Regulation of herbal medicine effect both herbal products and clinical practices

1. Current Practices and Regulation of
Herbal Medicine in the US
Michael Tims, PhD

2. Part I: what we will cover
Part I:
• How do we define legal status of plants?
• Statutory Authority – what does that mean?
• Product classification
• Consumer rights
• DSHEA

3. Which Plant is Illegal to Sell?

4. Legal Status -- Ayahuasca
• Plants and preparations are legal, as they contain no
DMT
• Brews made using DMT containing plants are illegal
since DMT is a Schedule I drug
• Challenges similar to those used by peyotist, Native
American Church.

5. Legal Status -- Salvia
• Not regulated under the Controlled Substances Act
• Alabama, Delaware, Illinois, Louisiana, Michigan,
Missouri, Ohio, Texas and others, have passed their
own laws

6. Legal Status Ma Huang
• FDA banned sale of ephedra-containing
supplements in in 2004
• Challenged by supplement manufacturers and
initially overturned, but ultimately upheld
• Herb shops in China Town

7. U.S. Regulation of
Botanical Products
• United States Department of Agriculture (USDA)
• Bureau of Alcohol, Tobacco, Firearms, and Explosives
• Drug Enforcement Administration (DEA)
• U.S. Fish and Wildlife Service
• Federal Trade Commission (FTC)
• Food and Drug Administration (FDA)

8. Regulation of Claims
• FDA maintains primary authority ofregulating
disease claims made in labeling and product
literature
• FDA label infraction = change label
• Now can assess punitive damages to those selling
unapproved drugs ($109 million against Lane Labs)
• Federal Trade Commission (FTC) maintains
primary authority of regulating claims in
advertisements
• FTC infraction = $ fine and review of future
marketing materials.

9. Food and Drug
Administration
• 1906 - Federal Food, Drug and Cosmetic Act (FDC
Act), as amended: United States Code, Title 21
• Regulates foods, drugs, cosmetics, medical devices
and their manufacture
• Prohibits commerce of any food that can cause harm.
• Manufacturers not required to prove safety-
presumption of safety.
• Does NOT regulate the practice of medicine

10. Statutory Authority for
Dietary Supplements
• Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 301 et.
seq.)
• Dietary Supplement Health and Education Act of 1994
(Pub. L. 103-417, 108 Stat. 4325)
• Dietary Supplement and Nonprescription Drug Consumer
Protection Act (Pub. L. 109-462, 120 Stat. 3469)
• Farm Security and Rural Investment Act of 2002 (Pub. L.
107-171, 116 Stat. 135-527)
• Food Allergen Labeling and Consumer Protection Act of
2004 (Pub. L. 108-282, 118 Stat. 905)
• Public Health Security and Bioterrorism Preparedness and
Response Act of 2002 (Pub. L. 107-188, 116 Stat. 594)
• FDA Food Safety Modernization Act (Pub. L. 111-353,124
Stat. 3885)

11. Product Classification:
Intended Use Doctrine
• Products are either foods, dietary supplements, or
drugs
• Regulations for the category apply
• Intended use is ascertained by accompanying
labeling claims, advertising materials, oral or
written statements

12. Food
• “Article intended as food”
• “Consumed for flavor, nutritive value…”
• Generally Recognized as Safe (GRAS)
• No regulatory category for functional food in the U.S.
• This whole category and accompanying regulatory
statutes is about to change

13. Drug
• “Articles intended for...diagnosis, cure, mitigation,
treatment or prevention of disease in man...animals”
• Intended to affect the structure or function of the
body
• Listed in an official compendium
• Must be Generally Recognized as Safe and Effective
(GRASE) i.e. premarket approval

14. Botanical Products
• If intended use is to cure, treat, mitigate, etc. they are
DRUGS
• Subject to current drug regulations
• Botanicals have unique qualities recognized by the
FDA:
– inherently more complex than synthetics
– more likely to be components in mixtures
– active constituents and activity not always well
defined

15. Botanical Products
1. Topical: Veregen, a green tea extract
– Genital warts
2. Oral: Crofelemer, for HIV-related diarrhea
– Derived from Croton lechlen (dragon’s blood)
latex
– Originally developed/standardized by Shaman
pharmaceuticals

16. Consumer Rights
• As interest in herbal medicine grew, out cries about the
market being “unregulated”
• FDA attempted to increase regulation
• Example of encapsulated black currant oil as a “food
additive”
• Courts overturned
• Grassroots efforts of consumers, manufacturers and
practioners lead to passage of Dietary Supplement and
Nonprescription Drug Consumer Protection Act
(DSHEA)

