wp 3 task 3.4 pharmaceutical and other specialty products task leader: alice grigore

C R O P S T O I N D U S T R YC R O P S T O I N D U S T R Y

WP 3Task 3.4 Pharmaceutical and other

specialty productsTask leader: Alice Grigore

Crops2IndustryCrops2Industry“Non-food Crops-to-Industry

schemes in EU27”


ContentContent1. Objectives2. Progress of work3. Results 4. Status of deliverables & milestones5. Problems encountered 6. Plans for the next 6 Months


1. Objectives

• to explore the potential and feasibility of the European

industry to make high-value biobased products

• to identify bio-industry demands on pharmaceutical and other

special products

• to identify restricting factors that inhibit broader industrial use

of the feedstocks


2. Progress of work Medicinal plants value chain – Establishing of the pathway to develop herbal products with high added-valueMarket research ● Choice of crop ● Site selection ● Crop establishment and management ● Harvest ● Processing ● Financial analysisScreening on the European specialty products based on medicinal and aromatic plants. Focus on the selected 5 MAP Pharma industry ● Cosmetics ● Dyes, colorants ● insecticides ● Selected crops and bio-based industry ● Economic aspectsQuality characteristics required for herbal substances, herbal preparations and herbal medicinal productsRegulatory environment concerning herbal medicineRestricting factorsRestricting factors in technology ● Restricting factors in economics ● Quality controlResearch gapsRecommendations


3. ResultsMedicinal plants value chain – Establishing of the pathway to develop herbal products with high added-value

The strategy for sustainable use of MAP has two main components: regulation of collection of medicinal plants from the wild → to protect biodiversitypromotion of cultivation→ to achieve a more stable production base and greater control over quality→provide new income opportunities to farmers→to meet demand


The product should meet market requirements EU is the largest single commercial market for MAPs; the annual

growth rate is estimated at 5 to 10%. Most of the herb market is supplied predominantly with imported

botanical raw materials

Germany is the largest importer, followed by France, Italy, Spain, UK

Germany is the largest exporter, followed by Poland, France,

Belgium, Spain, Bulgaria, Italy

Germany is also Europe’s largest (re-) exporter of MAP, followed by

France.

Market research


The global market for plant-derived drugs was worth an estimated

$19,5 billion in 2008. BCC Research expects this figure to grow to more

than $26 billion by 2011 and $32.9 billion by 2013.

Globally, cancer treatment is expected to become the largest

application of plant-derived drugs by 2011, with 24% of the market.

Indications in self-medication for herbal drugs include, in order of

sales volume: cough/cold, circulation, digestion, relaxation/sleep, pain

including muscles/joints, tonics/geriatrics (BCC Research)


Recent Comtrade statistics (2008-2009) show that:

As regards plants and parts of plants (including seeds and fruits), of a

kind used primarily in perfumery, in pharmacy or for insecticidal,

fungicidal or similar purposes, fresh or dried, whether or not cut,

crushed or powdered

imports exceed exports in Austria, Belgium, Czech Republic,

Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy,

Latvia, Lithuania, Luxembourg, Malta, Netherlands, Portugal, Romania,

Slovakia, Slovenia, Spain, UK,

exports exceed imports in Bulgaria, Cyprus, Hungary, Poland, Sweden


As regards essential oils (other than those of citrus fruit):

exports exceed imports - Austria, Bulgaria, France, Hungary,

Luxembourg

imports exceed exports - Belgium, Cyprus, Czech Republic,

Denmark, Estonia, Finland, Germany, Greece, Ireland, Italy, Latvia,

Lithuania, UK, Netherlands, Poland, Portugal, Romania, Slovakia,

Slovenia, Spain, Sweden


• increased costs of pharmaceutical-based health care

• search for new drugs and treatments of serious diseases

• consumers seeking an alternative to pharmaceutical drugs

•large pharmaceutical and OTC companies placing botanical

medicines more strongly on the mass

• increased emphasis on safety, efficacy and quality to conform to

international standards

• increased requests for organically certified raw material

• need for new and eco-friendly herbal-based products – insecticides,

dyes, etc.

Market trends that will potentially increase the demand for MAP are:


Quality characteristics required for herbal substances, herbal preparations

and herbal medicinal products

Pharmacopoeial tests and acceptance criteria

The European Pharmacopoeia contains important requirements

pertaining to certain analytical procedures and acceptance criteria

that are relevant to:

Herbal drugs - all mainly whole, fragmented or cut plants, plant

parts, algae, fungi, lichen in an unprocessed, usually dried form but

sometimes fresh.


