Department of Biotechnology Ministry of Science and Technology ...

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Dec 3, 2012 (4 years and 11 months ago)

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1

Department of Biotechnology

Ministry of Science and Technology

Government of India


CALL FOR PROPOSALS U
NDER VACCINE GRAND C
HALLENGE PROGRAMME


The Department of Biotechnology, Ministry of Science & Technology invites project
proposals from Indian scientis
ts for Research and Development under the recently
approved Vaccine Grand Challenge Programme (VGCP). The broad purpose of the
programme is to support research of scientific or technological nature that will
either enhance our understanding and provide a s
cientific basis of future vaccine
design and development or facilitate accelerated development and validation of
specific new or improved version of existing vaccines. The details of the programme
may be seen at DBT website
(
http://dbtindia.nic.in
)


The rapid review process and flexible funding system is designed to swiftly award
funding to scientists who are testing
novel
ideas that could lead to breakthroughs
in national and global health, as well as to accelerate de
velopment of existing leads.


The specific objectives of the programme are :


i.

To support novel ideas that will improve our understanding of how vaccines
can be designed, developed and delivered, particularly against diseases where
past research has not
been successful;

ii.

Development of specific new, improved or easy to deliver vaccine candidates

for all infectious and non
-
infectious diseases;



iii.

Vaccine related technologies: Novel platform technologies for vaccine delivery,
vector and related
biology and
adjuvants,
tools for measuring immune
response and synergistic use of multiple technologies in the vaccine field
;




2

iv.

Immunobiology related to potentially vaccine preventable diseases; newer
insights into immunobiology of major infectious or
chronic diseases and
cancer, new tools and technologies for defining protective immunity where it
is not known, immunity at extremes of ages, innate immunity, mucosal
immunology, immunological memory and any other relevant areas of vaccine
science;

v.

Imp
roved understanding of why oral vaccines are less efficacious in
developing countries
;



vi.

Development of infrastructure for pilot production and testing of vaccines

and



vii.

Preclinical and clinical validation of specific vaccine candidates
.


Full proposals a
nd concept proposals are welcome in areas of infectious disease,
chronic disease
including

cancer, degenerative diseases

and any others that are
relevant. N
etwork projects involving multiple institutions are encouraged. Creation
of infrastructure, trainin
g or
support for
small science meetings relevant to
proposed research will be considered. Public private partnership is e
ncouraged and

will be supported on the lines similar to existing DBT PPP programmes. Projects of
upto 5 years will
be
considered for in
itial funding
when relevant although it is
expected that the usual duration will be 3 years
. You may also enquire about any
other support that will enhance your own and group’s scientific productivity. A
specific programme advisor will be assigned to the
project who will communicate
with the investigators.

The format for submitting R&D projects may be seen at website:
www.dbtindia.nic.in
. The interested investigators may submit 10 copies to
Dr.
T.S.Rao, Adviser
, Department of Biotechnology, Ministry of Science and Technology,
Block

2 (6
th
-
8
th

Floor), CGO Complex, Lodi Road, New Delhi


110 003 Telefax :
011
-
24364065
, Fax : 011
-
24362884, E
-

mail
:
tsrao@dbt.nic.in
,
within
sixty days
from publication of this advertisement.

* * * * *


3


Department of Biotechnology

Ministry of Science & Technology,

Government of India.



ESTABLISHMENT OF
VACCINE
GRAND CHALLENGE PROG
RAMME
AT
DEPARTMENT OF BIOTEC
HNOLOGY, MINISTRY OF

SCIENCE AND T
ECHNOLOGY,
GOVERNMENT OF INDIA
.



A.

Introduction :


Each year 9.7 million children die
of infectious diseases,
4 million of them before
reaching
5 year of
age,
the
majority of these in developing countries. Development and deployment of effective vacci
nes
can prevent at least 2.6 million of the childhood deaths. Further, recent developments show that some
of the important cancers and autoimmune diseases are potentially vaccine preventable.


