medical publications for better patient care: …

2015 EUROPEAN MEETING OF ISMPP 1

2 0 1 5 E U R O P E A N M E E T I N G O F I S M P P

MEDICAL PUBLICATIONS FOR

BETTER PATIENT CARE:

INTEGRITY, INNOVATION,AND IMPACT

20-21 January, 2015

etc.venues, St. Paul’s - 200 Aldersgate London, UK



PUBLICATION PLANNING

FOR ‘MATURE’ PRODUCTS Joanna Hulme

Scientific Director

The Prime Medical Group



Joanna is an employee of The Prime Medical

Group

Any views and/or opinions expressed by the

presenter do not necessarily reflect those of

The Prime Medical Group


Outline

• Definition of ‘mature’ products

• Considerations for publication planning

• Inputs to publication plan

• Implementation

• Agency perspective


What is a ‘mature’ product?

www.pharmexec.com


Anticipated changes in drug spending

IMS Institute for Healthcare Informatics, 2014

61%

27%

12%

52%

36%

12%

2012

US$965 bn

2017

US$1200 bn

Branded Generic Other


Challenges in publication planning

for established products

Growth in volume and

diversity

Clinical evidence sources evolve

Regional diversity

Heterogeneity of stakeholders

Quality of data?

Changes in educational needs

Diversity of

product utilisation

Types of evidence change

Resource limitations

Lifecycle plans

Integrating market

feedback

Maintaining

quality and interest

Commitment to data

transparency Publication Planning

considerations

Global – local coordination


Inputs to publication plans


Long-range

medical strategy

Medical info

requests

MSL input

Treatment landscape

Franchise / lifecycle

plan

Clinical data (sponsored;

independent; RWE)

Local or regional needs

Global Publication plan • Breakdown of stakeholders and prioritised educational needs • Publication plan educational objectives

• Outputs to fulfil educational objectives

Regular, scheduled updates Ability to facilitate rapid responses to specific clinical issues / challenges

Publication landscape

External expert

guidance

Patient feedback

RWE

External environment Internal focus

Local / regional publication plan




Implementation of publication plans


• External focus

– Consider regional / local requirements

– Ensure publication plan is addressing genuine educational needs of different markets / stakeholders

• Publication planning processes

– Need for dedicated regional / local publication plans

– Global plan and processes must consider local needs and vice versa

– Use local expertise to understand cultural issues

– Identify and prioritise strategically important publications for global

and regional needs

• Integration

– Alignment within lifecycle plans, franchise plans

• Relationships

– Ensure relationships exist and are maintained with lead investigators from cooperative groups

– Support MSLs to talk to HCPs about publication plans


Agency perspective

• Increasing complexity

• Flexibility needed in level and type of support

–Consider strategic context and support required

• Increasing need for dedicated regional support

• Practical considerations

–Expertise / training

–Budget (cost-effective working processes)

–Prioritisation (internal and external)

–Where to publish

• Realities of journal selection

–Ensuring continued quality…



UNDERSTANDING THE IMPACT OF

PUBLICATIONS IN SPECIALIST

AREAS: GENERIC PHARMACEUTICALS

Angela Kaya, PhD & Debra Mayo Pharm D, MHA

Teva Pharmaceuticals

Wednesday, 21 January, 2015

9:00-10:35 AM



Debra Mayo and Angela Kaya are employees of

Teva Pharmaceuticals.

Any views and/or opinions expressed by the

presenters do not necessarily reflect those of Teva

Pharmaceuticals.


Generics will Represent a Larger Share of

the Market in Volume and Value Terms

Source: IMS (2013), ‘The Global Use of Medicines: Outlook through 2017’, www.imshealth.com


Types of Regulatory Application US & EU US New Chemical

Entities/Biologics Hybrid Applications Generic

Legislative Title 505(b)(1) & 351(a)

NDA

505(b)(2) & 351(k) 505(j)

ANDA

Data

Requirements

Full NDA

Clinical Studies

Required

Full 505(b)(2) Submission

A combination of new studies/pre-

existing data

315K submission still unclear

Proof of BE

Benefits Exclusivity Exclusivity No exclusivity

(except for first to generic

market)

