Transcript Slide 1

Clinically-Documented
Probiotics for Human Health
Brian Peeters
Strategic Sales Manager
Chr. Hansen A/S
Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
2
Chr. Hansen…
Founder Danish Pharmacist
Christian D.A. Hansen
Company founded in 1874
Fermenting bacteria cultures for more than 100 years
2,500 employees in 30 countries
Turnover of 500M EUR with double-digit organic growth
6% of turnover spent on R&D
225 employees in Research & Development
State-of-the-art production facilities
GMP pharma & food, Kosher, QC, HACCP,ISO 9002
Production facilities on 5 continents
Strong partnerships with customers
Everyday more than 500 million people consume
products containing Chr. Hansen ingredients
…when science matters
3
Chr. Hansen Group serving global customers all over the
world with >25 offices
4
Chr. Hansen Organizational Structure
Chr. Hansen
Cultures &
Enzymes
5
Natural
Colors
Health & Nutrition
Division is dedicated
solely to Probiotics
Health &
Nutrition
Chr. Hansen - World’s Largest Lactic Acid Bacteria Plant
Location: Avedore, Denmark
6
Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
7
Why Partner with Chr. Hansen?
Documented Efficacy and Safety
More than 450 research papers supporting Chr. Hansen
probiotic strains
More than 80 human clinical studies documenting strain
efficacy
Strains selected among the 8,700 strain deposits in Chr.
Hansen’s cell bank in Denmark
Extensive QC programs (cGMP)
Been producing and selling probiotics for >20 years
Scientific expertise
6% of turnover spent on R&D
225 employees in Research & Development
Patented processes and concepts
Novel equipment and production technologies
Strong research team developing new probiotics strains
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Why Partner with Chr. Hansen?
Product Supply
Market leader with world’s largest lactic acid
bacteria plant
Pharmaceutical Production (Pharma cGMP)
Global quality and safety policy ensuring high
standard in food production (ISO 9001/HACCP)
Consumer Friendly
Well-established safety
GMO-free products
“Big 8” Allergen-free products available
Internationally & Locally Affiliated
ISAPP, IPA, Norfood, PROBDEMO, LABIP
Leading probiotic research groups at universities &
institutes
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Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
10
Definition of “Probiotics”
The World Health Organization (WHO) and the Food and
Agriculture Association (FAO) define probiotics as:
“Live microorganisms that when
consumed in adequate amounts confer
a health benefit on the host.”
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Introduction to Probiotics
Probiotics means ”for life”
in Latin
Probiotics are live bacteria
with health benefits
10x more bacterial cells in
human body (~1014) than
there are human tissue
cells (~1013)
Gastrointestinal tract is
largest immune organ in
human body (80% of
Immune System is located
here)
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First scientist to discover
health benefits of probiotics
was immunologist Dr. Eli
Metchnikoff
Received Nobel Prize in
1908
Probiotics first
commercialized via
yogurts:
Yakult
introduced in
Japan in 1935
Danone’s Activia
introduced in
France in 1987,
U.S. in 2006
Strain Taxonomy
Note: Overview not exhaustive
Bacterial
group
Lactid acid
bacteria
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Bacterial
genus
Bacterial
species
Bacterial
sub-species
Bacterial
strains
Lactobacillus
paracasei
paracasei subsp.
paracasei
CRL-431
Bifidobacterium
acidophilus
paracasei subsp.
