VACCINES: VACCINES: TECHNOLOGY TRANSFER TO TECHNOLOGY TRANSFER TO

THE DEVELOPING WORLDTHE DEVELOPING WORLD

John H. BartonJohn H. BartonProfessor Emeritus, Stanford Law SchoolProfessor Emeritus, Stanford Law School

Former Visiting Scholar, NIH Department of Former Visiting Scholar, NIH Department of Clinical BioethicsClinical Bioethics

THIS IS A WORK-IN-PROGRESS: THIS IS A WORK-IN-PROGRESS: PLEASE CRITICIZE, ADVISE, PLEASE CRITICIZE, ADVISE,

CORRECT, AND SUGGEST, AS CORRECT, AND SUGGEST, AS NEEDED! NEEDED!

I speak purely for myself and not for I speak purely for myself and not for Stanford or NIH.Stanford or NIH.

VACCINE TECHNOLOGY VACCINE TECHNOLOGY TRANSFER STUDYTRANSFER STUDY

Why technology transfer?Why technology transfer?• Technology as engine of growth and scienceTechnology as engine of growth and science• Transfer as affecting access to products for local and Transfer as affecting access to products for local and

global marketsglobal markets• Variety of modes changing over timeVariety of modes changing over time• Severe restrictions under current international economic Severe restrictions under current international economic

lawlaw

Why vaccines?Why vaccines?• Crucial medical interventionCrucial medical intervention• Reasonably separable area (and very different history Reasonably separable area (and very different history

from pharmaceuticals)from pharmaceuticals)• InterestInterest

VACCINE TECHNOLOGY VACCINE TECHNOLOGY TRANSFER: OUTLINETRANSFER: OUTLINE

Heroic era (1891 => 1930s)Heroic era (1891 => 1930s)

National public health: Growth and National public health: Growth and divergence (193Os = >1990s)divergence (193Os = >1990s)

Global vaccination programs (1960s => Global vaccination programs (1960s => 2000s)2000s)

Era of privatization and biotechnology Era of privatization and biotechnology

(~1990 => (~1990 =>

I - HEROIC ERAI - HEROIC ERA Smallpox:Smallpox:

• Arm-to-arm vaccination – prehistoryArm-to-arm vaccination – prehistory• Jenner – 1798Jenner – 1798• Brazil – 1887 (predecessor of Butantan)Brazil – 1887 (predecessor of Butantan)

Rabies and Pasteur InstitutesRabies and Pasteur Institutes• Pasteur - 1885 Pasteur - 1885 • Pasteur InstitutesPasteur Institutes

Dakar – 1896Dakar – 1896 Saigon – 1891Saigon – 1891 Now a network of 29 institutes, including 22 in developing nationsNow a network of 29 institutes, including 22 in developing nations

Researchers trained at Institut PasteurResearchers trained at Institut Pasteur• Haffkine (Bombay) – 1899Haffkine (Bombay) – 1899• Oswaldo Cruz (Rio) – 1900Oswaldo Cruz (Rio) – 1900

NEW VACCINES IN THE HEROIC NEW VACCINES IN THE HEROIC DAYSDAYS

Typhoid (1896) – Wright (England) and others; trials in IndiaTyphoid (1896) – Wright (England) and others; trials in India

Cholera (1896) – Haffkine, Delhi & CalcuttaCholera (1896) – Haffkine, Delhi & Calcutta

Plague (1897) – Haffkine, Hongkong?Plague (1897) – Haffkine, Hongkong?

