steven d. lucio, pharmd, bcps

11/16/2015

1

STEVEN D. LUCIO, PHARMD, BCPSSENIOR DIRECTOR OF CLINICAL SOLUTIONS AND

PHARMACY PROGRAM DEVELOPMENTNOVATION, LLC

Biologics and Biosimilars: Preparing for the Future

LEARNING OBJECTIVES

1. Define “biosimilar” based current FDA guidance and describe similarities and differences between biosimilar and originator biologic agents

2. Review key aspects of the comparability exercise for approval of biosimilarsper current FDA guidance

3. Evaluate experience with biosimilars in the EU

4. Describe current and emerging biosimilars in the US

Learning Objectives

Top Pharmaceutical Sales (2014 vs 2010)

2014 2010

Drug ManufacturerUS Sales (millions)

Drug ManufacturerUS Sales (millions)

1 SMSofosbuvir (Sovaldi®)

Gilead $10,098 1 SMClopidogrel (Plavix®)

BMS $6,154

2 BAdalimumab (Humira®)

AbbVie $6,078 2 SMAtorvastatin (Lipitor®)

Pfizer $5,329

3 SMGlargine insulin (Lantus®)

Sanofi $5,759 3 SM

Fluticasone/ salmeterol inhaler (Advair®)

GSK $4,026

4 BEtanercept (Enbrel®)

Amgen $4,311 4 SM Aripiprazole (Abilify®)

Otsuka $3,606

5 BInfliximab (Remicade®)

J & J $4,154 5 SM Pioglitazone (Actos®)

Takeda $3,582

6 SMAripiprazole (Abilify®)

Otsuka $3,886 6 B Etanercept(Enbrel®)

Amgen $3,304

7 BRituximab (Rituxan®)

Roche $3,707 7 SM Montelukast(Singulair®)

Merck $3,219

8 BPegfilgrastim (Neulasta®)

Amgen $3,523 8 SMQuetiapine (Seroquel®)

AstraZeneca $3,107

9 SMFluticasone/ salmeterol (Advair®)

GSK $3,325 9 B Infliximab (Remicade®)

J & J $3,099

10 BBevacizumab(Avastin®)

Roche $2,928 10 BBevacizumab (Avastin®)

Roche $3,068

SM = small molecule drug, B = biologic drug

EvaluatePharma. Available at info.evaluategroup.com/rs/evaluatepharmaltd/images/SV2014.pdf. Accessed July 2015.

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Globally, Biologics Share of Total Prescription Medicine Sales is Increasing

11%

15%

18%

19‐20%

0

5

10

15

20

25

2002 2007 2012 2017

Biologics Share of T

otal S

ales (%

)

IMS Health. http://www.imshealth.com. Accessed June 2015.

Projected

The Patent Cliff and Growth Potential for the Biosimilars Market

Adapted from IMS Health. http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Healthcare/Life%20Sciences%20Solutions/Generics/IMSH_Biosimilars_WP.pdf. Accessed June 2015.

9.1

7.7

7.5

7.1

6.2

5.6

5.4

5.1

4.7

4.2

4.2

0 1 2 3 4 5 6 7 8 9 10

Adalimumab (Humira)

Etanercept (Enbrel)

Infliximab (Remicade)

Insulin Glargine (Lantus)

Rituximab (Mabthera)

Bevacizumab (Avastin)

Interferon Beta‐1A (Avonex, Rebif)

Trastuzumab (Herceptin)

Glatiramer Acetate (Copaxone)

Ranibizumab (Lucentis)

Pegfilgrastim (Neulasta)

Global Sales 2013, US$ BillionEU Expiry

DateUS Expiry

Date

2018 2016

2015 2028

2015 2018

Expired Expired

Expired 2016

2019 2017

Expired Expired

Expired 2019

2015 Expired

2016 2016

2015 Expired

Biosimilars are Projected to Moderate Drug Expenditures and Expand Patient Access to Biologics

• Continuing growth in US prescription drugs1

– Top drugs for 1st 9 months of 2014 based on expenditures

In clinics: infliximab, pegfilgrastim, epoetin alfa

In hospitals: infliximab, rituximab, pegfilgrastim

– 7–9% projected increases in total drug expenditures for 2015 across all settings

• Biosimilars are predicted to lead to a $44.2 billion reduction(range $13‐$66 billion) in direct spending on biologic drugs from 2014‐20242

1. SchumockGT, et al. Am J Health‐Syst Pharm. 2015;72:e19‐38.2. MulcahyAW, et al. http://www.rand.org/content/dam/rand/pubs/perspectives/PE100/PE127/

RAND_PE127.pdf. Accessed June 2015.

