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Presentation for Abuja Nigeria Aloe Extract

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Presentation for Abuja Nigeria  Aloe Extract Powered By Docstoc
					   Status of Medicinal and Aromatic Plants (MAPs) Utilization
 Globally Including Issues of Quality Control and Technologies for
         Large Scale Production of Plant Based Products

                                              S.S. Handa
                                   ICS-UNIDO Senior Specialist
                      Industrial Utilization of Medicinal and Aromatic Plants

                                     Expert Group Meeting
                                                  on
     “Strengthening South-South Cooperation and Technology Transfer/Adaptation for the
           Utilization of Neem in Production of Biopesticides and other Products”

                                              Organized by
          United Nations Industrial Development Organization (UNIDO)
                                         in collaboration with
         Federal Ministry of Environment, Housing and Urban Development (FMEHUD)
                                                   &
               the National Research Institute for Chemical Technology (NARICT)
                                       20-22nd November 2007
                            Sheraton Hotels and Towers, Abuja, Nigeria




                            MAPs utilization globally
                                                                   Phytopharmaceuticals
    Opportunities and bottlenecks
                                                                   Herbal drugs
    in MAPs based drug industry                                    Nutraceuticals
                                                                   Extracts
                                                                   Essential oils
                                         Bioresource
                                                                   Cosmeceuticals
                                       rich developing             Traditional medicines
Issues of quality                         countries                MAPs
     control                         need to inventorise
                                       their MAPs for
Quality and safety of              sustaintable industrial            Technologies for large scale
MAPs & their products                     utilization                         production
Causes of inconsistency
                                                             Why to extract MAPs?
Thirteen points of standardizing raw
material                                                     Parameters of making standardized extracts
Specifications of quality for herbal drugs,                  Utilization of extracts for formulations at
herbal drug preparations & herbal                            different levels of technologies
medicinal products
                                                             Processing technologies
Regulatory aspects of herbal drugs
                                                             General methods of extraction
Quality control vs. pharmacopoeia
                                                             Batch uniformity and GMP compliance
Constraints on quality control
                                                             Standardization of extracts
African countries for producing quality
                                                             Essential oils occurrence & production methods
herbal drugs in
                                                             Affordable & adaptable technologies for
national healthcare
                                                             production of essential oils




                                                                                                              1
                          MAPs Providing Global Opportunities for Business
                                                Phytopharmaceuticals                          MAPs
                                                Modern drugs
                          Insect repellants
                                                Drug leads
                          Insecticides
                                                Drug intermediates
                          Pesticides                                                        Herbal drugs

                          Fungicides                                                        Herbal drug preparation
                                                                                            Herbal Med production

                                                             MAPs
                                                                          M
                                                                           AP

                                                     s
                                                AP
Pharmaceutical Aids                                                             s
                                                        Global
                                               M
Gums                                                                                           Traditional medicines
Mucilages
                                                     Opportunity for




                                                                                    MAPs
                                                                                               Complementary Alternate
                                              MAPs



Edible dyes                                                                                    medicines
Sweeteners                                              Business                               House hold remedies




                                                                          M
                                                   s
                                                AP



                                                                           AP
                                                                              s
                                                       M
                                                             MAPs
                            Essential oils                                                 Nutraceuticals
                            Flavours                                                       Functional foods
                            Fragrances                                                     Food supplements
                            Perfumes                           Extracts
                                                                                           Beverages
                            Cosmetics




                          PLANT PARTS EXTRACTS AND HERBAL
                                        DRUGS
   PHYTOPHARMACEUTICALS




                                                                                                       ESSENTIAL
                                                                                                       ESSENTIAL




                                                HERBAL DRUG
                                                  INDUSTRY
                                                                                                          OILS
                                                                                                          OILS




                                              DRUGS FOR ISM




                                                                                                                         2
  WORLD MARKET MEDICINAL PLANTS BASED PRODUCTS

PHYTOPHARMACEUTICALS                 “Natural products – a well spring of drugs and drug leads”



   Number of drug molecules obtained/developed industrially from plants and used
   in modern medicines 121 in (1995); 130 in (1997); 143 (2000); 166 (2006)
   Plant steroids and terpenoids account for US # 22 billion global market p.a
   Taxol is estimated over a billion US $ p.a; Vinblastine and Vincristine amounts
   to US $ 100 million p.a
   Nicotine and Scopolamine patches now have combined sale of more than one
   billion US$.
   61% of the small molecule – new chemical entities (NCE) introduced as drugs
   world wide during 1981-2000 can be traced to or were inspired by natural
   products
   In both 2001 and 2002, about one quarter of the best selling drugs world wide
   were natural products or derived from natural products (Butler 2004)
   Of all available anticancer drugs between 1940-2002, 40% were natural
   products and 8% natural product mimics




