Herbal products, also known as botanical products or phytomedicines, are products made from plants to treat diseases or maintain health. Herbal products are made by extracting active ingredients from plant parts, such as leaves, bark, roots, seeds, or flowers. Herbal products, including dietary supplements, are regulated by the FDA. However, unlike pharmaceutical drugs, they do not require pre-market approval. Instead, manufacturers are responsible for ensuring the quality and safety of their products. The FDA establishes Good Manufacturing Practices (GMP) regulations for dietary supplements to ensure quality control during manufacturing. The safety of herbal products in the USA is overseen by various regulatory agencies, primarily the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC). To ensure a high degree of safety and effectiveness of herbal products and quality control standards during the manufacturing of herbal supplements and medicines, AHPA published GACP (Good Agriculture and Collection Practices) guideline in the American Herbal Pharmacopoeia.

1. Quality, Safety and Legislation for
herbal products in USA
Presentation by: Gowthami A H
Date:19/02/2024
Department of Pharmaceutical Regulatory Affairs
Regulatory Aspects of Herbals and Biologics

2. Contents
Herbal products
Regulation of Herbal drug in USA
Quality of Herbal drugs in USA
Good manufacturing practice
Safety of Herbal drugs in USA
Good Agriculture and collection practice
Global Regulatory Differences on Botanicals
Conclusion and References

3. Herbal products
 Herbal products, also known as botanical
products or phytomedicines, are products made
from plants to treat diseases or maintain health.
 Herbal products are made by extracting active
ingredients from plant parts, such as leaves, bark,
roots, seeds, or flowers.
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4. How a botanical product is regulated is dependent on its intended use and how the
product is labeled.
Botanical Product
Regulated as A
Drug
Botanical Product
Regulated as A
Dietary
Supplement
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5. Botanical Product Regulated as a Drug
 Botanical drugs are therapeutic materials derived
from plants, plant extracts, algae, fungi, or other
natural sources.
 These materials may come from a single plant or
a combination of multiple plants.
 As per the regulations of the US FDA, the
collective combination of these components is
recognized as the Active Pharmaceutical
Ingredient (API) for a botanical drug.
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6. Botanical products does not include:
Products that
contain animals or
animal parts and/or
minerals, except
when these are a
minor component
in a traditional
botanical
preparation
Materials derived
from botanical
species that are
genetically modified
with the intention
of producing a
single molecular
entity
Products produced
by fermentation of
yeast, bacteria,
plant cells, or other
microscopic
organisms,
including plants
used as substrates
Highly purified
substances, either
derived from a
naturally occurring
source or
chemically modified
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7. Approved botanical drugs
To date, two botanical products have fulfilled the Botanical Guidance definition of a
botanical drug product. Both botanical drug products have been approved for
marketing as prescription drugs (sinecatechins, Veregen® and crofelemer,
Mytesi™). There are some botanical drugs, including cascara, psyllium, and senna,
that are included in the over-the-counter (OTC) drugs.
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8. Botanical Drug Development Under INDs
 In the United States, to transform a product into a prescription
medicine, it must undergo the US FDA Investigational New Drug
(IND) Application process.
 This process is a crucial regulatory step for herbal medicines to
become prescription botanical drugs, manufacturers must
submit a botanical drug IND application to the US FDA.
 This botanical drug IND pathway shares similarities with the
traditional IND processes for small molecules, large molecules,
cell therapies, and gene therapies.
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9. Marketing of Botanical Drugs Under NDAs
 Any person who wishes to market a new drug in
the United States must submit an NDA and
obtain Agency approval prior to marketing the
new drug product for the proposed use ( 505 of
the FD&C Act).
 FDA may approve a drug product containing
such a drug substance for OTC sale pursuant to
an application submitted under section 505 of the
FD&C Act.
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10. Botanical Product Regulated as a
Dietary Supplement
 A botanical product is regulated under the general umbrella of foods as a dietary
supplement if it is intended to supplement a diet. A botanical-based dietary
supplement is taken orally and cannot make a disease claim to diagnose, cure,
mitigate, treat, or prevent disease.
 FDA regulates dietary supplements under a different set of regulations than those
covering "conventional" foods and drug products. Under the Dietary Supplement
Health and Education Act of 1994 (DSHEA)
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11.  FDA generally does not approve dietary supplement claims or
other labeling before use.
 Under the FD&C Act, a firm is responsible for ensuring that
the dietary supplements it manufactures or distributes are not
adulterated, misbranded, or otherwise in violation of federal
law.
 The FDA mandates that manufacturers notify them of “New
dietary ingredients (NDIs)” or ingredients used in dietary
supplements that were not marketed in the USA before 1994.
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12. FDA Labeling Requirements for Dietary Supplements
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13. Botanical Drug Market Report
11
 The global botanical drug market size was
USD 3268 million in 2021 and market is
projected to touch USD 48537 million by 2031,
at a CAGR of 4.0% during forecast period.
 Products like Ginkgo Biloba, ginseng,
echinacea, and garlic are the major selling
botanical products in the U.S.