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Small Molecule Drugs vs. Biologics

Mellstedt H. EJC Supplements. 2013;11:1‐11.

Unlike Producing Small Molecule Drugs, the Manufacturing Process for Biologics is Complex

Mellstedt H, et al. Ann Oncol. 2008;19:411‐419.

Cloning into DNA VectorTransfer into Host Cell

ExpressionScreening / Selection

Cell Productionin Bioreactors

Purification Through

Chromatography

CellExpansion

Recovery ThroughFiltration or

Centrifugation Characterizationand Stability

PurifiedBulk Drug

Originator Manufacturing Process Changes

• Small modifications may result in gradual changes

• Despite these differences, when the products are within a prespecified acceptable range, the products are marketed with no change in label

• If large alterations occur, analytical studies (and possibly additional clinical studies) are required to compare post‐change product with existing pre‐change product

Capillary ZoneElectrophoresis

Cation ExchangeChromatography

Glycan MappingChromatogram

Pre‐change

Post‐change

Post‐change

Pre‐change

Pre‐change

Post‐change

54

3

2

1

6

7

Time, min Time, min Time, min

18 22 26 30 34 38 42 46 14 18 22 26 30 10 15 20 25 30 35 40

Acidicvariants

Basicvariants

G0

G2

G2F

Man5

G0F(1,6)G1F

(1,3)G1F

Schiestl M, et al. Nature Biotechnology. 2011;29(4):310‐312.

Darbepoetin alfa Rituximab Etanercept

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Reference Biologics and Post‐Approval ‘Life Cycle’ Changes

0 5 10 15 20 25 30 35 40

Rituximab

Infliximab

Etanercept

Adalimumab

Abatacept

Changes in Manufacturing Process After Approval

Schneider CK. Ann Rheum Dis. 2013;72:315‐318.

Differences BetweenChemical Drugs and Biologics

Chemical Drugs Biologics

Size Small, low molecular weight Large, high molecular weight

Structure Simple, well‐defined Complex, heterogeneous

Manufacturing

• Reproducible chemical reactions

• Identical copies can be made

• Living cells or organisms

• Impossible to ensure identical copies

Characterization Completely characterizedImpossible to fully characterize molecular composition

Stability StableUnstable, sensitive to external conditions

Immunogenicity Mostly non‐immunogenic Immunogenic

Declerck PJ. GaBI Journal. 2012;1(1)13‐16.

Pathways for Approval in the US

DRUGS• Small‐molecules• Approved via FDCA

BIOLOGICS• Proteins• Approved via PHSA

New Drug Application

(NDA)

Safety and Efficacy must be

demonstrated

Abbreviated New Drug Application

(ANDA)

Bioequivalence must be

demonstrated

Biologics License Application (BLA)

351(a)

Safety and Efficacy must be

demonstrated

Biosimilar Biologics License Application

351(k)

Must demonstrate that it is highly

similar to reference

Interchangeable biosimilars require

more data

Extensive comparability exercise addresses drift (Q5E)

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Biosimilars are NOT Generics of Existing Biologics

• Traditional generic drugs are exact copies of existing drugs

• However, biosimilars are much bigger than a typical genericcopy of a small molecule

• Biologics are also made up of amino acids, which form uniquefolds and glycosylation patterns may also vary

• Therefore, they are muchmore complex

• Combined with the complicated manufacturing process, anexact copy of a biologic cannot be made

Weise M, et al. Blood. 2012;120:5111‐5117.

