Clinical development of biosimilars and key concepts
Biosimilars have transformed the treatment landscape in many therapy areas enabling clinicians to treat more patients . Regulatory approval of biosimilars requires demonstration of comparable clinical efficacy and safety with the reference biologic and the key steps in the process are described in this article
Irene Krämer PhD Pharmacy Dept , University Medical Center , Johannes Gutenberg- University , Mainz , Germany
A biosimilar is a highly similar version of an already approved biologic reference product ( RP ). 1 The active substance is manufactured using biotechnological processing , invariably recombinant DNA technology with mammalian host cells ( see article on manufacturing in this handbook ). Full data on the pharmaceutical quality plus additional quality studies comparing the structure and biological activity of the biosimilar with the RP are required for regulatory approval of biosimilars . The quality of the final product is assessed by checking the physicochemical properties , biological activity , purity , sterility , and stability . In contrast to generic medicinal products , which contain the same chemically-synthesised molecule , slight biological differences between a biosimilar and its RP mandate comparative pharmacokinetic and pharmacodynamic studies .
Key considerations in development The key considerations in development are :
• Characterisation
• Quality comparability
• Functional comparability
• Clinical comparability .
For more complex biologic medicines , efficacy , safety , and immunogenicity are demonstrated with comparative clinical studies . 2 , 3 However , confirmatory clinical trials with the biosimilar are not needed for every approved indication of the RP . After demonstration of biosimilarity in one ( generally the most clinically sensitive ) indication , extrapolation of the data to other indications is possible if the scientific evidence available addresses all specific aspects of these indications . 1 After approval , the safety of the RPs and biosimilars is monitored through the same pharmacovigilance activities . The different types and order of studies required for approval of RPs and biosimilars are illustrated in Figure 1 . 2
Licensing procedures of biosimilars are generally based on an assessment of comparability in quality , non-clinical and clinical studies . 2
Comparability Regulatory development for biosimilars differs from that required for the biologic RP . Whereas RP approval is a step-wise process based on preclinical evaluations and large-scale clinical trials , evaluation of biosimilars follows a ‘ totality of evidence ’ approach , which is a largely
FIGURE 1
Studies required for approval of the reference product and biosimilar ( adapted from 2 )
Risk management plan Risk management plan
Clinical studies
• Safety and efficacy
• PK / PD
• Immunogenicity
Comparative clinical studies
• Safety and efficacy
• PK / PD
• Immunogenicity
Comparative non-clinical studies
Non-clinical studies Comparative quality studies
Pharmaceutical quality studies Pharmaceutical quality studies
Reference product Biosimilar medicine hospitalpharmacyeurope . com | 9