POST 00920E : JE VACCINE INTRODUCTION

Follow-up on Post 00912E

3 May 2006

Only one contribution was received on this topic, by Anil Varshney
(mailto:[email protected]) from India.

Dear Vikram

Good to see you active on this forum.

As we discussed earlier more than a month back I made querries and search
to find out other manufacturers of this Chinese JE vaccine , I could not
find any. I had sent a request to Julie Jacob of PATH who is the Director
JE program and also to IVI in Seoul - but no response either.

The JE vaccine in public sector was first introduced in Andhra Pradesh in
2001, at that time I was serving as Project manager for PATH and provided
the technical expertise to the GOAP.

During that period also the possibilty of importing JE from China was
explored, but since at that time that particular vaccine was NOT
WHO-approved, the idea was shelved. Later standard mouse brain JE vaccine
was imported from Green Cross via UNICEF through open bidding.

The same JE vaccine was introduced in the state in 2001-02. PATH helped
the GOAP in this process as well as in surveillance and training in the
highly endemic districts for management of the JE cases.

The Chinese vaccine is better than the mouse brain. I also understand that
facilities at Kasauli were upgraded to manufacture the mouse brain vaccine
to meet the demand. Please also note that a number of importers from India
actually import the mouse brain vaccine for open market which also creates
shortages.

In 2001 there was a talk about South Korea being licensed to produce the
Chinese vaccine. I am not sure of the position now, there may be some
restriction by parent company if any licence has been granted ?

One has few choice :

Import from China as per their terms & conditions.
Production in the country by licencing of Chinese version.
Develop own version of JE ( needed as JE is endemic in many states and
routine immunization would need millions of doses every year).

As regards efficacy and protection the available data is supportive of the
same as being efficacious and having long immunity.

Regards ,

Dr Anil Varshney

former Project manager PATH
Former consultant to :

GOI, WHO- SEARO, UNICEF

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POST 00926E : JE VACCINE INTRODUCTION

Follow-up on Post 00912E and 00920E

18 May 2006

Julie Jacobson (mailto:[email protected]) from PATH is sending a
substantial update on JE Vaccine introduction. For more information,
please contact: [email protected]

or visit the Japanese Encephalitis Project Website at :

http://childrensvaccine.org/html/jep.htm

In response to the recent exchange on TechNet concerning Japanese
encephalitis (JE) vaccine introduction, and India's decision to introduce
JE vaccine specifically, I would like to provide an update and hopefully
clarify a few points. JE vaccination remains the best known way to prevent
the disease and, increasingly, countries seeking to prevent JE have
vaccine options available to protect their populations.

Last year, a JE outbreak with 6,584 cases claimed over 1,800 lives in
India.

Subsequently, and after careful review of its options, the Indian
ministry of health and family welfare decided to import the live,
attenuated vaccine known as the SA 14-14-2 vaccine from a Chinese
manufacturer.

This vaccine has been shown to be a highly effective and
safe vaccine, with almost 20 years' experience of its use in China.

It is
the only internationally licensed JE vaccine currently available in
sufficient supply to meet the needs of the Indian immunization program.
India intends to begin immunizing in high-risk districts this year.
Similarly, Nepal has decided to import the SA 14-14-2 vaccine for
widespread use this year after suffering a terrible outbreak with 2,341
cases in 2005.

The SA 14-14-2 vaccine has become more widely available in recent years.
It has been imported and licensed for use in South Korea (since 2001) and
in Nepal.

Use of the vaccine in these sites has provided excellent
efficacy and safety data.

In June 2005, WHO's Global Advisory Committee on
Vaccine Safety reviewed data on the vaccine and acknowledged its excellent
safety and efficacy profile (World Health Organization.

Global Advisory
Committee on Vaccine Safety, 9-10 June 2005.

Weekly Epidemiological
Record. 2005;80(28):242-243).

Its efficacy has been estimated to be
between 80 to 99 percent following a single dose.

Last year The Lancet
reported results of a trial in Nepal that showed a single dose of SA
14-14-2 JE vaccine was 99 percent effective after 1 year in protecting
children from JE.

Several studies have shown that side effects after
immunization with SA 14-14-2 JE vaccine are rare.

Where side effects have
been noted, the most common ones are fever and local reactions such as
tenderness, redness, and swelling.

The only other currently available JE vaccine is the inactivated mouse
brain-derived vaccine used by Japan, Taiwan, and Vietnam, among other
countries.

In India, the inactivated mouse-brain derived vaccine produced
by CRI, Kasauli, is used, but supply of this vaccine is limited.

