Botanical Integrity: Significance of Fit for Purpose Tests During 2018-05-15¢  WHY...

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  • Amit Chandra, Ph.D

    AMWAY R&D

    amitabh.chandra@amway.com

    Phytochemical Fingerprint

    Botanical Integrity: Significance of Fit for Purpose Tests During

    Botanical Product Development Process

  • WHY BOTANICALS IN SUPPLEMENTS:

     Colorful fruits and vegetables are healthy sources of beneficial nutrients.

     WHO recommends five servings (about 450g) of fruits and vegetables every day to meet these requirements.

     75% of adults fail to meet this recommendation.

     Supplements containing vitamins, minerals and botanicals help to close this gap.

     Hence “quality of” and “choice of” right botanical for the right health benefit is extremely important !

    (Nutrilite Health Institute-Global Phytonutrient Report,

    British J. Nutrn, 2014)

  • TYPICAL FORM OF BOTANICAL INGREDIENTS, ACTIVES v/s MARKERS:

    STANDARDIZED EXTRACT:  Ingredient with certified / consistent levels of

    phytonutrients produced via controlled manufacturing / extraction process

    MARKERS (are typically quality indicating):  Phytonutrients that are “unique to” and used as analytes for

    identifying and quantifying the botanical ingredient.

    Please note: It is typically the whole ingredient that offers / maintains health benefit (in a supplement)

     not specific phytonutrients !

  • ADULTERATION OF BOTANICALS IN DIETARY SUPPLEMENT COMPROMISING ITS INTEGRITY:

    (1)If any valuable constituent has been in whole or in part omitted or abstracted therefrom; or (2) if any substance has been substituted wholly or in part therefor; or (3) if damage or inferiority has been concealed in any manner; or (4) if any substance has been added thereto or mixed or packed therewith so as to increase its bulk or weight, or reduce its quality or strength, or make it appear better or of greater value than it is.

    21 US Code 342 – Adulterated Food

  • TYPICALLY OBSERVED

    ADULTERATIONS IN BOTANICALS

     ECONOMICALLY MOTIVATED ADULTERATION (Intentional): Fortifying botanical ingredients by adding “markers” to pass quantitative tests !

    It is by design, not accident !  Markers can be from synthetic / natural source

     ACCIDENTAL ADULTERATION (Incidental): Due to carelessness in chain of custody

    No traceability !  supply chain, violation of cGMP, cross contamination etc.

     FORTIFYING OR REPLACING BOTANICALS WITH PRESCRIPTION DRUGS (Intentional)

    For quick results !  In weight loss, body building, sexual enhancement

  • A holistic / qualitative analytical approach to identify the correct / intended botanical source SHOULD ALWAYS PRECEED its quantification in the product.

    HENCE, THE CHOICE OF FIT FOR PURPOSE ANALYTICAL METHOD IS OF PRIME IMPORTANCE HERE

    Chandra, A., in Korea-China Joint International Phytonutrient Symposium, Seoul, 2016, 147-156.

  • What is the purpose of method OR what is the question that is being asked (ID or Quant) ?

     Is there some benchmark sample (authentic sample/control/reference) for comparison ?

    Nature of botanical INGREDIENT (dehydrate or extract) ?

     ID of whole plant or a specific plant part / processed ingredient ?

    QUANTIFICATION OF INGREDIENT ?  Genus spp and / or phytonutrients (markers) ….?

    ANSWERS TO ABOVE WILL HELP TO CHOOSE THE PROPER ANALYTICAL TEST METHOD

    AKA “FIT FOR PURPOSE”

    CRITERIA TO CHOOSE FIT FOR PURPOSE METHODS?

  • AUTHENTIC BOTANICAL SAMPLE / CONTROLS / REFERENCE

    • CERTIFIED REFERENCE MATERIALS

    • VOUCHERED SPECIMENS,

    • SELF COLLECTED / GENERATED BASED ON HISTORICAL USE, (with

    documentation)

    • ETC…..

    DEPENDS ON YOUR PURPOSE.

    SAMPLE MUST REPRESENT MATERIAL OF INTEREST

     Example: Matrix, Harvest time, specific plant part, Standardization level

    IT HAS TO BE APPLES

    TO APPLES

    COMPARISON

  • QUALITATIVE METHODS USED FOR BOTANICAL ID

    GENETIC: Full genomic sequence

    DNA barcoding

    Next generation sequencing (NGS)

    BIOLOGICAL: Micro and Macroscopic, organoleptic…

    CHEMICAL: (Spectroscopic) Patterns, Phytochemical Fingerprints

    (Qualitative, Holistic)

    Selected method must be

    appropriate (fit for purpose) for

    answering the question that is

    being asked!

    Khan, I.A., Smillie, T. J.Nat. Prod., 2012, 75 (9), 1665-1673. Betz, J.M., et al. Anal. Bioanal. Chem., 2007, 389, 19-25.

  • TIPS FOR FLAGGING BOTANICALS THAT ARE

    VULNERABLE FOR THEIR INTEGRITY (PRONE TO

    ADULTERATION)

    • RESTRICTED / LIMITED SUPPLY CHAIN

    • COMPLEX STANDARDIZATION PROCESS

    • HIGH COST

    • GENERIC PHYTONUTRIENT MARKERS

    • ONE GENUS, MULTIPLE SPECIES

    • LACK OF MANF. – SUPPLIER PARTNERSHIP

  • IN THIS CONTEXT,

    I WILL NOW SHARE WITH YOU

    TYPICAL EXAMPLES OF BOTANICAL SUPPLEMENTS IN MARKET THAT ARE VULNERABLE FOR ADULTERATION !

