Panel discussion on...

Natural ingredients

Sourcing and exhaustive controls as key factors for highest quality extracts


Andrea Zangara

Head of Scientific Communications & Marketing

Euromed, Spain

Head of Scientific Communications & Marketing - Euromed S.A., Spain

Quality of the raw plant material (or biomass) can affect the efficacy and/or safety of the final extract. Botanicals must be grown, harvested, and verified properly to preserve plant integrity and bioactive profiles. Chemicals in plants known to have medicinal benefits are referred to as “active ingredients” or “active principles”, and their presence depends on several factors, including the plant species, the time and season of harvest, the type of soil, and the way the biomass is prepared, etc. A well-defined and constant composition of the starting material is one of the most important prerequisites to produce a quality extract.

Given the nature of finished products of plant origin, wherein plants themselves are not usually constant and are dependent on and influenced by many factors (including climate change), the development of integrated and efficient procedures to control the quality along the supply chain will minimize variability and provide pharmacopeial grade, consistent, and replicable products that can be properly validated in clinical trials.

Quality control

Plants contain complex mixtures of chemical compounds that work together to produce an effect on the body, though these bioactive matrices are rarely completely identified. Modern analytical techniques are continuously improving and will help in defining quality control parameters. However, identification of all of a plant’s constituents often fails because of the variety and complexity of the plant’s chemical structure, and selective analytical methods or reference compounds may not be available commercially. As emphasized, important primary factors that influence final quality always relate to appropriate raw material sourcing, harvesting techniques, and processing of the biomass. It’s critical to avoid misidentification of plants, lack of standardization, contamination, unintentional comingling of different plants causing adulteration, failure of good manufacturing practice, and incorrect preparations and/or dosages.

Botanicals may contain a variety of contaminants, including pesticides, heavy metals, aflatoxins, microorganisms, pyrrolizidine alkaloids, and polycyclic aromatic hydrocarbons (PAHs). These contaminants can come from a variety of sources, such as weeds, weather, location, soil, water used for irrigation, and other environmental conditions under which the plant was cultivated. From botanical macro- and micro-identification and control of active principles and potential impurities to chromatographic analyses, botanical raw materials should be exhaustively tested, in accordance with international standards such as pharmacopoeias and other regulations. A finished extract should meet minimum quality requirements for homogeneity, purity, and stability (1). A finished extract should be tested for an array of laboratory tests outlined in pharmacopeial monographs, and test results are ideally reported on a certificate of analysis (COA). This includes the method used to test for the active and marker compounds and the pharmacopeial reference source. The COA allows dietary supplement manufacturers to refer to the monograph, perform the same analysis, and verify COA test results. A reliable extractor should be able to provide the COA and, upon request, batch-specific chromatograms.

Quality control of botanical products requires the most up-to-date analytical techniques, such as HPTLC, HPLC, and GC coupled to several detectors, which all together allow to assure the phytochemical quality as well as the quality and safety for the impurities and contaminants.

Although it is generally believed that most herbal preparations are safe for consumption, some herbs like most biologically active substances could be toxic with undesirable side effects, that are mainly due to active ingredients, contaminants, and/or interactions with other drugs. A history of traditional usage is not always a reliable guarantee of safety since it is difficult for traditional practitioners to detect or monitor delayed effects (e.g., mutagenicity), rare adverse effects, and adverse effects arising from long-term use, such as for food supplements and nutraceuticals.

Because of the complexity of their chemical content and the variety of bioactivities, botanicals can provide the polypharmacology which single compounds may not achieve. Easier said than done, as such bioactive compounds may act individually and either positively or negatively; and their combination may affect multiple systems. An additional complication is represented by the possible synergy between these interacting actives, resulting in complex dose and time dependent effects. The difficulty of interpreting fragile positive effects and negative findings is a clear challenge for the researchers in this field. Therefore, results of clinical studies with botanical preparations should be specific to that preparation and not generalizable to other preparations, even from the same plant (2).

Extraction technologies

Various extraction technologies can be used to concentrate target molecules while preserving the natural phytochemical profile. The method of extraction can influence how much of a particular active constituent is present in the herbal product. Some phytochemicals are more soluble in water, while others are soluble in alcohol or oil. The method chosen varies from plant to plant, depending on the types of targeted active constituents. Different methods of extraction and standardization may yield extracts with distinctly different properties. This makes the transferability of clinical data from one extract to another almost impossible, unless bioequivalence (or phytoequivalence) and bioavailability trials are used to prove essential similarity or identical pharmacopeial criteria are strictly observed (2). A reliable extractor can determine the best extraction technique depending on the plant, the plant part, the active compounds, and type of extract required. Among others, it is worth noting the percolation, the maceration, and the supercritical fluid extraction that, in combination with different extraction solvents, can offer a wide variety of extracts.

Water extraction is a safe and eco-friendly procedure, as it eliminates the risk of potentially unsafe residuals of volatile solvents in the finished extract and the release of potentially contaminating compounds into the environment. Moreover, exposing some plant parts to alcoholic solvents may accidentally extract toxic alkaloids. For extracting water-soluble compounds such as polyphenols, water extraction is certainly a very safe procedure. Particularly when using demineralized water, which can improve solubility, stability, bioavailability, and even health properties of polyphenols. A recently published study found that brewing tea leaves with demineralized water improves the efficiency of extraction and antioxidant activity of polyphenols (3).

However, not all plant constituents relevant to human health are water-soluble, and in this case, traditional solvents are more appropriate. There are also other viable approaches to reduce contaminants while maintaining or even improving extraction efficiency, such as chromatographic resins, membrane filtration, supercritical fluid extraction, and hydrolysis.


Vincenzo Zaccaria

R&D Manager - Bionap

Giovanna Nicotra

Scientific and Marketing Director - EPO

Andrea Zangara 

Head of Scientific Communications & Marketing - Euromed

Benoit Daems

CEO - Fermedix

Lucia Ferron 

R&D Coordinator - FLANAT Research Italia

Eleanor Johnson

Data Analyst - FMCG Gurus

Julien Cases 

CSO - Flytexia

Cindy Romain 

Scientific Manager - Flytexia

Antonella Riva

Product Innovation and Development Manager - INDENA

Giovanna Petrangolini 

Senior Research Manager - INDENA

Domenico Avenoso 

Junior Product Scientist - INDENA

Chris Kilham

Medicine Hunter - KSM-66 Ashwagandha

Alessandro Giuseppe Tricomi 

Food Supplement Manufacturing - Natural Ingredients Solution

Raffaella Pignatiello 

Quality Control - Natural Ingredients Solution

Federica Zanzottera 

Market Manager, Nutraceutical – ROELMI HPC

Marco Biagi 

General Secretary – S.I.Fit. (Italian Society of Phytotherapy)

Cristina Airoldi 

Associate Professor in Organic Chemistry - University of Milano-Bicocca

Alessandro Palmioli 

Associate Professor in Organic Chemistry - University of Milano-Bicocca