The Vaccine Business

Current status, Challenges, and Opportunities

Rodney Carbis
Head Vaccine Development
International Vaccine Institute

BioMalaysia, 2011 Conference

Kuala Lumpur, Malaysia
November 21 23, 2011

International Vaccine Institute

Mission
To promote the health of people in developing countries by the
development, introduction and use of new and improved vaccines
- From: Constitution of IVI (1996)

Disease surveillance
Clinical trials
Vaccine development
Technology Transfer

Vaccine
demonstration
projects
Vaccine introduction
and Advocacy

Oral inactivated
Cholera vaccine

Typhoid and
paratyphoid
conjugate vaccines

The Value of Vaccines

Vaccines are the most cost-effective tools
for preventing death and disability from
infectious disease.

Luis Fermn Tenorio,

the last polio case in the
Americas
(Peru, 1991)

Ali Maouw Maalin,

last case of smallpox
(Somalia,1977)

Contrast between Vaccines and other Pharmaceuticals

Vaccines

Pharmaceuticals

Focus on prevention
not patients, but healthy people

Focus on treatment
patient is generally sick

Key role for the government agencies

Key role for the doctors and pharmacists

Very low acceptance of side effects

Acceptance of side effects varies with

severity of disease

Large clinical trials

5,000 to 10,000 subjects before registration
(67,000 for Wyeths Rotavirus vaccine)

Less demanding clinical trials

2000 to 3000 subjects before registration

Contrast between Vaccines and other Pharmaceuticals

Vaccines
High manufacturing complexity
Biological processes are difficult to
control

Pharmaceuticals
Medium manufacturing complexity
Easier to manage chemical synthesis in
most cases

Supply chain complexity generally require Supply chain less complex, many drugs
stored at room temperature
storage at or below 4oC
Very few generic products
(Due to manufacturing complexity)

Increasing generic threat

World Vaccine Market

US$ 21.05 Billion in 2010 at rate of 8-9 %.
Emerging markets growing at 16-17 %.
Rise in adult vaccines.
Increased uptake of hepatitis and influenza vaccines.

Therapeutic vaccines segment:

Cancer vaccines market
>US$8 billion by 2012.

No growth for EPI vaccines

continue to since year 2003.

World Vaccines Market 2008-2013 Future Forecast,

Critical Trends and Developments.

Three market segments

Market Type

Clients

Geographical areas
Mainly for developed
countries

Market organization

Commercial Market
Biggest markets in
value by far

Public or private

Donor Market
Biggest markets in
doses but low in
value

Managed by
Poor or developing
International
countries
organizations such
as WHO, UNICEF,
PAHO and GAVI**

Mostly EPI vaccines for

routine or mass
immunization

Closed market

Local clients

Local producers supply

the local needs with
EPI* vaccines

e.g. India, Indonesia,

China, Brazil, Cuba

Strongly regulated
market where
competition exists.

*Expanded program on immunization (EPI)

**World Health Organization (WHO), United Nations Childrens Fund (UNICEF), Pan American Health Organization (PAHO),
Global Alliance for Vaccines and Immunization (GAVI).
Source: Bionest Partners, Exane BNP Paribas

Value and volume of vaccines

2003-2004
Value of vaccines US$

Number of doses

16

14

11.4
billion doses

12
billion US$

5.6

13.7

10
8
6

3.1
3
1.7

1.6

0
Poor

0.8

0.7
Middle

Rich

Total

Countries

0
Poor

Middle

Rich

Countries

Most money is made in the rich countries

(high profit relatively low number of doses)

Most vaccines are delivered to poor and middle income countries

(low profit high number of doses)

Total

Supply to UNICEF
WHO prequalification
Most vaccines for national immunization programs in developing countries are acquired through procurement by UNICEF.
Vaccines must be prequalified by the WHO to be considered in these tenders.
Prequalification involves the National Regulatory Authority as well as the manufacturing company. Prequalification is
specific to a certain vaccine produced by a certain company. It does not mean that the company can apply for tender for all
its products only those that are prequalified.
How important is prequalification:

Manufacturers of
Pentavalent vaccine

Country

Prequalified Volume/value on the

product
International market

Bharat Biotech

India

No

Panacea Biotech

India

Yes

US$34.2M to UNICEF: >15M

doses

Shantha Biotechnics

India

Yes

US$340M contract with UNICEF

for 2010-2012

Berna Biotech/Crucell

Republic of
Korea

Yes

In 2008, supplied >29M doses

through UNICEF/GAVI

Serum Institute

India

No

Biological E

India

No

Increasing contribution from emerging

markets

Source: UNICEF Supply Division, 2011

Continuing contraction of the vaccine

industry
Big Pharma showing more interest in vaccines and taking positions in
developing country manufacturers:

$68 billion acquisition of Wyeth, Pfizer is now in the vaccine business

Abbott Laboratories spent $6.6 billion to purchase flu vaccine maker Solvay
Johnson & Johnson bought 18 percent of Dutch vaccine manufacturer Crucell
GSK signed a $78 million joint venture with China's Shenzhen Neptunus
Interlong Bio-Technique
Sanofi acquired a majority stake in Indian vaccine maker Shantha Biotechnics,

Novartis spent $125 million for an 85 percent stake in privately owned

Chinese vaccines company Zhejiang Tianyuan
Source: Spiegel Online GermanyAuthor: By Kerry Capell Titel: The Vaccine Renaissance; Published:November 25th 2009

Blockbusters in 2008
Sales greater than 1 billion US$
Vaccines approved in last five years have created new markets. These
leading products in 2008 totaled to US$10 billion

Worldwide markets more than doubled in last three years. It is forecasted that
sales will double again to US$50.7 billion by 2013.
Product

Company

Sales US$

Prevnar

Wyeth

2.7 billion

Gardasil

Merck

1.4 billion

Proquad/Varivax

Merck

1.3 billion

Infantrix

GSK

1.3 billion

Polio/whooping
cough/Hib vaccines

Sanofi Pasteur

1.1 billion

Influenza

Sanofi Pasteur

1.1 billion

Hepatitis Vaccines

GSK

1.2 billion

www. pipeline review. com . LaMerie Biologic Report Recommendation: The new vaccines

Vaccine Development
1910-2010

List of vaccine preventable diseases

Trends
Combination vaccines
To reduce the number of vaccinations children receive
vaccines are increasingly becoming multivalent.
3 valent
4 valent
5 valent
6 valent

DTwP
DTwP-Hep B
DTwP-Hep B-Hib
DTaP-Hep B-Hib-IPV

Measles combination vaccine

1 valent
3 valent

Measles
Measles/Mumps/Rubella

Trends
Multivalent vaccines
Protect against more strains.
Differentiation of one companies product from another to gain
market advantage.

Rotavirus
Rotarix (GSK)
1 strain G1[P8]
Rota Teq (Merck) 5 strains G1,G2, G3, G4, [P7, P1A]

HPV
Gardasil (Merck) types 16, 18, 6 and 11
Cervarix (GSK) types 16 and 18

Pnuemococcal conjugate
Prevnar (Wyeth now Pfizer) - (originally 7 valent)
Prevnar 13 (Wyeth now Pfizer) - (now 13 valent)

Synflorix (GSK) contains 10 strains

Trends
Safety
Increased emphasis on safety
Oral Live attenuated polio vaccine (OPV) has been replaced by the inactivated
polio (IPV) in industrialized countries. Issues with reversion to virulence with
one of the three strains in the OPV

Whole cell pertussis (wP) which is reactogenic has been replaced with acellular
pertussis (aP) in industrialized countries. Currently aP is too expensive for
routine use in developing countries.
Single use auto-disable syringes so that syringes cannot be reused.
Preservatives such as thiomersal being excluded from formulations (particularly
single dose presentations)

Trends
Manufacturing
Stronger emphasis on Validation
Use of single use technologies has
simplified validation.
Single use technologies are easier to
install and facilitate earlier time to
market than conventional equipment

Challenges
cGMP compliance
Vaccine manufacturers must comply with current Good Manufacturing Practice
(GMP), keeping track of the latest guidelines is time consuming and difficult.
cGMP is a part of the quality system used in the manufacturing, testing and
development of vaccines

Companies who fail inspections can expect to face

penalties. Fines and product bans are common but
often most damaging is the loss of consumer
confidence in the product.

