Natural Products: The Case for a Product Development Paradigm in Malaysian Natural Product Research...

NaturalNatural Products: The Products: The

Case for a Product Case for a Product Development Development

Paradigm Paradigm in Malaysian Natural in Malaysian Natural

Product Research Product Research Mohd. Murray HunterMohd. Murray Hunter

Kolej Universiti Kejuruteraan Utara Kolej Universiti Kejuruteraan Utara MalaysiaMalaysia

Traditional Natural Product Traditional Natural Product ResearchResearch

Bio-prospecting/or Flora of Specific Bio-prospecting/or Flora of Specific InterestInterest

Analysis of Compounds/CompositionAnalysis of Compounds/CompositionUsually Single Discipline ApproachUsually Single Discipline Approach Information Published or Information Published or

Disseminated at Conference/SeminarDisseminated at Conference/SeminarWork is Usually ForgottenWork is Usually Forgotten

New ExpectationsNew Expectations

Government’s New Bio-Technology Government’s New Bio-Technology PolicyPolicy

Funding Focus on Applications/Potential Funding Focus on Applications/Potential CommercialisationCommercialisation

Universities Becoming Commercially Universities Becoming Commercially OrientatedOrientated

Research Institutions Want Commercial Research Institutions Want Commercial ResultsResults

New Community ExpectationsNew Community ExpectationsPeer Hopes and ExpectationsPeer Hopes and Expectations

A New Paradigm Required To A New Paradigm Required To Meet Changing ExpectationsMeet Changing Expectations

Emphasis Shifting to Development Emphasis Shifting to Development and Potential Applicationsand Potential Applications

Possible CommercialisationPossible CommercialisationResearch Funding Tied to Research Funding Tied to

Results/OutcomesResults/Outcomes Institution Questions – Institution Questions –

Can it be Commercialised?Can it be Commercialised?

This Requires a Change in This Requires a Change in Natural Product ResearchNatural Product Research

What We Investigate?What We Investigate?How We Investigate?How We Investigate?Change in Outcome ObjectivesChange in Outcome ObjectivesUse Different MilestonesUse Different MilestonesUse of Multidisciplinary ApproachUse of Multidisciplinary ApproachNeed to Consider Wider IssuesNeed to Consider Wider IssuesLess Projects – Longer ProjectsLess Projects – Longer ProjectsHigher Degree of CollaborationHigher Degree of Collaboration

Requires a Jungle to Requires a Jungle to Marketplace ViewMarketplace View

Natural Product Development Process Natural Product Development Process (Aromatic) (Aromatic)

Biological Screening

Screening For Development Potential

Regulatory Screening

Market Development Environmental

Analysis

Evaluation of Capabilites

Market Analysis

Technical Development

Commercialis -ation Strategies

Development Process

Screening Process

Screening Screening ProcessProcess

Biological ScreeningBiological Screening

BioprospectingBioprospectingLiterature ReviewLiterature ReviewConsider Reintroduction of a CropConsider Reintroduction of a CropConsider Introduction of New CropConsider Introduction of New Crop

Identify Chemical Constituents of Identify Chemical Constituents of Essential Essential

OilOil

Screening For Development Screening For Development PotentialPotential

Match Chemical Constituents of Match Chemical Constituents of Essential Oil to Possible Market UsesEssential Oil to Possible Market Uses

Evaluate Application Potential of Evaluate Application Potential of Essential OilEssential Oil

Evaluate Yields, Cost of productionEvaluate Yields, Cost of productionEvaluate Time and Cost of Evaluate Time and Cost of

DevelopmentDevelopmentValue Determination (Use Criteria)Value Determination (Use Criteria)

ScreeningScreening

Require Knowledge of Essential Oil Require Knowledge of Essential Oil ApplicationsApplications

Require knowledge of International Require knowledge of International MarketMarket

Require Knowledge of International Require Knowledge of International RegulationsRegulations

Need to Collaborate with Industry Need to Collaborate with Industry PartiesParties

Screening ProtocolsScreening Protocols

Anti inflammatoryAnti inflammatoryAnti microbialAnti microbialSkin whiteningSkin whiteningUV absorbingUV absorbingAnti age activesAnti age activesFlavour & fragrance applicationFlavour & fragrance applicationAromatherapyAromatherapy

Evaluation Criteria (Aroma)Evaluation Criteria (Aroma)

The Novelty of the new essential OilThe Novelty of the new essential Oil

Dependent on the uniqueness of the Dependent on the uniqueness of the flavour/odour profile. Degree of novelty, flavour/odour profile. Degree of novelty, limited by the availability of substitutes. limited by the availability of substitutes. Can be considered novel, if considered a Can be considered novel, if considered a more cost effective source of a natural more cost effective source of a natural aroma chemical. Source of a natural aroma chemical. Source of a natural aroma chemical, not previously known to aroma chemical, not previously known to exist in economically extractable exist in economically extractable quantities.quantities.

