Introduction Hyrimoz ® , (GP2017 SDZ-ADL), is a biosimilar to Humira ® (REF-ADL). SDZ-ADL was approved in 2018 by both the United States Food and Drug Administration (US FDA) and European Medicines Agency (EMA) for the indications of REF-ADL not protected by orphan exclusivity. In 2023, the US FDA and EMA also approved a citrate-free high-concentration formulation (HCF) of SDZ-ADL. Totality of Evidence—the approach Approval of SDZ-ADL was based on data gathered using the US FDA, EMA and World Health Organization (WHO)-recommended step-wise Totality of Evidence approach. This approach is a robust dataset confirming high confidence in analytical, functional, pharmacokinetic (PK) and clinical biosimilarity between the biosimilar and reference medicine determined through analytical and clinical investigation. Evidence of biosimilarity Evidence supporting the biosimilarity of SDZ-ADL and REF-ADL was reported at each stage of investigation. Comprehensive comparative analytical and functional assessments demonstrated that SDZ-ADL was analytically indistinguishable from REF-ADL in required critical quality attributes, including receptor binding. Phase I clinical data showed PK similarity of SDZ-ADL and REF-ADL in healthy volunteers, with similar safety, tolerability and immunogenicity profiles. Phase III confirmatory efficacy and safety studies, ADACCESS (included in US/EU dossiers) and ADMYRA (separate to US/EU dossiers), both confirmed that SDZ-ADL’s efficacy, safety, and immunogenicity matched REF-ADL in all patient groups with no clinically meaningful differences. More recently, this data package was the basis for a citrate-free HCF of SDZ-ADL to be developed, and its PK, safety and immunogenicity were confirmed against the initially approved formulation of SDZ-ADL. Conclusion Overall, the Totality of Evidence provided for biosimilar adalimumab, SDZ-ADL, confirmed the analytical, functional and clinical similarity of SDZ-ADL to REF-ADL, supporting its regulatory approval and providing a data bridge with which to evaluate and support the approval of citrate-free HCF SDZ-ADL for clinical use. Plain Language Summary A biosimilar is a type of medicine that is designed to match the structure and function of a ‘reference’ biologic medicine. Hyrimoz ® (SDZ-ADL) is a biosimilar of the adalimumab reference medicine, Humira ® (REF-ADL). SDZ-ADL was approved in the US and Europe in 2018. For SDZ-ADL to be approved, a collection of evidence needed to be created, called the ‘Totality of Evidence.’ The purpose of this collection of data is to show there is a high confidence that the new biosimilar medicine matches the reference medicine, from the structure of the medicine to the effect of the medicine on the human body. For SDZ-ADL, this investigation started with comparing the physical structure and other functional properties of SDZ-ADL versus REF-ADL and ended with clinical studies in both healthy volunteers and in patients with diseases treated with adalimumab. This Totality of Evidence gathered for biosimilar adalimumab, SDZ-ADL, confirmed the similarity of SDZ-ADL to REF-ADL and therefore supported the approval of SDZ-ADL. In 2018, a citrate-free high-concentration version (high concentration formulation HCF) of REF-ADL was launched that matched REF-ADL. HCF REF-ADL has since become the primary formulation of REF-ADL used in practice. In 2023, a HCF version of SDZ-ADL was also approved in the US and EU based on evidence confirming that HCF SDZ-ADL matched SDZ-ADL. As SDZ-ADL had been previously confirmed to match the reference medicine, this meant that HCF SDZ-ADL could be directly compared against SDZ-ADL to confirm biosimilarity and support its approval.