  •  SIGNIFICANT INCREASE IN SUPPLY CHAIN

     LOWERING OF COST

     GENERIC PHYTONUTRIENT TARGET FOR STANDARDIZATION (Total flavonol- glycosides)

    EXAMPLE 1: GINKGO BILOBA LEAF EXTRACT

    Chandra A; Li Y; Rana J; Persons K; Hyun C; Shen S; Mulder T., J. Func. Foods, 3, 2011, 107-114

  • FIT FOR PURPOSE METHOD: PHYTOCHEMICAL FINGERPRINT

    OF FLAVONOL GLYCOSIDES BEFORE HYDROLYSIS

    R Q, K and I

    This is the signature profile / fingerprint of

    “authentic ginkgo leaf extract 24/6”

  • RESULTS AND CONCLUSIONS

    All

    Passed

    24%

    spec

    Chandra A; Li Y; Rana J; Persons K; Hyun C; Shen S; Mulder T., J. Func. Foods, 3, 2011, 107-114

    http://www.google.com/imgres?imgurl=http://mrhiggins.net/algebra2/wp-content/uploads/2008/06/smile.jpg&imgrefurl=http://mrhiggins.net/algebra2/&usg=__ep_DbPbMHdecznxEbs3g2L8gFhQ=&h=317&w=313&sz=47&hl=en&start=59&zoom=1&tbnid=AymskX_wkzFCeM:&tbnh=118&tbnw=117&ei=ryVqTvO3LeXb0QHcl5WdAg&prev=/search?q%3Dsmiley%2Bface%2Bsymbols%26start%3D42%26um%3D1%26hl%3Den%26sa%3DN%26tbm%3Disch&um=1&itbs=1 http://www.google.com/imgres?imgurl=http://www.istockphoto.com/file_thumbview_approve/56642/2/istockphoto_56642-smiley-12.jpg&imgrefurl=http://bodytypenutrition.co.uk/yi-mad-smiley-faces/&usg=__644KK4-i6Z6Nbo_-jbqNHrah334=&h=380&w=380&sz=32&hl=en&start=136&zoom=1&tbnid=m6BnyzGGTP2AEM:&tbnh=123&tbnw=123&ei=QzpqTuGRCuGosAKHmsy1Bg&prev=/images?q%3Dsmiley%2Bface%2Bimages%26start%3D126%26hl%3Den%26sa%3DN%26tbm%3Disch&itbs=1 http://www.google.com/imgres?imgurl=http://www.istockphoto.com/file_thumbview_approve/56642/2/istockphoto_56642-smiley-12.jpg&imgrefurl=http://bodytypenutrition.co.uk/yi-mad-smiley-faces/&usg=__644KK4-i6Z6Nbo_-jbqNHrah334=&h=380&w=380&sz=32&hl=en&start=136&zoom=1&tbnid=m6BnyzGGTP2AEM:&tbnh=123&tbnw=123&ei=QzpqTuGRCuGosAKHmsy1Bg&prev=/images?q%3Dsmiley%2Bface%2Bimages%26start%3D126%26hl%3Den%26sa%3DN%26tbm%3Disch&itbs=1

  • FLAGS:

     SIGNIFICANT INCREASE IN SUPPLY CHAIN

     LOWERING OF COST

     GENERIC STANDARDIZATION (Total Anthocyanins)

     ONE GENUS (Vaccinium spp) MANY SPECIES

    EXAMPLE 2: BILBERRY (Vaccinium myrtillus)

    Chandra A., Rana J., Li Y. J Agric Food Chem., 49 (8), 2001, 3515-3521

    Li Y; Chandra A, Persons K, Stern N, Shen S. 127th AOAC International, 2013, Aug 25-28, Chicago IL, USA

  • FIT FOR PURPOSE TEST: HPLC Fingerprint of

    anthocyanins in authentic Bilberry (as is )

    This is the signature profile / fingerprint of anthocyanins in

    “authentic bilberry extract”

    Chandra A., Rana J., Li Y. J Agric Food Chem., 49 (8), 2001, 3515-3521

  • Looks like black rice

    Looks like elderberry

    Could be amaranth dye !

    Li Y; Chandra A, Persons K, Stern N, Shen S. 127th AOAC International, 2013, Aug 25-28, Chicago IL, USA

    RESULTS AND CONCLUSIONS

    AUTHENTIC BILBERRY

    BC BR BB1 BB2 GR BB BBn CG A

  • RECOMMENDED FIT FOR PURPOSE ANALYTICAL TESTS FOR ENSURING BOTANICAL INTEGRITY

    DNA ORGANOLEPTIC MACROSCOPIC

    &

    MICROSCOPIC

    PHYTOCHEMICAL

    WHOLE

    DEHYD.

    EXTRACT

    STD. EXTRACT

    SPECIFIC

    PLANT PART * *

    BLENDED

    BOTANICALS

    TEST

    B O

    T A

    N IC

    A L

    *: RED FOR EXTRACTS

    * *

    RED: Not fit for purpose

    YELLOW: Limited fit

    GREEN: Fit for purpose

    RED FOR

    UNKNOWN

    BOTANICALS

    Chandra, A., in Korea-China Joint International Phytonutrient

    Symposium, Seoul, 2016, 147-156.

  • Quality By Design QbD ?

    • Quality by Design (QbD) is a proactive and

    systematic approach to development that begins

    with predefined objectives and emphasizes

    product and process understanding and process

    control, based on sound science and quality risk

    management.

    WHY: FOR Advancement of botanical integrity,

    safety and quality in the industry !

    Khan, I.A., Smillie, T. J.Nat. Prod., 2012, 7