   NEW DRUG DISCOVERY (2000 – 2005)

23 New drugs derived from natural sources
have been launched on the market during
2000-2005 after having                             been approved for
the treatment of

   Cancer                            neurological                        infections
  Cardiovascular                     metabolic                           immunological
  Inflammatory diseases              genetic disorders




                                                                                                  3
                       PLANT-
       RECENT FOUR NEW PLANT-DERIVED DRUGS IN GLOBAL MARKET



  Apomorphine Hcl,               deriv. of morphine              for chronic neurodegenerative
  APOKYN®, Bertek, 2004          Papaver somniferum              Parkinson’s disease short-
                                                                 acting D1&D2 receptor agonist is a
                                                                 potent dopamine receptor agonist

  Tiotropium bromide             deriv. of Atropine              for bronchospasm associated with
  SPIRIVA-HANDIHALER®            Atropa belladonna               chronic obstructive pulmonary
  Boehringer Ingelheim, 2004                                     disease (COPD) with longer
                                                                 lasting effect than Ipratropium

  Nitisinone, ORFADIN            deriv. of Leptospermone         for heredityary tyrosinaemia type 1
  Swedish Orphan, 2002           Callistemone citrinus           (HT-1), a severe inherited disease
                                 (bottle brush plant)            of fumaryl acetoacetate hydrolase
                                                                 (FAH)

  Galanthamine HBr               Amaryllidaceae                  Selective acetylcholinestrase
  REMINYL®, Janssen, 2001        alkaloid from                   inhibitor for Alzheimer’s disease
                                 Galanthus nivalis

  Arteether, ARTECEF®            Artemisinin deriv.              An antimalarial drug
  Artecef BV, 2000               Artemisia annua




           HERBAL DRUGS                                Global scenario

  The World Bank estimated global trade in MAPs and their products at US$ 5 trillion by
  2050 AD.
  Global herbal market is around $ 70.5 billion with an average annual growth of 10-12%
  p.a.




European Union       45%       $ 32 billion           Rest of Europe     4%          $ 2.8 billion
Asia                 19%       $ 12.2 billion         North America      10%         $ 7.8 billion
Others               7%        $ 4.6 billion




                                                                                                       4
HERBAL MEDICINES – GLOBAL MARKET PERSPECTIVES


Herbal medicine- the oldest form of healthcare known to
mankind and has played dominant role in the development of
modern medicine


WHO estimates 4 billion people of the world population currently
use herbal medicine for their primary healthcare


Herbal drug industry is one of the fastest growing industries.
Europe leads the world market followed by Asia, North America
and Japan




HERBAL MEDICINES – GLOBAL MARKET PERSPECTIVES


 Within Europe, Germany leads the market followed by France,
 Italy, the UK, Spain, Scandinavia and the Netherlands

 Germany comprises about half of the European market of
 herbal medicine and its annual per capita consumption of US$
 42.9 is about 10 times of any other European country

 North American market for herbal drugs is considered in its
 developmental phase as compared to European market and
 most of the herbal products are sold as dietary supplements

 The USA is the largest market for herbal products in North
 America




                                                                   5
      GLOBAL MARKET - HERBAL DRUGS

   THERAPEUTIC CATEGORY                                     PERCENTAGE

HERBAL PRODUCTS FOR C.V. DISEASES                               27.2

HERBALS FOR RESPIRATORY DISORDERS                               15.3

HERBALS AS DIGESTIVES                                           14.4

HERBAL TONICS                                                   14.4

HERBALS FOR MISCELLANEOUS DISORDERS                             12.0

HERBALS AS HYPNOTICS / SEDATIVES                                  9.3

HERBALS FOR TOPICAL APPLICATIONS                                  7.4




 NUTRACEUTICALS                   Promising Sector with enormous growth


 Health foods are known under different names throughout the world
 Nutraceuticals are food products supplemented with herbal ingredients, vitamins,
 minerals and nutrients or ingredients isolated/purified from conventional foods.


 These are the latest products in a succession of health food evolution constituting
 dietary supplement, fortified foods, foods and beverages with added bioactive
 ingredients.


 The strongest market driver for Nutraceuticals is the ‘baby boomer generation’
 which will be the largest buying consumer group in the years ahead.


 The USA leads the Nutraceutical market followed by the countries of Western
 Europe and Japan, will remain largest global producers and consumers.