tolerans
LC-01
Enterococcus
fermentum
Weissella
reuteri
Carnobacterium
delbrueckii
Streptococcus
rhamnosus
Lactococcus
plantarum
F-19
Probiotics – Mechanisms of Action
Inhibit adhesion
of pathogen cells
Produce surfaceactive substances
Modulates cytokine
production
Probiotic
strain
Produce
acids
Produce
bacteriocins
Inhibit growth of
pathogens
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Strengthen the
immune system
Produce
hydrogen
peroxide
Inhibit growth
of pathogen cells
Work as
co-aggregation molecules
Block the spread of
pathogens
Probiotics – Mechanisms of Action
Inhibit adhesion
of pathogen cells
Produce surfaceactive substances
Modulates cytokine
production
Probiotic
strain
Produce
acids
Produce
bacteriocins
Inhibit growth of
pathogens
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Strengthen the
immune system
Produce
hydrogen
peroxide
Inhibit growth
of pathogen cells
Work as
co-aggregation molecules
Block the spread of
pathogens
Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
16
Scientific interest in probiotics has grown significantly
since 2000…
PubMed Articles on Probiotics (#)
900
795
800
697
700
642
600
468
274
300
200
5
3
9
4
9
12
30
1992
1993
1994
1995
1996
1997
103
1991
100
395
2003
400
383
2002
500
140
174
17
2007
2006
2005
2004
2001
2000
1999
1998
0
…and so has the number of probiotic trials
Probiotic trials registered on www.clinicaltrials.gov NIH (#)
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24
25
21
20
15
15
10
5
0
0
1
<2003
0
2
2003
4
5
2004
5
2005
US trials
Non-US trials
18
6
6
2006
2007
Increasing interest in probiotics seen in recent years
Dietary supplements: Gone from 16 launches in ‘02 to 75 launches in ‘07
Probiotic product launches globally (#)
800
669
700
594
600
491
500
394
400
300
200
100
0
150
59
16
67
2002
Source: Mintel database; Global launches
19
38
96
8
31
116
54
124
242
8
223
191
13
29
51
197
Other
34
75
Cheese
Diet. suppl.
Fermented
milks
9
308
323
363
2005
2006
2007
107
2003
2004
Increasing number of dietary supplement probiotic
product launches in 2007 (driven by Europe)
Probiotic product launches globally; dietary supplements (#)
80
75
70
13 Rest of
World
60
54
50
38
40
31
30
20
10
0
7
51
14
20
17
19
2
7
1
6
7
6
3
15
3
9
17
13
2002
2003
2004
2005
2006
16
6
13
5
Source: Mintel database; Global launches
~35% average annual growth last 5 years
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35 Europe
8
Japan
19 US
2007
Chr. Hansen sees market drivers in probiotic supplement
market continuing to feed a strong growth
General
interest in
selfmedication
Taboo on
intestinal
issues
declining
Probiotic supplements
expected to continue
double-digit growth
Demographic
shift
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Consumer
awareness
below 50% in
most
countries
Trend towards
”natural
cure” rather
than pharma
Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
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Designing a Probiotic Product for the Military
1
8
Other
7
Shelf
stability
Potency
6
23
Indication
Your product
Dosage
form
5
2
Regulatory /
Claim
Strain(s)
Survival
through stomach
4
3
Indication
Chr. Hansen offers different indication concepts
1. Everyday Intestinal Balance
2. Antibiotic Associated Diarrhea
3. Traveler's Diarrhea
4. Children's Diarrhea
5. Immune Boost
6. Atopic Eczema*
7. Bacterial Vaginosis
*Concept supported by fewer clinical studies
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Indication
Chr. Hansen offers different indication concepts
1. Everyday Intestinal Balance
3. Traveler's Diarrhea
5. Immune Boost
*Concept supported by fewer clinical studies
25
Indication
Chr. Hansen offers different indication concepts
1. Everyday Intestinal Balance
2. Antibiotic Associated Diarrhea
3. Traveler's Diarrhea
4. Children's Diarrhea
5. Immune Boost
6. Atopic Eczema*
7. Bacterial Vaginosis
*Concept supported by fewer clinical studies
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Indication
1. Everyday intestinal balance
Covers a broad range of discomfort such as bloating, slow
constipation, diarrhea, and slight irritable bowel
Surveys show 15-20% of consumers are concerned about
their digestive health
12% of people worldwide suffer from self-defined
constipation according to large global omnibus study from
2006
Americas and Asia Pacific suffer nearly twice (17%) as
much as their European counterparts (9%)
40% of constipation sufferers attempt to treat their
constipation by changing their nutrition, despite research
showing that diet and lifestyle are not necessarily to
blame for the occurrence of constipation
Less than 1/3 of sufferers use laxatives
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Indication
Chr. Hansen offers different indication concepts
1. Everyday Intestinal Balance
2. Antibiotic Associated Diarrhea
3. Traveler's Diarrhea
4. Children's Diarrhea
5. Immune Boost
6. Atopic Eczema*
7. Bacterial Vaginosis
*Concept supported by fewer clinical studies
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Indication
3. Traveler's Diarrhea
“Travelers' diarrhea is the most common illness affecting
travelers. Each year between 20%-50% of international
travelers, an estimated 10 million persons, develop
diarrhea”
-Centers for Disease Control and
Prevention, U.S. Department of Health and
Human Services
Duration of travelers' diarrhea usually limited to 2-5 days
In some cases, symptoms may persist for months or
even years
Probiotic supplementation reduces the risk of diarrhea
caused by foreign bacteria from water, vegetables, fruit,
etc.