Evaluation CriteriaEvaluation Criteria

The Perceived Potential uses and The Perceived Potential uses and Applications of the New Essential Applications of the New Essential OilOil

Perfumers and Flavourists must Perfumers and Flavourists must perceive applications potential. perceive applications potential. Material must be stable and Material must be stable and versatile in harsh media of end versatile in harsh media of end products.products.


The Closeness of any Substitutes The Closeness of any Substitutes to the New essential Oilto the New essential Oil

Degree of ease new aroma from Degree of ease new aroma from essential oil can be duplicated by essential oil can be duplicated by synthesis or reconstitution. If close synthesis or reconstitution. If close substitutes available, new material substitutes available, new material must be more cost effective.must be more cost effective.


The Stability of the New The Stability of the New essential Oilessential Oil

Stability as an essential oil and Stability as an essential oil and stability in end products.stability in end products.


The Cost Price/Performance The Cost Price/Performance Ratio of the New Essential OilRatio of the New Essential Oil

Important in the application potential Important in the application potential of the new essential oil. New material of the new essential oil. New material must offer a perceptible must offer a perceptible odour/flavour at low concentrationsodour/flavour at low concentrations


The Toxicity Aspects of the New The Toxicity Aspects of the New Essential OilEssential Oil

Must be proven beyond doubt through Must be proven beyond doubt through expensive trials. Flavour and Fragrance expensive trials. Flavour and Fragrance houses will not consider using a new houses will not consider using a new essential oil unless it meets IFRA safety essential oil unless it meets IFRA safety and Toxicity recommendations and is and Toxicity recommendations and is included in the FEMA GRAS list. EU has included in the FEMA GRAS list. EU has recently regulated on a number of aroma recently regulated on a number of aroma materialsmaterials


The General Consistency of Quality The General Consistency of Quality and Supplyand Supply

Natural materials vary in quality according Natural materials vary in quality according to geographic origin, type of soil, level of to geographic origin, type of soil, level of nutrients in the soil, climate and weather, nutrients in the soil, climate and weather, rainfall, time of harvest, season, methods rainfall, time of harvest, season, methods of extraction, altitude and the incidence of of extraction, altitude and the incidence of pests and diseases. Risks of supply from pests and diseases. Risks of supply from natural disasters, wars, political conditions natural disasters, wars, political conditions and the inexperience of new producersand the inexperience of new producers


The Prevailing Market/Product The Prevailing Market/Product TrendsTrends

Market and product trends slowly Market and product trends slowly evolve. These are the results of evolve. These are the results of complex forces such as technology, complex forces such as technology, advertising and cultural influence upon advertising and cultural influence upon consumer tastes and preferences. A consumer tastes and preferences. A particular essential oil may become particular essential oil may become more or less important to industry, more or less important to industry, depending upon these trends.depending upon these trends.


The Current Level of TechnologyThe Current Level of TechnologyTechnology influences substitutes Technology influences substitutes

that are available and the costs of that are available and the costs of production.production.

Regulatory ScreeningRegulatory Screening

United StatesUnited States

- GRAS (- GRAS (Genarally Regarded as Safe)Genarally Regarded as Safe)RIFM RIFM – Collections of Monographs– Collections of MonographsFood and Drug AdministrationFood and Drug Administration

European UnionEuropean Union

REACHREACH

Registration, Evaluation and Registration, Evaluation and Authorisation Authorisation

of Chemicalsof Chemicals

Objectives of REACHObjectives of REACH

Protection of human health and the Protection of human health and the environmentenvironment

Maintenance and enhancement of the Maintenance and enhancement of the competitiveness of the EU chemical industrycompetitiveness of the EU chemical industry

Prevention of fragmentation of the internal Prevention of fragmentation of the internal marketmarket

Increased transparencyIncreased transparency Integration with international efforts Integration with international efforts Promotion of non-animal testingPromotion of non-animal testing Conformity with EU international obligations Conformity with EU international obligations

under the WTOunder the WTO

REACH StatusREACH Status

EU study being conducted on supply EU study being conducted on supply chain and innovation – report March chain and innovation – report March 20052005