17. DSHEA: Dietary Supplement
Health and Education Act (1994)
• Amended the FD&C Act
• Assured Consumers Access to Supplements
• Defined Dietary Supplements
• Established Regulatory Framework (FDA)
• Established Labeling Rules
• Created the Office of Dietary Supplements at the
National Institutes of Health

18. Dietary Supplement
• Prior to DSHEA, many botanicals regulated as food
additives or as drugs (both require pre--market approval)
• “...any product (other than tobacco) that contains a
vitamin, mineral, herb, or other botanical or amino
acid and is intended as a supplement to the diet.”
• A concentrate, metabolite, constituent, or combination
of the above

19. Part II: what we will cover
Part II:
• Regulatory paradigm
• Regulation of botanical supplements via cGMP
• How DSHEA influences the production of herbal
medicine
• Role of FTC
• Safety and opportunities

20. Regulatory Paradigm
• Supplements are food
• No premarket approval
• No mandatory formulation standards
• No product registration
• No approval of structure/function claims
• Manufacturer responsible for ensuring safety and
compliance
• Manufacturer responsible for reporting Safety and
Adverse Events
• FDA bears burden of proof for regulatory actions

21. New GMP Requirements
for Manufacturers
Comprehensive system of controls for documenting:
• identify
• strength
• composition accuracy of label
• adulteration
• manufacturing processes

22. Herbal Dispensatory: GMPs
Formal guidelines not applied if a “one--to--one”
relationship maintained
• Cleanliness
• Handling of botanicals
• Microbial contaminations (pathogen free)
• Adulterations
• Storage of herbs
• Alcohol extracts (handling alcohol)
• Instructions for use by clients (cooking, dosing, etc.)
• Educating students and office personnel

23. Dietary Supplement
Regulation
Companies prohibited from selling a DS that:
• Is toxic or unsanitary
• Makes false or unsubstantiated claims
• Claims to cure, treat, mitigate, etc…
• Is a new dietary ingredient without premarket notification
• Fails to be made according to cGMP (manufacturers only)
• Not labeled properly, fails to meet label claim
• Grandparented versus new ingredients

24. GMP Enforcement

25. Federal Trade Commission
When Identifying Claims
• Consider the ad as a whole, the "net impression"
conveyed by all elements of the ad, including the text,
product name, and depictions
• When an ad lends itself to more than one reasonable
interpretation, the advertiser is responsible for
substantiating each interpretation

26. Example 1
An advertisement claims that "university studies prove"
that a mineral supplement can improve athletic
performance. The advertiser has expressly stated the level
of support for the claimed benefit and is therefore
responsible for having "university studies" that document
the advertised benefit. Furthermore, the implied reference
to scientific evidence likely conveys to consumers the
implied claim that the studies are methodologically sound.

27. Example 2
An advertisement for a vitamin supplement claims that
90% of cardiologists regularly take the product. In addition
to the literal claim about the percentage of cardiologists
who use the product, the ad likely conveys an implied
claim that the product offers some benefit for the heart.
Therefore, the advertiser must have adequate support for
both representations.

28. Example 3
An ad for an herbal supplement makes the claim that the
product boosts the immune system to help maintain a
healthy nose and throat during the winter season. The ad
features the product name "Cold Away" and includes
images of people sneezing and coughing. The various
elements of the ad — the product name, the depictions of
cold sufferers, and the reference to nose and throat health
during the winter season — likely convey to consumers
that the product helps prevent colds. Therefore, the
advertiser must be able to substantiate that claim.

29. Example 4
An ad for a dietary supplement called "Arthricure" claims
that the product maintains joint health and mobility into
old age. The "before" picture shows an elderly women
using a walker. The "after" picture shows her dancing with
her husband. The images and product name likely convey
implied claims that the product is effective in the treatment
of the symptoms of arthritis, and may also imply that the
product can cure or mitigate the disease. The advertiser
must be able to substantiate these implied claims.

30. FTC Claims Substantiation
• Must have substantiation BEFORE a claim is made.
• Dose relationships, recognized mechanisms of action,
and statistical significance used to assess substantiation.
• The amount and type of evidence needed to substantiate
a claim is based on the nature of the claim. If a claim is
purported to be backed by scientific literature, the
literature must, therefore, be conducted in a manner as
to be scientifically valid for substantiating the claim.
– Carefully controlled trials.
– Historical use.
– Publication of claim in peer review journal

31. Industry vs. FDA
• Proactive – encouraged member compliance and
increased self-policing (comfrey)
• FDA lackedexpertise
• FDA approached problem solving with a
pharmaceutical hammer - analytical chemists and
toxicologists
• FDA risk/benefit analysis
• Adverse Event Reporting (AER) – suggested by
AHPA
• Ephedra (Ma huang) controversy