The grand challenge approach was originally deployed to solve,

unresolved mathematical theorems.
In recent years it has been used to create a list of scientific and technological challenges that must be
overcome to develop effective vaccines

by the Gates Foundation through global consultations. The
DBT has adopted t
his approach and a national consultation for vaccines. The Vaccine Grand
Challenge programme
include
s

the following:


1.

Accelerate development of new vaccines/improved single vaccines against (i) Infections
where natural infection is protective e.g. Rotaviru
s, Typhoid, Cholera, Japanese
encephalitis (ii) Against infections where natural infection is partially or minimally
protective e
.
g. HIV, TB, Malaria, Dengue, Influenza, Helicobacter
p
ylori; this may
require clever immuno design or delivery and adjuvants
to achieve desired efficacy
.



2.

Accelerate development of vaccines against cancer where there are considerable S&T
challenges, but there is also proof of principle that vaccines will work. For India, early
acceleration is needed to generate intellectual
property to remain globally competitive
.



3.

Create single dose

vaccines
,


4.

Create vaccines that do not require refrigeration
,


5.

Create needle
-
free vaccines
,


6.

Devise reliable testing systems for new vaccines
,



7.

Find novel ways to design analysis for effecti
ve, protective immunity
, and



8.

Learn which immunological responses provide immunity.


4



To accelerate development of existing candidates or develop new ones, an enterprise model for R&D
is now globally recommended as against traditional scientific project
funding. This is because vaccine
development is a long, multi stage process where critical actions must be taken in synergy and not
sequentially. The key steps in the process are (i) Develop specific candidates, create a pipeline as one
does not always k
now which one will work (ii) Create a stable formulation under GMP (iii)
Conduct
t
oxicolog
ical tests
in animals (iv)
Ensure h
uman safety (v)
Prove e
fficacy in humans (vi)
Establish
r
eproducible manufacturing under GMP (vii)
Obtain r
egulatory approvals (vi
ii)
Conduct p
ost market
monitoring for

rare but serious side effects.
Given stringent regulatory requirements,
the
need for
documentation is unique and data must be secured for ten years even after commercial release.


Varied type of infrastructures and
services, approved by FDA, and DCGI must be available, accessible
and affordable to investigators and SME’s to meet above steps.


Teams, must be sustained for a decade or more for continuity and focus, and new skills must be
incorporated to fulfill evolvin
g requirements.


Flexible governance and granting systems must ensure that
as well as
additional science funding,
cooperate granting system (where funding agency, project managers and investigators work as a team
for collective decision making) and subco
ntracting mechanisms are in place.

Rapid decision making
must allow building all
iances and partnerships. Public
-
private

partnership
s

national

and

global

where
necessary must be forged by deployment of a variety of existing Government of India schemes
throu
gh single window mechanisms. Th
e
s
e

mechanisms must be administered through
a
Task Force
in which members are vaccine

and
product development specialists, and
are
engaged and available on
long term basis.


In the Eleventh Plan, DBT had proposed the Grand
Challenge Scheme to create the above operational
conditions and granting systems and this was approved by the Planning commission. Given India’s
manufacturing prowess in the vaccine sector and a rapidly rising global demand, vaccine R&D is also
a tremendo
us economic opportunity.


B.

Vaccine Grand Challenge
P
rogramme
(VGCP)
-

The proposal



The Department of Biotechnology (DBT) initiated a programme to develop vaccines through
National Jai Vigyan Mission Programme on S&T for generation of new vaccines.
Several
candidate vaccines emerging from this effort are now in pipeline and some of them are into
pre
-
clinical or clinical trial stages e.g. vaccines for rotavirus, cholera, DNA rabies, Japanese
encephalitis, malaria etc. Vaccine candidates are available

for tuberculosis, typhoid, dengue
which need accelerated development through
GMP product formulation and
preclinical and
clinical development. R&D will be accelerated in these above areas and also where progress is
slow e.g. cancer vaccines, adjuvants and

vectors. Finally, the other identified grand challenges
(
as
listed in
the introduction
) will be funded through competitive and co
rporate
mechanisms.
Vaccine related infrastructure will be supported and existing inadequacies will be addressed
decisively.