Diarrhea is caused mainly by intake of E. coli,
Salmonella, or Campylobacter
Target group: Those persons traveling to “high-risk”
destinations where the food or water supply may contain
“non-native” or pathogenic organisms such as E. coli.
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Indication
Chr. Hansen offers different indication concepts
1. Everyday Intestinal Balance
2. Antibiotic Associated Diarrhea
3. Traveler's Diarrhea
4. Children's Diarrhea
5. Immune Boost
6. Atopic Eczema*
7. Bacterial Vaginosis
*Concept supported by fewer clinical studies
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5. Immune Boost
80% of the body’s immune cells are located in the
gastrointestinal tract
Having the right bacterial balance is important for
optimizing the immune system
Increased levels of IgA and phagocytes (immune cells and
cells which can engulf and destroy harmful components),
the better the immune system fights unwanted components
Probiotics are proven to be able to strengthen natural
defenses and stimulate the immune system
Immune health is the second largest indication area within
probiotics after intestinal health
Target group: Those who are under consistently high levels
of stress and/or those who have a weak or compromised
immune system.
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Indication
Chr. Hansen’s Clinically-Documented Probiotic Strains
Bifidobacterium (BB-12®)
Lactobacillus acidophilus (LA-5®)
Lactobacillus paracasei ssp. paracasei (CRL-431™)
Lactobacillus rhamnosus (GR-1®)
Lactobacillus reuteri (RC-14®)
Lactobacillus rhamnosus GG (LGG®)
BB-12®
Streptococcus thermophilus (TH-4™)
LA-5®
CRL-431™
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Other Chr. Hansen Strains
Lactobacillus delbrueckii ssp. bulgaricus LBA-40
Lactobacillus delbrueckii ssp. bulgaricus LBY-27
Lactobacillus paracasei ssp. paracasei LC-01
Lactobacillus rhamnosus LC-69
Bifidobacterium infantis BB-02
Bifidobacterium longum BB-46
Streptococcus thermophilus STY-31
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Strain
Strain
Chr. Hansen stains have documented efficacy
>450 research and clinical evaluations and >80 human clinical studies
Strains
Intestinal
balance
BB-12
7
BB-12 + LA-5
6
Antibiotic
Assoc.
Diarrhea
Traveler's
Diarrhea
Children's
Diarrhea
Immune
boost
Atopic
Eczema
2
3
4
4
4
BB-12 + TH-4
1
CRL-431
CRL-431 + BB12
1
LGG
2
BB-12 + LGG
1
6
1
BB-12 + LA-5
+ LGG
1
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2
15
6
7
2
BB-12 + LA-5 +
LBY-27 + STY31
GR-1 + RC-14
Bacterial
Vaginosis
2
8
Strain
Chr. Hansen stains have documented efficacy
>450 research and clinical evaluations and >80 human clinical studies
CHR
Product
Strains
Intestinal
Balance
BB-12
Stick
BB-12
7
AB-Cap
BB-12 + LA-5
6
Antibiotic
Assoc.
