who technology transfer initiative: supporting grantees ...biofarma 0.1 16 based on facility...

Partners' Meeting | Dubai | 25 March 20141

G. Torelli, WHO, 25 March 2014

7th Meeting with International Partners on Prospects for Influenza Vaccine Technology Transfer

to Developing Country Vaccine Manufacturers

WHO Technology Transfer Initiative: supporting grantees through

the next phase


FLUBIOVacina

Influenza

FLU VAC

Green Flu S CANTGRIP

Green Flu S+

NASOVAC

SIX PANDEMIC VACCINES APPROVED

PREQUALIFIEDPANDEMIC VACCINES TWO

TWO SEASONAL VACCINES APPROVED

PRODUCTION FACILITIES

PRE- and CLINICAL STUDIES

Enzavac

THREE

Nasovac-S MOREbeing completed

LAIV H5N2 Ph II - immunogenic

WHAT HAS HAPPENED SINCE THE LAST MEETING in 2013



� Desk review (reports, presentations, publications)� Assessment visits (9 sites Oct-Dec 2012) Assessment process:

Advance Questionnaire

Site visit with expert teams

Questionnaire covering:

Overall plansNational plansCurrent vaccines prodStaffing and structureProduction (process)FillingFacilityQA/QCSOPs

Training needsNational regulatory processProduct approval requirementsMarketing/business detailsBudgetary needsRsk analysis

2012 assessments




� 3-year workplans developed jointly with manufacturers,

based on the 2012 assessments

� New 3-year Cooperative Agreement with BARDA

� Collaboration with OGA-CDC

� 12 new grants issued

� Workshop on Enhancing Communication around

Influenza Vaccination (June 2013, Atlanta)

� Initiated work on conditions for sustainability




2016 TARGETS2016 TARGETS

Company / Country Vaccine Late stage** Licensed***

BCHT – China Seasonal LAIV X

Biofarma - Indonesia Seasonal X

Adjuvanted Pandemic [X]

Biovac – South Africa Seasonal* X

Adjuvanted pandemic* X

Birmex – Mexico Seasonal* X

Adjuvanted pandemic* X

Butantan – Brazil Adjuvanted pandemic X

Cantacuzino - Romania Seasonal X

Adjuvanted pandemic X

GPO - Thailand Pandemic LAIV (H5) X

Seasonal LAIV/IIV X

IVAC - Viet Nam Pandemic (whole virion) X

Seasonal (split) X

SII - India Seasonal LAIV (egg) X PQ?

Seasonal LAIV Tissue Culture X

Torlak - Serbia Seasonal (split) X

Pandemic (whole virion) X

• Fill-finish;

• ** includes vaccines in late stage clinical trials or regulatory dossier submitted;

• *** For pandemic vaccines outside of a pandemic, licensure = mock dossiers or other tentative approval;

11 7


2016 TARGETS2016 TARGETS

Company Current Predicted* NoteBirmex 0 120** Based on 15ug monovalent dose

Butantan 120 240 Based on adjuvanted7.5ug dose vaccine

Cantacuzino 9 36 Base on improved yields and adjuvanted 7.5ug dose

Torlak 0 6

Biovac 0 24** Based on target 8M seasonal supply.

SII 20 50** Based on submission TC LAIV and planned scale-up.

GPO 1.5 30** LAIV

IVAC 0 3**

Biofarma 0.1 16 Based on facility completion and adjuvant approval

BCHT 0 90** Based on strain-change approval

Green Cross 180 180 Has adjuvant technology, approved adjuvanted vaccine.

Total 330 795

.2016capacity by pandemicTable of maximum current and predicted

* to make estimations of predicted capacity we count vaccines that are licensed and also those that are in late stage development; ** unless company

has dose sparing technology approved or submitted for approval, we assume a dose of 15ug HA or a 107 PFU LAIV as experienced with H1N1,

enabling a conversion factor of 3 over the maximum annual seasonal capacity.

Total pandemic production capacity

at least 600 million


H7N9H7N9

� 4 grants for H7N9 development

– BUTANTAN, Inactivated � to Phase I

– SII and IEM, LAIV � to Phase I

– Bio Farma

� 2 other manufacturers working on H7N9 (IVAC, BCHT)

� Barriers:

– Reagents – a very long wait

– Ferret studies: costs, lab, availability of animals

� WHO CONDUCTING COORDINATED FERRET STUDIES

–

From Virology Down Under and Dr. Ian M Mackay


Meeting our targetsMeeting our targets

� A lot of progress has been made

– >300 million pandemic vaccine capacity already.

� A lot still needs to be made 2013-2016

– To bring candidates to approval, and

– To add another 300 million doses pandemic capacity

� Challenges

– Approval pathways for both seasonal and pandemic

– Sustainability


Animal studiesAnimal studies

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Activity A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D

Preclinical testing x x x x x x

Preclinical study x x x x x

Challenge in ferrets x x x x x x

Non-clinical mice study x x x x

Toxicology & ferret studies. x x x x

Preclinical immunogenicity x

Preclinical toxicology x x x x x

Repeated dose toxicity x x x x x x x x

Developmental toxicity x x x x x x x x x x

Immunogenicity study x x x x x

Single dose toxicity x x x x x

Immunogenicity x x x x x

Preclin immunogenicity (mouse) x x x

Toxicology (rat) x x x

Toxicology (mouse/rat) x x x x x x

Ferret challenge (conducted by WHO) x x x

Preclinical immunogenicity x x x

Preclinical toxicology x x x x

Immunogenicity (mice) x x x

Toxicology (rat) x x x x x x

Ferret challenge x x x x x x


Clinical TrialsClinical Trials

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Activity A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D

Phase I x x x xPhase II x x x x xPhase III x x x x x xPhase I x x x x x xPhase II x x x x xPhase III x x x x x x xPhase I x x x x x xPhase II x x x x x xPhase III x x x x x xPhase I x x x xPhase II/III x x x x x x xPhase I x x x x xPhase II x x x x x x x xPrime-Boost x x x x x xPhase I x x x x x xPhase II x x x x x x x x x x x xPhase I/II x x x x xPhase II/III x x x x xPhase I x x xPhase II/III x x x x x x x xPhase I x x x x x xPhase II/III x x x x x x xPhase I x x x x xPhase II x x x x x


Support to manufacturersSupport to manufacturers

� WHO technical support will continue

– Technical advice,

– Visits by TAG and consultants,

– Interactions with MoH

� In collaboration with PATH

� Particular focus on support for preclinical and clinical development:

– Study Protocol Templates being developed

– Workshop for manufacturers and NRAs the design, conduct and

regulatory review of non-clinical and clinical studies in support of

initial vaccine approval, annual strain change, process

modification, and prequalification (tentatively end June/early July)


Maintaining the gainsMaintaining the gains

� Sustainability of the capacity that you are establishing

needs to be addressed.

� The HHS/WHO Workshop Series has allowed the

stakeholders to comprehensively examine the different

factors and drivers involved.

� You will hear tomorrow how the knowledge that was

gained will be used to move this agenda forward.

who technology transfer initiative: supporting grantees ...biofarma 0.1 16 based on facility...

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