Business of Biosimilars & Biobetters 2011 Le… · 18.09.2011 · Chief Regulatory Science...

Dr. Nigel A.S. HernandezPresident & Founder

Lessons Learned from Biosimilar Development in the Established European Marketplace

Business of Biosimilars & Biobetters 2011Seaport World Trade Center, Boston, MASeptember 2011

© 2011 Center for the Study of Regulatory Affairs Inc.

Keys Areas• Lessons Learned from Biosimilar Development in the Established

European Marketplace• European countries are furthest ahead in biosimilar development,

with Germany and the UK leading the way. • Hear what CenSRA takes into account when evaluating biosimilars• Estimate the effect a growing marketplace will have on biosimilar

pricing strategies• Discuss the long term benefits of creating biosimilars in a highly

regulated market, including the opportunity to easily move to less-regulated marketplaces

• Analyze regional-specific opportunities for commercializing biosimilars

© 2011 Center for the Study of Regulatory Affairs 2

Outlines • Introduction to CenSRA• Drug Development Economics• ‘The Birth’ of the Legal Framework for Biosimilar Medicines in

the European Union • When Can Biosimilar Medicines Applications Take Place? • What are the Data Requirements? • INN/International Non-proprietary Name • Post-Authorization • Biosimilar Medicines in the Market Place • CenSRA Vision


Acronyms• EU European Union• EMEA (EMA) European Medicines Agency• CHMP Committee for Medicinal Products for Human Use• EC European Commission• WHO World Health Organization• MS Member State• MAA Marketing Authorization Application• MAH Marketing Authorization Holder• DE Data Exclusivity• ME Market Exclusivity• INN International Non-Proprietary Name• ADR Adverse Drug Reaction• RMP Risk Management Plan• PASS Post Authorization Safety Study


Speaker BiographyEXPERIENCE:• Founder and Chairman, Center for the Study of Regulatory Affairs• Chief Regulatory Science, Quality & Food Safety Officer, GloboFruit, LLC• Chief Regulatory Science Officer, GMP Regulatory Science Partners• Academic Appointments: University of Maryland University College,

Previous: West Virginia University & Northeastern University

NORTHEASTERN UNIVERSITY• Doctor of International Biomedical & Food Regulatory Science.• MSc., Regulatory Affairs for Drugs, Biologics & Medical Devices• Masters Certificate, International Biopharmaceutical Regulatory Affairs• Masters Certificate, Medical Devices Regulatory Affairs (US, EU, Japan)

BOSTON UNIVERSITY• Master of Science, Advertising

EDINBURGH BUSINESS SCHOOL• Master of Business Administration

SYRACUSE UNIVERSITY• BA/ BS

REGULATORY AFFAIRS CERTIFIED (RAC)EMEA – PHARMACOVIGILANCE CERTIFIED (RPPV)


ABOUT CENSRAAbout the Center for the Study of Regulatory Affairs


Introduction• CenSRA - The Center for the Study of Regulatory

Affairs addresses regulatory affairs within each category of regulated agents: drugs, biologics, medical devices and combination products.

• An innovative regulatory center that will serve all constituencies in the medical products community –industry, regulators, researchers, clinicians, patients, associations and academic centers – to share knowledge to accelerate the regulatory paradigms and best practices for the discovery and commercialization of new medical products for improving patients lives and outcomes.

© 2011 Center for the Study of Regulatory Affairs Inc. 7

Partnership BuildingLegislators & Policy

MakersNIH, NSF

Centers & Labs

Science Organizations

Schools, Colleges, Universities

Informal ScienceEducation Institutions

Business, Industry,Foundations

National and Int’lOrganizations

Patient and DiseaseGroups

Federal, State & LocalAgencies

Center for the Study of Regulatory Affairs


DecisionsData Knowledge Impact

The CenSRA Framework

• Regulatory Agencies

• Industry Associations

• Databases/Internet• People• Institutes/Centers

• Research Requests• RGRA (Regulatory

Strategy and Risk Assessments)

• Regulatory Workshops

• Roundtables• Regulatory training

• Regulatory/ registration strategies

• Clinical trial designs

• Comments• Position Papers

• Faster approvals• Compliance• Competitive

labeling• Favorable

legislation• Industry

leadership• Policy leadership

• Web 2.0 framework

• Newsletters• Newsflashes• Reports

Inform Analyze Distribute Recommend Impact


Information

DRUG DEVELOPMENT ECONOMICS

The Business of Drug Development is Approval


© 2011 Center for the Study of Regulatory Affairs

Target

Qualified lead

Qualified candidate

Product in human

lead generation

candidate generation

Milestone: high affinity/specificity

Milestone: acceptable PK/production characteristics and efficacy in animal disease models

Milestone: acceptable safety, established production process

The Discovery Value Chain

11

lead compound

The Economics?Consequences of weak

drug regulatory capacity

Irrational consumption and prescription,

substandard, counterfeit, harmful, useless drugs on

sale

Consequences of regulatory inaction

Death to industry, patients, loss income,

increased health costs, market failure?