Diarrhea
Traveler's
Diarrhea
Children's
Diarrhea
Immune
Boost
Atopic
Eczema
2
3
4
4
4
BB-12 + TH-4
1
CRL-431
QuatroCap
CRL-431 + BB-12
1
LGG
2
BB-12 + LGG
1
35
6
2
15
6
7
2
BB-12 + LA-5 +
LBY-27 + STY-31
1
BB-12 + LA-5
+ LGG
1
GR-1 + RC-14
Bacterial
Vaginosis
2
8
Strain
Chr. Hansen with >450 scientific publications
Scientific publications registered by strain (#)
LGG
BB-12
CRL-431
BB-12, LGG
BB-12, LA-5
LA-5
RC-14, GR-1
BB-12, LA-5, LBY-27, STY-31
LR-35
GR-1
BB-12, TH-4
BB-12, BB-46
BB-46
LGG, RC-14, GR-1
RC-14
BB-12, LA-5, LGG
BB-12, CRL-431
LA-2
Other combinations incl. reviews
0
Source: CH internal abstract database
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20
40
60
80
100
120
140
BB-12 + LA-5 for everyday intestinal balance
Clinical study example
BB-12 and LA-5 tested on 15 healthy adults with
tendency to constipation
Shioya et al.2000
(days)
9
Placebo
BB-12 + LA-5
8
*
7
6
6.5
5.5
5
4
3
2
1
0
Stool frequency (days/10 days)
37
Strain
BB-12 for everyday intestinal balance
Clinical study example
BB-12 tested on 209 elderly with constipation living
in residential homes
Pitkälä et al. 2007
(%)
35
Placebo
30*
BB-12
27 *
30
25
20
20
14
15
10
5
0
38
Normal bowel movements
Normal bowel movenments
(% of days)
at least 30% of days
(% of participants)
Quatro-Cap-4 for Lowering Risk of Traveler's Diarrhea
Clinical study example
165 tourists going to Egypt were treated with Quatro caps or placebo: 1 cap 3 times daily starting 2 days
prior to departure ending the last day of travel
Black et al. 1989 ; Black 1995
Share of tourists with diarrhea
80%
Placebo
Quatro
Share of tourists with diarrhea
80%
71%
70%
70%
60%
60%
*
43%
50%
40%
30%
30%
20%
Trial I
10%
0%
39
76%
*
51%
50%
40%
20%
Placebo
Quatro
Trial II2
10%
n = 41
n = 40
0%
n = 45
n = 39
BB-12 for Everyday Immune Boost
Clinical study example
Effect of BB-12 on phagocytic activity in 14 healthy
adults
Schiffrin et al. 1997
Before trial
Milk (controls)
Fermented milk
6 weeks after trial
Share active phagocytes (%)
*
100
90
80
87
*
70
60
50
40
61
BB-12
42
39
Before trial
Milk
(controls)
30
20
10
0
40
Fermented
milk
6 weeks
after trial
Dosage Forms
Standard forms:
Capsules
Sticks
Powder blends
Chewable tablets
Individual customization:
Capsules
Sticks
Chewable tablets
Sachets
Tablets
and more upon request…
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Dosage
form
Dosage Forms….For the Military
Dosage
form
1st Choice
Standard forms:
Capsules
Sticks
Powder blends
Chewable tablets
Individual customization:
Capsules
Sticks
Chewable tablets
Sachets
Tablets
and more upon request…
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Dosage Forms….For the Military
2nd
Choice
Dosage
form
1st Choice
Standard forms:
Capsules
Sticks
Powder blends
Chewable tablets
Individual customization:
Capsules
Sticks
Chewable tablets
Sachets
Tablets
and more upon request…
43
Dosage Form: Sticks
Best dosage form for wide range of ambient temperature
and humidity fluctuations
Relatively little loss of viable organisms @ 25C over 18
months
Very low sugar content (maximum 0.4 g sugar per dose)
Can be customized to contain higher doses to further extend
shelf-life over time at various temperature ranges
Consumer Appeal
Easy to take – no tablets to swallow
Easy to consume – only a small amount of powder (1g)
Easy to mix into foods and drinks - cold or lukewarm
Easy to open – tear off top
Easy to carry – in your pocket, bag or lunch box
Easy to store – room temperature storage is ok
Selections
Taste: Vanilla, neutral or per your selection
Technology: Soluble or non-soluble
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Dosage
form
Dosage Form: Capsules
Consumer benefits
Easy to take – small capsule size
Easy to open – for powder administration
Easy to carry – Alu-tube or blister card
Easy to store – at room temperature
Easy to relate to – capsules are a
traditional dosage form for supplements
Selections for capsule type
Type: Gelatin or Vegetables (Vegetable
recommended)
Size: 000 – 5 (size 3 recommended)
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Dosage
form
Other Dosage Forms
Dosage
form
Powders
Delivered in small vial to consumer to take a
tablespoon and sprinkle onto food or
beverage
Also relevant dosage form when used for
infant formula
Chewable Tablets
Children-friendly
Sachets
Sachets are quadrant-shaped bags with
powder…
…different from sticks being rectangle bags
Tablets
Typically 500-1500 mg per tablet
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What is potency?
Potency
What is a CFU?
CFU = Colony Forming Units
One CFU = one live bacteria cell
“Live” defined as being able to multiple and thereby form a colony
How to count the cells?
Small amounts of powder is weighing and diluted up to commonly 1,0 E+09
Suitable dilutions with lactic acid bacteria are poured onto plates and mixed with medium
After anaerobic incubation commonly 3 days at 37oC, the colonies are manually counted
Different cell count is seen as cells are live microorganisms
Only cells assessed as being colony forming are to be counted
What is potency?