Diphtheria (1923) – Ramon (France) (antitoxin earlier)Diphtheria (1923) – Ramon (France) (antitoxin earlier)

TB (BCG) (1927) – France, but based partly on work in SaigonTB (BCG) (1927) – France, but based partly on work in Saigon

Tetanus (1927) – Ramon (France)Tetanus (1927) – Ramon (France)

Pertussis (1933) – Denmark & USPertussis (1933) – Denmark & US

Yellow fever (1935) – RF (Lagos & New York); Pasteur (Dakar); trials in Yellow fever (1935) – RF (Lagos & New York); Pasteur (Dakar); trials in BrazilBrazil

DYNAMICS OF HEROIC ERADYNAMICS OF HEROIC ERA

Scientists had to go where the disease was Scientists had to go where the disease was (Arrowsmith syndrome)(Arrowsmith syndrome)

Colonial policy Colonial policy (“mission civilisatrice,” (“mission civilisatrice,” ““every colony should have its Institut every colony should have its Institut Pasteur”)Pasteur”)

Public health interest in more Public health interest in more sophisticated developing nations (Brazil)sophisticated developing nations (Brazil)

THE TECHNOLOGY IN THE THE TECHNOLOGY IN THE HEROIC DAYSHEROIC DAYS

Production involved small institutes Production involved small institutes doing both research and production doing both research and production (technology based on animal and (technology based on animal and flask culture)flask culture)

Technology acquired through Technology acquired through personal study (Institut Pasteur)personal study (Institut Pasteur)

SMALLPOX VACCINE SMALLPOX VACCINE PRODUCTION – OSWALDO PRODUCTION – OSWALDO

CRUZ – EARLY 20CRUZ – EARLY 20THTH CENTURY CENTURY

Fernandes 2004

II - GROWTH AND DIVERGENCEII - GROWTH AND DIVERGENCEDURING THE MID 20DURING THE MID 20THTH CENTURY CENTURY

New vaccinesNew vaccines

New technologiesNew technologies

New regulationsNew regulations

NEW VACCINESNEW VACCINES

Polio (Salk & Sabin)Polio (Salk & Sabin) MeaslesMeasles MumpsMumps Hepatitis BHepatitis B MeningococcusMeningococcus Haemophilus influenzaHaemophilus influenza CombinationsCombinations

New technologiesNew technologies

Culture on chick embryos Culture on chick embryos (Goodpasture, Walter Reed, 1931)(Goodpasture, Walter Reed, 1931)

Tissue culture (Enders, 1949)Tissue culture (Enders, 1949) Biotechnological production of Biotechnological production of

specific antigens (1980s)specific antigens (1980s) Conjugate vaccines (1980s)Conjugate vaccines (1980s) Plus improved separation methods Plus improved separation methods

and improved assaysand improved assays

NEW REGULATORY NEW REGULATORY STANDARDSSTANDARDS

““Jim” and Biologicals Act – 1902Jim” and Biologicals Act – 1902 Cutter incident – 1955 – led to creation of Cutter incident – 1955 – led to creation of

Division of Biologics Standards in NIH, now Division of Biologics Standards in NIH, now in FDAin FDA

GMP and management of input materials GMP and management of input materials 1963 and 19761963 and 1976

Management of air pressure – 1978/87?Management of air pressure – 1978/87? Documentation and Team Biologics --Documentation and Team Biologics --

1990s1990s

MEANWHILE, BACK IN THE MEANWHILE, BACK IN THE DEVELOPING WORLDDEVELOPING WORLD

World War IIWorld War II

Independence and conversion of colonial Independence and conversion of colonial public health systems into national ones, public health systems into national ones, often fighting for limited resources (later often fighting for limited resources (later on with IMF and World Bank pressures on on with IMF and World Bank pressures on health budgets)health budgets)

Lack of major scientific research programs Lack of major scientific research programs comparable to those of the developed comparable to those of the developed world (until Brazil, China, India in about world (until Brazil, China, India in about 1980s)1980s)

THE BASIC PATTERN:THE BASIC PATTERN: Many small scale producers (WHO found Many small scale producers (WHO found

74 rabies vaccine producers in 1984, many 74 rabies vaccine producers in 1984, many still using live animals)still using live animals)

Frequent GMP problemsFrequent GMP problems

Did not make most advanced vaccinesDid not make most advanced vaccines• OPV, not IPV, partly because of WHO pressureOPV, not IPV, partly because of WHO pressure• Whole-cell pertussis, not acellularWhole-cell pertussis, not acellular

