clinically-documented probiotics for human health brian peeters strategic sales manager chr. hansen...
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Clinically-Documented Probiotics for Human Health
Brian Peeters
Strategic Sales Manager
Chr. Hansen A/S
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Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
3
Chr. Hansen… Company founded in 1874Fermenting bacteria cultures for more than 100 years2,500 employees in 30 countriesTurnover of 500M EUR with double-digit organic growth6% of turnover spent on R&D
225 employees in Research & DevelopmentState-of-the-art production facilities
GMP pharma & food, Kosher, QC, HACCP,ISO 9002
Production facilities on 5 continentsStrong partnerships with customersEveryday more than 500 million people consume products containing Chr. Hansen ingredients
Founder Danish Pharmacist Christian D.A. Hansen
…when science matters
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Chr. Hansen Group serving global customers all over the world with >25 offices
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Chr. Hansen Organizational Structure
Cultures & Enzymes
NaturalColors
Health & Nutrition
Chr. HansenHealth & Nutrition Division is
dedicated solely to Probiotics
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Chr. Hansen - World’s Largest Lactic Acid Bacteria PlantLocation: Avedore, Denmark
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Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
8
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
Why Partner with Chr. Hansen?
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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
Why Partner with Chr. Hansen?
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Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
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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
First scientist to discover health benefits of probiotics was immunologist Dr. Eli Metchnikoff
Received Nobel Prize in 1908
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)
Probiotics first commercialized via yogurts:
Yakult introduced in Japan in 1935
Danone’s Activia introduced in France in 1987, U.S. in 2006
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Strain TaxonomyNote: Overview not exhaustive
Bacterial genus
Bacterial species
Bacterial sub-species
paracasei subsp.paracasei
Bacterial strains
paracasei
acidophilus
fermentum
Lactobacillus
Bifidobacterium
Enterococcus
Lactid acid bacteria
Bacterial group
CRL-431
LC-01
reuteri
delbrueckii
rhamnosus
plantarum
Weissella
Carnobacterium
Streptococcus
Lactococcus
paracasei subsp.tolerans
F-19
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Probiotic Probiotic strainstrain
Inhibit adhesion of pathogen cellsProduce surface-
active substances Produce hydrogen peroxide
Inhibit growth of pathogen cells
Produce acids Produce
bacteriocins
Inhibit growth of pathogens
Work as co-aggregation molecules
Block the spread of pathogens
Strengthen the immune systemModulates cytokine
production
Probiotics – Mechanisms of Action
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Inhibit adhesion of pathogen cellsProduce surface-
active substances Produce hydrogen peroxide
Inhibit growth of pathogen cells
Produce acids Produce
bacteriocins
Inhibit growth of pathogens
Work as co-aggregation molecules
Block the spread of pathogens
Strengthen the immune systemModulates cytokine
production
Probiotics – Mechanisms of Action
Probiotic Probiotic strainstrain
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Agenda
Introduction
Why Chr. Hansen as Preferred Supplier
Basics of Probiotics
Market Trends
Designing a Probiotic Product for the Military
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Scientific interest in probiotics has grown significantly since 2000…
5 3 9 4 9 12 30
103140
174
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383 395
468
642697
795
0
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1991
1992
1993
1994
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1996
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1998
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2007
PubMed Articles on Probiotics (#)
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…and so has the number of probiotic trials
0 0
4 5 6 6
1 2
5
15
21
24
0
5
10
15
20
25
30
<2003 2003 2004 2005 2006 2007
Probiotic trials registered on www.clinicaltrials.gov NIH (#)
Non-US trials
US trials
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Increasing interest in probiotics seen in recent yearsDietary supplements: Gone from 16 launches in ‘02 to 75 launches in ‘07
67 107223
308 323 363
1631
38
54 517534
96
124
116
191
197
2913
9
88
59
0
100
200
300
400
500
600
700
800
2002 2003 2004 2005 2006 2007
150
Probiotic product launches globally (#)
242
394
491
594669
Fermentedmilks
Diet. suppl.Cheese
Other
Source: Mintel database; Global launches
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Increasing number of dietary supplement probiotic product launches in 2007 (driven by Europe)
615
917 13
191
33
65
8
7
6 19
1713
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2
77
1420
13
0
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2002 2003 2004 2005 2006 2007
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Probiotic product launches globally; dietary supplements (#)
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51
75
US
Source: Mintel database; Global launches
Japan
Europe
Rest ofWorld
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~35% average annual growth last 5 years~35% average annual growth last 5 years
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Chr. Hansen sees market drivers in probiotic supplement market continuing to feed a strong growth
Probiotic supplements expected to
continue double-digit growth
Taboo on intestinal
issues declining
Demographic shift
General interest in
self-medication
Trend towards ”natural
cure” rather than
pharma
Consumer awareness below 50%
in most countries
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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
Indication Regulatory /Claim
Strain(s)
Dosageform
Shelfstability
Survival through stomach
Potency
Other
2
3
18
7
65
4
Your product
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Chr. Hansen offers different indication concepts
Indica-tion
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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Chr. Hansen offers different indication concepts
Indica-tion
1. Everyday Intestinal Balance
3. Traveler's Diarrhea
5. Immune Boost
*Concept supported by fewer clinical studies
26
Chr. Hansen offers different indication concepts
Indica-tion
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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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
Indica-tion
28
Chr. Hansen offers different indication concepts
Indica-tion
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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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.