• Signed into law on March 23, 2010

• Created the 351(k) or “biosimilar” pathway granting FDA authority to approve “highly similar” versions of previously approved reference biologics

• Intended to be an “abbreviated” process

• Biosimilar applicants must be able to ensure safety, purity and potency of their products

Biologics Price Competition and Innovation Act of 2009

FDA. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/UCM216146.pdf. Accessed July 2015.

Definitions

Per the FDA, Biosimilar or Biosimilarity means:

• That the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; and

• There are no clinically meaningful differencesbetween the biological product and the reference product in terms of the safety, purity, and potency of the product

FDA. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htm. Accessed June 2015.

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FDA Specifications for Biosimilars vs. Reference Biologic

Biosimilar ProductSpecification

Comparisonwith Reference

Formulation May be different

Delivery device/container May be different

Routes of administrationMay obtain licensure for fewer than all routes of administration for which reference product is licensed

Conditions of useMay obtain licensure for fewer than all conditions of use for which reference product is licensed

Strength Must be the same

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/ucm290967.htm

Biologics: A Regulatory Perspective

351(a)Originator

351(k)Biosimilar

351(k)Interchangeable Biosimilar

351(a)Non‐originator Biologic

351(a)Next‐generation “Bio‐better”

Description First‐tomarket biologic molecule; will likely be the reference product

“Highly similar” to reference product; approved via biosimilarspathway

A biosimilar deemedthat can be substituted for the reference without permission from prescriber

It is “another brand name” of an already approved biologic

Biologic that has been altered to achieveimproved clinical outcomes

Depth of data submitted to the FDA

“Standard” data package: efficacy and safety

Abbreviateddata package for comparability

Abbreviated data package for comparability; more information on efficacy and safety

“Standard” datapackage: efficacy and safety

“Standard” datapackage: efficacy and safety

Compared to originator?

N/A Yes Yes Yes or no Likely (standard of care)

Implications Biosimilar pricing; explicit regulatoryoversight on comparison with reference; possible pharmacist substitution (for interchangeable); potential for indication extrapolation

Different pricingstructure; substitution issues; cannot extrapolate indications

New entity

Adapted from: Lucio et al. Am J Health Syst Pharm. 2013;70(22):2004‐2017.

Biologics: A Regulatory Perspective (G‐CSF Example)

351(a)Originator

351(k)Biosimilar

351(k)Interchangeable Biosimilar

351(a)Non‐originator Biologic

351(a)Next‐generation “Bio‐better”

BiologicFilgrastim(Neupogen)

Filgrastim‐sndz(Zarxio)

None yet approvedTbo‐filgrastim(Granix)

Pegfilgrastim(Neulasta)

Original Date of Approval

February 20,1991

March 6, 2015 N/A August 29, 2012 January 31, 2002

www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed July 2015.

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Demonstrating Biosimilarity:General Principles

• The clinical efficacy and safety of the biologic molecule has already been demonstrated (ie, by the innovator)

• The biosimilar sponsor only requires evidence that the candidate biosimilar is not significantly different from the reference product

– Goal is not to replicate unnecessary clinical trials

– Smaller‐scale direct comparisons and extrapolation

• When a biosimilar is approved, there should not be an expectation that there will be differences in safety and efficacy

FDA. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htm. Accessed June 2015.

Biosimilar Evaluation–Step‐wise Totality of Evidence Approach

Clinical

Animal Studies

Clinical Immunogenicity

Clinical Knowledge (post‐market experience)

Human PK/PD

Structural and Functional Characterization

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htm

Comparative Analytical Data

Structural Analyses

• Primary structures (aasequence)

• Higher order structures (including aggregation)

• Enzymatic post‐translational modifications (such as glycosylation, phosphorylation)

• Other variations, modifications

Functional Assays

• In vitro– Biological assays

– Binding assays

– Enzyme kinetics

• In vivo– Animal models of disease


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Analytical Studies are the Foundation for Biosimilar Development

• If extensive structural and functional comparability assessment does not reveal significant differences between a biosimilar and reference biologic, it is highly unlikely that trials in patients would uncover any difference in safety and efficacy

De Mora F. Br J Clin Pharmacol. 2015 Apr 11. [Epub ahead of print]Weise M, et al. Blood. 2014;124:3191‐3196.