Additional exclusivity for

orphan drug status or

pediatric indications

Non-substitutable Substitutable

EU New Chemical

Entities

Hybrid Applications Generic

EU Directive Article (8) 3 Article (10) X* Article (10) 1&2

Data

Requirements

Full submission

Clinical Studies

Required

Full Hybrid Submission

A combination of new studies/pre-

existing data

Proof of BE

Benefits Exclusivity No Exclusivity

(except for Orphan drugs)

No Exclusivity

(except for first to generic

market)

Additional exclusivity

for orphan drug status

or pediatric indications

Non-substitutable Substitutable

* Types of Applications: Article 10a Well-established use; Article 10b Fixed dose combination;

Article 10c Informed Consent; Article 10(3) Hybrid; Article 10(4) Similar Biological


Generics – Clinical Studies/

Additional Studies

• Reference countries which may require as a part of their generics application a study conducted in the reference country

– China

– Japan

– South Korea

– Russia

– Mexico

– Brazil

– Others

• Studies may be conducted as a part of a clinical waiver (dependent on country’s guidelines/requirements)


Expectations for Publications

Branded

Data Manuscripts: All data from clinical

studies are published

Review Articles: Limited only by company policy

Meeting Presentations: Determined by # of

studies and subanalyses

Focus: Drug/TA

Publication Planning: Full plan

Hybrid

Data Manuscripts: All data from clinical studies are published Review Articles: Limited Meeting Presentations: Determined by # of studies/subanalyses and interest Focus: Technology/delivery system/innovations Publication Planning: Medium – full plan, timing may be shifted dependent on ability to discuss new technology/delivery systems/innovations

Generics

Data Manuscripts: All data from clinical

studies are published

Review Articles: Very limited

Meeting Presentations: Limited (region)

Focus: Bioequivalence (BE) in specific

populations

Publication Planning: Limited to regional

planning with possibility

of global perspective


Challenges for Publications Planning

Hybrid

Timing: Organizational

commitment to generate and disseminate NEW data Budget: May be limited Risk: Increased scrutiny by innovator product owner Audience: May have limited interest

Authors: There many be a conflict with innovator product owner for biosimilars, new combinations, etc Journal: May have limited interest Opportunity: Health

economics/market access may be a focal point Unanswered topics of interest

Timing: Efficient execution of clinical trials—available data Budget: Full budget

Risk: Regulatory, legal, and compliance risk assessment Audience: Very interested Authors: Very interested Journal: Very interested for first in market/limited interest in

“me-toos” Opportunity: New drug/new therapeutic area

Branded Generics

Timing: Dependent on

reference country and reference country regulatory timeline Budget: Very limited Risk: Very limited Audience: Very limited interest/may be local or

regional Authors: Local/regional only Journal: Local/regional only Opportunity: Dependent on life cycle may be able to wrap up all regional publications in a review

article


Conclusion

• Accurate, transparent and comprehensive reporting of all clinical trial data regardless of branding or type of regulatory filing

• Use good publication practice regardless of branding or type of regulatory filing

• Refer to ICMJE for guidance on authorship for the publication of clinical trial data – PASS and Phase IV

• Need a greater rate of acceptance and more journals who accept less than cutting-edge science /clinical publications for the good of the patient


Resources

• Handoo S; Arora V, Khera D, Nandi PK, Sahu SK. A comprehensive

study on regulatory requirements for development and filing of

generic drug globally. Int J Pharm Invest. 2012 Jul-Sep; 2(3): 99-

105.

• FDA type of applications:

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDr

ugsareDevelopedandApproved/ApprovalApplications/

• FDA Guidance for Industry: Applications Covered by Section

505(b)(2)

http://www.fda.gov/downloads/Drugs/Guidances/ucm079345.p

df

• FDA (draft) Guidance for Industry: Reference Product Exclusivity

for Biological Products Filed Under Section 351(a) of the PHS Act

http://www.fda.gov/downloads/drugs/guidancecompliancereg

ulatoryinformation/guidances/ucm407844.pdf

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/



http://www.fda.gov/downloads/Drugs/Guidances/ucm079345.pdf

http://www.fda.gov/downloads/Drugs/Guidances/ucm079345.pdf

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm407844.pdf




• DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use http://ec.europa.eu/health/files/eudralex/vol-1/dir_2001_83_consol_2012/dir_2001_83_cons_2012_en.pdf

• EMA Procedural advice for users of the centralised procedure for generic/hybrid applications http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004018.pdf