 Asia and Pacific, Latin America, Africa and middle East are set to provide the
 fastest growth for the nutraceutical industry. China will see the most impressive
 jump in nutraceutical production & consumption USA ($ 10 – 37 billion); EUC ($ 15-
 20 billion); JAPAN ($ 10-14 billion)




                                                                                       6
 NUTRACEUTICALS – POTENTIAL & GROWTH
   OF BUSINESS IN DIFFERENT COUNTRIES

COUNTRY/REGION                 CONTRIBUTION %AGE                                 GROWTH
                                                                      2004          2010        %age
UNITED STATES                                  32                     43.4          65.6        51
CANADA                                          3                     3.5           5.4         54
JAPAN                                          23                     32           46.1         44
EUROPE                                         30                     39.9          59.9        50
ASIA PACIFIC                                    9                     11.3          17.5        55
LATIN AMERICAS                                  2                     2.3            3.5        52
MIDDLE EAST                                     1                     1.2            1.7        42



                          Herbal Drugs-Perspective in the New Millennium 2006, Ranbaxy Science Foundation, India




          PLANT PRODUCTS AS MEDICINES AND FOOD

Momordica charantia                Oryza sativum
Aegle marmelos
Syzigium cumini
Murraya koenigii
                                                                                     Withania somnifera
                                                                                     Sida cordifolia,
                                                                                     Boswellia serrata,
                                                                                     Commiphora wightii


                                        PLANTS USED
                       FOOD             FOR FOOD
                                        AND MEDICINE



                                                           MEDICINE
                              SPICES

Zingiber officinalis
Curcuma longa
Carum carvi, Piper
nigrum
Anethum sowa




                                                                                                                   7
                                Requisites for an Extract
PLANT                Size of plant       nature of plant                                       SOLVENT
                                            material               nature of
MATERIAL               material                                    solvent

         origin of plant                                                                concentration
            material                                                                    of solvent
   degree of                                                                                   polarity of
   processing                                                                                  solvent

   moisture

                                                   extract
         type
                                                                                                   filling
                                                                                                   height
    time


        Flow                                                                        hydrostatic
        velocity                                                                    pressure
                           temperature                            batch size
                                            pressure
MANUFACTURING
                                                                                    MANUFACTURING
METHOD
                                                                                    EQUIPMENT




 GLOBAL DEMAND FOR HERBAL EXTRACTS IN
         NUTRACEUTICAL SEGMENT

                                               1987 TO 2002                      AGR 11-13%

 ITEM                                DEMAND VALUE (BILLION US$)                % ANNUAL GROWTH
                                     1987     1997         1999   2002         1987/199     1997/2002
                                                                               7
 HERBAL EXTRACTS                     0.52      1.73        2.9     2.96          12.9          11.3

 VITAMINS                            0.68      1.38        2.3     1.93          7.2            7.0

 MINERALS & NUTRIENTS                1.14      2.39        1.6     3.31          7.7            6.7
 TOTAL                               2.34      5.50        6.8     8.20          8.9            8.3

                   SOURCE: THEODORE 1997; FREEDONIA GROUP INC 2001 (a)
                                AGR: ANNUAL GROWTH RATE




                                                                                                             8
 MAJOR GLOBALLY SOLD PLANT EXTRACTS
      BASED ON TRADITIONAL USE
      PLANT           LOCAL NAME         ACTIVE CONSTITUENTS           INDICATION

Hypericum             St. John’s wort   Hypericins                    Antidepressant
perforatum                              Hyperperphorin

Panax ginseng         Ginseng           Ginsanosides                  Adaptogen

Withania somnifera    Indian ginseng    Withanolides                  Adaptogen
                      (Ashwagandha)

Serenoa repens        Saw palmetto      22 – 28 C fatty acid methyl   B. P. H.
                                        esters

Valeriana officinalis Valerian          Valepotriates                 Sedative

Zingiber officinale   Ginger            Oleoresin                     Anti-emetic




    MAJOR GLOBALLY SOLD PLANT EXTRACTS
       NOT BASED ON TRADITIONAL USE



             PLANT             ACTIVE-CONSTITUENTS               MAIN USE

   Gingko biloba               Gingkolides                Vascular insufficiency
     (Gingko)                                             P.A.F. Antagonist

   Echinacea angustifolia Echinacosides                   Immunostimulant
     (Black sampon)

   Vaccinium myrtillus         3-O-glycosides of          Venous insufficiency
     (Blue berry)              delphinidin, cyanidin      retinopathies
                               and petunidin




