Dialogue on the stability of probiotics Learning from the US Dietary Supplements market Fernando Ferrer, MBA Auditorium ANVISA Basilia, Brazil. June 19, 2017
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 Multinational Partnerships LLC 2
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. Fernando Ferrer, MBA Multinational Partnerships LLC 3
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. Fernando Ferrer, MBA Multinational Partnerships LLC 4
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 55
Natural products 1 introduction 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 Fernando Ferrer, MBA Multinational Partnerships LLC 6
Definition of probiotics Live microorganisms which when administered in adequate amounts confer a health benefit on the host 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 Source: WHO http://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf Fernando Ferrer, MBA Multinational Partnerships LLC 7
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 O 2 in radioactive waste are vital for humans Fernando Ferrer, MBA Multinational Partnerships LLC 8
most bacteria reside only in the colon (which has a volume of 0.4 litres) The bacterial content of the colon exceeds all other organs http://biorxiv.org/content/biorxiv/ear ly/2016/01/06/036103.full.pdf Fernando Ferrer, MBA Multinational Partnerships LLC 9
Most common microorganisms used as probiotics Lactobacillus Bifidobacterium genera Other bacterial genera, including Enterococcus, Streptococcus, and Escherichia Fungus Saccharomyces boulardii Fernando Ferrer, MBA Multinational Partnerships LLC 10
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 Bifidobacterium lactis strain Bb12 and Streptococcus thermophilus strain 49 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 Fernando Ferrer, MBA Multinational Partnerships LLC 11
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 Fernando Ferrer, MBA Multinational Partnerships LLC 12
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. Fernando Ferrer, MBA Multinational Partnerships LLC 13
Summarizing Natural Products - Microorganisms Consumer Regulations Industrialized products Fernando Ferrer, MBA Multinational Partnerships LLC 14
2 Learning from the US Dietary Supplements market Stability of formulations of probiotics in the US market FOOD SUPPLEMENTS
Probiotics as Food Supplements Exhibition at Drugstores Fernando Ferrer, MBA Multinational Partnerships LLC 16
Examples of current products in the US market DECLARING JUST THE CONTENT
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. Fernando Ferrer, MBA Multinational Partnerships LLC 20
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 Fernando Ferrer, MBA Multinational Partnerships LLC 21
Examples of current products in the US market DECLARING POTENT AT TIME OF MANUFACTURE
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 Fernando Ferrer, MBA Multinational Partnerships LLC 23
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 Fernando Ferrer, MBA Multinational Partnerships LLC 24
Examples of current products in the US market DECLARING POTENT PRIOR TO EXPIRATION
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. Fernando Ferrer, MBA Multinational Partnerships LLC 26
Bayer 2 billion cells serving 1 capsule Prior to expiration Store at a room temperature. Avoid excessive heat. Replace cap after use. Fernando Ferrer, MBA Multinational Partnerships LLC 27
Examples of current products in the US market DECLARING POTENT AT THE TIME OF MANUFACTURE AND PRIOR TO EXPIRATION
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. Fernando Ferrer, MBA Multinational Partnerships LLC 29
P&G 4mg 1 billion CFU serving 1 capsule Contains 1 x 10 9 (one billion) live bacteria/cfu when manufactured, and provides an effective level of bacteria (1x10 7 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. Fernando Ferrer, MBA Multinational Partnerships LLC 30
Loses might be up to 99% and 80% in 2 years Align 1000 million to 10 million Rite Aid 5 billion to 1 billion Fernando Ferrer, MBA Multinational Partnerships LLC 31
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. Fernando Ferrer, MBA Multinational Partnerships LLC 32
3 discussion 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? Fernando Ferrer, MBA Multinational Partnerships LLC 33
No
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 Fernando Ferrer, MBA Multinational Partnerships LLC 35
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, MBA Multinational Partnerships LLC 36
Muito Obrigado Thank you Fernando Ferrer, BSc. MBA Phone + 1 908 326 6417 fferrer@multinationalpartnerships.com Multinational Partnerships is a Registered Trade Mark of Multinational Partnerships LLC
Members of Fernando Ferrer, MBA Multinational Partnerships LLC 38
Members of Fernando Ferrer, MBA Multinational Partnerships LLC 39