Factors to Consider in Development of

Nutraceutical and Dietary Supplements

Learning Objectives
 Botanicals useful as nutraceuticals and dietary supplements
 Major aspects for development of nutraceuticals and dietary supplements
 Identification and authentication of the plant material
 Metabolomics approaches for food science and nutrition research
 Quality control, standardization, and scientific validation of botanicals
 Pharmacovigilance and regulatory affairs of nutraceuticals and dietary supplements

Nutraceuticals - diet supplements that deliver a concentrated form of a presumed bioactive

agent from a food, presented in a nonfood matrix and used in dosages with the purpose of
enhancing human health care.
-nutritional products which have effects that are relevant to health (European
Nutraceutical Association)
-any substance that is a food or a part of a food and provides medical or health benefits,
including prevention and treatment of disease(American Nutraceutical Association)

Dietary supplements- as a product (other than tobacco) that includes one or more of the dietary
ingredients like a vitamin, a mineral, an herb or other botanical, an amino acid, or any other
substance used to supplement the diet by increasing total dietary intake, metabolite, constituent,
extract, or combination of such. ( US Drug Supplement Health and Education Act of 1994)

Important aspects in the develoment of nutraceuticals and dietary supplement:

 Efficacy
 Safety
 Stability

BOTANICALS AS NUTRACEUTICAL AND DIETARY SUPPLEMENTS

Botanical-based products are the backbone of the health food market and various types of
products have been developed and promoted.

According to the World Health Organization (WHO), about 5.6 billion people (80% of
the world’s population) depend on medicinal plants for their primary health care needs, and they
are most widely used for the treatment of various acute and chronic diseases. Botanicals have
been traditionally used for promotion and management of human health issues, e.g., Ginkgo
biloba, Allium sativum, Camellia sinensis, Coffea arabica, Daucus carota, Emblica officinalis,
Dillenia indica, Glycine max, Moringa oleifera, and Vitis vinifera.
 Factors for development and evaluation of herbs used in development of nutraceuticals.

DEVELOPMENT AND PROCESS VALIDATION OF BOTANICALS AS FUNCTIONAL

FOOD
All botanicals and their derived products should be properly characterized and
standardized through analytical techniques. The available data on the individual products should
be obtained on a sufficient number of batches for the evaluation of natural variability and the
establishment of suitable specifications. Details of sampling schedules should be considered with
appropriate deliberation for analytical and batch to batch variability in the nutraceuticals
preparation. These are some of the important processes which need to be validated very carefully
in each and every step.

Botanical Source
 Identity
 Scientific name (plant family, genus, species with name of authority, and if relevant,
variety, and chemotype), common names/local names
 Part(s) of the plant used
 Geographic origin (continent, country, region)
 Environmental conditions
Growth Conditions
 Wild or cultivated
 Good agricultural practice
 Site of collection, time of harvest, stage of growth
 Drying, fermentation
 Storage conditions
 Pre- and postharvest phytosanitary treatments (e.g., use of pesticides)

Raw Material (e.g., Dried Plant Material)

 Specifications according to standard reference (e.g., Pharmacopeias) including:
 Identity tests e.g., macroscopic examination, microscopy, FT-IR, thin layer
chromatography (TLC), high-pressure liquid chromatography (HPLC), gas
chromatography (GC)
 Quantitative tests to determine
o Constituents relevant for the beneficial effects
o Constituents of toxicological relevance

Process Applied to Starting Material

 Steps of preparation (e.g., extraction process, solvents)
 Methods used
 Specific precautions (light, temperature sensitivity)

Botanical Preparation
 Standardization criteria (markers: toxic or physiologically active constituents, other
relevant constituents; plant_extract ratio)
 Specifications (level/range for markers)
 Physicochemical properties of the relevant constituents (stability)
 Purity criteria (e.g., microbiological, mycotoxins, pesticides, heavy metals, residual
solvents, other contaminants) either by chain control or analysis
 Level and nature of excipients
 Formulation methodology
 Storage conditions

