HPE Biosimilars: Where are we and what is next? - Page 13

In addition , biosimilars have benefited from dramatic improvement of the industrial purification technologies developed in the two last decades ( such as nanofiltration ) and of the analytical methods for determining the nature and the size distribution of aggregates . 18 This can also be said for HCPs , such as the generalisation of the industrial purification proteins by affinity chromatography on protein A columns that eliminate nearly all the foreign proteins . These methods were often not available for originator biologics . Thus , it can be shown that biosimilars are have fewer impurities and variabilities from batch to batch than for the originator . As an example , the in vitro anti-TNFα activity of the originator etanercept ( Enbrel ® ) can vary from batch to batch by ± 25 % of the theoretical value ; ( range 75 – 127 for a normalised value of 100 ). However , GP2015 , a biosimilar accepted by the EMA , varies by only ± 5 % ( 93 – 102 ). 19
The other causes of immunogenicity do not depend on the biologic used but on factors that are only related to the patients and their pathology . For example , immunogenic-related side effects of rituximab originator and the biosimilar CT-P10 are about 4 % in patients treated for follicular lymphoma regardless of the drug , but reach 27 % for originator and 13 % for the biosimilar in patients treated for rheumatoid arthritis . 20 This can be also observed for another mAbs such as infliximab , adalimumab and etanercept .
A study has demonstrated that the human immune system is not able to differentiate between biosimilars and originator despite its inherent sensitive to subtle differences between antigens . In this study , sera from patients with inflammatory bowel disease were cross-reactive with infliximab originator and CT-P13 , respectively , demonstrating that the ADAs formed by the immune system recognised the infliximab originator and biosimilar as identical , 21 , 22 providing absolute proof of similarity of their antigenic properties .
Conclusions Because scientific data and real-life clinical experiences show that biosimilars have the same efficacy and safety profile as the corresponding originators , there is no great reason not to use them widely . However , the implementation of biosimilars varies dramatically from country to country . Incentive policies applied to biosimilars were found to be heterogeneous across countries , and uptakes of biosimilars were also heterogeneous between different therapeutic classes and countries . 23
The acceptance rate for biosimilars seems to be governed mainly by the prescriber ’ s environment . Indeed , in hospital , the use of drugs is highly regulated , depending on the drug and therapeutic committee and the tenders , the prescribers , the role of the pharmacy team , the medical organisation itself , the financial benefits of biosimilars , and the incentive policies at local or national levels . Taken together , these regulatory systems can remove any potential conflicts of interest against the implementation of biosimilars . By contrast , when biologics are mainly prescribed by the community doctors and dispensed by community pharmacies , the penetration of biosimilars is dramatically lower because it is largely non-regulated . Moreover , there is currently a wide gap in terms of policies to support the adoption of biosimilars between countries ( some offering more incentives than others ). The heterogeneity of healthcare systems , as well as the physician prescribing culture and practice , and the level of knowledge and the influence of pharmacists , could also explain the different uptake by country .
However , as pointed out by Moorkens et al , 24 the main hurdles in all countries remain a poor knowledge of biosimilars among key stakeholders , and the lack of education , especially for physicians and patients . Thus , it is crucial to improve knowledge of biosimilars for the prescribers , who are the key stakeholders . Pharmacists are ideally situated to provide patient education at both the hospital and community levels . Therefore , continuous education about the structure of biologic drugs , their unique properties and their pharmacological actions and safety profiles is crucial for pharmacists and should be encouraged . For example , the European Society of Oncology Pharmacy has developed a 25-hour learning module on biologics , which is included in its 100-hour education programme , EUSOP ( European Specialisation in Oncology Pharmacy ).
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