Only
about 500,000 doses are produced annually-about enough to vaccinate a
maximum of 250,000 children.

The dosing schedule for this vaccine is
complex, with several doses required to achieve protection, and there are
issues with compliance and affordability with this vaccine.

Nonetheless,
it will be important to continue JE immunization in those Indian states
that have already been protecting infants and children previously with JE
vaccine, even as India expands its JE coverage to include other states at
risk of JE.

Regarding the question of prequalification of the SA 14-14-2 vaccine, the
process of WHO's prequalification of a vaccine involves evaluation to
determine the acceptability of a vaccine to enable procurement by United
Nations (UN) agencies such as the United Nations Children's Fund (UNICEF).
WHO prequalifies vaccines because international procurement agencies do
not have a national regulatory body to advise them on the appropriateness
of a vaccine.

At the national level, this responsibility lies with the
National Control Authority.

WHO does not approve vaccines; it only
prequalifies them for purchase after careful evaluation related to safety,
efficacy, and production.

There are currently no prequalified JE vaccines,
as no manufacturers have applied for prequalification.

The inactivated
vaccine, which has been used widely, was never prequalified by WHO.
Currently, a file is in preparation for submission to WHO for
prequalification of the SA 14-14-2 JE vaccine.

Concerning JE vaccines under development, two are in advanced stages of
clinical development:

• ChimeriVax-JE

The ChimeriVax-JE (Acambis) vaccine is not yet available and not licensed
anywhere, but trial results so far look promising. Acambis has a
collaboration with Bharat Biotech in India. The vaccine is a live,
recombinant JE vaccine (which uses Yellow Fever 17D as its backbone
combined with the SA 14-14-2 vaccine virus. Phase III clinical trials are
underway in adults in Australia, but no pediatric trials have begun. Plans
are underway to initiate trials in children and infants in India.

• Intercell's JE vaccine

An inactivated, vero-cell derived JE vaccine is under development by
Intercell but is currently not licensed or available. It is undergoing
adult Phase III clinical trials in Europe, the United States, and
elsewhere, but no pediatric trials have begun. This vaccine also looks
very promising. Intercell has a collaboration with Biological E in India
to develop this vaccine. Plans are underway to initiate trials in children
and infants in India.

No other JE vaccines are currently available and, as yet, none of the new
JE vaccines being developed has been licensed for infants and children,
the primary group to be targeted for this vaccine in endemic settings.
Information from clinical trials in this age range will be important
before the vaccines under development can be considered for use in JE
immunization programs.

With regards to the availability of the live SA 14-14-2 vaccine from
China, the vaccine is produced by several producers in the country but
currently only the Chengdu Institute of Biological Products (CDIBP) has
authority to export outside of China. Supply from this manufacturer is
being increased and pricing for public sector lower income countries (GNP
> 1000USD) is available to facilitate access.

It is hoped that the range of JE vaccine options and supply will expand in
the future. PATH is closely following the progress in development of these
vaccines. An encouraging sign is that countries like India, South Korea,
Nepal, and others are taking steps to protect their populations by
licensing JE vaccines at country level. As JE immunization plans move into
action, even more infants and children will be spared from the impact of
this devastating disease.

I hope this update about JE vaccine options is useful.

Julie Jacobson, MD
Director, PATH's Japanese Encephalitis Project
PATH

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POST 00934E : JE VACCINE INTRODUCTION

Follow-up on Posts 00912E, 00920E and 00926E

2 June 2006

Two further contributions were received on this topic. The first is from
Vijay Kiran (mailto:[email protected]) from India and the second from
Julie Milstien (mailto:[email protected]) from the United States /
France.

This is in response to the update presented by Julie Jacobson on the
Introduction of JE vaccine in India.

The introduction of SA-14-14-2 is a boon for the Southeast Asian region
specially India in view of the disease burden and the ineffective vector
control measures.

May be it is useful to mention the historic perspective of the mouse brain
vaccine usage in Andhra Pradesh, the challenges of vaccine procurement,
vaccine administration, the vaccine efficacy, and the Political commitment.

I request Julie Jacobson to give a little background on the decision to
changeover from Mouse-brain vaccine to introduction of SA-14-14-2.

Dr. Vijay Kiran,
Country Representative
IMMUNIZATIONbasics (USAID)
India

Dear Claude,

Julie Jacobson has given persuasive arguments for the use of SA-14-14-2
live attenuated JE vaccine.

If I were in her place, I would probably do
exactly the same thing.

So why has WHO not given its unqualified support
to the product?