                                                                                       9
 SOME TOP SELLING HERBAL EXTRACTS (STANDARDIZED) IN
                    WORLD MARKET
   Aloe vera                    Hydrastis canadenis
   Allium sativum               Humulus lupulus
   Andrographis paniculata      Mentha piperita
   Boswellia serrata            Matricaria chamomilla
   Capsicum indicum             Ocimum santum
   Centella asiatia             Panax ginseng
   Cassia angustifolia          Phyllanthus amarus
   Curcuma longa                Silybum marianum
   Coleus forskohlii            Serenoa repens
   Crataegus oxycantha          Salacia reticulata
   Commiphora mukul             Salixalba
   Emblica officinalis          Tinospora cordifolia
   Echinacea angustifolia       Tribulus terrestris
   Ephedra sinica               Tanacetum parthenium
   Eleutherococcus senticosus   Valerian officinalis
   Garcinia cambogia            Vitex negundo
   Glycyrrhiza glabra           Withania somnifera
   Gymnema sylvestra            Zingiber officinale
   Gingko biloba




  ESSENTIAL OILS PRODUCTION
WORLD PRODUCTION DOMINATED BY BRAZIL 40%
    FOLLOWED BY USA 20% AND INDIA 15 %

        WHEN COMPARED IN VALUE TERMS


 IT IS HIGHEST FOR USA (26%) FOLLOWED BY INDIA 21%
                    AND BRAZIL 8%




                                                        10
                  ESSENTAIL OILS: GLOBAL VIEW
 World Production of Essential oils (Estimated) 150,000 tons excluding Turpentine
 oil which alone is 300,000 tons


 Developing countries have great potential for production of E.O. 65% produced in
 developing countries, 35% in industrialized countries


 Seven leading countries Brazil, China, India, Indonesia, Egypt, Morocco and Turkey
 produce 85% among developing nations


 Major exporters of E.O.: Brazil, China, India, European Union, USA and Indonesia
 account for 66% of essential oil exports


 Major importers: E.U., USA, Japan, Canada, Switzerland account for more than 70%
 of the total volume import


 Basic requirements for establishing an E.O. business:
 a) Market demand b) Raw material availability c) E.O. quality




ESSENTAIL OILS: GLOBAL VIEW                                              continue…
 Constraints for establishing an E.O. industry in developing countries
   a)      Lack of awareness of economic benefits of E.O. industry
   b)      Technology and skilled manpower
   c)      Inadequate infrastructure
   d)      Inventories for information and plant resources
   e)      Market intelligence
   f)      Credit facilities for business development
   g)      Unsupportive govt. policies


        Regulatory aspects E.O. are regulated products. Several legislations
        contain clauses which relate to definition, quality, labeling, packing,
        shipping, registration of E.O.


        Biocides Directive of the E.U. includes many essential oils, antibacterials
        and insect repellents are considered as biocides. Use of E.O is increasing in
        veterinary practice


  Future expectations
   1.      Low price oil (less than $ 20/kg) will have better chance
   2.      Consumption of E.O. in China and India for cosmetic, toiletries, drinks and processed
           food will increase
   3.      New production sites in sub Saharan Africa, Australia and South America




                                                                                                   11
                                              Item                       Demand value (million US$)
COSMECEUTICALS                                                    1989    1993    1998     2003       2008
                                              Aloe extract        38      46      63       86         115

                                              Botanical           180     230     345      505        720
Global market : US$ 22 billion                extract

Fastest growing sector: Anti-aging products   Others              22      34      67       113        174


Skin care products $ 5.4 billion in 2005      Phyto-chemicals     19      37      65       106        173


Botanical ingredients for use in cosmetics    Essential oils      101     113     150      200        258
                                              Other natural       85      115     180      265        385
and toiletries      8% annual growth          products

                                              Total               265     345     525      770        1,105




  Manufacturers are now frequently replacing vitamins with herbal ingredients
  such as Serenoa repens, Panax spp., Ginkgo biloba.
  Aloe vera is most demanded in cosmetic industry
  US market for cosmetics : US$ 2.5 billion where the market for botanicals for use
  in cosmetic and toiletries are at $ 345 m (1998), 505 m (2003) and 750 m
  (2008)




 BOTANICAL EXTRACT DEMAND IN COSMETIC AND
        TOILETRIES FROM 1989 TO 2008
   ITEM                                DEMAND VALUE (MILLION US $)
                                      1989                1993            1998           2008 *

