Foreword
Joao Goncalves PharmD PhD Faculdade de Farmácia Universidade Lisboa , Portugal
Through history , the treatment of disease , while always multimodal , has been strongly influenced , and even dominated , by select therapeutic strategies over particular periods of time . This is now the case for biologics , which account for more than 50 % of new therapeutic entities under development , and of which monoclonal antibodies ( mAbs ) are the largest class .
Relative to small molecule drugs ( SMD ), biologic drugs are often more selective in their actions , which translates to an improved ratio of beneficial effects relative to unwanted toxicity . However , biologics are much larger , and much more complex , molecules than typical SMDs . Consequently , biologics could be most appropriately considered as complex distributions of molecular entities , rather than as unique chemical compositions . Variability exists within and between preparations of a biologic regarding post-translational modifications ( e . g ., the extent and nature of glycosylation and sialylation ), chemical modifications ( e . g ., deamidation and oxidation of labile functional groups ), presence of aggregates , and the presence of host cell proteins ( i . e ., proteins relating to the cells used for production of the biologic ). These and other product variables have been associated with significant effects on the pharmacokinetics , pharmacodynamics , immunogenicity , and safety of the biologic . As such , pharmacists , physicians , and other healthcare professionals have been faced with uncertainties regarding the safety and utility of preparations of biologics that are marketed as being ‘ biosimilar ’ to a reference product ( RP ).
A biosimilar is a biotherapeutic , intended to be highly similar to an already marketed RP and approved through a stringent regulatory process . Since the first biosimilar was approved , the biosimilar drug development arena has transformed . The regulatory perspectives have shifted with evolving science ; however , the key principles have remained the same , designed to ensure that the proposed biosimilar will not have any clinically meaningful differences in terms of its safety , immunogenicity and efficacy , compared with the RP .
A small molecule intending to be a generic product also undergoes a similar exercise ; however , it is well established that for most small molecules , an identical entity can be synthesised . This is not only due to the simplicity of the molecule but also the ability to characterise that the generic molecule is indeed identical to the RP . A battery of in vitro assays and a clinical pharmacokinetic bioequivalence study confirm biological equivalence . The in vitro tests and the bioequivalence studies serve as a surrogate for the confirmation that the small molecule generic will not have any meaningful differences in terms of its safety and efficacy to the small-molecule RP . Given the complexity and heterogeneity of most biologics , the term identical is not well suited , as it is not possible for any two batches ( even from the same manufacturer ) to be ‘ identical .’ The term equivalent is therefore replaced with ‘ similar .’ The requirements for demonstration of this ‘ similarity ’ are significantly more for a biologic compared with that for small molecules .
This handbook is therefore not intended to be a static educational exercise but a comprehensive overview of biopharmaceutical issues , regulatory processes , economic impact and practical use of biosimilars while also ensuring that the pharmacist can learn to apply this expertise to develop confidence in their
This resource will serve as an excellent primer for all pharmacists and clinicians as we move into what might become a new era of medicine ; an era dominated by the use of biologics and biosimilars use to optimise patient outcomes and provide cost-effective treatment . With a rising adoption of biosimilars in the US , the field is gathering even more momentum . A flourishing biosimilars market could broaden patients ’ access to advanced treatments at more affordable prices and alleviate healthcare costs . Payors and providers could use the savings to improve overall patient care .
This handbook also provides a practical and clinical perspective to the use of biologics , including consideration of controversial topics such as the interchangeability of RPs and biosimilars . In the case of interchangeablity , the European Medicines Agency and the Heads of Medicines Agencies have now issued a joint statement confirming that biosimilar medicines approved in the European Union ( EU ) are interchangeable with their reference medicine or with an equivalent biosimilar . While interchangeable use of biosimilars is already practised in many member states , this joint position harmonises the EU approach . It brings more clarity for healthcare professionals and thus helps more patients to have access to biologic medicines across the EU .
This resource will serve as an excellent primer for all pharmacists and clinicians as we move into what might become a new era of medicine ; an era dominated by the use of biologics and biosimilars . hospitalpharmacyeurope . com | 3