Final Product (Food or Supplement Containing the Botanical Preparation)

 Fate in food or formulated product (e.g., stability)
 Industrial food processing
 Preparation for consumption

Intended Use
 Description of the product, i.e., food or food supplement as consumed
 Product composition (list of ingredients, concentration of active ingredients)
 Purpose of the product, anticipated health effects
 Proposed use: frequency, duration, level of consumption, population/defined target
groups
Dietary Exposure
 Estimated dietary exposure of the active ingredient(s) via product and habitual diet taking
into account geographical/cultural variation
 Estimated dietary exposure in nontarget groups taking into account geographical/cultural
variation
 Assessment of consequences of aggregate exposure (combined exposure from other
products in which the active ingredient(s) is/are added and/or present naturally)

Dietary Consequences
 Assessment of the nutritional consequences of the introduction of the new product

IDENTIFICATION AND AUTHENTICATION OF THE PLANT MATERIAL

The botanical identification and authentication is the first crucial step to avoid confusion,
admixtures, or adulterations in the botanicals. The useful active compounds in plants for
nutraceuticals preparation are among the huge diversity of secondary plant products that are
often specific for certain plants or plant groups. Characters and individuality that can be used to
identify the plant material, which can be grouped into different categories.

Macromorphology
In this category all the visible characters present in the plant specimens should be described. All
significant characters including roots, leaves, stems, flowers, and fruits must be consulted.

Microscopy
The plant material used may not be available as a whole but traded as parts of the plant.
Microscopic characters comprise the structure of hairs on plant surfaces, the presence of crystals
in the tissues, or the occurrence of specialized cells. These types of characteristics can be most
commonly found in the monographs of various pharmacopoeias or other compilations.

Phytochemical Characteristics
A fingerprint profile of all the compounds is usually characteristic for an individual plant or part
of a plant. The analyzed compounds may or may not be the bioactive substances, but quite often
are characteristic marker substances only. The chemical fingerprints obtained by various
chromatography techniques including TLC/HPTLC/HPLC of nutraceutical preparations should
be also documented.

DNA Sequence
As the genetic composition is unique for each species and is not affected by age, physiological
conditions, and environmental factors—DNA-based markers are also used in identification of
inter/intraspecies variation. Random amplified polymorphic DNA-based molecular markers have
been found to be useful in differentiating species of medicinal plants. From the last two decades
an important approach for plant identification has emerged based on their individual plant DNA
sequences. The DNA sequence is unique for an individual and similar between closely related
individuals. Some DNA regions are conserved within a specific taxon but differ between taxa.
These parts of the DNA sequence can be used to study the relationship of taxa (phylogeny) or to
identify a specific taxon, often referred to as DNA barcoding. Therefore, these can also be
applied in processed products, as is the case in plant extracts.
PHARMACOVIGILANCE
Pharmacovigilance is the process of monitoring, evaluating, and communicating drug
safety, which has profound implications that depend on the integrity and collective responsibility
of all parties such as consumers, health professionals, researchers, academic, media,
pharmaceutical industry, drug regulators, governments, and international organizations. The
main objective of pharmacovigilance is to extend the safety monitoring and detect any adverse
drug reactions that have previously been unrecognized in evaluation during clinical trials.
Although these methods were developed for monitoring modern medicines they are also
applicable for evaluating the safety and toxicity of nutraceuticals products.
The Medicines and Healthcare Products Regulatory Agency define some significant problems in
the regulation of herbal medicines in the United Kingdom which include :
(1) lack of knowledge about the products being used
(2) limited use of yellow card adverse drug reporting scheme;
(3) lack of uniform manufacturing standards, mostly of unlicensed products
(4) herb- drug interactions of herbal medicines.

Phytovigilance- the term used for pharmacovigilance of herbal drugs