Challenges faced by Pharma/BIO

• Competitive and market changes• Turnover • New scientific knowledge and discoveries • Regulatory changes/ new standards • New disease knowledge • Potential indications• Financial & Capital Markets


Biosimilars: Europe’s New Opportunity ?

“Biosimilars offer new opportunities both for the growth of our generic industry and for the control of our national health expenditure.”


Günter Verheugen, Vice-President EU Commission April 2006

14

Chance favorsonly the

prepared mind

(Pasteur)

Serendipity

Science, Management, Predictability

15© 2011 Center for the Study of Regulatory Affairs Inc.

TIME & COST: 8-12 YEARS & $800M-1.2B

Source: Page 70 Scientific American April 2000 Understanding Clinical Trials


REGULATORY LANDSCAPEThe Regulatory Landscape, what it maters….


Legislation has publicly stated goals, but• Are they well resourced?• Are they well planned? • Are they independent?• Are the interests aligned?• Are they informed by all

relevant stakeholders?• Are they free of political or

other bias?


FEEDBACK

PERSPECTIVESDevelopmentImplementationEvaluation

EVALUATION STAGESPlanning & designConducting the evaluationInstitutionalizing change

POLITICS

LAW

TACTICSFramingInterpersonal influenceTimingInformation and analysis

STANDARDSUtilityFeasibilityProprietyAccuracy

PUBLIC POLICY

The Policy Connection

CHANGE AGENTSEventsKnowledgeInterest GroupsIndividuals

INFLUENCERS


The Biosimilar Regulatory Landscape


The EU Trinity


EUROPEAN COMMISSION

COUNCIL OF MINISTERSEUROPEAN PARLIAMENT

• Guardian• Protectors• Sole Right

• Decision Taker• Representer

• Co-legislator;• Representer

21

Sounds easy right?


EU Legislation

EP

EC

Council 27

22


Careful development…over timePharmaReview

2001

Directive 2003/63/EC“Annex I” published:

recognition of ‘biosimilars’

Directive 2001/83/ECas amended published

AdoptedDirective

takes effect

Legal

Regulatory

2001 2002 2003 2004 2005 2006

2001 2002 2003 2004 2005 2006

EMEA’s biosimilar ‘quality issues’and ‘non-clinical and clinical

issues’ draft guidelines published

EMEA’s Revised ‘comparability’

guidelines published

EMEAreleases

biosimilar‘conceptpapers’

EMEA’s product specific Draft guidelines released for hGH, insulin, EPO and

G-CSF.

EMEAworkshop

Firstbiosimilarapproved

EU Framework for Biosimilars:

Legal certainty• Clear legal basis• Abbreviated data package

Flexibility• Case by case approach• General and product

specific guidelines


key forinvestments

adjustments of datarequirements (science, technology, experience)

• Art.10.4./Directive 2001/83/EC as amended (31 March 2004)

24

BIOSIMILAR APPLICATIONS?When Can Biosimilar Medicines Applications Take Place?



15 Years Maximum Market Exclusivity for Reference Product:

e.g. the marketingauthorization is granted tooriginator in year 12

Maximum 5 years extension ofSupplementary ProtectionCertificate (SPC)

10 12 20 25

10 Years

(new: 8+2+1)

Data exclusivity (DE) period of reference product

Biosimilar application,registration andauthorization

NO Patent LinkageSubmission of biosimilar applications only possible after DE expiry

Patent Duration

WHAT’S COVERED?Which Products are Covered?


Legal Perspective

• In principle the concept of “similar biological medicinal (biosimilar) products” applies to any biological medicine

• ‘Generic approach’ is legally not excluded


Spectrum of Complexity


(source: Dr. John Purves/EMEA)

Science

Chemicals Recombinant DNAtechnology

Blood derived Immunologicals Advancedtherapy

FullDossierBiosimilarGeneric

(essentially similar)

*

*Legislation

* Future Developments ?