Challenges
Limited manufacturing capacity
Very little surge capacity as redundant capacity is costly, long timelines to
respond to increased demand.
For many vaccines there are only one or two producers.
Demand for pediatric vaccines is predictable and is related to the birth cohort.

Lack of capacity creates vulnerabilities should demand suddenly increase such

as occurred during the 2009-10 H1N1 outbreak.

Challenges
As disease is controlled by vaccination the need for vaccination is less obvious.

Pressure from anti vaccine groups can also reduce vaccine acceptance and
coverage.
Complacency can lead to re-emergence of disease as occurred in Russia in the
1990s

Adjuvants
An immunologic adjuvant acts to accelerate, prolong,
or enhance antigen-specific immune responses when
used in combination with specific vaccine antigens
Aluminum salts were first used in the 1920s.
New adjuvants introduced in the last decade.

Adjuvant
Name

Class

Company

Indications

Status

Alum

Mineral salts

Various

Various

Marketed (EU, USA)

MF59

Oil-in-water emulsion

Novartis

Influenza

Marketed (EU)

AS03

Oil-in-water emulsion

GSK

Influenza

Marketed (EU)

AS04

Alum + TLR4 antagonist

GSK

AS01

Liposome, MPL, QS-21

GSK

Hepatitis B, human
Marketed (EU, USA)
papillomavirus
Malaria

Phase 3

Vaccine Delivery Technologies

Flumist (influenza vaccine)
is delivered intranasal

Traditionally vaccines were

delivered by Intramuscular or
subcutaneous injection

Some vaccines are delivered orally, live attenuated polio,

inactivated and attenuated cholera, attenuated typhoid

Intradermal delivery.
Microneedles impregnated
with antigen dissolve in the
dermis to deliver the
vaccine.
Sanofi have just licensed
Fluzone for intradermal
delivery very narrow
needle 1.5mm long and 9mg
per strain instead of 15mg

Stabilization
Storage of vaccines is costly, generally require refrigeration
Experience with monovalent H1N1 vaccine for the 2009/2010 season.
Significant losses due to expiry of product.
- US: 71 out of 162 million doses.
- Australia: 9.7 out of 19 million doses.

Vaccine recall due to inadequate stability.

- 13 lots of live attenuated H1N1 influenza.
- One lot split H1N1 pediatric vaccine (800,000 doses).

Substantial amount of work being done

on developing more stable formulations
to reduce product loss and reduce the
dependence on the cold chain

Future
Phase III vaccines in development
Disease

Company

Drug Name

Smoking addiction

Nabi Biopharmaceuticals

NicVAX

Grass Allery

ALB Abello

GRAZAX

Grass Allery

Allergy Therapeutics

Pollinex Quattro Grasses

Ragweed Allergy

Allergy Therapeutics

Pollinex Quattro Ragweed

Grass Allery

Fornix Biosciences

Oralgen Grass Pollen

Grass Allery

Greer Labs

Sublingual-oral immuno-therapy

Grass Allery

Paladin Labs

Oralair Grasses

Pollen Allergy

Schering-Plough/Merck

Allergy Immunotherapy Tablet

Dengue

Sanofi Pasteur

ChimeriVax

Diabetes

Diamyd Medical

Diamyd

ETEC infection

Intercell

Traveler's Diarrhea vaccine patch

Herpes virus

GlaxoSmithKline

Simplirix

Leishmaniasis

Tehran University of Medical Sciences

Alum-ALM

Malaria

GlaxoSmithKline

Mosqurix

Shigellosis

NICHHD, NIH

N/A

Other interesting disease targets

Vaccines currently in phase II trials
Disease

Clinical development phase

Alzheimer's

Phase II

Ebola

Phase II

Hepatitis C

Phase II

Hypertension

Phase II

HIV/AIDS

Various phases

MRSA

Phase II

(Methicillin-resistant Staphylococcus aureus)

Multiple Sclerosis

Phase II

Obesity

Preclinical

Cancer

Many in various stages of development

Thank you