EU study on impact of REACH on new MSEU study on impact of REACH on new MSEU parliament to review REACH EU parliament to review REACH

legislation second half 2005 legislation second half 2005 (Environment is lead committee)(Environment is lead committee)

New “slightly modified” version of New “slightly modified” version of REACH to be talked about early 2006REACH to be talked about early 2006

SCCP ResponsibilitySCCP Responsibility SCCP (The Scientific Committee on Consumer SCCP (The Scientific Committee on Consumer

Products – previously called the SCCNFP: Scientific Products – previously called the SCCNFP: Scientific Committee on Cosmetic & Non Food Products) is Committee on Cosmetic & Non Food Products) is an expert committee set up under the EC Health an expert committee set up under the EC Health and Consumer Protection DG. SCCP reports to the and Consumer Protection DG. SCCP reports to the EC H&CP Scientific Steering Committee on matters EC H&CP Scientific Steering Committee on matters relevant to the EC countries in their defined area. relevant to the EC countries in their defined area. The committee comprises a diverse range of The committee comprises a diverse range of experts in toxicology from industry, the medical experts in toxicology from industry, the medical fields and tertiary institutions.fields and tertiary institutions.

SCCP/SCCNFP have provided scientific opinions on SCCP/SCCNFP have provided scientific opinions on a wide range of ingredients used in personal care a wide range of ingredients used in personal care products including actives & excipients for oral products including actives & excipients for oral care, haircare and skincare products.care, haircare and skincare products.

Cosmetic Products in EU are Cosmetic Products in EU are regulated by Directive 76/768/EEC regulated by Directive 76/768/EEC

and Amendmentsand AmendmentsSection 7(a) of 76/768/EEC states:-Section 7(a) of 76/768/EEC states:-

“ “Assessment of the safety for human Assessment of the safety for human health of the finished product. To health of the finished product. To that end that manufacturer shall take that end that manufacturer shall take into consideration the general into consideration the general toxicological profile of the ingredient, toxicological profile of the ingredient, its chemical structure and its level of its chemical structure and its level of exposure”.exposure”.

Biocidal Products DirectiveBiocidal Products Directive

High level of protection of human High level of protection of human health and environment.health and environment.

Harmonisation of requirements for Harmonisation of requirements for authorisation of biocides.authorisation of biocides.

Types of Biocidal ProductsTypes of Biocidal Products

DISINFECTANTS & GENERAL DISINFECTANTS & GENERAL BIOCIDAL PRODUCTSBIOCIDAL PRODUCTS

PRESERVATIVESPRESERVATIVESPEST CONTROLPEST CONTROLOTHER BIOCIDAL PRODUCTS OTHER BIOCIDAL PRODUCTS Preservatives for food or feedstocksPreservatives for food or feedstocks Antifouling productsAntifouling products Embalming and taxidermist fluidsEmbalming and taxidermist fluids Control of other vertebratesControl of other vertebrates

Information RequiredInformation Required

GeneralGeneralNomenclatureNomenclaturePurityPurityPhysical propertiesPhysical properties- MPMP- BPBP- DensityDensity- Rel. Vap. DensRel. Vap. Dens- VPVP- Log PoWLog PoW- SolubilitySolubility


SCCP (Cont.)SCCP (Cont.)Acute ToxicityAcute Toxicity- Acute OralAcute Oral- Acute DermalAcute Dermal- Acute InhalationAcute Inhalation

Irritation/CorrosivityIrritation/Corrosivity- Skin IrritationSkin Irritation- Mucous MembraneMucous Membrane- Skin SensitisationSkin SensitisationDermal/Percutaneous AbsorptionDermal/Percutaneous Absorption

Repeat Dose ToxicityRepeat Dose Toxicity- Repeat Dose oral/dermal/inhalation (28 day)Repeat Dose oral/dermal/inhalation (28 day)- Subchronic 90 day oral/dermal/inhalationSubchronic 90 day oral/dermal/inhalation- Chronic (>12 months)Chronic (>12 months)


SCCP (Cont)SCCP (Cont)Mutagenicity/Mutagenicity/GenotoxicityGenotoxicityCarcinogenicityCarcinogenicityReproductive ToxicityReproductive Toxicity- Two Generation Reproduction ToxicityTwo Generation Reproduction Toxicity- TeratogenicityTeratogenicityToxicokineticsToxicokineticsPhoto induced ToxicityPhoto induced Toxicity- Phototoxicity- PhototoxicityHuman DataHuman DataCase studies of poisonings, allergic reactionsCase studies of poisonings, allergic reactions