14. Preference of consumers for natural therapies
Concern regarding undesirable side effects of
modern medicines
The belief that herbal medicines might be of
effective benefit
Tendency towards self-medication
Improvement in quality, proof of efficacy and
safety of herbal medicines.
High cost of synthetic medicines
Several
important
factors have
contributed to
the growth of
phytotherapeutic
market
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15. Factors affecting quality of herbal medicines
• Substitution of inferior varieties
• Substitution of exhausted drugs (cloves, fennel)
• Artificially manufactured substitutes
• Objects added to increase weight of material for sale (stones, lead shot)
Adulteration
• Light
• Temperature
• Humidity
• oxidation
Deterioration
of herbal
products
• Synthetic pharmaceuticals added to the plant material for
pharmacological activity ( Herbal Viagra)
• Adding citral to oil of lemon
• Benzyl benzoate to balsam of peru
Addition of
synthetic
principles
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16. Examples
 Senna is a natural laxative commonly used in
herbal teas and supplements to relieve
constipation.
 Adulteration may involve the addition of cheaper
substitutes or fillers, which can compromise the
quality and effectiveness of the product.
 Dog senna , palthe senna and mecca or Arabian
and Bombay senna are common adulterants of
senna.
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17.  Chinese star anise ( Illicium verum) is a well-
known spice used in many culture.
 Caribbean and Latino populations typically
use a tea infusion of its fruit as a carminative
and sedative for treatment of infants.
 Japanese star anise ( Illicium anisatum) is a
close relative that has been well documented
to cause neurologic and GI toxicities
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18. Public Notification: Herb Viagra Male Sexual
Stimulant contains hidden drug ingredient
 FDA laboratory analysis confirmed that Herb Viagra
contains sildenafil, the active ingredient in Viagra, an
FDA-approved prescription drug for erectile dysfunction.
 FDA’s approval of Viagra is restricted to use under the
supervision of a licensed health care professional.
 This undeclared ingredient may interact with nitrates
found in some prescription drugs, such as nitroglycerin,
and may lower blood pressure to dangerous levels.
16

19.  Herbal products, including dietary supplements, are regulated by the FDA.
However, unlike pharmaceutical drugs, they do not require pre-market approval.
Instead, manufacturers are responsible for ensuring the quality and safety of their
products.
 The FDA establishes Good Manufacturing Practices (GMP) regulations for dietary
supplements to ensure quality control during manufacturing.
17
Quality of Herbal Drugs in USA

20. 18
21 CFR Part 111- Current Good Manufacturing Practice In Manufacturing,
Packaging, Labeling, Or Holding Operations For Dietary Supplements
Subpart A - General
Provisions
Subpart B - Personnel
Subpart C - Physical
Plant and Grounds
Subpart D - Equipment
and Utensils