Herbal drug preparation - are obtained by subjecting herbal

substances to treatments such as extraction, distillation, expression,

fractionation, purification, concentration or fermentation. These

include comminuted or powdered herbal substances, tinctures,

extracts, essential oils, expressed juices and processed exudates.•Herbal medicinal products (the term includes “traditional

medicinal product”) - any medicinal product, exclusively containing

as active substances: ►one or more herbal substances

► one /more herbal preparations,

► one/more herbal substances in

combination with one/ more herbal

preparations.


The experience and data accumulated during the development of a

herbal medicinal product should form the basis for the setting of

specifications.

Specifications = a list of analytical or biological procedures which

provide assurance that the appropriate quality of the product will be

maintained. The setting of specifications is part of an overall control

strategy which includes control of raw materials and excipients, in-

process testing, process evaluation/validation, stability testing and

testing for consistency of batches, intended to ensure safety and

efficacy.

Design and development considerations


A key issue in manufacturing herbal products and medicines is

standardization. Standardization is the process of producing herbal

extracts or phytochemicals in which product potency is guaranteed

through consistency in specific active compound content level. This

process requires high knowledge in phytochemical analysis and

process technology to ensure the quality assurance required.

Product value increases in the following order: fresh material <

dried powder < non-standardized extract < freeze/spray dried

extract < standardized extract < phytomedicine.


Regulatory environment concerning herbal medicineThe herbal medicinal market in Europe is currently affected by

substantial changes of the regulatory environment.

General intention is to harmonize the regulation of medicinal products,

food and other consumer goods at centralized European level.

Difficulties come from:

-the heterogeneity of the starting material itself (chemical composition,

natural variability, diverse sources),

-the heterogeneity of plant preparations (plant part used, type of

preparation, manufacturing process), and the lack of accurate

quality/safety data for often non-standardized low price products.


There are great differences between Member States in the

definition and categorization of herbal medicines. A single

medicinal plant may be defined as a food, a functional food, a dietary

supplement or a herbal medicine in different countries, depending on

the regulations applying to foods and medicines in each country.

→This makes it difficult to define the concept of herbal medicines for

the purposes of national drug regulation and also confuses patients

and consumers.


Besides EMEA, other key players are involved in the regulation of

herbal market:

-European Directorate for the Quality of Medicines (EDQM) with the

Commission of the European Pharmacopoeia (Ph Eur) and the

European Scientific Cooperative on Phytotherapy (ESCOP, founded

1989). The EDQM includes 36 European Member States and 20

observers such as the American FDA and the WHO. Its role is to

harmonise the quality standards for use by healthcare

professionals.


Screening on the European specialty products based on MAP Focus on the selected 5 medicinal plants

Pharmaceutical and other specialty crops are the starting point for a

wide range of products:

● essential oils ● human and veterinary drugs ● herbal health products

● inks ● colorants and dyes ● perfumes ● beauty products ● novel

plant protection products ● a range of intermediate products from

which the above are manufactured


In the past 20 years, 28% of new drug entities were either natural

products or derived from them as semi-synthetic derivatives →

importance of plants as a source of new drug moleculesdeveloping new therapeutic strategies for cardiovascular and

infectious diseases, diabetes, obesity, cancer and allergy.

a wide range of medicinal preparations: tea, tinctures, medicinal

oils, essential oils, compresses or plasters, eye washes, balsams,

cataplasms, as well as a great number of pharmaceutical forms:

tablets, capsules, syrups, ointments, hydrophilic gels, eye-drops,

nasal sprays and drops.

Pharma industry


In the last years a new concept has developed – cosmeceutics -

cosmetic products that include ingredients designed not only to

enhance the appearance but to also have a positive physiological

effect at the cellular level.

The use of new products is increasing: men’s grooming products,

anti-aging products, spa-at-home, detoxification products.

Cosmetics


There is an increasing development of new natural compounds able

to substitute chemical additives for food and beverage industry (as

antioxidants or colorants)

Natural dyes are rarely used in modern dyeing, except by specialist

companies and craft dyers. Only a limited number of plant species

exhibit the potential for large-scale production and some of them can

be used as dyestuffs only for food, but not for textiles. Method for

obtain and purify compouds and stability studies must be developed.

Dyes, colourants


Alternative insecticides normally mean the insecticides are less

toxic to humans and breakdown more rapidly in the environment

than conventional insecticides. → “environmentally friendly”.

