Skye Lininger and Greg Heartman NDI III UNPA 2 17
Working Towards an Authoritative NDI List Dr. Skye Lininger, CEO, Healthnotes
1 © © 2017 2017 Healthnotes, Healthnotes,Inc. Inc.
“Big Data” Comes to Dietary Supplements • What is “Big Data?” – Data sets that are so large or complex that traditional data processing applications are inadequate – Challenges include analysis, capture, data curation, search, sharing, storage, transfer, visualization, querying, security, updating, and information privacy
2
© 2017 Healthnotes, Inc., Confidential.
Analysis Uncovers Data Challenges Specific to Dietary Supplements • • • • • •
3
No standardized language or taxonomy for DIs Important and necessary information is fragmented A wide variety of terms are used for the same ingredient Incomplete, ambiguous, or incorrect terminology is regularly used on supplement labels Lack of specificity and lumping together of specific forms under a large umbrella term (e.g. “polyphenols”) Difficulties understanding how regulatory, safety, and DSHEA enforcement applies to specific forms of DIs
© 2017 Healthnotes, Inc., Confidential.
Vitature™ “Big” Data • 55,972 SKUs • 2,749 brands • 306,221 scientific studies with abstracts • 15,918 ingredients (including plant parts) – 965 branded ingredients – 1,936 raw material suppliers – ~28% of SKUs have “proprietary blend” (DI amounts not listed) – 50-60% of SKUs have one or more DI that is not unlisted or ambiguous – Herbs of Commerce (HOC), GRAS, NDI, or Industry “Pre-DSHEA” lists (CRN, AHPA, NPA/NNFA, UNPA) • 3,569 unique DIs or 22% listed (12,349 or 78% not listed)
Cloud-based Software for Managing Compliance Between Suppliers and Manufacturers
4
© 2017 Healthnotes, Inc., Confidential.
Powerful Reporting—e.g. Instant Overview of the Melatonin Marketplace • Melatonin – 245 brands – 574 SKUs – Health Topic (S/F category)
5
© 2017 Healthnotes, Inc., Confidential.
Powerful Reporting—e.g. Complexity of the Supplement Industry
SKU with most DIs = 185 Average is 9.5 DIs per SKU
6
© 2017 Healthnotes, Inc., Confidential.
Statements from the Draft Guidance • How will FDA determine ODIs? –“Because of the uncertainty about the existence of supporting evidence, FDA does not accept the inclusion of an ingredient on an industry list of pre-DSHEA dietary ingredients as proof that the ingredient is not an NDI. However, in response to comments, we [FDA] are prepared to develop an authoritative list of pre-DSHEA ingredients, based on independent and verifiable data. Because FDA does not generally have access to marketing records for dietary ingredients and dietary supplements, the documentation of pre-DSHEA marketing would have to be supplied by industry.” (Draft Guidance, page 19)
7
© 2017 Healthnotes, Inc., Confidential.
Statements from the Draft Guidance • Existing ODI lists and Herbs of Commerce (1992) unlikely to be “solely determinative” • “If you rely on Herbs of Commerce as evidence that your dietary ingredient is not an NDI, we recommend that you maintain additional documentation showing that the botanical was marketed as a dietary ingredient before October 15, 1994. The documentation should specify the plant part from which the botanical dietary ingredient was derived, and for botanical extracts it should also specify the extract type.”
8
© 2017 Healthnotes, Inc., Confidential.
Statements from the Draft Guidance • “FDA’s current thinking is that the two main factors for playing an ingredient on an authoritative list of pre-DSEHA ingredients would be: (1) adequate documentation of marketing for use as or in a dietary supplement in the U.S. before October 15, 1994; and (2) a precise description of the identity of the ingredient market. Records offered to support an item’s inclusion on the list should specify the date of marketing in the U.S. and clearly identify the ingredient marketed on that date.” (page 20)
9
© 2017 Healthnotes, Inc., Confidential.