©2014 Novation Confidential.23

What are We Measuring When We Evaluate Biologics?

Schiff M, et al. Ann Rheum Dis. 2014;73:86‐94.

Animal Data

• Animal toxicity studies

– Useful when uncertainties remain about the safety of the proposed product prior to initiating clinical studies

• Animal PK and PK measures*

• Animal immunogenicity assessments*


*may be useful in some circumstances

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Clinical Studies

• Clinical study(ies) should be designed to establish statistical evidence that the proposed product is neither inferior to the reference product by more than a specified margin nor superior to the reference product by more than a specified margin


Clinical Studies

Li EC, et al. Drug DiscovToday. 2015;20(S2):1‐9.http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ ucm290967.htm

Endpoints and study populations are selected that will be clinically relevant and sensitive in detecting clinically meaningful differences

Extrapolation of Indications

Extrapolation of data from a clinical trial of a biosimilar conducted in one disease to support approval for additional indications for which the reference product is already licensed

• Factors to be considered:

– Clinical experience with the reference product

– Mechanism(s) of action in each indication

– Target receptors

– Product structure and target/receptor interactions

– PK and biodistribution in different patient populations

– Differences in the safety/immunogenicity profile between indications

Weise M, et al. Blood. 2014;124:3191‐3196.http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htm

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The Challenge of Biosimilar Extrapolation?


Does comparability here →

Equal comparability here? →

Scott BJ, et al. J Clin Pharmacol. 2015;55(S3):S123‐32.

The Challenge of Biosimilar Extrapolation?


What Can We Learn From Europe?

• “Biosimilars have been on the

European Market for several years

and have performed as expected in

all licensed indications, including

extrapolated indications.”

• “In our view, generation of

redundant or merely ‘comforting’

data should not be requested.

Instead extrapolation should be

based on sound and objective

scientific criteria.”Weise M, et al. Blood. 2014;124:3191‐6.


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Immunogenicity

• Concern for all biologics (not just biosimilars)

• Consequences– Loss of efficacy

– Neutralization of endogenous protein and administered biologic agent

– General immune responses (allergy, anaphylaxis)

• FDA guidance regarding immunogenicity assessment– Comparative parallel design (head‐to‐head study)

Ebbers HC, et al. ExpOpin BiolTher. 2012;12:1473‐1485.Chamberlain PD. Biosimilars. 2014;4:23‐43.http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htm

Number of PRCA Case

s

Substitute polysorbate 80

for HSA

0

20

40

60

80

<1997 1998 1999 2000 2001 2002 2003

PRCA cases associated with Eprex

One change in the formulation of an established biopharmaceutical led to unpredicted immunogenicity

Biopharmaceutical Formulation: Effects on Immunogenicity

Boven K, et al. Nephrol Dial Transplant. 2005;20 Suppl 3:iii33‐40. Locatelli F, et al. Perit Dial Int. 2007;27(S2):S303‐S307.

Coated rubber syringe stoppers

• Important to assure safety

– Consider risks seen in reference

– Are there any new safety concerns?

– Population‐based assessments gives larger N to identify rare safety concerns

– Might be mandatory for some products

• Biosimilar manufacturers should work with FDA early to discuss approach

Pharmacovigilence


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Interchangeability

Per the FDA, Interchangeable or Interchangeabilitymeans:

• The biological product is biosimilar to the reference product

• It can be expected to produce the same clinical result as the reference product in any given patient

• For a product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the product and its reference product is not greater than the risk of using the reference product without such alteration or switch


Interchangeability

• Interchangeable is an FDA designation– Requires higher standards than ‘biosimilarity’ alone

• A product with an interchangeable designation may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product

• HOWEVER– FDA approval requirements for interchangeable designation and trial

design for testing are not finalized

– State substitution laws will impact practice

– Any biological product under consideration for substitution must first be approved as "interchangeable" by the FDA

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htmhttp://www.ncsl.org/research/health/state‐laws‐and‐legislation‐related‐to‐biologic‐medications‐and‐substitution‐of‐biosimilars.aspx.