5

Under Jai Vigyan Mission, few novel vaccine leads have emerged.
However, several
weaknesses were identified during the analysis of 10
th

five year plan programme that serve as
barriers to technology/product development. These are (i) the

time taken
on each phase of
activity is too long (ii) decision making DBT committees
that are fashioned around science
funding meet infrequently for effective accelerated product

development by (iii) resources
required were grossly underestimated. (iv) Industry finds

the long gestation and paucity of
funds for continuing investment unaffordable (v) lack of public private partnership mechanism
in DBT in the past vi) Need regulatory complicity to get FDA
and DCGI

approvals with strong
financial implications
. (vii) compe
tition from global companies (viii) lack of preclinical and
clinical development skills in SME’s engaged in vaccine work (ix) Two vaccine projects
(Rot
a
virus & Malaria) were salvaged with massive help from Gates Foundation or its
subsidiaries in the past,
but this is now becoming difficult to access and they will directly
giving money to multi nationals and DBT’s inability to financially support industry R&D
substantially is a limiting factor. (x) inability to engage problem solving consultants due to
their

high fees. Vaccine R&D poses a number of risks to companies, which choose what they
perceive as the best business opportunities. The vaccine business is expensive, risky and with a
smaller market than pharmaceuticals. Marketing vaccines can be uncertain v
accines can be
variable and unpredictable.Uncertain demand for vaccine is one obstacle, especially since
much of the anticipated market is in developing countries, where the ability to pay for a
vaccine is limited so the companies fear that they will not b
e able to charge commercially
feasible prices.



The vaccine `Grand Challenge Programme’ is an improvement on the Jai Vigyan Mission in
that it attempts to overcome/address most of the
above
identified deficiencies.


C.

Mission of the Proposed
Programme



To accelerate development of affordable, effective vaccines, adjuvants, diagnostics for
measuring immune response and vaccine delivery technologies and to facilitate clinical
development consistent with highest ethical and regulatory standards.


D.

Objec
tives:



To accelerate development of candidate vaccines for which earlier leads are available and to
take them through pre
-
clinical and
,

if successful
,

clinical development and commercialization.



i
)

To develop and commercialize vaccines against the
following

diseases

:


-

Rotavirus

-

Cholera

-

Typhoid

-

Rabies ;
a
nimal, human (DNA b
ased
)

-

Anthrax




6


ii)

To take into pre clinical

and clinical development new
vaccine
s

against

:

-

Malaria

-

Dengue

-

Tuberculosis

-

Japanese Encephalitis




iii)
To take
through
R&D and
at least
upto
pre
-
clinical

development the following new



and improved vaccines :


-

Influenza (H
5
N1)


-

Hepatitis E


-

Protein based pneumococcal vaccine


-

Acellular pertussis vaccine

-

Paratyphoi
d vaccine



iv
)

To investigate new
approaches for

development of
vaccines against



-

HIV


-

C
ancer




v) A
ccelerat R&D programmes for development of adjuvants, delivery systems and




vectors. Support future grand challenges in V
accinology
,




Research will be initiated to develop new vectors that could be used for delivery of
potential

vaccine antigen. These could be based on attenuated viruses or non
-
pathogenic bacteria. These vectors, besides delivering the vaccine antigen, may
also
provide the adjuvant effect. In addition, these live vectors are likely to give Th1
immune responses that are considered important for viral vaccines.





iv)

To create and strengthen the following vaccine related infrastructure and facilities




Infr
astructure for pre
-
clinical development
i.e. animal testing.





I
mmunogen design centre with
process development and formulation lab.
to be
managed by an

existing DBT institute.




Clinical development unit for design, analysis, implementation of phase I/III

clinical
trials in an existing
DBT institute
as an anchor unit and

supported by

partner centres in
six not for profit institute
s
/centres in public and
nongovernmental

sector. These
facilities will be extended to SMEs and public sector institutions.



vi
i)

To manage technology transfer from academia to industry in the vaccine field.


viii)

To forge international partnership in vaccine development for
licensing

of key
technologies, and for co development of hard to develop vaccines.



ix)

To set up Tec
hnology Policy Unit for vaccines.