Case Study: Complexity—55 Total Echinacea “Ingredients” in Taxonomy 8 Echinacea ingredients appear in HOC or on “pre-DSHEA lists.” There are 1,094 SKUs that list Echinacea on the label.
Ingredient
HOC
NDI
GRAS
AHPA
CRN
NPA
Echinacea spp.
0
0
0
0
1
0
Echinacea angustifolia Root Powder Echinacea purpurea Aeriel Parts Powder Echinacea purpurea Leaf Powder
0 0 0
0 0 0
0 0 0
0 0 0
1 1 1
0 0 0
Echinacea angustifolia Echinacea pallida Echinacea purpurea Echinacea tennesseensis
10
1 1 1 1
0 0 0 0
© 2017 Healthnotes, Inc., Confidential.
0 0 0 0
1 1 1 0
1 1 0 0
1 0 1 0
47 Echinacea “Ingredients” Not on Any List. Are All Potential NDIs? Echinacea Plant Parts
47 Echinacea ingredients not on any pre-DSHEA list—but currently listed on products labels. 27 are Plant Parts “…using a different part of a plant (e.g., using an extract of plant leaves where the root extract from the same plant is a pre-DSHEA dietary ingredient) would create an NDI…” 20 are Extracts “…using a solvent to prepare an extract from a pre-DSHEA dietary ingredient creates an NDI because the final extract contains only a fractionated subset of the constituent substances in the original dietary ingredient.” 11
Echinacea angustifolia Aerial Parts Echinacea angustifolia Dried Echinacea angustifolia Leaf Echinacea angustifolia Leaf Powder Echinacea angustifolia Powder Echinacea angustifolia Root Echinacea pallida Root Echinacea purpurea Aerial Parts Echinacea purpurea Flower Echinacea purpurea Leaf Echinacea purpurea Powder Echinacea purpurea Root Echinacea purpurea Root Dried Echinacea purpurea Root Powder Echinacea purpurea Seed Echinacea Purpurea Whole Plant Echinacea purpurea Whole Plant Concentrate Echinacea simulata Echinacea spp. Aerial Parts Echinacea spp. Aerial Parts Juice Echinacea spp. Dried Echinacea spp. Flower Echinacea spp. Leaf Echinacea spp. Leaf Powder Echinacea spp. Powder Echinacea spp. Root Inc., Confidential. © 2017 Healthnotes, Echinacea spp. Whole Plant
Echinacea Extracts Echinacea angustifolia Extract Echinacea angustifolia Leaf Extract Echinacea angustifolia Leaf Powder Extract Echinacea angustifolia Root Extract Echinacea angustifolia Whole Plant Extract Echinacea pallida Root Extract Echinacea purpurea Extract Echinacea purpurea Leaf Extract Echinacea purpurea Powder Extract Echinacea purpurea Root Dried Extract Echinacea purpurea Root Extract Echinacea purpurea Root Powder Extract Echinacea purpurea Seed Extract Echinacea purpurea Whole Plant Extract Echinacea spp. Extract Echinacea spp. Leaf Extract Echinacea spp. Leaf Powder Extract Echinacea spp. Powder Extract Echinacea spp. Root Extract Echinacea spp. Whole Plant Extract
Ambiguity Increases Complexity—Echinacea spp The label listing “Echinacea spp.” is ambiguous. It does not describe the specific species (Latin binomial). Vitature estimates 22% of botanicals listed on labels are ambiguous.
Ingredient
Echinacea spp. Echinacea spp. Aerial Parts Echinacea spp. Aerial Parts Juice Echinacea spp. Dried Echinacea spp. Flower Echinacea spp. Leaf Echinacea spp. Leaf Powder Echinacea spp. Powder Echinacea spp. Root
12
HOC
NDI
GRAS
AHPA
CRN
NPA
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
0
0
Echinacea spp. Extract 0 0 Echinacea spp. Leaf Extract 0 0 Echinacea spp. Leaf Powder Extract 0 0 Echinacea spp. Powder Extract © 2017 Healthnotes, 0 0 Inc., Confidential.