Brazil as major exceptionBrazil as major exception

Brazil – 1943Brazil – 1943Probably making yellow fever vaccine at Oswaldo Probably making yellow fever vaccine at Oswaldo

CruzCruz

Lacerda and Mello (2003)

THE RESULT:THE RESULT:APPROXIMATE STATISTICSAPPROXIMATE STATISTICS

DTP COVERAGE - 1980DTP COVERAGE - 1980

Industrialized countriesIndustrialized countries 60 %60 % Latin AmericaLatin America 38 %38 % South AsiaSouth Asia 5 % 5 % East AsiaEast Asia 5 % 5 % MidEastMidEast 25 %25 % Sub-Sahara AfricaSub-Sahara Africa 5 % 5 %

Hadler et al, Vaccination Programs in Developing Countries in Plotkin & Hadler et al, Vaccination Programs in Developing Countries in Plotkin & Orenstien, VaccinesOrenstien, Vaccines

TECHNOLOGY TRANSFER DURING THE TECHNOLOGY TRANSFER DURING THE MID AND LATE-20MID AND LATE-20THTH CENTURY CENTURY

Early on – probably through personal contact, Early on – probably through personal contact, international meetings, and perhaps international international meetings, and perhaps international education among scientists education among scientists

Later in period – serious donor efforts:Later in period – serious donor efforts:• RIVM – Vacsera (1980s)RIVM – Vacsera (1980s)• CIDA, Connaught, UNICEF, AID – Pakistan (1981 and CIDA, Connaught, UNICEF, AID – Pakistan (1981 and

1984)1984)• Statens Serum Institut – Razi (1985)Statens Serum Institut – Razi (1985)• Canada plus Oswaldo Cruz – Nigeria (1986)Canada plus Oswaldo Cruz – Nigeria (1986)• Netherlands, Japan – Bio Farma (1991 & 1992)Netherlands, Japan – Bio Farma (1991 & 1992)• World Bank – China (mid 1990s)World Bank – China (mid 1990s)

III - NEW ERA OF GLOBAL III - NEW ERA OF GLOBAL PROGRAMSPROGRAMS

Eradication campaignsEradication campaigns• PAHO & smallpox – 1950-67PAHO & smallpox – 1950-67• WHO - Global smallpox – 1967-77WHO - Global smallpox – 1967-77• WHO - Polio – 1985-200?WHO - Polio – 1985-200?

EPI – 1974EPI – 1974

CVI – 1990CVI – 1990

GAVI – 2000GAVI – 2000

Emergence of UNICEF/Rotary purchase system Emergence of UNICEF/Rotary purchase system with tiered pricingwith tiered pricing

PROCUREMENT FOR THE PROCUREMENT FOR THE GLOBAL PROGRAMSGLOBAL PROGRAMS

Smallpox (1960-77) – encourage Smallpox (1960-77) – encourage local procurement (smallpox animal local procurement (smallpox animal technology) – developing nations technology) – developing nations supplied at least 80 % of own needssupplied at least 80 % of own needs

Polio (1985-200?) – at first entirely Polio (1985-200?) – at first entirely developed-nation procurement, some developed-nation procurement, some developing-world manufacturers by developing-world manufacturers by the 1990sthe 1990s

EPI & PROCUREMENTEPI & PROCUREMENT

EPI created in 1974.EPI created in 1974.

Latin American Revolving Fund – 1979 - Latin American Revolving Fund – 1979 - supported by national health ministries.supported by national health ministries.

UNICEF procurement system (1978?) – UNICEF procurement system (1978?) – supported by donors, including Rotary and supported by donors, including Rotary and now Gates – with PAHO, now purchases now Gates – with PAHO, now purchases roughly 70 % (by dose) of world’s roughly 70 % (by dose) of world’s childhood vaccine near marginal cost. childhood vaccine near marginal cost.