DATA REQUIREMENTS?What are the Data Requirements?


Regulatory Perspective• For the type and quantity of data to be

provided, the EU legislative framework refers to detailed guidelines

• But guidelines are NOT mandatory before submission and approval

• Guidance follows science– Guidance is built on experience gained through

scientific advice procedures and assessment of marketing authorization application

– Guidelines do not have legal force – but a justification for non compliance must be provided


Current EU Biosimilar Guidelines


http://www.emea.europa.eu/htms/human/humanguidelines/multidiscipline.htm

Overarching Guideline (CHMP/437/04).“Guideline on Similar Biological Medicinal Products”

Biotechnology- derived proteins

Quality

Non-clinical

------------Clinical

Non-Clinical

----------------------------

Clinical

Non-Clinical

----------------------------

Clinical

Non-Clinical

----------------------------

Clinical

Non-Clinical

----------------------------

Clinical

Non-Clinical

----------------------------

Clinical

Insulin Somatropin GCSF Epoetinunder review

LMMHIFN- α

Defines philosophyand principles

General guidelines

Annex guidelines -specific datarequirements

Non-Clinical

----------------------------

Clinical

32

Example: Omnitrope® Approved before Somatropin Guidance• Omnitrope Positive

Scientific Opinion 26 Jan 2006

• Approval of Omnitrope 18 April 2006

• Adoption of guideline22 Feb 2006

• Came into effect1 June 2006


EMEA/CHMP/BMWP/94528/2005

33

High Level Scientific Evaluationby EMEA and EC Approval


INNINN International Non-proprietary Name


Purpose of INN

• Classification / nomenclature– Identification of pharmaceutical substances

• WHO Guidance on INN – broad scope– Pharmacopoeia, labelling, product

information, drug regulation, basis for product names (generics)…


INN is NOT…

• Identification of a drug product or its impurities

• Statement of therapeutic equivalence and/or substitution

• Means of managing the practice of medicine

• Traceability and pharmacovigilance apply to drug products


Current INN Policy

• INNs for glycosylated rDNA proteins– Core name based on Amino Acid sequence– Greek letter added: ‘differences in

glycosylation’• Difficult to define ‘differences’

– eg, batch to batch differences


INNs for Biologicals

• EU consideration at WHO level:– INNs should have “high level” utility –

identification– Up to Regulatory Authorities to assess

Benefit / Risk– AA sequence basis for INN– Presence/absence of glycosylation

compared to native protein• Discussions continue


Nomenclature: Same INNDecision lies with RegulatorsWith regard to the nomenclature of biosimilars, we do not endorse the idea that any difference in glycosylation automatically leads to a different INN. We have serious doubts that this stance could be scientifically justified. We are also concerned that the WHO is promoting a double-standard policy on biosimilars.


G.Lalis/Director General EC -Statement on WHO INN Policy at EGA Annual Conference Paris 2 Junehttp://www.egagenerics.com/doc/GLalis_speech_egaconf2008.pdf

POST-AUTHORIZATIONAfter Market – So What?


Pharmacovigilance

• Company Risk Management System must be in place– Risk Management Plan

• Pharmacovigilance activitiesRoutine pharmacovigilancePASS

– Risk minimization activitiesLabelling (counter-indication, advice, warning)


Traceability of ALL Biologics

All biological drugs need to be monitored• An adverse reaction report for any biological

drug should always include– full name of the biological drug– batch number

• Where information is missing, Member States/MAHs should ensure that reports are followed up for completion


G. Lalis/Director General ECon Pharmacovigilance for BiosimilarsEGA Annual Conference Paris 6/08

Furthermore we have written to Member States' regulatory authorities to take necessary measures to ensure • a method to link suspected adverse reaction

reports to specific products (such as a unique product identifier) and

• to ensure that prescribing doctors know which glycoprotein has been given to their patient.


BIOSIMILARS MARKETPLACEBiosimilar Medicines in the Market Place


Biosimilar Drugs in the EU Market• National pricing approvals and reimbursement

have been agreed without any major barriers• Market in-roads are made• Patients and healthcare professionals are• catching up• But scare tactics still ongoing by certain

interested parties


Economics


Bio similar Market

Supply side

policies

Demand side

policies

Regulatory Pathway

47

Economics


Bio similar MarketSupply

side policies

Demand side

policies

Regulatory Pathway

Hospital/Pharmacists Patients Doctors

Regulators

Ministriesof Health

Price &reimbursement

Authorities

Manufacturers

Wholesalers &Pharmacies

Hospitals

48

Message from the European Commission• ………….’we are confident that if a

product goes through all the steps and meets all the requirements and gets at the end an approval through a Commission Decision, it means that this product is as safe and efficacious as any other product authorised by the European Commission in the EU’.