0
0
1
0
What About Actives? • Echinacea contains actives which are often listed on labels. • Most are not on any pre-DSHEA list, GRAS, or NDI filings.
13
© 2017 Healthnotes, Inc., Confidential.
Vitature Ingredient Data Structure and Software Framework • Current Vitature capabilities – Full Ingredient Taxonomy (15,918) – Sources and Forms – Brand Names, Common Names – Suppliers (1,936) – Product Categories – Studied Topics (306,221) – Warnings and Advisories (Prop 65, FDA Safety Alert and Advisories List, Adulteration, USDA High Risk List) – Side Effects and Interactions – Regulatory status (ODI, HOC, NDI, GRAS) – Filed GRAS statements – NDI submissions and FDA responses (in partnership with AHPA) – Claims support – SIDI protocol fields for Vendor Qualification and Material Management – Supporting documents for raw materials (e.g. manufacturing process flowcharts, certifications, allergen, solvents, and certificates of analysis)
14
© 2017 Healthnotes, Inc., Confidential.
Demo
Cloud-based Software for Managing Compliance Between Suppliers and Manufacturers
15
Ingredient Data Structure and Software Framework—Possible Additions • Required examples of documentation dated prior to 10/15/94 – Written business records – Promotional materials – Press reports – Sales records – Bills of lading – Sales contracts – Manufacturing records – Commercial invoices – Magazine advertisements – Mail order catalogs – Sales brochures – Identity – Form – Proof ingredient was marketed as a dietary ingredient
16
© 2017 Healthnotes, Inc., Confidential.
Data Framework Discussion Q: Does Industry need an ingredient taxonomy (organized structure) database with pre-DSHEA (10/15/94) documentation? Who should create this resource: FDA or Industry?
17
Contact Skye Lininger for More Information +1 503-517-4511 / [email protected]
© 2017 Healthnotes, Inc.
1 © © 2017 2017 Healthnotes, Healthnotes,Inc. Inc.
“Big Data” Comes to Dietary Supplements • What is “Big Data?” – Data sets that are so large or complex that traditional data processing applications are inadequate – Challenges include analysis, capture, data curation, search, sharing, storage, transfer, visualization, querying, security, updating, and information privacy
2
© 2017 Healthnotes, Inc., Confidential.
Analysis Uncovers Data Challenges Specific to Dietary Supplements • • • • • •
3
No standardized language or taxonomy for DIs Important and necessary information is fragmented A wide variety of terms are used for the same ingredient Incomplete, ambiguous, or incorrect terminology is regularly used on supplement labels Lack of specificity and lumping together of specific forms under a large umbrella term (e.g. “polyphenols”) Difficulties understanding how regulatory, safety, and DSHEA enforcement applies to specific forms of DIs
© 2017 Healthnotes, Inc., Confidential.
Vitature™ “Big” Data • 55,972 SKUs • 2,749 brands • 306,221 scientific studies with abstracts • 15,918 ingredients (including plant parts) – 965 branded ingredients – 1,936 raw material suppliers – ~28% of SKUs have “proprietary blend” (DI amounts not listed) – 50-60% of SKUs have one or more DI that is not unlisted or ambiguous – Herbs of Commerce (HOC), GRAS, NDI, or Industry “Pre-DSHEA” lists (CRN, AHPA, NPA/NNFA, UNPA) • 3,569 unique DIs or 22% listed (12,349 or 78% not listed)
Cloud-based Software for Managing Compliance Between Suppliers and Manufacturers
4
© 2017 Healthnotes, Inc., Confidential.
Powerful Reporting—e.g. Instant Overview of the Melatonin Marketplace • Melatonin – 245 brands – 574 SKUs – Health Topic (S/F category)
5
© 2017 Healthnotes, Inc., Confidential.