MORE ON THE 1990s REVOLUTION MORE ON THE 1990s REVOLUTION IN PROCUREMENTIN PROCUREMENT

EPI/UNICEF initially purchased from developed nations – but EPI/UNICEF initially purchased from developed nations – but faced severe shortages and high prices as suppliers merged faced severe shortages and high prices as suppliers merged and reached capacity limits during 1990s.and reached capacity limits during 1990s.

10 of 14 developed-world manufacturers partially or totally 10 of 14 developed-world manufacturers partially or totally stopped production of traditional vaccines during 1998-stopped production of traditional vaccines during 1998-2001 (UNICEF).2001 (UNICEF).

CVI study of quality and development of matrix in 1993-94.CVI study of quality and development of matrix in 1993-94.

WHO developed a prequalification system – 1989(?).WHO developed a prequalification system – 1989(?).

Now UNICEF buys more than 2/3 of its non-OPV vaccines Now UNICEF buys more than 2/3 of its non-OPV vaccines from major developing-nation manufacturers – and small from major developing-nation manufacturers – and small developing-nation manufacturers discourageddeveloping-nation manufacturers discouraged

IV - CONTEMPORARY ERAIV - CONTEMPORARY ERA

Patents and intellectual propertyPatents and intellectual property• TRIPS, stronger developed-world systemsTRIPS, stronger developed-world systems

BiotechnologyBiotechnology• Heavy private sector role in developed world, Heavy private sector role in developed world,

with important public components, especially with important public components, especially in vaccinesin vaccines

Privatization & emergence of private Privatization & emergence of private sector developing-world industrysector developing-world industry• Political and economic thrust throughout worldPolitical and economic thrust throughout world

Fiocruz Facility - 2001Fiocruz Facility - 2001

http://www.pharmaceutical-technology.com/projects/fiocruz/

ECONOMICS OF DEVELOPED-WORLD ECONOMICS OF DEVELOPED-WORLD VACCINE INDUSTRYVACCINE INDUSTRY

In addition to development cost, very In addition to development cost, very substantial manufacturing fixed cost and substantial manufacturing fixed cost and difficulty in changing due to regulationdifficulty in changing due to regulation

Relatively low markup opportunity for Relatively low markup opportunity for mass-use childhood vaccinesmass-use childhood vaccines

Patent-based product exclusivity relatively Patent-based product exclusivity relatively rare, except on newer vaccines and not rare, except on newer vaccines and not generally on mass-use children’s vaccinesgenerally on mass-use children’s vaccines

PATENT ROLESPATENT ROLES

Barriers to entry generally based less on patents Barriers to entry generally based less on patents than on regulatory costs and economies of scale than on regulatory costs and economies of scale

But patents used on components (adjuvants, But patents used on components (adjuvants, particular molecules, and processes)particular molecules, and processes)

Vaccine industry therefore does have to cover Vaccine industry therefore does have to cover royalty costs for intermediates royalty costs for intermediates

VACCINE PATENT LITIGATION: VACCINE PATENT LITIGATION: RECENT CASESRECENT CASES

Boehringer Ingelheim Vetmedica v. Schering Plough (CAFC Boehringer Ingelheim Vetmedica v. Schering Plough (CAFC 2003) – process for growing and isolating virus2003) – process for growing and isolating virus

Medeva Pharma Ltd. v. Am. Home Prods. (2001) – method Medeva Pharma Ltd. v. Am. Home Prods. (2001) – method of detecting pertussis antigenof detecting pertussis antigen  

Embrex v. Service Engineering (CAFC 2000) – method of Embrex v. Service Engineering (CAFC 2000) – method of injecting vaccine into egginjecting vaccine into egg

Evans Medical v. American Cyanamid (CAFC 1999) – Evans Medical v. American Cyanamid (CAFC 1999) – pertussis antigen and vaccine based on it (parallel litigation pertussis antigen and vaccine based on it (parallel litigation in Europe)in Europe)