Indica-tion
30
Chr. Hansen offers different indication concepts
Indica-tion
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 BoostIndica-
tion
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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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®)
Streptococcus thermophilus (TH-4™)BB-12®
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
Strain
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Chr. Hansen stains have documented efficacy>450 research and clinical evaluations and >80 human clinical studies
Strain
StrainsIntestinal balance
Antibiotic Assoc.
Diarrhea
Traveler's Diarrhea
Children's Diarrhea
Immune boost
Atopic Eczema
Bacterial Vaginosis
BB-12 7 2 3 4
BB-12 + LA-5 6 4
BB-12 + TH-4 4
CRL-431 1
CRL-431 + BB-12 1
LGG 2 6 2 15 6 7
BB-12 + LGG 1 2
BB-12 + LA-5 + LBY-27 + STY-31
1 2
BB-12 + LA-5 + LGG
1
GR-1 + RC-14 8
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Chr. Hansen stains have documented efficacy>450 research and clinical evaluations and >80 human clinical studies
Strain
CHRProduct
Strains
Intestinal
Balance
Antibiotic Assoc. Diarrhea
Traveler's
Diarrhea
Children's
Diarrhea
Immune Boost
Atopic Eczema
Bacterial
Vaginosis
BB-12 Stick
BB-12 7 2 3 4
AB-Cap BB-12 + LA-5 6 4
BB-12 + TH-4 4
CRL-431 1
CRL-431 + BB-12
1
LGG 2 6 2 15 6 7
BB-12 + LGG 1 2
Quatro-Cap
BB-12 + LA-5 + LBY-27 + STY-31
1 2
BB-12 + LA-5 + LGG
1
GR-1 + RC-14 8
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Chr. Hansen with >450 scientific publications
Source: CH internal abstract database
0 20 40 60 80 100 120 140
Other combinations incl. reviewsLA-2
BB-12, CRL-431BB-12, LA-5, LGG
RC-14LGG, RC-14, GR-1
BB-46BB-12, BB-46BB-12, TH-4
GR-1LR-35
BB-12, LA-5, LBY-27, STY-31RC-14, GR-1
LA-5BB-12, LA-5BB-12, LGG
CRL-431BB-12LGG
Scientific publications registered by strain (#)
Strain
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BB-12 + LA-5 for everyday intestinal balanceClinical study example
Strain
BB-12 and LA-5 tested on 15 healthy adults with tendency to constipation
Shioya et al.2000
5.5
6.5
0
1
2
3
4
5
6
7
8
9
Stool frequency (days/ 10 days)
Placebo
BB-12 + LA-5
*
(days)
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BB-12 for everyday intestinal balanceClinical study example
20
14
27
30
0
5
10
15
20
25
30
35
Normal bowel movements
(% of days)
Normal bowel movenments
at least 30% of days
(% of participants)
Placebo
BB-12
**
(%)
BB-12 tested on 209 elderly with constipation living in residential homes
Pitkälä et al. 2007
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Quatro-Cap-4 for Lowering Risk of Traveler's DiarrheaClinical study example
71%
43%
0%
10%
20%
30%
40%
50%
60%
70%
80%
PlaceboQuatro
*
Share of tourists with diarrhea
Share of tourists with diarrhea
n = 41 n = 40 n = 45 n = 39
Trial I Trial II
*
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
76%
51%
0%
10%
20%
30%
40%
50%
60%
70%
80%
PlaceboQuatro
Trial 2
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BB-12 for Everyday Immune BoostClinical study example
42 39
87
61
0
10
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30
40
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60
70
80
90
100
Before trial Milk(controls)
Fermentedmilk
6 weeksafter trial
Before trialMilk (controls)Fermented milk6 weeks after trial
*
*
Share active phagocytes (%)
Effect of BB-12 on phagocytic activity in 14 healthy adults
Schiffrin et al. 1997
BB-12
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Dosage Forms
Standard forms:CapsulesSticksPowder blendsChewable tablets
Individual customization:CapsulesSticksChewable tabletsSachetsTablets
and more upon request…
Dosageform
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Dosage Forms….For the Military
Standard forms:CapsulesSticksPowder blendsChewable tablets
Individual customization:CapsulesSticksChewable tabletsSachetsTablets
and more upon request…
Dosageform
1st Choice
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Standard forms:CapsulesSticksPowder blendsChewable tablets
Individual customization:CapsulesSticksChewable tabletsSachetsTablets
and more upon request…
Dosageform
1st Choice
2nd Choice
Dosage Forms….For the Military
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Dosage Form: SticksBest dosage form for wide range of ambient temperature and humidity fluctuationsRelatively little loss of viable organisms @ 25C over 18 monthsVery 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 AppealEasy to take – no tablets to swallowEasy to consume – only a small amount of powder (1g)Easy to mix into foods and drinks - cold or lukewarmEasy to open – tear off topEasy to carry – in your pocket, bag or lunch boxEasy to store – room temperature storage is ok