What’s in a Name?Two Differing Viewpoints

Traynor K. Am J Health Syst Pharm. 2014;71(6):446‐447.Carroll J. Manag Care. 2013;22(12):6‐7.

Biosimilars should have the same exact

non‐proprietary name as their respective

reference

Biosimilars should each have a distinct

non‐proprietary name to distinguish them

from the originator and other biosimilars

Pros:

• Improved pharmacovigilance

• Recognize that these are distinct

products

Cons:

• Confusion about whether they are

“highly similar”

• May impede adoption

• Issues with substitution

Pros:• Communicate that these products are

“highly similar”• Facilitate adoption and substitution of

interchangeable biologics

Cons:• Hard to trace for [rare] adverse events

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Biosimilar Naming

• WHO Proposed Guidance

– Biological qualifier: INN + 4‐letter, randomly assigned suffix

• Filgrastim in the US (approved indications varies)

– Filgrastim (reference biologic, Neupogen)

– Tbo‐filgrastim (non‐originator biologic [351(a)], Granix)

– Filgrastim‐sndz (biosimilar [351(k), Zarxio)

http://www.who.int/medicines/services/inn/bq_innproposal201407.pdf. Accessed June 2015. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed June 2015.


What’s In a Name (of a Biosimilar)?

• Published August 28th

• All biologics receive a distinct, four letter suffix

• Suffix must be devoid of meaning

• Proposed effect on G‐CSFs

• Filgrastim = Filgrastim‐jcwp

• Filgrastim‐sndz = Filgrastim‐bflm

• Tbo‐filgrastim = Filgrastim‐vkzt

• Peg‐filgrastim= pegfilgrastim‐ljfd

European Biosimilars Experience

Active Substance Products Approval

Epoetin alfaAbseamedBinocrit

Epoetin Alfa Hexal

8/20078/20078/2007

Epoetin zetaRetacritSilapo

12/200712/2007

Filgrastim

AccofilBiograstim

Filgrastim HexalGrastofilNivestim

RatiograstimTevagrastim

Zarzio

9/20149/20082/200910/20136/20109/20089/20082/2009

Folitropin alfaBemfolaOvaleap

3/20149/2013

InfliximabInflectraRemsima

9/20139/2013

Insulin glargine Abasaglar/Abasria 9/2014

Somatropin Omnitrope4/2006

http://www.ema.europa.eu. Accessed June 2015.

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Biosimilars Market Uptake in Europe

Assessing biosimilar uptake and competition in European markets 2014. www.imshealth.com/. Accessed June 2015.

Percent of T

reatm

ent Days, 2013

Experience with Biosimilars in the EU

• Safety and efficacy of approved and marketed biosimilars has been consistent with experience with the reference biologics, with no specific safety issues identified

Mikhail A, Farouk M. AdvTher. 2013;30:28‐40.Gascon P, et al. Support Care Cancer. 2013;21:2925‐2932.Chamberlain PD. Biosimilars. 2014;4:23‐43.http://ec.europa.eu/enterprise/sectors/healthcare/files/docs/biosimilars_report_en.pdf. Accessed Jan 2015.

Bloomberg Business, April 22, 2015; FiercePharma, July 6, 2015

Financial Impact of Biosimilars in Europe

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Non‐originator (“me‐too”) Biologics ≠ Biosimilars

Regulatory Requirements Vary in Different Parts of the World

Examples:• Reditux (rituximab): India• Kikuzubam (rituximab): Mexico• Yi Sai Pu (etanercept): China• Etanar (etanercept): China• Genfaxon (interferon beta): Russia

Scheinberg M, Kay J. Nat Rev Rheumatol. 2012;8:430‐436.http://gabionline.net/Reports/Biosimilars‐in‐emerging‐markets. Accessed June 2015.

Biosimilars in the US

Drug INN ManufactureraBLA

submittedFDA

approval

Zarxio™ filgrastim‐sndz Sandoz 7/2014 3/2015

Remsima infliximab Celltrion Inc. 8/2014 ?

pegfilgrastim Apotex Inc. 12/2014 ?