N. Rossignol at 6th EGA symposium on biosimilar medicines 2008

49

WHAT IS CRITICAL?The Regulatory Science Function is Critical


The RA Function Is Critical


PharmacyNursingEngineeringLaboratory ScienceTechnical WritingMedicine

StatisticsLaw

RA ProfessionalsAre Not Born, They are Made

GLOBAL DEVELOPMENTIs Global Development a Myth or Reality?


Global Development for Biosimilars• Streamlining the development process• Avoids repetition of unnecessary trials• Increases access through affordable medicines• Increases competition

– Market competition from biosimilar drugs willdrive the biotechnology industry to do what itdoes best – discover new drugs that enhance,sustain, and save lives.


Market Share Value by Country in Q2


COUNTRY Human Growth Hormone

Erythropoetin Granulocytehormone colony stimulating factor

US 6.6% 0 0Japan 0 0 0France 12.5% 2.0% 3.8%Germany 5.1% 52.1% 31.0%Italy 15.3% 0.2% 18.5%Spain 1.4% 1.6% 7.1%UK 1.0% 0.9% 24.0%

Leaders & Numbers• Sandoz (Teva and Hospira right behind)

• Global Biologics Market Sales in 2009 exceeded $125 Billion

• 2011 Biosimiliars accounted for only $89 million in sales (Sandoz Omnitrope acounts for 33%)

• Germany – greatest market share in Europe and Worldwide.


SWOTSTRENGTHS

• Lower cost structure• Development is more calculable versus

research on new drug leads• Biosimilars are a reality

WEAKNESS• Lack of credibility in the prescribing

community• Lack of credibility in the policy forming

community• Lack of Credibility as an industry

OPPORTUNITIES• Favorable pricing and reimbursement

policies• Driving further innovation• Continued growth of developing, non-

saturated markets

THREATS• Evolving regulatory environment not

always aligned with industry interests• Technology improvement and shifts• Intellectual property domain

BIOSIMILARS


SWOT Analysis• Timing Matters • Dare to be different• Keep it simple• Don’t play on IP• Prepare deep pockets for financing

the expected


STRATEGIES?What does this all mean?


Strategies for Success• Analyze new regulatory impacts - build and use the links that

create rnetworks.• Collaborate internally/externally and work together to share

information and expertise.• Align behavior with dynamic strategy - understand and deliver

regulatory intelligence that affect business outcomes across the network (partners, customers, collaborators, industry).

• Leverage competency - focus on core competencies and collaboration, entrusting your network to do more with less.

• Integrate partners and collaborators proactively.• Operate at net speed - respond quickly and decisively to rapidly

changing regulatory policy and market dynamics.


Strategies for Success• Provide a vital link by working outside the framework

of government and industry to ensure informed analysis and independent guidance.

• Reach globally and virtually - Collaborate or exchange knowledge regardless of time or regulatory diversity.

• Manage Knowledge dynamically - leverage data from internal and external sources to create competitive advantage.

• Build strong market presence and credibility.• Develop brand awareness and create a need for why

your Biosimilar should be approved.


The Benefit/Risk Evaluation Fallacy

Benefits

Risks

Reduce Preventable and Quality Risks

Reg. Agency

PROVIDER

PATIENT

61

62

What is safety? Safety is not Absolute• ≠ zero risk (absence of injuries and deaths)• Involves overall assessment of benefit/risk

Safety is not Exclusive• ≠ only experience with the drug• Involves comparison across

drugs/interventions

Safety is not Static• A safe drug/device today may be “unsafe”

and outmoded tomorrow• Experimental risk versus Situational risk

Safety is Evolutionary…only the real world can tell….What about efficacy?

62


THANK YOU

63

Dr. Nigel A.S. HernandezPresident & Founder

Lessons Learned from Biosimilar Development in the Established European Marketplace

Business of Biosmiliars & Biobetters 2001Seaport World Trade Center, Boston, MASeptember 2011


Business of Biosimilars & Biobetters 2011 Le… · 18.09.2011 · Chief Regulatory Science...

Documents

Transcript of Business of Biosimilars & Biobetters 2011 Le… · 18.09.2011 · Chief Regulatory Science...