HPE Biosimilars in Oncology | Page 6

Biosimilar approval pathway ( 351 ( k )) The 351 ( k ) pathway was developed by the FDA after authorization through the BPCIA . This is the abbreviated pathway that is utilized by manufacturers to have a product reviewed by the FDA for approval as a biosimilar or interchangeable biosimilar . Unlike the ANDA process for small molecule drugs , the complexity of the biologic molecules and the manufacturing process makes it impossible to determine that a biosimilar will have no clinically meaningful differences to the reference product through a primary measure such as bioequivalence . Rather , the 351 ( k ) pathway relies on a stepwise , ‘ totality of evidence ’ approach and requires physicochemical analyses , animal studies , clinical studies evaluating immunogenicity , pharmacokinetics and pharmacodynamics , and limited safety and efficacy data in at least one condition approved for use for the reference product . The biosimilar must have the same mechanism of action , route of administration , dosage form , and strength for the indications being sought as the reference product . 26
Reference product This is the originator biologic that was licensed under the BLA . This application includes the full efficacy and safety data for registration under section 351 ( a ) of the Public Health Service Act . This is the product against which a proposed biosimilar product is compared . 6
Substitution Substitution is the FDA-preferred term that refers to a change in treatment by someone other than the prescriber and may be regulated by the law . Substitution is also termed non-medical or
An understanding of the terminology and definitions around biologics and biosimilars is critical in order to have a grasp of the regulatory processes and implementation considerations in their use administrative substitution . With small molecule generic products , substitution is common without the notification or intervention of the prescriber . The pharmacist can automatically substitute a generic product unless the prescriber or patient direct otherwise . However , with biologics and biosimilars , almost all States have developed regulations related to the substitution of biosimilars for the reference biologic . Generally , this is only permitted by a pharmacist without the intervention of the prescriber with an interchangeable biosimilar . Even in these cases , most States require the pharmacist to communicate with the prescriber and patient regarding the substitution . 27
Switching According to the BPCIA , the term switching is used when transitioning to or from a biosimilar that has been designated as interchangeable . Generally this refers to the situation where a patient is on a reference biologic and is switched ( often for cost reasons ) to a biosimilar . There have been theoretical concerns that switching may result in some risk of immunogenicity that could alter the efficacy or safety of the treatment . However , as more experience with biosimilars has been gained , it does not appear that there is significantly more risk in switching to a biosimilar than the risk of switching
28 – 30 between two lots of a reference biologic .
Conclusions An understanding of the terminology and definitions around biologics and biosimilars is critical in order to gain a grasp of the regulatory processes and implementation considerations in their use .
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