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

Mainly recombinant protein drugs

Recombinant protein drugs

• 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.

Authorized in the EU

Authorized in a region with a well-established regulatory framework

• Same standards required by the national regulatory agency for originator products.

• Full chemistry and manufacture data package.

• Primary and higher-order structure.

• Post translational modifications.

• Process-related and product-related impurities.

• In-vitro such as cell-based assays and receptor-binding studies.

Accelerated degradation studies and studied under various stress conditions

Accelerated degradation studies and studied under various stress conditions

• 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.

Pharmacodynamic (PD) markers should be selected and comparative PK/PD studies may be appropriate

Comparability margins should be pre-specified and justified

Observer or double-blinded. Equivalence or non-inferiority

• 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.

• 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.