The opinion of the GACVS speaks only to the reported
adverse events related to use of the product and the design of the
clinical trials to assess safety, but does not consider production
consistency nor quality of the product.

These depend on the existence at
the level of the manufacturer of a well thought out and efficient quality
system, to ensure consistency of production.

The quality system should be
overseen by a fully functional national regulatory authority (NRA).

This
is the kind of information that the WHO prequalification process can
evaluate, and at present there is no other process available to provide
this information objectively at the global level.

Countries should ensure that the vaccines they use are under the oversight
of independent and competent NRAs, and that these NRAs are satisfied with
the consistency and quality of any vaccines they intend to use, as well as
with clinical information on their safety and efficacy. If this assurance
cannot be provided, they should avoid using products that do not meet
these criteria. The WHO prequalification process provides this kind of
assurance for countries lacking such NRA input. It will be to everyone's
advantage if the SA-14-14-2 product as manufactured by Chengdu can
successfully undergo the prequalification process as soon as possible.

Julie

Dr Julie Milstien,
Montpellier, France

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POST 00940E : 00934E : JE VACCINE INTRODUCTION

Follow-up on Posts 00912E, 00920E, 00926E and 00934E

15 June 2006

Julie Jacobson (mailto:[email protected]) from the United States,
responds to Vijay Kiran’s request.

In a recent exchange on TechNet concerning Japanese encephalitis (JE)
vaccine introduction, there was interest in knowing more about the
decision to use the SA 14-14-2 vaccine in India, and specifically in
Andhra Pradesh.

As Dr.

Vijay Kiran points out, the Indian state of Andhra
Pradesh (AP) previously used the inactivated, mouse brain-derived vaccine
to prevent JE.

Through a partnership project between the Government of
Andhra Pradesh (GoAP) and PATH, more than 4 million doses of this JE
vaccine were procured from both domestic and international markets between
2000 and 2005 all purchased directly by the AP government.

This program
was a landmark for India showing the systematic use of vaccine for JE
control could work in India.

Last year the Indian Ministry of Health and Family Welfare made the
decision to license and import the live, attenuated JE vaccine known as SA
14-14-2 from its manufacturer in China, the Chengdu Institute of
Biological Products.

The SA 14-14-2 vaccine has been shown to be a highly
effective and safe vaccine, with almost 20 years' experience of use in
China.

It is the only internationally licensed JE vaccine currently
available in sufficient supply to meet the needs of the Indian
immunization program.

The Indian MOH visited the facility in China and
inspected the production and clinical data.

The vaccine is made in
compliance with the WHO Guidelines for Live JE Vaccine Productions and was
deemed to be appropriate for importation.

To date, the AP government has procured approximately 4 million doses of
inactivated mouse brain-derived vaccine from the Central Research
Institute in Kasauli, India, and imported from the Republics of Korea and
Vietnam. For the remainder of 2006, the GoAP is procuring 1 million doses
of inactivated, mouse brain-derived vaccine from Vietnam. It then plans to
transition to use of the SA 14-14-2 vaccine, beginning in 2007.

A number of challenges are associated with use of the mouse brain-derived
vaccine:

• It has a three-dose schedule, with one booster required every three years;
• Vaccine production has been insufficient, and therefore the supply is
  limited; and
• Limited vaccine availability coupled with affordability issues meant
  that the AP government could only target its village-wide mass campaigns
  at a limited number of children (2 to 12 years of age) in 16 high-risk
  districts out of 23 districts.

In order to better protect all of its high-risk population against JE, and
after considering its vaccine options, the GoAP determined that the SA
14-14-2 JE vaccine has several advantages:

• It is a single-dose vaccine;
• It is available at an affordable price and in adequate supply;
• Its supply is supported by the national government of India; and even
  with patients who received previous doses of the mouse brain-derived
  vaccine, initial evidence supports that the SA 14-14-2 JE vaccine can be
  used for follow-up vaccination.

These factors, together with a greater supply of the SA 14-14-2 vaccine
beginning in 2007, will allow AP to adopt a district-wide approach,
thereby protecting more of the population at risk.

The Indian national government's decision to approve licensure of the JE
vaccine manufactured in China is already helping other states, such as
Uttar Pradesh (UP), to protect children against JE. Since May 2006, 6.3
million children in UP were vaccinated with the SA 14-14-2 vaccine.

Control of JE in AP, UP, and elsewhere in India is improving. Sustained JE
vaccination will protect generations to come. Regular JE surveillance and
detection, better case management, and routine JE immunization in
JE-affected districts are essential measures for improved JE control.

Julie Jacobson, MD

Director, PATH's Japanese Encephalitis Project

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