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product is expected to produce the same clinical result as the reference product in any given patient . This is expected even if a patient is switched back and forth between the reference product and the interchangeable biosimilar . The intent of the interchangeable product designation is that these products could be substituted at the pharmacy without the input of the prescriber . Therefore , biosimilar products may not be substituted without contacting the prescriber , or unless established within a health system ’ s internal formulary protocols approved by the medical staff .
Interchangeable biosimilars must meet the same requirements as biosimilars but are subject to additional regulatory requirements to prove no differences in outcomes or toxicities for patients when switching between the reference product and the biosimilar . The guidance for the interchangeable product designation was not finalized until May 2019 . 19 At time of writing , three biosimilars approved in the US ( in inflammatory disease , diabetology and ophthalmology ) have received the interchangeable product designation . The lack of an interchangeable designation does not mean that patients cannot be safely switched from a reference product to a biosimilar . In fact , two large analyses of switching studies have provided reassurance that the risk of immunogenicity-related safety concerns or diminished efficacy with a single switch from a reference biologic to a biosimilar is negligible or
20 , 21 absent .
Naming conventions A contentious issue in the biosimilar approval process is naming . In order to assure that products can be clearly distinguished for pharmacovigilance purposes , a naming convention that can support this is required . The FDA has decided that new biologics and biosimilars will be differentiated by assigning each a unique name consisting of a core name and an FDA-designated suffix ( for example , replicamabcznm ). The suffix must :
• Be unique and consist of four lower case characters that are ‘ devoid of meaning ’
• Be non-proprietary
• Have at least three characters that are distinct
• Be attached to the core name by a hyphen
• Be free from legal barriers that would restrict its use . 22
Subsequently the FDA determined that biologics that were previously approved would not need to be renamed retrospectively . This approach has been criticized because the complexity of the name could make it difficult to clearly communicate between healthcare professionals and patients . Furthermore , the use of a non-memorable suffix might actually lead to errors in selecting the wrong product . 23
Biobetters Finally , one of the strategies that has been developed by manufacturers to fend off biosimilar competition is to develop related biologics that have been ‘ improved ’ from the originator biologic . Often referred to as ‘ biobetters ’, these improvements could include new strengths or formulations that could impact the route or rate of administration , the tolerability of the product , or the duration of action ( for example , pegylation to increase halflife ). 24 These biobetter products are not biosimilars because they are not expected to produce the same clinical efficacy and safety as the reference biologic . Therefore , these products must go through the full BLA licensing process for approval .
Conclusions Healthcare professionals should have a thorough understanding of the regulatory framework for the approval of biosimilars and interchangeable products . They should be able to discuss issues around the overall regulatory approach including the requirements for clinical trials , the process of indication extrapolation , issues around interchangeability and switching , and the need for pharmacovigilance . This knowledge will enable better clinical and formulary decision-making , and improve communication regarding biosimilars with patients .
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