The most known natural insecticides are pyrethrins, limonene

and linalool which are volatile molecules. This sector needs to be

developed.

Insecticides


Selected crops and their applications


Selected crops in EU 27 countries

An internet survey regarding species selected – Calendula

officinalis, Lavandula angustifolia, Mentha piperita, Echinacea

angustifolia and Plantago lanceolata – and their various uses in

different European countries showed that

these herbs are used for various purposes and are presented

in various forms

most of the raw material used by these manufacturers comes

from own plantations


COSMETICS


EXTRACTS


Selected crops in RomaniaData received from few important Romanian manufacturers show that: Small and medium companies prefer to develop their own network starting

from raw material to final product. The products are designed mainly for medicinal and cosmetic use High income in the last year were obtained mainly from tea, tablets,

capsules, volatile oil, solution for spa use and syrup sales The products are impossible to substitute with one synthetic drug (herbal

products are usually mixture of active principles). Herbal products are

adjuvant in classical medicine or have a preventive action. In

pharmacological testing, the activity is compared to synthetic drugs.


Restricting factorsRestricting factors in technology:

Processing methods (primary and specific) conduct to herbal products

of higher yield, lower operating costs, and faster production times.

Products diversity- new products come from new technologies and

new equipment .• Adequate processing methods The obtainment of a selective

extract mostly leads to the high price of the product.• Herbal products can be sold in a variety of forms; packaging also

plays an important role to attract consumers.

→Need for appropriate equipment for extraction, processing,

conditioning and packing herbal products


- the product price (and not the product quality) is the most important

factor that affects buying decision for many market segments. Local

production have to compete with the import of cheap products and

raw materials (especially from China and India)

Restricting factors in economics


In the case of medicinal plants which are used directly as

pharmaceuticals, the quality and thus the concentration of active compounds is much more relevant than the total yield (for

example, increasing the plant product concentration by applying

deliberately drought stress would be compensated by decreasing

yields in biomass)

Inspite of the widespread usage of herbal pharmaceuticals there is a

lack of proper standardization and quality control of the drugs.

The problem is often due to the special characters associated with

plant origin medicines (for example, Echinacea phytomedicines with

multiple activities, species, and formulations)

Quality control


• Some producers choose to use encapsulated dried and milled plants

instead of selective extracts or some choose to sell adulterated essential

oils. For example, as regards

-Roots of Parthenium integrifolium L., have been found to be

adulterants/substitutes for Echinacea root;

-Lavender oil is often adulterated by acetylated lavandin, aspic, synthetic

linalool, linalyl acetate,

-Mentha oil is the most adulterated oil, usually with Mentha arvensis -difficult

to detect even at 85% or with synthetic compounds)


Research gaps

There are several ways in which plant science can address future

demand in this area.

-optimising the profile and possibly increasing the content of active

components of the raw material itself.

-better preservation of these phytochemicals during crop maturation,

post-harvest treatment and storage.

-the factors that play a major role in bioactivity during processing

should be at least maintained and possibly enhanced.


- improvement of plant performance and quality in different

environments by revealing genetic and epigenetic mechanisms

controlling plant plasticity in response to environmental stimuli

ex. Cold or drought tolerant M. x piperita suitable for Finnish climate

conditions; Lavandula for dry areas

- hybrids are generally less susceptible to environmental fluctuations

than their parents.

-Herbicide-resistant crops his means less spraying, less traffic on

the field, and lower operating costs.


-As regards innovative products, the areas that could be developed

are -pesticide and insecticide based natural compounds.

-organic products

-environmentally friendly methods for crop protection

(allelopathic plants)

-Phytotherapy in veterinary medicine is a domain which

needs further study.


Focus on quality

- the consumers must understand that the quality is more important

than price.

- development of stable molecular markers which assure without

doubt the quality of herbal medicines.

- conducting clinical trials in Europe in order to comply with

regulatory requirements for product registration, especially in

Germany and France which regulate botanical products mainly as

drugs. In the past 20 years, completely new markets were created for

botanicals based upon scientific support.


4. Status of deliverables & milestones

Results mentioned abovewere delivered on time

to coordinator


5. Problems encountered

Information on the specialty crops and crop products sector is

difficult to analyze, because of its extreme diversity and

variability and is limited by the reluctance of certain parts of

the industry to document for commercial reasons.


6. Plans for the next 6 months

Update report with relevant data


THANK YOU !

wp 3 task 3.4 pharmaceutical and other specialty products task leader: alice grigore

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