Information RequiredInformation RequiredBPDBPDGeneral:-General:- Substance identification (CAS, IUPAC, formula etc)Substance identification (CAS, IUPAC, formula etc) Substance information – colour, purity, physical propertiesSubstance information – colour, purity, physical properties SpectraSpectra Synonyms and trade namesSynonyms and trade names ImpuritiesImpurities AdditivesAdditives Quantity used in EUQuantity used in EU LabellingLabelling Hazard classification and labellingHazard classification and labelling Usage pattern – including application, types of use, volume per application, Usage pattern – including application, types of use, volume per application,

recovery, industry typesrecovery, industry types Manufacturing methodManufacturing method Existing exposure restriction and limitsExisting exposure restriction and limits HazardsHazards Degradation productsDegradation products


BPD (Cont)BPD (Cont)Physical & Chemical PropertiesPhysical & Chemical Properties MPMP BPBP VPVP ViscosityViscosity DensityDensity GranulometryGranulometry Partition coefficientPartition coefficient Solubility in different mediaSolubility in different media Surface TensionSurface Tension Flash point, flammability, explosivity Flash point, flammability, explosivity Oxidising propertiesOxidising properties Dissociation constantDissociation constant


BPD (Cont)BPD (Cont)Environmental Environmental PhotodegradationPhotodegradation Stability in water and soilStability in water and soil Monitoring dataMonitoring data Field studiesField studies Transport between environmental Transport between environmental

compartmentscompartments Actual use degradation modelActual use degradation model Biodegradation, BOD/CODBiodegradation, BOD/COD BioaccumulationBioaccumulation


BPD (Cont)BPD (Cont)EcotoxicityEcotoxicity Acute toxicity to:-Acute toxicity to:-

FishFish Aquatic invertebrates Aquatic invertebrates Aquatic plants (e.g. algae)Aquatic plants (e.g. algae) Micro-organisms Micro-organisms

Chronic toxicity to:-Chronic toxicity to:- FishFish Aquatic invertebratesAquatic invertebrates

Toxicity to:-Toxicity to:- Sediment dwelling organismsSediment dwelling organisms Terrestrial plantsTerrestrial plants Soil dwelling organismsSoil dwelling organisms Other non mammalian terrestrial speciesOther non mammalian terrestrial species

Biotransformation and KineticsBiotransformation and Kinetics

Information RequiredInformation RequiredBPD (Cont)BPD (Cont)ToxicityToxicity Acute oralAcute oral Acute inhalationAcute inhalation Acute dermalAcute dermal Skin irritationSkin irritation Eye irritationEye irritation SensitisationSensitisation Repeat dose toxicityRepeat dose toxicity Genetic toxicity in vitroGenetic toxicity in vitro Genetic toxicity in vivoGenetic toxicity in vivo Carcinogenicity Carcinogenicity Toxicity to fertilityToxicity to fertility Developmental toxicity/teratogenicity Developmental toxicity/teratogenicity Exposure experienceExposure experience


BPD (Cont)BPD (Cont)Effect Against Target OrganismEffect Against Target Organism FunctionFunction Effects on organisms to be controlledEffects on organisms to be controlled Organisms to be protectedOrganisms to be protected UserUser Resistance Resistance

End point summary Risk AssessmentEnd point summary Risk Assessment

Information RequiredInformation RequiredTests Required for Original REACH RegistrationTests Required for Original REACH Registration Melting/freezing point Boiling point Relative density Vapour pressure Surface tension Water solubility (or water extractivity for polymers) n-Octanol-water partition coefficient Flash point or flammability Explosivity Auto-flammability Oxidising properties Granulometry Skin irritation or corrosivity evaluation or in vitro tests Eye irritation evaluation or in vitro test Skin sensitisation evaluation or local lymph node assay Ames test In vitro chromosome aberration test Acute Daphnia toxicity Algal growth test Ready biodegradation

Development ProcessDevelopment Process

Environment Analysis Environment Analysis

Opportunities & Opportunities & ThreatsThreats

Evaluation of Resources & Evaluation of Resources & CapabilitiesCapabilities

ResourcesResources - Funding- Funding - Time- Time - Facilities & Infrastructure- Facilities & Infrastructure - Equipment- Equipment - Literature- Literature CapabilitiesCapabilities - Available Skills (Research Team)- Available Skills (Research Team) - Experience- Experience

Market AnalysisMarket Analysis

Knowledge of IndustryKnowledge of IndustryKnowledge of Potential ApplicationsKnowledge of Potential ApplicationsKnowledge of CustomersKnowledge of CustomersUnderstanding of Derived DemandUnderstanding of Derived DemandUnderstanding of TrendsUnderstanding of TrendsUnderstanding of Other Understanding of Other