Connaught v. SKB (CAGC 1999) – purification of pertactinConnaught v. SKB (CAGC 1999) – purification of pertactin

BIOTECHNOLOGY AND PPPsBIOTECHNOLOGY AND PPPs

Developed world biotechnology based on NIH, biotech startups, Developed world biotechnology based on NIH, biotech startups, and license to Pharmaand license to Pharma

For developing world - PPPsFor developing world - PPPs• Especially HIV, malaria, TBEspecially HIV, malaria, TB• Public/private partnershipsPublic/private partnerships• Virtual development modelVirtual development model• Most of research (except clinical trials) in developed worldMost of research (except clinical trials) in developed world

These groups must be concerned about research tool patents, at These groups must be concerned about research tool patents, at least insofar as they do research in developed worldleast insofar as they do research in developed world

Patents Patents generallygenerally a less serious issue for developing world firms a less serious issue for developing world firms (for traditional childhood vaccines) – but access to trade secret (for traditional childhood vaccines) – but access to trade secret data may be harder!data may be harder!

PRIVATIZATIONPRIVATIZATION

Political & fiscal reasonsPolitical & fiscal reasons

Economic reasons – higher salaries Economic reasons – higher salaries and greater management flexibilityand greater management flexibility

ExamplesExamples• VACSERA (Egypt) 1973 and 2002VACSERA (Egypt) 1973 and 2002• BioFarma (Indonesia) 1997BioFarma (Indonesia) 1997

OTHER MOTIVES FOR CREATING OTHER MOTIVES FOR CREATING DEVELOPING NATION DEVELOPING NATION

MANUFACTURERSMANUFACTURERS

Vision of biotechnology as a technology of Vision of biotechnology as a technology of the futurethe future• Indian Department of BiotechnologyIndian Department of Biotechnology• Cuban CIGBCuban CIGB

Private sectorPrivate sector• Serum Institute of India 1966 Serum Institute of India 1966 • Shantha ~ 1990Shantha ~ 1990• BharatBharat 1996 (created by Krishna Ella, U 1996 (created by Krishna Ella, U

of Wis.)of Wis.)

DEVELOPING NATION DEVELOPING NATION MANUFACTURERS IN TODAY’S WORLDMANUFACTURERS IN TODAY’S WORLD

Acquisition by UNICEF favors Europe and Acquisition by UNICEF favors Europe and several developing-nation manufacturers – several developing-nation manufacturers – and UNICEF is the key international market and UNICEF is the key international market for the developing-world firmsfor the developing-world firms

There are now many developing-world There are now many developing-world manufacturers (20 in DCVMN), of whom 12 manufacturers (20 in DCVMN), of whom 12 have met WHO prequalification standardshave met WHO prequalification standards

THE CURRENT DEVELOPING WORLD THE CURRENT DEVELOPING WORLD SUPPLIERS TO UNICEF AND THEIR SUPPLIERS TO UNICEF AND THEIR

TECHNOLOGY SOURCESTECHNOLOGY SOURCES BioFarma (Indonesia, OPV, DPT)BioFarma (Indonesia, OPV, DPT)

• Dutch & Japanese governments Dutch & Japanese governments Fiocruz/Biomanguinhos (Brazil, YF)Fiocruz/Biomanguinhos (Brazil, YF)

• 1980-83, 2000 Assistance from Japan1980-83, 2000 Assistance from Japan• 1999, 2003 Alliances with GSK1999, 2003 Alliances with GSK

Institut Pasteur (Dakar, YF)Institut Pasteur (Dakar, YF)• Long term French inputLong term French input

Serum Institute of India (world’s largest producer of measles and Serum Institute of India (world’s largest producer of measles and DTP, 5DTP, 5thth largest vaccine firm) largest vaccine firm)• 1996 alliance with SKB1996 alliance with SKB• 200? NIH, PATH, WHO license for Meningococcal vaccine; also RIVM on 200? NIH, PATH, WHO license for Meningococcal vaccine; also RIVM on

