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May 28th, 2015 Daniel S. Fabricant, Ph.D.

CEO & Executive Director, NPA daniel.fabricant@npainfo.org

STATES ALIVE: OUR RECENT EXPERIENCE

WITH THE NY AG 1

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�  114th Congress – pro-business, R-House, R-Senate ¡  Friends in high-places

�  Upcoming presidential cycle �  Issues – Federal GMOs, FSA/HSA redo, FTC, FDA/

DoJ accountability, NDI draft guidance and FSMA implementation

January, 2015 - Once upon a time in a land far, far away…….

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Fire One

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�  Ag claimed to have tested a few lots of BDS from Walmart, Walgreens, Target and GNC.

�  Claimed to find other ingredients, and raised a possible risk of allergens

�  AG asked for C & D on selling the lots/batches of those products

�  Data was scant, not peer-reviewed �  No formal filing �  Press hit pieces – tidal wave – used two messages

¡  GMP non-compliance ¡  “Public Health Catastrophe”

What happened?

“Botanicals” in the Food & Dietary Supplement marketplace

Ingredients & Raw materials

¡  Raw herb & powders

¡  Botanical Extracts ÷ Ratios (5:1, 10:1, 50:1 etc) No standardization to chemical

markers

¡  Standardized Botanical Extracts ÷ Specific chemical markers or chemical classes

¡  Highly enriched phytochemicals from botanicals

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Why Authenticate?

�  Ensure identity of product �  Safety �  Confirm the right product is used �  Provide traceability in a finished product �  Ensure accidental or economically motivated

adulterants are not present �  Comply with regulatory guidelines

DNA Barcoding

�  A process of closely examining the sequences of DNA to identify unique sections and comparing those to collected/fingerprinted references

�  While many genes in the DNA can be the same, they can vary greatly in specific sections and can be characteristic markers even in closely related species

�  Provides great opportunity for speciation and confirmation

�  Used extensively for a few decades, primarily in living/ animal species

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DNA Barcoding

�  Recent years garnered significant academic & research interest in speciation of the plant kingdom

�  Plant kingdom is extremely complex with multiple variables ¡  Species /variants

÷  Example: 50-150 variants of holy basil; ~15 species of Actaea (black cohosh is one of them)

¡  Geographical variability

¡  Harvest time variability ÷  Seasonal variability

¡  Plant part of use ÷  Root; aerial parts, flowers, seeds etc

Plant DNA extraction challenges

�  Presence of polysaccharides, polyphenols and other secondary metabolites

�  Numerous protocols are published each year

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DNA extraction from cinnamon bark

Other DNA testing remarks •  Supplements containing plant extracts should be tested using

analytical methods targeting active components rather then source DNA

•  Multi-marker reference database is required for accurate

identification

•  Species level resolution in many plant species will require multiple markers

•  Trace contamination with other plant species might occur at any stage of manufacturing process

•  Validated protocols involving NGS approach should be developed for authentication of herbal supplements and raw herbal materials

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¡  Heat

¡  Low or high pH i.e. extreme acidic or basic environments

¡  Non-aqueous solvents

DNA Barcoding Limitations - DNA denaturing

DNA Barcoding Technique – Processing Effects

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DNA Barcoding Limitations

�  Complex procedure – ground for potential errors

�  Cannot differentiate plant part

�  Sequences are affected by level of processing and can cloud identification procedures

�  Cannot identify/differentiate chemical components

�  Level of validation of identification methods can have an impact on test samples

�  Integrity of data in databases for verified reference materials – possible errors

Take home messages on DNA Barcode testing

•  DNA in plant powders is less degraded in comparison with plant extracts and suitable for authentication

•  Plant powders with low DNA content and/or heavy polysaccharide

content (such as bark powders) might be problematic for DNA extraction and contaminated by traces of other powders, which can be preferentially amplified by PCR

•  Such contamination can occur at any time during harvesting, processing or warehouse handling of plant materials

•  Two or more markers will be required for species level resolution •  NGS is required for identification of mixed source samples

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Take home messages

•  Bioac1ve  components  extrac1on  involves  manufacturing  processes  not  aiming  for  DNA  extrac1on  and  possibly  leading  to  DNA  degrada1on,  especially  if  water-­‐based  extrac1on  and  high  temperatures  are  involved  

•  DNA  degrada1on  will  be  different  in  each  process  

•  Supplements  prepared  with  plant  extracts  are  likely  to  have  very  low  concentra1on  of  degraded  DNA  (if  any)  

•  DNA  extrac1on  and  subsequent  PCR  might  be  problema1c  due  to  high  concentra1on  of  poten1al  inhibitors  

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�  Questions on substantiation of claims for St. John’s Wort, Ginkgo biloba, Panax ginseng by the original 4 retailers

Second round

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�  4 major manufacturers of BDS – requests data on how the products meet quality specs, similar request

�  A few new ones – data on claims for gluten free, hypo allergenic

�  Nature’s made, Nature’s way, Nutraceutical, NBTY

Third time is the charm?

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�  “Formation of a coalition of state attorneys general from Connecticut, Indiana and Puerto Rico to further investigate the business practices of the herbal supplement industry.”

�  Bipartisan �  Language pulls in products recalled for drugs –

these products aren’t DS but…..

4th course?

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�  Agreed to do some DNA barcoding where the tech was available

�  Response was mixed �  State and class action suit relief �  Q1 – on the street �  3 other major retailers – no settlement at present �  Read the settlement carefully – exact same products

allowed back on the shelf and AG not sure part 111 goes far enough (supply chain)

GNC settlement

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�  Letter from 14 states and territories AG’s for congress to investigate BDS

�  Connecticut, District of Columbia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Massachusetts, Mississippi, New Hampshire, Northern Mariana Islands, Pennsylvania and Rhode Island

�  Sent to Senate Commerce (Moran (R-KS)/Blumenthal (D-CT) and E & C health subcommittee (Pitts (R-PA)/Pallone (D-NJ))

Drive for 5 - Keep the cards and letters coming

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What have we done?

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�  Sent over 6,000 email messages specific to the issue, around 2k to NY AG’s office

�  Started to use social media �  More willingness to send to Congress then the states

Grassroots

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�  AG will continue to work in the area – supply chain issues & issue with how botanicals are labeled

�  Too much press – we will get a congressional challenge in the 114th

�  The positioning will be different than previous challenges – open amendment tree – congress is actually passing legislation

�  Other state challenges �  Watch state pre-emption in GMO debate �  More bad press

Next steps

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�  Engage with the states – RAGA/DAGA, etc. �  Grassroots �  No mon, no fun �  Transparency – questions on testing, product quality,

all the way through the supply chain, push our message out

What we need to do

� Daniel Fabricant, Ph.D. Natural Products Association 1773 T Street, NW Washington, DC 20009 Phone: (202)-223-0101 ext. 101 Fax: (202)-223-0250 daniel.fabricant@naturalproductsassoc.org www.naturalproductsassoc.org

Thank You!