Potency is minimum number of CFU in one gram (powder) or in one dosage (capsules,
tablets, etc)
Example: Potency of 1.0 E+09 per capsule means there is minimum 1 billion CFU per
capsule
Which potency to communicate to consumers?
Best practice towards consumers is to state minimum potency at end of shelf life
Chr. Hansen recommends products providing a daily dose of 1 to 10 Bil CFU
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Chr. Hansen guarantees potency
at point in value chain agreed with customer
Powder
production
Potency
point
#1
Bulk
dosage
forms
Final
dosage
form
Potency
point
#2
Boxing &
labeling
Distribution
Store
shelfing
Potency
Consumption
End of
shelf life
Potency
point
#3
Potency
point
#4
5B
1B
Illustrative example of potency decline:
6.5B
5.5B
Chr. Hansen guarantees CFU count all the way to potency point #4 when delivering in final packaging material
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Shelf
stability
“The Shelf-Life Equation”
=
Shelf life
×
×
Water Activity
Temperature
Oxygen
Rule-of-thumb recommendation:
24 months
49
=
≤0.15 aw
x
≤25OC
x
≤5%
Shelf
stability
What we do to maximize shelf stability
I. Strain
• Strains selected based on superior stability
II. Excipients
• Excipients with extra low aw chosen
III. Handling
• Raw materials and products are handled in such a way that we
minimize exposure to aw, temperature, and oxygen
IV. Production
• We minimize mechanical processing
• We add probiotics as close to final filling as possible
• We have for customers preparred Standard Operating Procedures
V. Packaging
• We discuss choice of product packaging with our customers
•Air tight
•Moisture impermeable
•Oxygen free (filled with nitrogen)
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Shelf
stability
Types of packaging
Recommended for capsules and tablets
Alu-tube
Glass container
Plastic container
w/ desiccant
Not recommended
Plastic
Container
(PET)
Aclar blister
PVDC-alu blister
Recommended for powder
Stick
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Sachet
Not optimal,
but best blister type
Alu-alu blister
Shelf
stability
Desiccant
Desiccant types
Bentonite
Activated clay
Absorbs moisture steadily
in given period
Silicagel
Chemically produced salt
Absorbs moisture steadily
in given period
Molecular Sieve
Crystallized aluminum
silicate
Absorbs moisture quickly
within short period (up to
20% of its own weight)
Desiccant applications
Desiccants reduce water activity level
Water activity
Desiccant
lid
0.18
0.16
0.16
0.16
0.14
0.11
0.10
0.12
Desiccant
lining
0.10
3 months
0.08
6 months
0.06
0.04
0.02
Desiccant
bags
0.02
0.01
0.00
Alu-tube with
Plastic
dessicant lid container with
(Molecular Sieve)
dissicant lining
(Molecular Sieve)
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0 months
Moisture Vapor Transmission Rate by type
of packaging material
Moisture Vapor Transmission Rate (MVTR)
• The rate at which moisture will permeate
through a barrier over time
• Measures the barrier performance of
different types of packaging
Freeze-dried products are very hygroscopic and
will absorb available moisture quickly
High-barrier packaging materials (glass,
aluminum, and plastic vial) are recommended
for reducing moisture and oxygen migration.
Plastic vial with desiccant lining permits 0.5mg
moisture to enter vial, but desiccant absorbs 1g
of moisture
Shelf
stability
MVTR examples
Glass
0
Aluminum
0
HDPE
3,8
PVDC
4,0
PP
6-10
LDPE
18-23
PET
19-46
Measured at 37.8°C and 100% RH (g/25μ/m2/day)
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Summary
Supplementation with Probiotics may help soldiers prevent
pathogen-based GI disturbances such as food poisoning, water
contamination, etc.
Probiotics have been shown to increase the strength of the
immune system of individuals who are under chronically-high
levels of stress
In the field, the best dosage form for soldiers would be the
probiotic stick or sachet
In the military food service setting, making single serve
packets of probiotic capsules available with meals would be
ideal.
GOAL FOR END RESULT: Improved overall health of the soldiers
and thus possibly significant cost savings for the Military (via
reduced healthcare and sick leave).
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THANK YOU!
For more information, please
contact:
Brian Peeters
[email protected]
Office: (415) 503-1834
Together
we improve the quality of
food and health
for people all over the world
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