Hib technologyHib technology Shantha Biotechnics (India, OPV, Hepatitis B)Shantha Biotechnics (India, OPV, Hepatitis B)

• Collaboration with Indian research laboratories and support from OmanCollaboration with Indian research laboratories and support from Oman

SOME OTHER MAJOR DEVELOPING SOME OTHER MAJOR DEVELOPING WORLD PRODUCERSWORLD PRODUCERS

Butantan (Brazil) Butantan (Brazil)

China (Chengdu, Lanzhou, Shanghai, Shenzen)China (Chengdu, Lanzhou, Shanghai, Shenzen)

CIGB (Cuba) (WHO prequalified)CIGB (Cuba) (WHO prequalified)

Instituto Finlay (Cuba, 6 vaccines)Instituto Finlay (Cuba, 6 vaccines)

Bharat (India) (NIH licensee on rotavirus vaccine, Bharat (India) (NIH licensee on rotavirus vaccine, grants from Gates)grants from Gates)

EXAMPLES OF OTHER CONTEMPORARY EXAMPLES OF OTHER CONTEMPORARY TECHNOLOGY TRANSFER PROGRAMSTECHNOLOGY TRANSFER PROGRAMS

Merck license to China (1989)Merck license to China (1989)

University of Ottawa & CubaUniversity of Ottawa & Cuba

Chiron-Behring joint venture to Chiron-Behring joint venture to manufacture rabies vaccine in Gujurat manufacture rabies vaccine in Gujurat (facility in 1991, venture in 1998(facility in 1991, venture in 1998

WHO and DCVMN (2001) (NIH is a WHO and DCVMN (2001) (NIH is a member)member)

BEGINNINGS OF GLOBALIZATION?BEGINNINGS OF GLOBALIZATION?

(E.G. DEVELOPING-NATION SUPPLY TO (E.G. DEVELOPING-NATION SUPPLY TO DEVELOPED-WORLD)DEVELOPED-WORLD)

GSK & Cuba – license to use Cuban GSK & Cuba – license to use Cuban meningitis B technology – 1999meningitis B technology – 1999

Berna Biotech (Swiss) purchase of Berna Biotech (Swiss) purchase of GreenCross (Korea) – 2002GreenCross (Korea) – 2002

Wyeth & Bharat – manufacture HiB Wyeth & Bharat – manufacture HiB on license - 2003on license - 2003

VACCINE TECHNOLOGY VACCINE TECHNOLOGY TRANSFER: SUMMARY CHARTTRANSFER: SUMMARY CHART

TECHNOLOGYTECHNOLOGY ECONOMICSECONOMICS POLITICSPOLITICS REGULATIONREGULATION LEGAL AND LEGAL AND INTELLECTUAL INTELLECTUAL PROPERTYPROPERTY

TECHNOLOGY TECHNOLOGY TRANSFERTRANSFER

HEROICHEROIC LowLow Low costLow cost Colonial policy Colonial policy plus altruismplus altruism

Nearly absentNearly absent AbsentAbsent Institut PasteurInstitut Pasteur

MID-CENTURYMID-CENTURY MovingMoving Increasing costIncreasing cost National health National health programsprograms

Strengthening Strengthening from a low from a low basebase

AbsentAbsent WHO, national WHO, national institutes, institutes, meetings, meetings, education?education?

ERADICATION ERADICATION PROGRAMSPROGRAMS

MovingMoving Pressure by Pressure by buyersbuyers

Altruism, global Altruism, global budget issuesbudget issues

Strengthening, Strengthening, WHO WHO prequalificationprequalification

Nearly absentNearly absent WHO, expert WHO, expert groups, donor groups, donor fundingfunding

CURRENTCURRENT HighHigh High cost/low High cost/low margin, margin, economies of economies of scalescale

Self-Self-sufficiency, sufficiency, biotechnology, biotechnology, donor politics, donor politics, privatizationprivatization

Very high Very high domestic and domestic and parallel WHO parallel WHO prequalificationprequalification

Strengthening Strengthening but mainly on but mainly on intermediates intermediates and processesand processes

WHO DCVMN, WHO DCVMN, biotechnology biotechnology programs, programs, corporate corporate strategic strategic alliances, alliances, donorsdonors

educationeducation

FUTURE?FUTURE? HighHigh Globalization?Globalization? Access?Access?