Powerful Reporting—e.g. Complexity of the Supplement Industry
SKU with most DIs = 185 Average is 9.5 DIs per SKU
6
© 2017 Healthnotes, Inc., Confidential.
Statements from the Draft Guidance • How will FDA determine ODIs? –“Because of the uncertainty about the existence of supporting evidence, FDA does not accept the inclusion of an ingredient on an industry list of pre-DSHEA dietary ingredients as proof that the ingredient is not an NDI. However, in response to comments, we [FDA] are prepared to develop an authoritative list of pre-DSHEA ingredients, based on independent and verifiable data. Because FDA does not generally have access to marketing records for dietary ingredients and dietary supplements, the documentation of pre-DSHEA marketing would have to be supplied by industry.” (Draft Guidance, page 19)
7
© 2017 Healthnotes, Inc., Confidential.
Statements from the Draft Guidance • Existing ODI lists and Herbs of Commerce (1992) unlikely to be “solely determinative” • “If you rely on Herbs of Commerce as evidence that your dietary ingredient is not an NDI, we recommend that you maintain additional documentation showing that the botanical was marketed as a dietary ingredient before October 15, 1994. The documentation should specify the plant part from which the botanical dietary ingredient was derived, and for botanical extracts it should also specify the extract type.”
8
© 2017 Healthnotes, Inc., Confidential.
Statements from the Draft Guidance • “FDA’s current thinking is that the two main factors for playing an ingredient on an authoritative list of pre-DSEHA ingredients would be: (1) adequate documentation of marketing for use as or in a dietary supplement in the U.S. before October 15, 1994; and (2) a precise description of the identity of the ingredient market. Records offered to support an item’s inclusion on the list should specify the date of marketing in the U.S. and clearly identify the ingredient marketed on that date.” (page 20)
9
© 2017 Healthnotes, Inc., Confidential.
Case Study: Complexity—55 Total Echinacea “Ingredients” in Taxonomy 8 Echinacea ingredients appear in HOC or on “pre-DSHEA lists.” There are 1,094 SKUs that list Echinacea on the label.
Ingredient
HOC
NDI
GRAS
AHPA
CRN
NPA
Echinacea spp.
0
0
0
0
1
0
Echinacea angustifolia Root Powder Echinacea purpurea Aeriel Parts Powder Echinacea purpurea Leaf Powder
0 0 0
0 0 0
0 0 0
0 0 0
1 1 1
0 0 0
Echinacea angustifolia Echinacea pallida Echinacea purpurea Echinacea tennesseensis
10
1 1 1 1
0 0 0 0
© 2017 Healthnotes, Inc., Confidential.
0 0 0 0
1 1 1 0
1 1 0 0
1 0 1 0
47 Echinacea “Ingredients” Not on Any List. Are All Potential NDIs? Echinacea Plant Parts
47 Echinacea ingredients not on any pre-DSHEA list—but currently listed on products labels. 27 are Plant Parts “…using a different part of a plant (e.g., using an extract of plant leaves where the root extract from the same plant is a pre-DSHEA dietary ingredient) would create an NDI…” 20 are Extracts “…using a solvent to prepare an extract from a pre-DSHEA dietary ingredient creates an NDI because the final extract contains only a fractionated subset of the constituent substances in the original dietary ingredient.” 11
Echinacea angustifolia Aerial Parts Echinacea angustifolia Dried Echinacea angustifolia Leaf Echinacea angustifolia Leaf Powder Echinacea angustifolia Powder Echinacea angustifolia Root Echinacea pallida Root Echinacea purpurea Aerial Parts Echinacea purpurea Flower Echinacea purpurea Leaf Echinacea purpurea Powder Echinacea purpurea Root Echinacea purpurea Root Dried Echinacea purpurea Root Powder Echinacea purpurea Seed Echinacea Purpurea Whole Plant Echinacea purpurea Whole Plant Concentrate Echinacea simulata Echinacea spp. Aerial Parts Echinacea spp. Aerial Parts Juice Echinacea spp. Dried Echinacea spp. Flower Echinacea spp. Leaf Echinacea spp. Leaf Powder Echinacea spp. Powder Echinacea spp. Root Inc., Confidential. © 2017 Healthnotes, Echinacea spp. Whole Plant