7


E.

Outcomes for performance measurement:




Unlike R&D, the vaccine development consists of a defined set of tasks that have to be
conducted in a certain sequential order. First, a specific antigen and formulation must
be
investigated in efficacy and safety tests. Second, a process must be developed and validated by
which the vaccine can be reproducibly manufactured at large scale, at reasonable costs, and
with a specified quality. Third, the prototype vaccine must be te
sted in sequential clinical trials
including pre
-
clinical toxicology studies in order to establish an efficacy and safety profile in
humans and to develop schemes by which the vaccine can be optimally applied under field
conditions and in different target
and tests, a detailed documentation of all methods, trials, and
findings is finally submitted for regulatory approval followed by commercial launch of the
vaccine. It takes minimum 12
-
15 years from R&D level to product development.


Performance of the
Vacc
ine
Grand Challenge Programme will be measured in terms of
the following :




Evaluation of candidate vaccines against
Rotavirus, cholera, typhoid, rabies
in clinical setup
and commercializ
ation
.



Candidate vaccines against m
alaria, dengue, tuberculosis, Jap
anese encephalitis will be taken
into pre
-
clinical testing and clinical development upto phase
-
I/II.



Development of new and improved candidate vaccines for influenza, hepatitis
-
E, protein based
pneumococcal vaccine, acellular pertussis and paratyphoid



D
evelopment of
new
technology platforms in
vaccin
ology and develop new
adjuvants and
delivery system
s
.



To set up major infrastructure including establishment of units for clinical development
service, immunozen design, technology policy , BSL3 facility and

process development
&
formulation lab.
etc.



Establishment of FDA standard data management centre (health bioinformatics).


F.

Organizational Structure
-

Governance



The Vaccine Grand Challenge Programme would be governed through the Vaccine
Developmen
t Board appointed by the Department of Biotechnology, Ministry of Science &
Technology with support of Technical Advisory Groups and vaccine specific programme
committees (
O
rganizational structure
at Annexure
-
I)


G.

Some of the key features for granting m
echanisms to be deployed through this assessment and
decision making ma
chinery.


1.

Preliminary grant for nascent ideas followed by full grants for those that show promise.


2.

Planning grant for proposal writing as a team with consultant support.


3.

Centre of Exc
ellence and programme support as per existing DBT schemes but through the
vaccine grand challenge apex committee.


8


4.

Research strengthening grants for retaining key team members on contract hiring basis,
extendable every 5 years.


5.

Engagement of consultants f
or problem solving as per Government of India norms.


6.

Public Private Partnership projects strictly according to SBIRI and B
IPP

( when approved),
and pharma fund rules.


7.

Cooperate grants, where R&D is jointly managed by investigators and by a professiona
l team
engaged by the programme on a part time basis.


8.

Subcontracting of work to not for profit organization, public institutes and industry through an
open, competitive process.


9.

Consortium projects with other ministries or agencies in the country and int
ernationally.


H
.

Location:



Initially at Department of Biotechnology, CGO Complex, New Delhi, subsequently it will be
shifted to new place where premises will be hired and renovated.


I.

Specific Activities for 200
8
-
0
9




The programme would start imme
diately after the necessary approvals have been obtained. The
VGCP would address accelerated evaluation of candidate vaccines developed under DBT
supported projects. Additionally, the following infrastructure related measures will be initiated
i) clinical
development unit and atleast two partn
er centres ii) Immunogen design, process
development and formulation lab.
iii) Data management centre

and t
echnology policy unit for
vaccines in an existing institute.


J.

