HPE HPE Fresenius Kabi handbook - Page 25

on the long-term efficiency and safety of biosimilars. Because different manufacturing and purification processes, and even distinct storage conditions and distribution chains, make it almost impossible to replicate the reference molecules, there are currently concerns regarding the structure, purity, and immunogenicity of the biosimilars. In addition, different biosimilars for the same reference product may present varying features and may not be interchangeable. Despite the much anticipated reduced healthcare costs associated with the use of these molecules, which partially result from the less extensive clinical development program required to support product registration with the regulatory authorities (evaluation of the similarity of physicochemical, preclinical, and clinical data only), biosimilar products may impact clinical practice and patients in other ways. 2,3 Immunogenicity, thought to be a function of a molecule’s physicochemical features, is a key safety item from the regulatory point of view and can be determined using in vitro (recognition and binding assays with an array of antibodies against the drug) and in vivo (cross-reactivity assay of anti-drug antibodies isolated from treated patients) methods. However, negative results in vitro may not necessarily exclude immunogenic responses in actual patients, and the immunogenicity might not be comparable across studies due to differences in methodologies, patient populations, prior exposure to the reference product, concomitant drug use, and the disease itself. For these reasons, immunogenicity testing is a requirement in safety evaluations as well as in post-marketing pharmacovigilance programmes. 2,4 Clinicians must also be aware of how biosimilars can affect patient adherence to treatment so that potential issues can be addressed early on, before any switch from a branded drug to its copy (in particular how patients view these replacement drugs in terms of potency and efficacy). 1 Many factors are known to contribute to poor adherence, including difficulties administering a drug, and inconvenient, complex, and strict regimens. However, patients’ attitudes towards medications can also negatively impact the way they feel about their new treatment regimens (for example, uncertainty about the quality of the replacement drug, fear of side effects, difficulties using a new delivery system). 5 Educational initiatives focusing on the science behind the manufacturing process and on the available clinical experience with biosimilars are therefore needed and can ultimately lead to improved treatment plans, and subsequently clinical outcomes, for patients together with improved treatment adherence. 3 Increased awareness of these drugs, how they are developed, and the current regulatory framework, can play a significant role in increasing confidence regarding their use, not only for clinicians but also for patients Pharmacists As for clinicians, pharmacists need to be aware of the potential benefits and concerns of biosimilars because they are likely to see increasingly higher numbers of prescriptions for these drugs in the next years as the patents and exclusivity periods for several biologics expire, hence the need to be able to provide recommendations regarding optimal use for patients. 1 This is of particular relevance in countries such as the USA, where pharmacists are allowed to fill a prescription with the brand drug or a replacement without consulting the physician or the patient. In some countries, insurance plans or governmental directives may even mandate a switch to a biosimilar whenever possible in order to reduce the burden to healthcare systems. However, switching from branded drugs to biosimilars has been reported to affect dosing accuracy and adherence in some cases, resulting in dosing errors or treatment lapses. 5 Pharmacists should be aware that questions about interchangeability (the practice of substituting one drug for another with the same clinical effects under similar conditions by the prescriber or with his/her agreement), switching (the practice of substituting one drug for another with the same therapeutic intent), and automatic substitution (the practice of substituting one drug for another interchangeable drug at the pharmacy level without consulting the prescriber), as defined in the EU, still persist and that these practices are not consistent between countries. 4 Switching and substitution can in fact constitute a cause of anxiety for patients who have doubts about the efficacy and safety of biosimilars and who may associate unrelated, undesirable events with the new regimen. In addition, nomenclature and traceability are particularly important for pharmacists to facilitate the identification of the active ingredient, and pharmacovigilance programmes should distinguish between the brand names of the biosimilar and reference drug, including batch manufacturing information. 4 Patients The main advantage of biosimilars is the potential to provide similar clinical benefits with cost savings, thereby allowing more patients to have access to treatments that might otherwise be a prohibitive expense in the long term, with limited availability and accessibility due to restrictions in insurance and public payer coverage, limited reimbursement, and high out-of-pocket costs. Inadequate insurance hospitalpharmacyeurope.com | 2019 | 25