   ALOE EXTRACT                         38                 46              63             115
   BOTANICAL EXTRACTS                  180                230              345            720
   OTHERS                               22                 34              67             174
   PLANT ACIDS & ENZYMES                19                   37            65             173
   ESSENTIAL OILS                      101                113              150            258
   OTHER NATURAL                        85                115              180            385
   PRODUCTS

   TOTAL                               265                345              525           1,105

* Estimates;       Source : FREEDONIA GROUP




                                                                                                              12
     PLANTS AND THEIR PRODUCTS FOR COSMETIC USE



A. Vegetable oils, fats and waxes                 Castor oil, coconut oil,
                                                  peanut oil, almond oil,
                                                  cocoa butter, shea butter

B. Essential oils and Oleoresins                  Geranium, jasmine, citrus,
                                                  vetiver, clove nutmeg,
                                                  patchouli, sandalwood,
                                                  mint, ceder wood

C. Vegetable saps and extracts                    Gums, resins, gels (saps),
                                                  extracts

D. Natural colours                                Indigo, Curcumin, marigold,
                                                  Lawsonia, flame of the
                                                  forest

E. Raw plant material                             MAPs, seaweeds, algae




TM/CAM
TM               Maintained popularity in number of Asian, African and Latin American
                 countries. Among Asian countries Japan, China and India have the highest
                 percapita consumption of TM

JAPAN            Many fold increase in “Kampo” medicine sale >$ one billion p.a.
                 (prescription drugs 78.6%; OTC 21.4%)

CHINA            TCM 30-50% of total medicine consumption. 35% out patients and 22%
                 in-patients use TCM

INDIA            Multi-drug system country, market of ‘AYUSH’ drugs $ one billion
                 (Rs.5,500 crores) of which major share 84% is for Ayurvedic drugs

MALAYSIA         TM market in 2005 $ 842 million and will be $ 1.36 billion by 2010

SINGAPORE        12% of the daily out patients visit TM practitioners

R.P.D KOREA      TM account for 12% of the total drug output

AFRICA           80-90% population rely upon MAPs products for healthcare needs

LATIN AMERICAS   70-80% population rely upon traditional herbal drugs




                                                                                            13
ESTIMATES OF GLOBAL TRADE FIGURES FOR MAPs & THEIR PRODUCTS

 Six leading countries are Hong Kong, Japan, Germany, USA, South Korea World Trade
 in MAPs and their products $ 70 billion with annual growth rate 7%, the figure
 expected to reach $ 5 trillion by 2050 (World Bank)


 China leading export country for MAPs and India is second largest exporter


 Widely varying figures are quoted, making it difficult to analyse data for
 international trade


 Industry is complex with little vertical integration, generally reluctant to share data


 Cross trading between companies is commonly practiced (in many cases,
 manufacturers do not even know the original source of the MAPs raw material)


 MAPs find applications across a range of industries, and trade statistics wherever
 applicable do not identify plants individually and /or by application




                 MAPs SUPPLY SOURCE


Asia, Africa and Latin America > 80% wild, (China 60% India 90%)

Majority wild harvested material sourced from developing nations.

Of 1200 traded plants (volume 30,000 tons) in Europe, 90% are
collected from wild

China, India, Spain, Argentina, Hungry and Poland cultivate MAPs on
larger scale

In China >250 species commercially cultivated out of which 60 species
have performed well

In India 40 species in highest demand are under commercial cultivation

In Latin Americas several exotic and introduced species are cultivated




                                                                                           14
        A FEW HARD FACTS OF BUSINESS
                FROM HERBALS
Expanding global market for herbals: People’s increasing faith in
NATURALS; self medication for mild ailments using herbals

Market potential is curtailed by lack of standardization and scientific
validation of many herbal medicines

Crisis the Pharma industry is facing and the limitations of conventional
“silver bullet” approach in drug development

Developing modern drugs from herbals can bring the better of the two
worlds together

Herbal source promises to alleviate the “dry spell” which the pharma
industry is currently facing




    BOTTLENECKS OF PLANT BASED DRUG INDUSTRY


WILD SOURCE OF RAW                    CULTIVATION
 MATERIAL
                                      •Agrotechnology
•Inconsistency
                                      •Planting material
•Supply irregular
                                      •No buy-back system
•Loss of biodiversity
                                      •No control on price structure
•Unskilled collectors
                                      •Lack of incentives
•No economic mapping
                                      •Small land holdings
•No inventory
•Multilingual names                   TRADE & MARKETING
•Adulteration                         •Lack of consumption data &
POST HARVEST TECHNOLOGY                market survey
•Mode & stage of harvesting           •Unorganized trade
•Drying processes                     •No price control
•Garbling                             •Unethical advertising
•Packing                              •Business strategy
•Storage                              •IPR issues