21. Subpart E - Requirement to
Establish a Production and
Process Control System
Subpart F - Requirements
for Quality Control
Subpart G - Requirements
for Components, Packaging,
and Labels and for Product
that you receive for
Packaging or Labeling as a
Dietary Supplement
Subpart H - Requirements
for the Master
Manufacturing Record
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22. Subpart I - Requirements for
the Batch Production Record
Subpart J - Requirements
for Laboratory Operations
Subpart K - Requirements
for Manufacturing
Operations
Subpart L - Requirements
for Packaging and Labeling
Operations
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23. Subpart M - Holding and
Distributing
Subpart N - Returned
Dietary Supplements
Subpart O - Product
Complaints
Subpart P - Records and
Recordkeeping
21

24.  The safety of herbal products in the USA is overseen by various regulatory agencies,
primarily the Food and Drug Administration (FDA) and the Federal Trade
Commission (FTC).
 To ensure a high degree of safety and effectiveness of herbal products and quality
control standards during the manufacturing of herbal supplements and medicines,
AHPA published GACP (Good Agriculture and Collection Practices) guideline in the
American Herbal Pharmacopoeia.
22
Safety of Herbal Drugs in USA

25.  Good Agricultural and Collection Practices
(GACP) is a quality assurance system for medicinal
plants. It's a set of guidelines for medicinal plant
producers on how to improve the safety, efficacy,
and quality standards of raw materials used in the
preparation of herbal medicines.
 GACP consists of the practices used during
agricultural production, from planting and
harvesting until it's packaged and then transported.
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Good Agricultural and collection practices

26. Botanical
identity and
quality
Post-harvest
handling
Harvest of
plants
General farm
standards
Wild collection
Cultivation
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GACP

27. In EU member states, botanicals are regulated as
herbal medicinal products by EMA's Committee on
Herbal Medicinal Products (HMPC). To market a
herbal medicine in EU member states, three key
pathways can be taken: traditional use registration,
well-established use marketing authorisation, and
stand-alone or mixed application.
Global Regulatory Differences on Botanicals
25

28. In Canada, botanicals are regulated as natural health products under HC’s Natural
and Non-prescription Health Products Directorate (NNHPD). HC defines NHPs as
naturally occurring substances that are used to restore or maintain good health
including herbal remedies, homeopathic medicines, and traditional medicines. To
market a natural health product in Canada, the sponsor must obtain a natural
product number (NPN), or DIN-HM for homeopathic medicines, from the NNHPD.
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29. Pre-market authorizations requirements
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30. Herbal products offer promising benefits, ensuring their quality and safety requires
collaboration among regulatory bodies, manufacturers, healthcare professionals,
and consumers. Continuous vigilance, transparent labeling, adherence to Good
Manufacturing Practices (GMP), and evidence-based research are crucial in
maintaining public trust and maximizing the potential benefits of herbal products
while mitigating potential risks. By upholding rigorous standards and fostering
open communication, the USA is promoting marketplace where herbal products
contribute positively to health and wellness.
Conclusion
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31. 1. What is a Botanical Drug? [Internet]. Available from: https://www.fda.gov/about-
fda/center-drug-evaluation-and-research-cder/what-botanical-drug (accessed on 15-
02-2024)
2. Bailey RL. Current regulatory guidelines and resources to support research of dietary
supplements in the United States. Crit Rev Food Sci Nutr. 2020;60(2):298-309.
3. Sapoliya, Niravkumar & Shah, Mamta. (2022). Regulations on Herbal Products in
India, United States and European Union: A Review. Int. J. Drug Regul. Aff. 10. 67-
72.
4. Thakkar S, Anklam E, Xu A, et al. Regulatory landscape of dietary supplements and
herbal medicines from a global perspective. Regul Toxicol Pharmacol.
2020;114:10464.
References

32. 5. Thillaivanan S, Samraj K. Challenges, constraints and opportunities in herbal
medicines-a review. Int. J. Herb. Med. 2014;2(1):21-4
6. Good Agriculture and Collection Practices [Internet]. Available from:
https://www.ahpa.org/good_agriculture_and_collection_practices (accessed on 17-
02-2024)
7. Botanical Drug Development: Guidance for Industry (2016) [Internet]. Available
from: https://fda.gov/regulatory-information/search-fda-guidance-
documents/botanical-drug-development-guidance-industry (accessed on 17-02-2024)

33. THANKYOU