SelectionsTaste: Vanilla, neutral or per your selectionTechnology: Soluble or non-soluble
Dosageform
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Dosage Form: CapsulesDosage
form
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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Other Dosage Forms
PowdersDelivered in small vial to consumer to take a tablespoon and sprinkle onto food or beverageAlso relevant dosage form when used for infant formula
Chewable TabletsChildren-friendly
SachetsSachets are quadrant-shaped bags with powder……different from sticks being rectangle bags
TabletsTypically 500-1500 mg per tablet
Dosageform
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What is potency?Potency
Chr. Hansen recommends products providing a daily dose of 1 to 10 Bil CFUChr. Hansen recommends products providing a daily dose of 1 to 10 Bil CFU
What is a CFU? CFU = Colony Forming UnitsOne 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 mediumAfter anaerobic incubation commonly 3 days at 37oC, the colonies are manually countedDifferent 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
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Chr. Hansen guarantees potency at point in value chain agreed with customer
Powderproductio
n
Bulk dosage forms
Finaldosage
form
Boxing &labeling
Distri-bution
Storeshelfing
Consump-tion
1B
Illustrative example of potency decline:
5B5.5B6.5B
End of shelf life
Potency point
#1
Potency point
#2
Potency point
#3
Potency point
#4
Chr. Hansen guarantees CFU count all the way to potency point #4 when delivering in final packaging material
Chr. Hansen guarantees CFU count all the way to potency point #4 when delivering in final packaging material
Potency
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“The Shelf-Life Equation”
Shelfstability
≤25OC≤0.15 aw ≤5%
Shelf life
×= ×Water Activity Temperature Oxygen
24 months = x x
Rule-of-thumb recommendation:
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What we do to maximize shelf stability
I. Strain
II. Excipients
III. Handling
IV. Production
V. Packaging
• Strains selected based on superior stability
• Excipients with extra low aw chosen
• Raw materials and products are handled in such a way that we minimize exposure to aw, temperature, and oxygen• We minimize mechanical processing
• We add probiotics as close to final filling as possible• We have for customers preparred Standard Operating
Procedures
• We discuss choice of product packaging with our customers
•Air tight•Moisture impermeable•Oxygen free (filled with nitrogen)
Shelfstability
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Types of packaging
Shelfstability
Recommended for capsules and tablets
Alu-tube Glass containerPlastic container w/ desiccant
Stick Sachet
Recommended for powderNot optimal,
but best blister typeAlu-alu blister
Not recommended
Plastic Container(PET)
Aclar blister PVDC-alu blister
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Desiccant
Shelfstability
Desiccant lid
Desiccant lining
Desiccant bags
Desiccant applications Desiccants reduce water activity level
0.16 0.16
0.02
0.11
0.01
0.10
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
Alu-tube with
dessicant lid
Plastic
container with
dissicant lining
0 months
3 months
6 months
Water activity
(Molecular Sieve)
(Molecular Sieve)
Desiccant types
BentoniteActivated clay Absorbs moisture steadily in given period
SilicagelChemically produced saltAbsorbs moisture steadily in given period
Molecular SieveCrystallized aluminum silicateAbsorbs moisture quickly within short period (up to 20% of its own weight)
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Moisture Vapor Transmission Rate by type of packaging material
Shelfstability
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.
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)
Plastic vial with desiccant lining permits 0.5mg moisture to enter vial, but desiccant absorbs 1g of moisture
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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 stressIn the field, the best dosage form for soldiers would be the probiotic stick or sachetIn 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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Togetherwe improve the quality of food and health for people all over the world
THANK YOU!
For more information, please contact:
Brian Peeters
Office: (415) 503-1834