• EMA Q&A on generics/hybrid applications: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000035.jsp&mid=WC0b01ac058002708f

http://ec.europa.eu/health/files/eudralex/vol-1/dir_2001_83_consol_2012/dir_2001_83_cons_2012_en.pdf





http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004018.pdf





http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000035.jsp&mid=WC0b01ac058002708f




• State Food and Drug Administration of the People’s Republic of China (SFDA): http://eng.sfda.gov.cn/WS03/CL0768/61645.html

• Pharmaceutical and Medical Device Agency, Japan: http://www.pmda.go.jp/english/service/outline_s.html

• Korean Food and Drug Administration: http://www.kfda.go.kr/eng/index.do

• Federal Commission for Protection against Sanitary Risks (Mexico): http://www.cofepris.gob.mx/Paginas/Idiomas/Ingles.aspx

• Brazalian Health Surveillance Agency: http://portal.anvisa.gov.br/wps/portal/anvisa-ingles/anvisaingles/Home/!ut/p/c5/04_SB8K8xLLM9MSSzPy8xBz9CP0os3hTQwNfRydDRwN_N2cjA08XVzOPUF8PL08jU6B8pFm8AQ7gaADS7evoYeRh6GzgbmHp4WbgaWTp62Rm4GxgYmAA0Y2QD_F3Aco7hjqbmfsZWhib09BuOujG4_JwUDjj9zlIHo_5fh75uan6BbmhQBBhkGXiqAgAh0l8iA!!/dl3/d3/L2dJQSEvUUt3QS9ZQnZ3LzZfTUFIMkgxQzBHODlIRjBJMjlNQjYwQzA0MDA!/?WCM_GLOBAL_CONTEXT=/wps/wcm/connect/Anvisa+Ingles/Anvisa/Home

• National Center of Pharmaceutical Products Expertise (Russia): http://pharmareg.ru/content/view/18/37/

http://eng.sfda.gov.cn/WS03/CL0768/61645.html

http://www.pmda.go.jp/english/service/outline_s.html

http://www.kfda.go.kr/eng/index.do

http://www.kfda.go.kr/eng/index.do

http://www.cofepris.gob.mx/Paginas/Idiomas/Ingles.aspx

http://www.cofepris.gob.mx/Paginas/Idiomas/Ingles.aspx

http://pharmareg.ru/content/view/18/37/

http://pharmareg.ru/content/view/18/37/


Definitions

• Branded Drug

– A brand name drug is a drug marketed under a proprietary, trademark-protected name

• Generic Drug

– A generic drug is the same as a brand name drug

in dosage, safety, strength, how it is taken, quality, performance, and intended use

– By law, a generic drug product must contain the

identical amounts of the same active ingredient(s)

as the brand name product

– Drug products evaluated as "therapeutically

equivalent" can be expected to have equal effect and no difference when substituted for the brand

name product


Definitions

• Biosimilar drug

– Highly similar versions of biologics, those medicines made from living microorganisms found in plant or animal cells

• New Molecular Entity (NME)

– An active ingredient that has never before been marketed in the United States in any form

• New Therapeutic Entity (NTE)

– A new acronym to describe a model for combining APIs, reformulating them, or developing new delivery mechanisms

• Branded Generic

– Generic drug that has a trade name


Other Issues

• Comparators

• P-values ? (driving for statistical significance or

clinical significance)

• Different regulatory and access regulations

• Health Economic data v clinical data

• US v Europe v ROW access issues

• Ability to get results published

• Access to data? 2014 move toward

transparency…


Hybrid Sector Companies Company Portfolio Examples

Abbvie Androgel, Duodopa

Shire Lialda, Intuniv

Teva Pain, respiratory, hormonal contraception

Endo International Pain, sex hormones, contraception

Novartis Tobi

Sandoz Biosimilars

Johnson & Johnson ADHD, oncology, pain

Hisamitu Topical pain killers in Japan

Actavis GI, sex hormones

Mundi Pharma Pain, respiratory

Pfizer Pain, hormonal contraception

Chiesi Fostair

Celgene Abraxane

Source: IMS (2014). The Third Sector. A Growing Opportunity in the Pharmaceutical Market?


Summary

• Heterogeneity of audience

• Regionalisation

– Variations in educational needs across

markets

• Importance of strategic focus

• Maintaining interest

• Working in a resource-limited environment

– Budgets

– Author prioritisation

medical publications for better patient care: …

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