Functions:



The
VGCP
will serve

as a nation
al
programme
devoted to addressing
vaccine and related,
needs of India’s public health system

specially for national immunization programme
.
Its focus
will be on development of cost effective vaccines and vaccine delivery systems.
It will
do so
by accelera
ting development of already generated leads, as well as through new candidate
development. The other function will be to create an enabling infrastructure to serve public
sector and SME needs. It will also
provide
enabling
support

to concerned agencies

fo
r
diffusion of the technologies into the social systems.

Finally, it will attempt to create cost
reduction strategies for existing products.



9

K.

Linkages



The
VGCP
will primarily function through effective linkages with
all institutions in India
where
the vaccine related projects are implemented by DBT including institutions of
ICMR
,
DST,
CSIR
,
small and medium
vaccine industries,

medical and engineering schools in

addition
to DBT supported autonomous institutions
.

The s
ervices available will be access
ible to all
agencies. The
unit
will

work closely with and through the recently established Translational
Health Science and Technology Institute, particularly its extramural unit.



Several types of linkages will be established (i) Academia


Academia (i
i) Academia
-
Industry
(iii) International linkages

such as NIH/NIAID, GAVI, PATH etc
.



L.

Relationship with other
international
organizations



The
VGCP
would develop a strong international cooperation programme under bilateral
collaborations or with inte
rnational agencies pursuing similar
vaccine development projects
especially with NIH, NIAID, WHO, Gates Foundation, PATH, ICGEB and other international
institutes
. The
unit
may enter into agreement for cooperation with relevant national, regional or
intern
ational organizations, foundations and agencies, both public and private.


M.

Need and justification for the project in the context of national priorities:


There are many major reasons for investment in this area.


1.

India accounts, for nearly 1/3
rd

of all

vaccine preventable diseases.


2.

The global vaccine market is likely to increase from US $ 6 billion to US $ 31 billion
by 2013.


3.

Vaccine biologicals are a major contributor to be biotech industry turnover in India.


4.

India is a global brand as a reliable, h
igh quality vaccine manufacturing nation.


5.

A large pool of biologists, bioengineers, clinical trialists, infectious disease specialists,
CRO’s, medical schools offer a unique talent pool in this field.


6.

India has a well established private and public immun
ization programme with capacity
to deliver vaccines in the remotest part of the country, to the poorest people.




Nature and magnitude of problems to be addressed:

The

main focus in terms of problem
will be development of vaccines and vaccine related tec
hnologies for major infectious diseases
and cancer vaccines, vaccine delivery technologies, adjuvants, vectors, innovations such as
needle free injection, single dose immunization, mucosal
vaccines

etc.



10

N.

Estimated yield from the Project and economic im
plications



The

expected economic benefits by development and commercialization of rotavirus and
cholera vaccine alone would generate revenues of ~Rs.300
-
400 crore annually and the malaria
and dengue will be ~Rs.200
-
300 crore turnover annually. Further,

the infrastructure created
under vaccine grand challenge programme for providing services through clinical development
services and technology policy units will generate additional revenue by providing services to
SMEs as per international standards servi
ces. Further va
ccine
s

are the fastest growin
g biotech
area with the entire pharma
/biological sector and India
is considered a global hub in this sector.
The demand is high because GAVI, supported by multiple donor, purchase through UNICEF
for the entire d
eveloping world. India itself is a large consumer for its immunization
programme.


Further t
he global vaccine market is set to become almost double by the year 2010 and
expected to reach $21.05 billion by 2010 from $11.42 billion in 2006 and $31.36 billio
n by
2013. It is also expected that unprecedented product innovations and global recognition of the
benefits of immunization with new and improved prophylactic, therapeutic and adult vaccines
will be available in the market.


A
ccording to a recent Frost
& Sullivan report, the developed markets in North America,
Europe and Japan account for almost 80% of the global vaccine market. However, there is a set
of emerging markets such as Africa, Asia (India and china in particular) and Latin America
which are fa
st becoming the backbone for the growth of global vaccines market. There is a real
opportunity for the Indian vaccine manufacturers to tap these emerging markets, they could
also ramp up their R&D pipeline by attracting large funding that are going into d
eveloping
vaccines by focusing on biotech based vaccines.