Echinacea Extracts Echinacea angustifolia Extract Echinacea angustifolia Leaf Extract Echinacea angustifolia Leaf Powder Extract Echinacea angustifolia Root Extract Echinacea angustifolia Whole Plant Extract Echinacea pallida Root Extract Echinacea purpurea Extract Echinacea purpurea Leaf Extract Echinacea purpurea Powder Extract Echinacea purpurea Root Dried Extract Echinacea purpurea Root Extract Echinacea purpurea Root Powder Extract Echinacea purpurea Seed Extract Echinacea purpurea Whole Plant Extract Echinacea spp. Extract Echinacea spp. Leaf Extract Echinacea spp. Leaf Powder Extract Echinacea spp. Powder Extract Echinacea spp. Root Extract Echinacea spp. Whole Plant Extract
Ambiguity Increases Complexity—Echinacea spp The label listing “Echinacea spp.” is ambiguous. It does not describe the specific species (Latin binomial). Vitature estimates 22% of botanicals listed on labels are ambiguous.
Ingredient
Echinacea spp. Echinacea spp. Aerial Parts Echinacea spp. Aerial Parts Juice Echinacea spp. Dried Echinacea spp. Flower Echinacea spp. Leaf Echinacea spp. Leaf Powder Echinacea spp. Powder Echinacea spp. Root
12
HOC
NDI
GRAS
AHPA
CRN
NPA
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
0 0 0 0
0
0
Echinacea spp. Extract 0 0 Echinacea spp. Leaf Extract 0 0 Echinacea spp. Leaf Powder Extract 0 0 Echinacea spp. Powder Extract © 2017 Healthnotes, 0 0 Inc., Confidential.
0
0
1
0
What About Actives? • Echinacea contains actives which are often listed on labels. • Most are not on any pre-DSHEA list, GRAS, or NDI filings.
13
© 2017 Healthnotes, Inc., Confidential.
Vitature Ingredient Data Structure and Software Framework • Current Vitature capabilities – Full Ingredient Taxonomy (15,918) – Sources and Forms – Brand Names, Common Names – Suppliers (1,936) – Product Categories – Studied Topics (306,221) – Warnings and Advisories (Prop 65, FDA Safety Alert and Advisories List, Adulteration, USDA High Risk List) – Side Effects and Interactions – Regulatory status (ODI, HOC, NDI, GRAS) – Filed GRAS statements – NDI submissions and FDA responses (in partnership with AHPA) – Claims support – SIDI protocol fields for Vendor Qualification and Material Management – Supporting documents for raw materials (e.g. manufacturing process flowcharts, certifications, allergen, solvents, and certificates of analysis)
14
© 2017 Healthnotes, Inc., Confidential.
Demo
Cloud-based Software for Managing Compliance Between Suppliers and Manufacturers
15
Ingredient Data Structure and Software Framework—Possible Additions • Required examples of documentation dated prior to 10/15/94 – Written business records – Promotional materials – Press reports – Sales records – Bills of lading – Sales contracts – Manufacturing records – Commercial invoices – Magazine advertisements – Mail order catalogs – Sales brochures – Identity – Form – Proof ingredient was marketed as a dietary ingredient
16
© 2017 Healthnotes, Inc., Confidential.
Data Framework Discussion Q: Does Industry need an ingredient taxonomy (organized structure) database with pre-DSHEA (10/15/94) documentation? Who should create this resource: FDA or Industry?
17
Contact Skye Lininger for More Information +1 503-517-4511 / [email protected]
© 2017 Healthnotes, Inc.