Retacrit™ epoetin zeta Hospira 1/2015 Completeresponse letter

Grastofil™ filgrastim Apotex Inc. 2/2015 ?

Etanercept Sandoz 10/2015 ?

The Pink Sheet, FDA Performance Tracker, Biosimilars, accessed 11/15/2015

Ongoing litigation will determine the exact date of biosimilar launch!

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Biosimilar Filgrastim–FDA‐approved, 351(k) Pathway

Amgen G‐CSF Sandoz G‐CSF

Brand name Neupogen Zarxio

Generic name Filgrastim Filgrastim‐sndz

Application type BLA BLA‐Biosimilar 351(k)

Ingredient r‐metHuG‐CSF r‐metHuG‐CSF

MolecularWeight 18,800 daltons 18,800 daltons

Protein length 175 amino acids 175 amino acids

Expression system E. coli E. coli

Dosages 300 mcg, 480 mcg 300 mcg, 480 mcg

Dosage forms Vial and syringe (both PF) Syringe (PF)

Storage conditions 2° to 8°C 2° to 8°C

Drugs@FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/103353s5184lbl.pdf. Accessed June 2015.Drugs@FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125553lbl.pdf. Accessed June 2015.

Approved for 5 of the 6 indications of the originator product

Biosimilar Filgrastim Clinical Studies

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM428780.pdfhttp://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM428782.pdfLi EC, et al. Drug Discov Today. 2015;20(S2):1‐9.

• Comparative pivotal studies (US‐licensed Neupogen as the reference product )

– PK/PD study (EP06‐109) in healthy volunteers

– Comparative safety and efficacy study (EP06‐302) in breast cancer patients

• Supportive data

– 4 PK/PD studies in healthy volunteers

– 1 Single‐arm safety and efficacy study in breast cancer patients

– Data from healthy stem cell donors (performed as part of the European submission package as well as post marketing approval in Europe)


Biosimilar Filgrastim Clinical Response

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM428780.pdf

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Biosimilar Filgrastim

• “The results of the clinical development program suggest that the Applicant’s data meets the requirement for a demonstration of ‘no clinically meaningful differences’ between the proposed product and the reference product in terms of safety, purity, and potency”

• “FDA’s analysis of the efficacy and safety results of EP06‐302 focused on Cycle 1 and these data provided additional support that there are no clinically meaningful differences between EP2006 and US‐licensed Neupogen.”

From the FDA Briefing Document, Oncologic Drugs Advisory Committee Meeting. January 7, 2015.

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM428780.pdf.

Content Comparision of Originator and Biosimilar G‐CSF (Filgrastim‐sndz Approval)

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM428781.pdf

Accessing Information on Biosimilars

• FDA Biosimilar Guidances

• FDA Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations

• FDA Briefing Documents

• European Medicines Agency Scientific Guidelines on Biosimilar Medicines

• European Public Assessment Reports (materials for each biosimilar approved by the EMA)

• Peer‐reviewed literature

• Generics and Biosimilars Initiative

• Biosimilars Forum

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Practice Considerations for Biosimilars

• Which biosimilar agents are relevant to your practice?

• What is the timing for the introduction of these biosimilars?

• What factors will be important for incorporation of biosimilars into your clinical practice?

– Is there a formulary review process?

– Reimbursement issues

– Documentation, record‐keeping

• Pharmacovigilence

• Biosimilars education

– Multidisciplinary teams

– Patients

Summary

• Biologics are complex drugs that cannot be made “generic”

• A biosimilar is a biologic demonstrated to be highly similar to a reference product through appropriate comparative, head to head quality, non‐clinical and clinical studies

• Analytical studies of structure and function form the basis for the development of a biosimilar

• The comparability exercise used to demonstrate that a biosimilar is “highly similar” to a reference biologic is scientific, robust, and regulated

• Biosimilar uptake continues to increase in Europe, and no specific safety issues have been identified for approved and marketed biosimilars

• The first biosimilar is now approved in the US, with more under FDA review

• Incorporation of biosimilars into US clinical practice offers opportunity for health care cost savings and increased patient access to biologic therapies