Sponsored – Biosimilars: Production to patient | 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 .
References 1 IQVIA . Medicine use and spending in the US : A review of 2017 and outlook to 2022 institute report . www . iqvia . com / insights / the-iqvia-institute / reports / medicine-use-and-spending-inthe-us-review-of-2017-outlookto-2022 ( accessed August 2020 ). 2 Brill A , Ippolito B . The economics of biologic drugs : A further response to Bach et al . Health Affairs Blog . www . healthaffairs . org / do / 10.1377 / hblog20190807.554429 / full / ( accessed August 2020 ). 3 Food and Drug Administration . Implementation of the Biologics Price Competition and Innovation Act of 2009 . www . fda . gov / drugs / guidance-compliance-regulatoryinformation / implementationbiologics-price-competition-andinnovation-act-2009 ( accessed August 2020 ). 4 Food and Drug Administration . Biological product definitions . www . fda . gov / files / drugs / published / Biological-Product- Definitions . pdf ( accessed August 2020 ). 5 Food and Drug Administration . Drugs @ FDA Glossary of terms . www . fda . gov / drugs / drugapprovals-and-databases / drugsfda-glossary-terms ( accessed August 2020 ). 6 Food and Drug Administration . Biosimilar and interchangeable products . www . fda . gov / drugs / biosimilars / biosimilarand-interchangeableproducts # reference ( accessed August 2020 ). 7 Generics and Biosimilar Initiative GaBi Online . FDA definitions of generics and biosimilars . http :// gabionline .
net / Biosimilars / General / FDAdefinitions-of-generics-andbiosimilars ( accessed August 2020 ). 8 Academy of Managed Care Pharmacy Biosimilars Resource Center . What is a biobetter ? www . biosimilarsresourcecenter . org / faq / what-is-a-biobetter / ( accessed August 2020 ). 9 Drug Discovery & Development . Next generation of biosimilars and biobetters : challenges and opportunities . www . drugdiscoverytrends . com / next-generation-of-biosimilarsand-biobetters-challenges-andopportunities / ( accessed August 2020 ). 10 Food and Drug Administration . Guidance for industry : Q8 ( R2 ) Pharmaceutical Development . Revision 2 . www . fda . gov / media / 71535 / download #:~: text = Critical % 20 Quality % 20Attributes % 20 ( 2.2 ), ensure % 20the % 20 desired % 20product % 20quality ( accessed August 2020 ). 11 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use . ICH Harmonised Tripartite Guideline . Pharmaceutical Development Q8 ( R2 ). https :// database . ich . org / sites / default / files / Q8 _ R2 _ Guideline . pdf ( accessed August 2020 ). 12 Ramanan S , Grampp G . Drift , evolution , and divergence in biologics and biosimilars manufacturing . BioDrugs 2014 ; 28:363 – 72 . 13 Wong HK . Will product drift cause a rift ? Pharma Manufacturing 2019 . www . pharmamanufacturing . com /
articles / 2019 / will-product-driftcause-a-rift / ( accessed August 2020 ). 14 Tesser JRP , Furst DE , Jacobs I . Biosimilars and the extrapolation of indications for inflammatory conditions . Biologics 2017 ; 11:5 – 11 . 15 Food and Drug Administration . Immunogenicity assessment for therapeutic protein products . https :// www . fda . gov / media / 85017 / download ( accessed August 2020 ). 16 Boehncke WH , Brembilla NC . Immunogenicity of biologic therapies : causes and consequences . Expert Rev Clin Immunol 2018 ; 14:513 – 23 . 17 Food and Drug Administration . Considerations in demonstrating interchangeability with a reference product : Guidance for industry . www . fda . gov / media / 124907 / download ( accessed August 2020 ). 18 Food and Drug Administration . Biosimilar and interchangeable biologics : More treatment choices . https :// www . fda . gov / consumers / consumer-updates / biosimilar-and-interchangeablebiologics-more-treatmentchoices ( accessed August 2020 ). 19 Food and Drug Administration . New drug application ( NDA ). www . fda . gov / drugs / typesapplications / new-drugapplication-nda ( accessed August 2020 ). 20 Food and Drug Administration . Abbreviated approval pathways for drug product : 505 ( b ) ( 2 ) or ANDA ? www . fda . gov / drugs / cder-small-businessindustry-assistance-sbia / abbreviated-approval-pathwaysdrug-product-505b2-or-anda-
september-19-2019-issue ( accessed August 2020 ). 21 Food and Drug Administration Abbreviated New Drug Application ( ANDA ). www . fda . gov / drugs / types-applications / abbreviated-new-drugapplication-anda ( accessed August 2020 ). 22 Alabanza A . What are the regulatory differences between an NDA and BLA ? Nuventra Pharma Sciences . www . nuventra . com / resources / blog / regulatorydifferences-between-an-nda-bla / ( accessed August 2020 ). 23 Food and Drug Administration . Therapeutic Biologics Applications . www . fda . gov / drugs / types-applications / therapeuticbiologics-applications-bla ( accessed August 2020 ). 24 Food and Drug Administration . Biologics License Applications ( BLA ) Process ( CBER ). https :// www . fda . gov / vaccines-bloodbiologics / development-approvalprocess-cber / biologics-licenseapplications-bla-process-cber ( accessed August 2020 ). 25 Koyfman H . Biosimllarity and interchangeability in the Biologics Price Competition and Innovation Act of 2009 and FDA ’ s 2012 Draft Guidance for Industry . Biotechnol Law Rep 2013 ; 32:238 – 51 . 26 Hung A , Vu Q , Mostovoy L . A systematic review of US biosimilar approvals : What evidence does the FDA require and how are manufacturers responding ? J Manag Care Spec Pharm 2017 ; 23:1234 – 44 . 27 National Conference of State Legislatures . State laws and legislation related to biologic medications and substitution
of biosimilars . https :// www . ncsl . org / research / health / statelaws-and-legislation-relatedto-biologic-medications-andsubstitution-of-biosimilars . aspx ( accessed August 2020 ). 28 Edwards CJ et al . Switching to biosimilars : current perspectives in immune-mediated inflammatory diseases . Expert Opinion Biol Ther 2019 ; 10:1001 – 14 . 29 Barbier L et al . The efficacy , safety , and immunogenicity of switching between reference biopharmaceuticals and biosimilars : A systematic review . Clin Pharmacol Ther 2020 ; published online 31 March 2020 . 30 Cohen HP et al . Switching reference medicines to biosimilars : A systematic literature review of clinical outcomes . Drugs 2018 ; 78:463 – 8 .
6 | 2021 | hospitalpharmacyeurope . com