Financial Financial sustainability?sustainability?

ICH?ICH? Research tool Research tool issues?issues?

Bio-terrorism Bio-terrorism concerns?concerns?

Global Global integration?integration?

REFLECTIONS – TECHNOLOGY REFLECTIONS – TECHNOLOGY TRANSFER PATTERNTRANSFER PATTERN

Phase I (for vaccines, pre 1930) – artisan-level technology, Phase I (for vaccines, pre 1930) – artisan-level technology, easily copiedeasily copied

Phase II (for vaccines, 1930-1995) – growth of many Phase II (for vaccines, 1930-1995) – growth of many producers at local level, restricted by access to capital producers at local level, restricted by access to capital rather than to technologyrather than to technology

Phase III (1995-20??) – globalization and integration, Phase III (1995-20??) – globalization and integration, controlled by market structure, regulation, economies of controlled by market structure, regulation, economies of scale in research and productionscale in research and production

Note that all this depends onNote that all this depends on• The possible scale for the initial technology transferThe possible scale for the initial technology transfer• The timing of the spread compared with global political events The timing of the spread compared with global political events

such as the current moves to free trade and intellectual such as the current moves to free trade and intellectual propertyproperty

REFLECTIONS AND PENDING REFLECTIONS AND PENDING ISSUES FOR VACCINES - IISSUES FOR VACCINES - I

How long will the global donor market be there?How long will the global donor market be there?• Recent dependence on GatesRecent dependence on Gates• Possibility of donor fatigue – we’re now in a global version of the public health Possibility of donor fatigue – we’re now in a global version of the public health

modemode• Procurement policy?Procurement policy?• Relevance of growing private market in India (and possibly elsewhere)?Relevance of growing private market in India (and possibly elsewhere)?

The PPP’s:The PPP’s:• What likelihood of success?What likelihood of success?• What roles for DC or LDC manufacturers?What roles for DC or LDC manufacturers?• Continued support for procurement as the number of products grows (c.f. Continued support for procurement as the number of products grows (c.f.

problems of integrating Hepatitis B into the EPI package)?problems of integrating Hepatitis B into the EPI package)?

BioterrorismBioterrorism• Suspicions of Iran and CubaSuspicions of Iran and Cuba• VisasVisas• Export limitationsExport limitations• New development models in the U.S.New development models in the U.S.

REFLECTIONS AND PENDING REFLECTIONS AND PENDING ISSUES FOR VACCINES - IIISSUES FOR VACCINES - II

Strategic licenses between developed and developing Strategic licenses between developed and developing nation firms:nation firms:• Mechanism of technology transfer for serving LDC market – Mechanism of technology transfer for serving LDC market –

what incentives for each side? Role in access?what incentives for each side? Role in access?• Possibility of future off-shore production? – importance of labor Possibility of future off-shore production? – importance of labor

costs? Feasibility of maintaining quality standards? Trends in costs? Feasibility of maintaining quality standards? Trends in economies of scale? Trends in integration?economies of scale? Trends in integration?

Consolidation on a global scale?Consolidation on a global scale?• Economic or research motivations?Economic or research motivations?• Regulation, patents, and access to developed world markets?Regulation, patents, and access to developed world markets?• Choice of markets by developing-country manufacturers?Choice of markets by developing-country manufacturers?

QUESTIONS, CRITICISMS, AND QUESTIONS, CRITICISMS, AND SUGGESTIONS?SUGGESTIONS?

Thank you!Thank you!

jbarton@stanford.edujbarton@stanford.edu