                                                                           15
 BOTTLENECKS......continued

                                              LACK OF QUALITY CONTROL
                                              •Quality lacks in raw material,
                                               production packing, labeling
                                              •Stability studies lack
PROCESSING TECHNOLOGY                         •Analysis methods
•Age old methods                              •Training facilities
•Energy loss                                  •Validation of efficacy & safety
•Lack of protocols                            •Regulatory aspects
•GMP noncompliance
•No documentation
•Process parameters                           NEED FOR R&D
•Process controls                             •Unexplored flora and indigenous
                                               knowledge
•Lack of training
                                              •Meagre investment
•Acquisition and adoption of technology
 lacking                                      •Lack of Govt. support
                                              •Laying of multidisciplinary approach
                                              •Claims validation and safety assessment
                                              •Value added components
                                              •Modern approach to drug discovery




                  USE OF EXTRACTS - RATIONALE
                                                                              GLYCOSIDES
               Rt, Rtbk, St, Stbk, Lf, Fl, Fr, Frp, Frd, Sd, Wp                  ANTHRAQUINONE
                                                                                 SAPONIN
                                                                                 CYANOPHORE
  CELLULAR                    NON CELLULAR                                       ISOTHIOCYANATE
  MATERIAL                      MATERIAL                                         FLAVONOL
                                                                                 ALCOHOL
                                                                                 ALDEHYDE
                   PRIMARY                     SECONDARY                         LACTONE
                                                                                 PHENOL
                  METABOLITES                  METABOLITES
                                                                              TANNINS
                         HOT EXTRACTION             COLD EXTRACTION              ELLAGITANNIN
STARCH                   • DECOCTION               • MACERATION                  GALLITANNIN
CARBOHYDRATES                                                                 ALKALOIDS
POLYSACCHARIDES          • SOXHELT                 • PERCOLATION
                                                                                 PYRIDINE –
AMINO ACIDS             50% AQ. ALC       ALCOHOLIC           AQUEOUS            PIPERIDINE
ENZYMES                                                                          TROPANE
                                                                                 QUINOLINE
    STEAM DISTILLATE      MEDIUM              NON                                INDOLE
                          POLAR              POLAR               POLAR
                                                                                 IMIDAZOLE
                                                                                 STEROIDAL
         VOLATILE OIL      RESINS            LIPIDS             STEROIDS         AMINES
                                                                                 PURINES
         HYDROCARBON       Oleoresin         FIXED OILS         CARDIAC
         ALCOHOL           Oleo-gum          FATS                BILE ACIDS
         ALDEHYDE          Balsam            WAXES               HORMONES
         KETONE                              Prostaglandins
         ESTER                               Fatty Acids




                                                                                                  16
     EXTRACTION OF MAPs
Extraction,    as   the     term    is    used
pharmaceutically, involves separation of
medicinally active portions of plant or animal
tissues from the inactive or inert components
by using selective solvents by appropriate
extraction technology. The products so
obtained are relatively impure liquids,
semisolids or powder intended only for oral or
external use.




                                                 17
18
19
Batch uniformity and GMP compliance

Pre-requisites
• Uniform quality of raw material
• Consistency of extraction solvent, process & equipment

Methods to ensure batch uniformity
• Mixing of lots with different DER, check internal composition
  before mixing
• Liquid extracts adjusted by concentration or dilution
• Dried extracts by addition of inert diluents




                                                                  20
 Standardization of extracts
First choice for total composition, finger print
profile
Second choice for maximum number of known
active constituents
Third choice for one major active constituent
Fourth choice for inactive marker
DER only to supplement the analysis, but not as a
sole parameter




                                                    21
22
23
24
25
Quality is Wholesome!
                                Quality

       Statutory                                            Market
     requirements                                         Expectations


                                Technical
       Imposed by authorities   Experience
       Must to do business                                       Important and
       Violation leads to                                        realistic
       punishment                                                Decides the fate of
       Guarentees the minimum                                    the product
       standards                                                 Both product and
                                                                 packaging standards
                                Quality Standardization          play a role
                                Quality production
                                Quality testing
                                Quality monitoring
                                Quality assurance




                                                                                       26
Safety is the fundamental principle...
                       …Critical component of quality management
                                       Adulteration with other
                                       medicines and potent chemical
                                       substance
                     Misconception that
                     all natural are safe                           Poor quality products




