Dialogue on the stability of probiotics · 2019-08-30 · • Science and usage show us the benefits and safety of using probiotics. • Food and dietary supplements do not have the

Dialogue on the stability of probiotics

Auditorium ANVISA

Basilia, Brazil. June 19, 2017

®

Learning from the US Dietary Supplements market

Fernando Ferrer, MBA

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Fernando Ferrer, MBA © Multinational Partnerships LLC 2

Disclaimer

The views and opinions expressed in this session are those of the individual presenters and should not be attributed to their employers nor the organizers of this event.

Fernando Ferrer, MBA

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Objective

Discuss the world scenario on the regulation of probiotics and the divergences for the framing of these products in the categories of medicines and foods. The intend is also to discuss requirements for the development, use of claims and production of probiotics.

Discutir o cenário mundial sobre a regulação de probióticos e as divergências para o enquadramento destes produtos nas categorias de medicamentos e alimentos. Pretende-se também debater os requisitos para o desenvolvimento, uso de alegações e produção dos probióticos.

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Abstract

• Natural products challenge us to create and accept different standards. • Science and usage show us the benefits and safety of using probiotics. • Food and dietary supplements do not have the same technical

requirements of stability for medicines; however, this stability is taken into consideration from the moment of developing every industrial production formula.

• The variety of probiotics and their multiple applications in industrialized products makes it difficult to develop and implement regulations covering each and every one of its technicalities.

• This presentation shows the stability information of some probiotic products marketed in the US as dietary supplements.

• The proposed way to rapidly advance with a regulatory and industrial agreement is to break paradigms for a better inclusion of natural products, to seek simpler and broader regulations, and to understand and accept the technical reasons considered by industry to neutralize the aspects that may affect the stability of probiotics in food and medicines.

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Content

Dialogue on the stability of probiotics

① introduction

② Learning from the US Dietary Supplements market

③ discussion

Conclusion

Fernando Ferrer, MBA Multinational Partnerships LLC 5

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Natural products

• Natural products are small molecules produced naturally by any organism including primary and secondary metabolites.

• They include very small molecules, such as urea, and complex structures, such as Taxol.

• As they may only be isolable in small quantities, have interesting biological activity and chemical structures, natural product synthesis poses an interesting challenge in organic chemistry.

Source: Nature, founded in 1869. http://www.nature.com/subjects/natural-products

① introduction

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Definition of probiotics

Live microorganisms which when administered in adequate amounts confer a health benefit on the host

Source: WHO http://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf

Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food London, Ontario, Canada, April 30 and May 1, 2002

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Bacteria

• are among the first forms of life that appeared on Earth

• can be found virtually everywhere

– at temperature below 0°C or above 120°C

– low (0.007 atm) or high pressure (380 atm)

– with or without O2

– in radioactive waste

• are vital for humans

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The bacterial content of the colon exceeds all other organs

most bacteria reside only in the colon (which has a volume of 0.4 litres)

http://biorxiv.org/content/biorxiv/early/2016/01/06/036103.full.pdf

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Most common microorganisms used as probiotics

• Lactobacillus

• Bifidobacterium genera

• Other bacterial genera, including Enterococcus, Streptococcus, and Escherichia

• Fungus Saccharomyces boulardii

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FDA Generally Recognized as Safe (GRAS)

GRN No. Substance Date of closure

660 Bacillus coagulans GBI-30, 6086 13-Jan-17 601 Bacillus coagulans SBC37-01 spore preparation 28-Apr-16 597 Bacillus coagulans SNZ1969 spores preparation 29-Feb-16 526 Bacillus coagulans strain Unique IS2 spores preparation 23-Mar-15 377 Bifidobacterium animalis subsp. lactis strain Bf-6 29-Sep-11

445 Bifidobacterium animalis subsp. lactis strains HN019, Bi-07, Bl-04 and B420 10-Apr-13 455 Bifidobacterium breve M-16V 30-Sep-13 454 Bifidobacterium breve M-16V 27-Sep-13 453 Bifidobacterium breve M-16V 27-Sep-13

49 Bifidobacterium lactis strain Bb12 and Streptococcus thermophilus strain Th4 19-Mar-02

268 Bifidobacterium longum strain BB536 8-Jul-09 670 Inactivated Bacillus coagulans GBI-30, 6086 15-Mar-17

Source: webpage FDA, list of some probiotics listed by May 17, 2017

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https://www.accessdata.fda.gov/scripts/fdcc/?set=GRASNotices&id=660&sort=GRN_No&order=DESC&startrow=1&type=basic&search=BACILLUS



https://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=377&sort=FDA_s_Letter&order=ASC&startrow=1&type=basic&search=BIFIDO








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FDA Generally Recognized as Safe (GRAS) (2)

