance activities . The BsUFA III aims to ensure safe and effective biosimilar therapeutic options are developed for patients. Per the explanatory note on general fees payable to EMA, the primary and additional fees are listed for applications, extensions, variations, renewals, inspections, and more, including the costs for scientific advice requests (initial and follow-up) .
Furthermore, with the EMAs announcement of biosimilars being interchangeable earlier this year, the cost that sponsors face for biosimilar development would be relatively less, and the processes would be more simplified . However, the FDA and federal law requires manufacturers to provide additional supporting evidence to demonstrate interchangeability between biologic products, such as clinical switching studies, which could hinder bringing more biosimilars that can be interchanged to the market.
Critical differences in biosimilar regulatory pathways of the USA and the EU contribute towards biosimilar penetration in the respective regions. Inevitably, there is a need for biosimilars to treat chronic conditions at more affordable prices. Biologics patents have been expiring and continue to do so, leaving ample opportunity for the biosimilar market to grow. However, it is essential to have access to a more systematic approach to biosimilar development and rapid market access.
In addition to providing regulatory affairs and pharmacovigilance services, DDReg offers comprehensive support in biosimilar development by creating and validating regulatory strategies per stringent regulatory authority guidelines like the US FDA and EMA. Our team conducts a meticulous gap analysis to ensure compile dossiers that include the necessary data on manufacturing, pre-clinical & clinical testing per the regulatory requirements.
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