Developments & Improving Developments & Improving Technology and KnowledgeTechnology and Knowledge

Top Twenty Essential Oils Produced in Top Twenty Essential Oils Produced in the Worldthe World

Essential OilEssential Oil Botanical NameBotanical Name Volume Volume (Tonnes)(Tonnes)

Under Threat Under Threat CosmeticsCosmetics

Under Threat Under Threat BiocidesBiocides

Under threat Under threat FragranceFragrance

OrangeOrange Citrus sinensisCitrus sinensis 2600026000 XX XX

CornmintCornmint Mentha ArvensisMentha Arvensis 43004300

EucalyptusEucalyptus Euc. globulusEuc. globulus 37283728 XX XX XX

CitronellaCitronella Cym winterianusCym winterianus 28302830 XX XX XX

PeppermintPeppermint Mentha piperitaMentha piperita 23672367

LemonLemon Citrus limonCitrus limon 21582158 XX XX

Euc. CitriodoraEuc. Citriodora Eucalyptus citriodoraEucalyptus citriodora 20922092 XX XX XX

Clove LeafClove Leaf Syzygium aromaticumSyzygium aromaticum 19151915 XX XX XX

CedarwoodCedarwood (US) (US) Juniperus virginianaJuniperus virginiana 16401640

Litsea cubebaLitsea cubeba Litsea cubebaLitsea cubeba 10051005 XX XX

SassafrasSassafras (Brazil)(Brazil)

Ocotea pretiosaOcotea pretiosa 10001000 XX XX

LimeLime Citrus aurantifoliaCitrus aurantifolia 973973 XX XX

SpearmintSpearmint Mentha spicataMentha spicata 851851

Cedarwood Cedarwood (China)(China)

Chamaecyparis Chamaecyparis funebrisfunebris

800800

LavandinLavandin Lavandula intermediaLavandula intermedia 768768 XX XX

SassafrasSassafras (China)(China)

Cinnamomum Cinnamomum micranthummicranthum

750750 XX XX

CamphorCamphor Cinnamomum Cinnamomum camphoracamphora

725725

CorianderCoriander Coriandrum sativumCoriandrum sativum 710710

GrapefruitGrapefruit Citrus paradisiCitrus paradisi 694694 XX XX

PatchouliPatchouli Pogostemom cablinPogostemom cablin 563563 XX XX

Essential Oil Technical Essential Oil Technical DevelopmentDevelopment

Project Preparation and Early Project Preparation and Early WorkWork

- Stakeholders- Stakeholders

- Team- Team

- Objectives- Objectives

- Funding- Funding

- Plan- Plan


Land SelectionLand Selection

- Suitable (Soil, Rainfall, drainage, - Suitable (Soil, Rainfall, drainage, access)access)

- Climate- Climate

- Location- Location

- Tenure- Tenure

- Future Expansion- Future Expansion


Development of Propagation Development of Propagation MaterialMaterial

- Easy to Domesticate?- Easy to Domesticate?

- Seed Collection (genetic variance)- Seed Collection (genetic variance)

- Other Propagation Methods- Other Propagation Methods


PlantingPlanting

Harvesting TechniquesHarvesting Techniques

Extraction Extraction

TechniquesTechniques


Are Developed Techniques able to Are Developed Techniques able to Create a Create a

Viable and Economic Industry?Viable and Economic Industry?

Marketing StrategiesMarketing Strategies

Marketing StrategiesMarketing Strategies

Develop in Conjunction with Develop in Conjunction with International CompanyInternational Company

- They will have their own strategy- They will have their own strategyRaw MaterialRaw MaterialFinished ProductFinished ProductLocal MarketLocal Market International MarketInternational Market

ConclusionConclusion

Emphasis Shifting to Development Emphasis Shifting to Development and Potential Applicationsand Potential Applications

Possible CommercialisationPossible CommercialisationResearch Funding Tied to Research Funding Tied to

Results/OutcomesResults/Outcomes Institution Questions – Institution Questions –

Can it be Commercialised?Can it be Commercialised?

ConclusionConclusion

Multi-disciplinary ApproachMulti-disciplinary ApproachMarket OrientationMarket OrientationFocus on Research ObjectivesFocus on Research ObjectivesEconomic BasisEconomic BasisHeavy Influence of Regulatory Heavy Influence of Regulatory

RestrictionsRestrictions

Thank YouThank You

Natural Products: The Case for a Product Development Paradigm in Malaysian Natural Product Research...

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