GRN No. Substance Date of closure

502 Lactobacillus acidophilus La-14 19-Aug-14 357 Lactobacillus acidophilus NCFM 19-Apr-11 171 Lactobacillus acidophilus, Lactobacillus lactis, and Pediococcus acidilactici 7-Dec-05 429 Lactobacillus casei strain Shirota 10-Dec-12 231 Lactobacillus casei subsp. rhamnosus strain GG 29-May-08 531 Lactobacillus fermentum CECT5716 20-Mar-15 410 Lactobacillus reuteri strain DSM 17938 26-Mar-12 254 Lactobacillus reuteri strain DSM 17938 18-Nov-08 410 Lactobacillus reuteri strain DSM 17938 26-Mar-12 440 Lactobacillus reuteri strain NCIMB 30242 12-Feb-13 288 Lactobacillus rhamnosus strain HN001 1-Nov-09 281 Lactobacillus rhamnosus strain HN001 produced in a milk-based medium 31-Aug-09

Source: webpage FDA, list of some probiotics listed by May 17, 2017















https://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=531&sort=FDA_s_Letter&order=ASC&startrow=1&type=basic&search=lactobacillus







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Loses in any food or medical industrialized product

Formulas must include overdoses to cover inherent loses in

Manufacturing

Analytical method(s)

Storage(s) and logistics

“One size doesn't fit all”. Variations due to diverse factors, e.g. components, product, forms, technologies, environment, etc.

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Summarizing

Natural Products - Microorganisms

Regulations

Industrialized products

Consumer

FOOD SUPPLEMENTS Stability of formulations of probiotics in the US market

② Learning from the US Dietary Supplements market

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Probiotics as Food Supplements Exhibition at Drugstores

DECLARING JUST THE CONTENT Examples of current products in the US market

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Rite Aid – 250mg Saccharomyces boulardii

serving 1 capsule

Content or potency is not related to manufacture or expiration dates

Store at room temperature. For best results, we recommend you store this product in the original package.

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RB– 2 billion viable cells serving 1 capsule

Potency is not related to manufacture or expiration dates :“guaranteed for …labeled potency”, but has a “% of survivability” claim

DECLARING POTENT AT TIME OF MANUFACTURE

Examples of current products in the US market

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Church & Dwight - PB8 14 billion Serving size 2 caps

Bacteria count will vary after time of manufacture. Store in a cool, dry place; best if refrigerated after opening

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N’s B - 20 billion live cultures serving 1 capsule

20 billion active cultures per serving guaranteed at the time of manufacture. Refrigerate after opening

DECLARING POTENT PRIOR TO EXPIRATION


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i-Health – 10 billion CFUs serving 1 capsule

Guaranteed potency thorough date on box when stored according to instructions. Store Culturelle in a cool , dry place away from direct sunlight. Keep Culturelle at room temperature or below.

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Bayer – 2 billion cells serving 1 capsule

Prior to expiration Store at a room temperature. Avoid excessive heat. Replace cap after use.

DECLARING POTENT AT THE TIME OF MANUFACTURE AND PRIOR TO EXPIRATION


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Rite Aid – 5 billion CFUs serving 1 capsule

Product contains 5 billion live cells when manufactured and a minimum of 1 billion live cells at time of expiration Store at 25°C (77°F). Avoid excessive heat and humidity. Protect from humidity.

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P&G – 4mg – 1 billion CFU serving 1 capsule

Contains 1 x 109 (one billion) live bacteria/CFU when manufactured, and provides an effective level of bacteria (1x107 CFU)* until at least the “best by” date *10 million

Store at room temperature. For best results we recommend you store Align in the original blister package.

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Loses might be up to 99% and 80% in 2 years

Align

1000 million to 10 million

Rite Aid

5 billion to 1 billion

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Loses in any food or medical industrialized product

Formulas must include overdoses to cover inherent loses in

Manufacturing

5 – ? %

Analytical method(s)

5 - 25%

Storage(s) and logistics

? – 10’000%

“One size doesn't fit all”. Variations due to diverse factors, e.g. components, product, forms, technologies, environment, etc.

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Discussion

• Is it feasible for natural products to respond always to the “rational” of synthetic products created by man?

• Is it impossible to create and implement an efficient regulatory system that can fully encompass the wide range of probiotics?

• Is the industry cheating the consumers and the authorities when adding an overdose?

③ discussion

No

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Simplicity

Complicating simplicity is simple but

simplifying the complex is very difficult

• “Simplicity is the ultimate sophistication.” — Leonardo da Vinci

• “Don’t make the process harder than it is.“ — Jack Welch

• “Life is really simple, but we insist on making it complicated.” – Confucius

• “Simplicity is the most difficult thing to secure in this world; it is the last limit of experience and the last effort of genius. “ — George Sand

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Conclusion

• Break paradigms. Natural products require a different vision than synthetic products created by man.

• Simplify. The wide variety of probiotics and their applications in the areas of food and medicine can be regulated based on a simple and broad regulation.

• Compliance. Industrialized products require overdosages that are specific to each process and product, levels can not be generalized; the industry is not intending to mislead the system and the addition of an overdose is sustained by valid reasons.

Fernando Ferrer, BSc. MBA Phone + 1 908 326 6417

[email protected]

Muito Obrigado Thank you

®

Multinational Partnerships® is a Registered Trade Mark of Multinational Partnerships LLC

mailto:[email protected]

mailto:[email protected]

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Documents

Dialogue on the stability of probiotics · 2019-08-30 · • Science and usage show us the benefits and safety of using probiotics. • Food and dietary supplements do not have the