Biosimilars Biosimilars The Evolving Pathway to Licensure The Evolving Pathway to Licensure BIO International Convention BIO International Convention June 28, 2011 June 28, 2011 David G. Adams David G. Adams Venable LLP Venable LLP 202- -344 344- -8014 8014 202 dadams@venable.com dadams@venable.com 1
Biologics Price Competition Biologics and Innovation Act Healthcare Reform Healthcare Reform – – Title VII Title VII Signed into law March 23 Signed into law March 23 Public Health Service Act Amended Public Health Service Act Amended New 42 U.S.C. 262(k) New 42 U.S.C. 262(k) Licensure of Licensure of “ “Biosimilar Biosimilar” ” and and “ “Interchangeable Interchangeable” ” Biological Products Biological Products 2 2 2
Two Standards for Licensure Two Standards for Licensure Biosimilarity Biosimilarity “ “Highly similar Highly similar” ” to reference product to reference product “ “Notwithstanding minor differences in clinically inactive Notwithstanding minor differences in clinically inactive components” ” components “ “No clinically meaningful differences No clinically meaningful differences” ” re safety, purity and re safety, purity and potency potency Interchangeability Interchangeability “ “Can be expected to produce the same clinical result Can be expected to produce the same clinical result” ” in in “any given patient any given patient” ” “ Risk of safety or diminished efficacy of alternating or Risk of safety or diminished efficacy of alternating or switching not greater than the risk of continued use of switching not greater than the risk of continued use of reference product reference product 3 3 3
Biosimilar Application Biosimilar Application Studies re characterization, safety, and Studies re characterization, safety, and efficacy efficacy Analytical studies to show Analytical studies to show “ “highly similar highly similar” ” Animal studies Animal studies Including assessment of toxicity Including assessment of toxicity Clinical study or studies Clinical study or studies including immunogenicity including immunogenicity stud(ies stud(ies) ) For one or more appropriate conditions of Reference For one or more appropriate conditions of Reference Product Product FDA can waive any of these study FDA can waive any of these study requirements requirements 4 4 4
Biosimilar Application Biosimilar Application Pediatric Studies required for approval of NDAs Pediatric Studies required for approval of NDAs Biosimilar considered to be new active ingredient Biosimilar considered to be new active ingredient Unless FDA determines Biosimilar to be Unless FDA determines Biosimilar to be “ “interchangeable interchangeable” ” Other Information Other Information Same Same mechanism(s mechanism(s) of action ) of action To extent known for Reference Product To extent known for Reference Product Conditions licensed for Reference Product Conditions licensed for Reference Product Same strength, dosage form, and route of administration Same strength, dosage form, and route of administration Manufacturing facility/processes Manufacturing facility/processes REMS if requested by FDA REMS if requested by FDA Optional information Optional information -- -- Interchangeability Interchangeability 5 5 5
More Restrictive than Hatch- -Waxman Waxman More Restrictive than Hatch Scheme Scheme No pathway analogous to 505(b)(2) No pathway analogous to 505(b)(2) No new condition of use No new condition of use No new active ingredient No new active ingredient No difference in strength, dosage form, route of No difference in strength, dosage form, route of administration administration No reliance on more than one Reference Product No reliance on more than one Reference Product No clinically meaningful differences in safety or No clinically meaningful differences in safety or efficacy efficacy 6 6 6
Exclusivity Exclusivity for Reference Product for Reference Product Exclusivity for original BLA licensure Exclusivity for original BLA licensure 12 12- -year delay in licensure of Biosimilar year delay in licensure of Biosimilar 4 4- -year delay in submission of Biosimilar year delay in submission of Biosimilar application application Delay calculated from date of original licensure of Delay calculated from date of original licensure of Reference Product Reference Product No new exclusivity for product changes made No new exclusivity for product changes made through license supplements through license supplements Pediatric and orphan exclusivity Pediatric and orphan exclusivity 7 7 7
Exclusivity Exclusivity for Modification for Modification Limited exclusivity for new BLA for modification to Limited exclusivity for new BLA for modification to previously licensed biologic previously licensed biologic Same sponsor Same sponsor or or Same manufacturer Same manufacturer Exclusivity only for: Exclusivity only for: Modification to Modification to “ “structure structure” ” that affects safety, purity, or that affects safety, purity, or potency potency “ “Non Non- -structural structural” ” change that change that does not does not result in new result in new indication, route of administration, dosing schedule, indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength dosage form, delivery system, delivery device, or strength Possible exclusivity for OTC switch, different safety or efficac Possible exclusivity for OTC switch, different safety or efficacy y profile, new sponsor and manufacturer profile, new sponsor and manufacturer 8 8 8
Exclusivity for Interchangeability Exclusivity for Interchangeability For first biosimilar determined interchangeable For first biosimilar determined interchangeable Delays determination of interchangeability for Delays determination of interchangeability for subsequent biosimilars subsequent biosimilars Periods of delay Periods of delay -- -- earlier of: earlier of: One year after the first commercial marketing One year after the first commercial marketing 18 months after final court decision or dismissal re all 18 months after final court decision or dismissal re all patents subject to infringement suit under patent patents subject to infringement suit under patent resolution provisions resolution provisions 42 two months after determination of interchangeability 42 two months after determination of interchangeability -- -- if lawsuit still pending if lawsuit still pending 18 months after licensure 18 months after licensure -- -- if no lawsuit filed if no lawsuit filed 9 9 9
Transitional Provisions for Protein Transitional Provisions for Protein Products Products Proteins and analogous products added to definition Proteins and analogous products added to definition of “ “biological product biological product” ” of Exception for chemically processed polypeptides Exception for chemically processed polypeptides Some classes of proteins historically approved as Some classes of proteins historically approved as drugs rather than licensed as biologics drugs rather than licensed as biologics Hormones Hormones Insulin Insulin 10 10 10
Transitional Provisions for Proteins Transitional Provisions for Proteins (cont.) (cont.) During 10 During 10- -year period following enactment: year period following enactment: NDA or ANDA can be filed for product within class of NDA or ANDA can be filed for product within class of proteins for which an NDA was approved prior to proteins for which an NDA was approved prior to enactment of biosimilar provisions enactment of biosimilar provisions Unless there is a BLA for an appropriate reference drug Unless there is a BLA for an appropriate reference drug 10 years after enactment date: 10 years after enactment date: Proteins approved as drugs deemed to be licensed as Proteins approved as drugs deemed to be licensed as biologics biologics No protein application can be submitted under drug No protein application can be submitted under drug approval provisions approval provisions 11 11 11
Other Provisions Other Provisions Patent resolution outside of FDA approval Patent resolution outside of FDA approval process process Processes for FDA guidance documents Processes for FDA guidance documents Public input Public input Process for FDA recommendation re user fees Process for FDA recommendation re user fees 12 12 12
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