Technology Transfer:

Developing Countries Vaccine Manufacturers’

Perspectives

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 Definition and Scope
Definition • The transfer of all technologies and knowledge necessary for
autonomous development and manufacture of vaccines,
from raw materials to licensed product, for domestic and
international markets, ideally including PQ
Goal • To increase access for local populations to needed vaccines
• To increase/pursue affordability
• To improve sustainability /self-sufficiency
• To build local knowledge in biotechnology /economy
• With positive public health impact on disease burden
• To share experiences and stimulate collaborations
Stakeholders • Industry
• Product development partners (PDPs)
• Government and public health agencies
• National Regulators
• Advocacy groups

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Technology Transfers need to be sustainable

• This implies that the technology should be applied to where it is

most needed (e.g. to address local or regional health needs) and if
it has wider applications it could result in the benefit of
international markets (supply to NGOs, e.g. MSF, Red Cross, etc.
and UN agencies such as UNICEF, UNHCR)

• The term “local” may also be used to imply nationality of

ownership, such that “local production” would refer to control
over production facilities by nationals of the host developing
country

• Manufacturers need to be profitable to ensure sustainability

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 DCVMN: 37 manufacturers from 14 countries and
number of birth cohorts regionally (in thousands)

11'135
4‘710

47‘164 61‘196

Middle East Africa

10‘793 Asia Pacific

Latin America

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Members as of July 2012 Members with WHO PQ vaccines http://www.who.int/immunization_monitoring/data/en/
 Analysis of Trends of Vaccine Types in
Technology Transfer over last 20 years*

Meningococcal (1)
DTP (2) Others (9) Influenza (20)
Pneumococcal (2)
Rabies (3)
Cholera (3)
Dengue (3)
Typhoid (3) Hepatitis (13)
Japanse encephalitis (4)
Polio (4)
Hemophilus (6)
Rotavirus (11)
Measles(7)
…a large number for influenza, hepatitis B, and rotavirus
*Increasing Access to Vaccines through technology transfer and local production. World Health Organization report available at
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http://www.who.int/phi/publications/Increasing_Access_to_Vaccines_Through_Technology_Transfer.pdf
 Vaccine Technology Transfer Flow
North-South / South-South/ South-North
PDPs**

Multinational Government
Companies Institutions*

Developing
Country
Manufacturers
*e.g. NIH, Universities
**e.g. PATH, IVI, Wellcome
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 Technology transfer in developing countries: a selection
Vaccine Provider/ Recipient Country of Direction Access
Facilitator destination
Pneumococcal GSK Biomanguinhos Brazil North-South Domestic
conjugate GSK GSK Singapore International
Rotavirus NIH/PATH Bharat India North – South International
NIH Butantan Brazil Domestic
NIH/PATH Wuhan/Chengdu China International
Measles- Institute of Serum Institute India North-South International (PQ)
mumps-rubella Zhagreb of India
Meningitis A NIH/PATH- Serum Institute India North-South International (PQ)
conjugate WHO of Indioa
Rabies Novartis Novartis India North-South International (PQ)
Crucell Zydus Cadila India International (PQ)
Japanese Intercell BioE India North-South International
encephalitis (Austria)
Cholera Crucell Statens Labs. Sweden North-North International (PQ)
Vabiotech Shanta India South-South International (PQ)
Influenza GSK Chengzhen China North-South Domestic
Nobilon GPO Thailand Domestic
Sanofi Birmex Mexico Domestic
Sanofi Butantan Brazil Domestic
Hepatitis E and NIDVD Xiamen Innovax China South-South Domestic &
HPV International
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Adapted from Milstien & Kaddar, Vaccine 28 (2010) 2115–2121; & http://www.who.int/immunization_standards/vaccine_quality/PQ_vaccine_list_en/en/index.html
 Example 1 : GSK-Biomanguinhos
private provider to government receiver
• Step-wise approach to TT of
Haemophilus influenzae b
1. Importation of bulk material and
formulation, filling, freeze drying
polysaccharides, packing and quality
control 1999-2003
2. Conjugation of polysaccharides and
tetanus toxoid using imported materials
2003-2007
3. Conjugation using locally produced
tetanus toxoid 2004-2006
4. Non-inferiority study using the 2nd step
vaccine as control 2005 2007
5. Licensing by ANVISA 2007
6. Pharmacovigilance
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* Kmetzsch CI, [et al.]. J Pediatr(Rio J). 2003; 79(6):530-6:
 Example 2 : NIH/CBER-SII
Government provider to
private company/consortium receiver
Meningitis A conjugate vaccine for MVP Consortium was created to
preventing outbreaks in African Belt address three critical elements
Countries
Conjugation
Technology
(CBER/NIH)

MVP
PATH-WHO
Raw materials Manufacturer
(SynCo) (SII)

MenAfriVac TM
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http://www.who.int/gho/epidemic_diseases/meningitis/en/index.html
 Achieving Success
Success Factors & • Clear outline of goals and expectations of both parties
• Well defined scope of technology transfer

Pre-Requisites* • Availability of skilled personnel

• Access to investment capital
• Availability of suitable input materials: e.g. APIs, excipients
• Adequate infrastructure development: electricity, water and
transport
• Access to relevant technologies
• Adequate regulatory environment
• Achieving economies of scale: sufficient market size to allow
efficient manufacturing, ideally of more than one product

Win-win • Equity between partners and equitable technology transfer

that meets both partners expectations

Sustainability • Recipient should have full Control once transferred , i.e.

‘freedom to operate’ internationally

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* Trends in local production of medicines. 2011 WHO report: http://www.who.int/phi/publications/en/
 Example 3: Influenza Vaccine:
Technology transfer from
Sanofi-Aventis to Butantan, Brazil
• An industrial plant has been constructed for production of
Seasonal and Pandemic vaccine

• Production of Southern Hemisphere vaccines and possible

production for Northern Hemisphere vaccines

• A pilot plant was refurbished for production of H5N1 and H1N1

strain pandemic vaccines

• Novel MPLA adjuvant has been tested for antigen sparing in a

clinical trial
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 Conclusions
We see technology transfer as
• transfer of all technologies, knowledge and skills necessary for de novo
autonomous manufacturing vaccines, from raw materials to the licensed
product, in a sustainable manner
Our aims are
• Meet local needs
• Develop expertise and acquire technologies
• Find appropriate partners
• Help to build regulatory capacity for approving and
monitoring production facilities
• Promote innovative financial incentives,
e.g. direct and indirect subsidies, and local procurement
• Seeking cooperation between stakeholders

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 Further considerations
• When most countries request for tech transfers, they may be driven by the need to
be self sufficient in vaccine production for both private and governmental
enterprises, as appropriate

• Efficient and sustainable production of vaccines requires achieving economies of

scale and this may be difficult in smaller countries, otherwise there will be
incurring higher cost for vaccines supply (e.g. Europe 90’s)

• It is important for governments to appreciate the risks of vaccines’ production and

scale, and ensure sustainability of local production while mitigating risks (e.g.
diversified product lines, stable procurement mechanisms)

• National policies with respect to local production of vaccines are best when
balancing the risks of investments and procurement, e.g. by encouraging
manufacturing by public-private partnerships

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Trends in local production of medicines. 2011 WHO report: http://www.who.int/phi/publications/en/
Thank You

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