32. Adverse Events Reports
Requirements:
– company whose name is on label must maintain
records of all adverse event reports for 6 years
Serious adverse event defined as an event that:
– results in death or life threatening experience
– hospitalization, medical or surgical intervention
– significant disability, congenital anomaly or birth
defect
“Hydroxycut” – 23 idiosyncratic hepatoxicities
– after ephedra removed from formulation
– unknown which ingredient(s) responsible

33. AERs by Product Category
400
350
300
250
200
150
100
50
0
Vit/min
(25%)
Herbal
(7%)
Comb
(39%)
Other
(9%)
Mult
prods
(13%)
Unknown
(7%)

34. Most Common Single Product AERs
(n = 792)
• Bayer One A Day: 100(13%)
• “Total Body Formula”: 97 (12%)
• Centrum (all formulas): 40 (5%)
• Flintstone Vitamins (all formulas): 34 (4%)
• Calcium products (conventional): 35 (4%)

35. Seriousness of DS AERs: Jan--Oct,2008
300
250
200
150
100
50
0
Death Hospital Req Int Other
serious

36. Non--regulatory Science
Organizations
Office of Dietary Supplements (NIH)
– fund efforts to develop and validate methods to reliably
identify and quantify biologically active and marker
compounds, adulterants or contaminants.
United States Pharmacopeial Convention (USP)
– establish compendial standards (monograph)
enforceable by FDA
– monographs used to define product as
misbranded
National Institute of Standards and Technology (NIST)
– botanical Standard Reference Materials

37. Part III: what will we cover
Part III
• Consumer demand for herbal clinical practice
• To license or not?
• Regulation of clinical herbalism
• Informed consent

38. Where We are Today
Consumer driven revival:
• Almost 50% of US consumers want alternative care
• Herbal supplements industry alone worth $65 billion
• Licensing exists for acupuncturists, naturopaths,
• nutritionists, and wellness counselors

39. What would it look like for herbalists to
be recognized as health practioners?
• Legal recognition
• Consumer access
• Consumer confidence

40. Herbal/Alternative Medicine today
• Increasing use
• Increasing visibility
• Increasing research
• Limited by legal issues originating 100 years ago
• Important to question the history of herbal medicine to
uncover the bones of how decisions got made

41. Consumers Looking for Alternatives
• Effective treatment for chronic diseases of day
• Access to worldwide health information
• Individualized therapy
• Promotion of self-care, empowerment, participation in
healing process
• Minimized adverse effects
• Lower costs
• Paradigm shift to Wellness

42. Federal Protection Healthcare Consumers
• In general, Bill of Rights protects citizens from federal
encroachment
• So far, courts have not agreed that we have a
constitutional right to medical care of our choice
• The 14th amendment appears to be more fertile ground
with focus on privacy rights translated to autonomous
decision-making about health care

43. State Regulation of Medicine
• Regulate the “Practice of Medicine”
• Maryland (1888) licensed only graduates of med school or
those passing licensing exam
• Today specific definition based on licensing by Board of
Physicians or health profession
• Several licensed practitioners are allowed to practice
herbal medicine – naturopaths, chiropractors,
acupuncturists and physicians

44. Health Freedom Laws
Protect alternative and complementary medicine practices
(including herbalists)
• Don’t conduct clearly medical practices (surgery)
• Don’t harm
• Don’t pretend to be a physician or licensed
• Disclose education, training and services to clientele
Has not been passed in Maryland, Virginia or Deleware

45. Health Freedom Laws Passed
2015 Nevada
2013 Colorado
2009 New Mexico
2008 Arizona
2005 Louisiana
2003 Rhode Island
2001 California
1999 Minnesota
1994 Oklahoma
1976 Idaho

46. Health Freedom Bills
• Protect consumers
• Eliminate prosecutions for practicing without a license
• Paradigm shift away from supremacy of physician
expertise and control of health care choices
• Embracing patient responsibility for wellness
Still, why is there no licensing apparatus for herbalist?

47. Practice - Language
• Diagnosis or treatment – don’t use
o Instead we assess physiological function rather than
diagnose pathophysiological conditions (disease)
• Prevent
o We promote and maintain wellness

48. Informed Consent-Full Disclosure
• Services to be provided
• Background on training and experience
• Roles and responsibilities in practitioner-client
relationship
• Does not take the place of appropriate medical care

49. California Provision: Full Disclosure
• Practitioner is not a licensed physician
• Therapy is alternative
• Services to be provided are not licensed by the state
• Description of the nature of services to be provided
• The theory of treatment upon which therapies are based
• Educational background and experience regarding
services to be provided
• Obtain written acknowledgement from client that they
have been provided with aforementioned info