                   Mistaken use of
                   wrong species            Problems
                                                                             Innate toxicity
                                                                    Interactions with other
                       Incorrect dosing                             medicines


                                        Misuse of herbal drugs by health
                                        care providers and consumers




Herbal and Modern Drug Interaction

                              Consequence of simultaneous usage


                                            Warfarin, Aspirin, Ticlopidin, Dipyridamole,
   Ginkgo biloba
                                            Clopidogrel
   Hypericum
                                            Warfarin. Antidepressants
   (St. Johnswort)

   Kava-Kava                                Sedatives, Antipsychotics, alcohol

   Ginseng                                  Warfarin

   Ephedra                                  Decongestants, Stimulants, Caffeine



                         Safety study of herbal drugs needs to include effect on
                         cytochrome P450 drug metabolizing enzyme, which can
                         have marked effect on other drugs taken concomitantly.




                                                                                               27
Herbal Drug Standardization


   The standardization of Herbal drug and preparation
   thereof is not just an analytical operation


   It does not end with identification and assay of an
   active principle, rather it embodies total information
   and controls that are necessary to guarantee
   consistency of composition




Causes of Incosistency in Herbal Drugs


               Regional / lingustic nomenclature
               Ecotypic, genotypic, chemotypic
               variations
               Harvesting period
               Method of drying
               Storage conditions
               Mode of grinding and particle size
               Extraction procedure
               Nature of formulation




                                                            28
When to Collect the Plants

                               Flowers
                               Just before fully expanded


            Fruits                               Roots and Rhizomes
            Fully ripe                            As the aerial parts
                                                  die down

                         Considerations of
                          Collecting Plant
                               Parts
            Barks                                    Gums and Gum resins
            After a period of damp                   During dry weather
            weather


                                Leaves
                                As the flowers are
                                begining to open




 Segments of Post Harvest Care

                                     Collection


                     Storage                            Harvesting


                               Medicinal Plants
                                Post Harvest
                                Technology
                     Packing                             Drying



                                     Garbling




                                                                           29
 Drying of Medicinal Plants

       Drying as soon as possible after collection
       Open air drying avoiding sun drying
       Drying by artificial heat/solar drying
                                                0
          LVS, Herbs, Flowers between 20-40 C
                                          0
          Barks and roots between 30-60 C
       Over drying – to be avoided
       Open air drying by cutting into thin slices
         [fruits/underground parts] or chopping / [aerial parts]



       Slow drying where enzymatic action desired
       [Vanila pods, Cocoa seed Gentian roots]




Storage of Medicinal Plants

        Moisture during storage                     Temperature and
        is the biggest enemy of                     humidity controlled
        crude drugs                                 storage premises




                                                             Protected from
        Degree of
        comminution           Storage                        light




         Storage place must be                       No spray of insecticide
         clean and free from                         or pesticide during
         rodents and insects                         storage




                                                                               30
Good Agricultural Practices [GAP]
          Seeds and propagation materials
           Authentic and high quality

          Cultivation
           SOP
           soil and fertility              Primary processing:
           Irrigation                       Washing
           Plant protection                 drying [no drying on the ground/sunlight;
                                            special requirements for open air drying;
         Harvest                            must be protected from rainfall]
           GHP
           plant quality                    Protection against birds, insects, rodents
                                            and domestic animals
           equipment
           no damaged/perished plant
                                            Promptly and properly packaged
           avoid soil/toxic weeds
           no damaging/prevent heating
                                            Permanently fixed labelling as per the
           container
                                            national regulations
           documented pest control




 Stadardization of Plant Drugs

                                     Authentication

                           Radioactive             Foreign matter
                           contaminants
                                                            Organoleptic
             Microbial count                                evaluation

             Heavy metals                                   Macroscopy and
                                                            microscopy
             Pesticide residue
                                                            Volatile matter
             Marker component
                                                Ash value
                     Chromatographic
                     profile
                                  Extractive value




                                                                                         31
Specifications of Herbal drugs
         BOTANICAL CHARACTERISTICS                         BIOLOGICAL/GEOGRAPHICAL VARIATION

                       Definition
                       Characters
                                                                      STABILITY OF CONSTITUENTS
                       Identification
                       macroscopy
                       microscopy                     Herbal
                                                                                    PRE/POST HARVEST
          PHYTOCHEMICAL CHARACTERS                    Drugs                         TREATMENTS

                                                                                        Pesticides
            Known therapeutic constituents                                              Fumigants
            Toxic constituents
                                                            CULTIVATION/HARVESTING
                                                            DRYING CONDITIONS
         Identification    Tests            Assay

