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Table 1 Comparison of requirements for the evaluation of SEBs between different regions [13]

From: Potential impact of subsequent entry biologics in nephrology practice in Canada

  EU Australia Japan WHO Canada Korea, India, Singapore, Malaysia
Synonym Biosimilars Biosimilars Follow-on Biologics Similar Biotherapeutic Product Subsequent Entry Biologic Biosimilars
Scope Mainly recombinant protein drugs Recombinant protein drugs
Principles • Generic approach is not appropriate for SEB.
• SEB should be similar to the reference biologic with respect to quality, safety and efficacy.
• Step-wise comparability approach: the reduction of non-clinical and clinical data required will only be considered after the similarity of the SEB and reference biologic is proven in terms of quality.
• Case by case approach for different classes of products.
• Pharmacovigilance is stressed.
Reference product Authorized in the EU Authorized in Japan Authorized in a region with a well-established regulatory framework
Manufacture • Same standards required by the national regulatory agency for originator products.
• Full chemistry and manufacture data package.
Physio-chemical • Primary and higher-order structure.
• Post translational modifications.
Purity • Process-related and product-related impurities.
Non clinical • In-vitro such as cell-based assays and receptor-binding studies.
Stability Accelerated degradation studies and studied under various stress conditions Not necessary Accelerated degradation studies and studied under various stress conditions
Pharmacokinetic study design & criteria • Single dose, steady-state studies or repeated determinations of pharmacokinetics
• Cross over or parallel.
• Include absorption and elimination characteristics.
• Use the traditional 80-125% equivalence range.
PD Pharmacodynamic (PD) markers should be selected and comparative PK/PD studies may be appropriate
Efficacy Comparability margins should be pre-specified and justified Observer or double-blinded. Equivalence or non-inferiority Equivalence
Safety/pharmacovigilance • Pre-licensing safety data and risk management plan. Post authorization safety and/or efficacy studies may be required.
• Adverse reactions must be reported.
• Same rules apply to reference biologic and SEB.
INN vs. new generic name INN Unique generic name Suffix “BS” added to INN INN with biological qualifier (proposed) INN but will follow WHO guidance INN
Extrapolation of indications • Assessed on a case-by-case basis.
• At least one clinical study required in the most sensitive population measuring the clinical endpoints likely to show a difference.
  1. Adapted from [13].