           TLC               Total ash                           Microbial levels
           Chemical          Acid insoluble ash                  Aflatoxins
           reactions                                             Heavy metals etc
                             Foreign matter
                             Extractable matter
                             Particle size
                             Water content




Specifications of Herbal drug Preparation

                  PHYTOCHEMICAL                               QUALITY OF HERBAL
                 CHARACTERISTICS                                    DRUGS


                                                                              STABILITY OF
            Identification          Assay                                     CONSTITUENTS


           CHROMATOGRAPHIC PROFILE
           • HPLC/UV- Diode – array
           • HPLC/MS                                Herbal Drug                 MICROBIAL STABILITY
           • GC/MS                                  Preparations
           • TLC-DENSITOMETRY

                                                                                DRYING
           METHOD OF PREPARATION FROM                                           CONDITIONS
           HERBAL DRUG

                                                    SAFETY AND EFFICACY
           Definition              Characters       CONSIDERATIONS              MICROBIAL LEVELS
                                                                                RESIDUAL SOLVENTS
                                                                                IN EXTRACTS
             STATE : SOLID, LIQUID ETC.             BATCHES USED IN             WATER CONTENT
             RATIO HERBAL DRUG TO                   PRECLINICAL/CLINICAL        AFLATOXINS
             HERBAL DRUG PREPARATION                TESTING
             OR RATIO HERBAL DRUG TO                                            HEAVY METALS
             EXTRACTION SOLVENT                                                 PESTICIDES
                                                                                FUMIGANTS ETC.




                                                                                                       32
Specifications of Finished HMP
                         QUALITY OF HERBAL DRUG PREPARATIONS

                                                                   STABILITY OF THE
           DESCRIPTION OF         HERBAL MEDICINAL                 ACTIVE CONSTITUENTS
           DOSAGE FORMS
                                     PRODUCTS
                                                                   FORMULATION/
            IDENTIFICATION                                         PACKAGING
            •   CHROMATOGRAPHIC    MANUFACTURING PROCESS
                PROFILE
                                                                   SAFETY AND
                                                                   EFFICACY
                                       TEMPERATURE EFFECTS         CONSIDERATIONS
            ASSAY                      RESIDUAL SOLVENTS
                                       ORGANIC AND
                                       INORGANIC IMPURITIES        BATCHES USED IN
                                       MICROBIAL LIMITS            PRECLINICAL/ CLINICAL
           SPECIFIC TESTS                                          TESTING
                                   ORAL LIQUIDS

                                   •   UNIFORMITY OF DOSAGE
    TABLETS AND HARD CAPSULES      •   pH.; WATER CONTENT; SPECIFIC GRAVITY
    DISSOLUTION/DISINTEGRATION     •   MICROBIAL LIMITS : ANTIMICROBIAL AND
    HARDNESS/FRIABILITY                ANTIOXIDATIVE PRESERVATIVE CONTENT
    UNIFORMITY OF DOSAGE UNITS     •   EXTRACTABLES : ALCOHOL CONTENT
    WATER CONTENT                  •   DISSOLUTION : PARTICLE SIZE DISTRIBUTION
    MICROBIAL LIMITS               •   REDISPERSIBILITY : RECONSTITUTION TIME




      REGULATORY ASPECTS

                    HERBAL DRUGS




                                                                                           33
Herbal Drug in Different Countries

                                     Variable Situations
   Strong foundation of traditional medicines having nationally
   recognized parallel traditional systems along with western
   medicine, of course with varying degrees of acceptance
   integration and assimilation
                                                            -India and China
   Move to give legitimacy to the traditional healers whose medical
   practice has been the mainstay of the local people, even after
   western medicine made its appearance and took firm roots
                                                             -Africa
   A new and growing consumer interest in the use of natural
   medicine opening burgeoning markets for health promotion
   porducts aimed at improvement of physical well being but not
   recognised by the governments including drug authorities
                                                             -Europe and USA




 Q.C vs Pharmacopoeia


      No Pharmacopoeia in the world is comprehensive
      enough to cover all the medicinal herbs


      No Pharmacopoeia is able to give concrete methodology
      for routine quality control of medicinal herbs. It shows
      the limitations of basic approach of developing
      standards in line with allopathic synthetic medicines




                                                                               34
           THE EUROPEAN PHARMACOPOEIA
                                   Till 2000                   2002              Latest 5th Edition
                                                                                 & 8th supplement

HERBAL DRUGS                            73                      106                  133


PLANT MATERIAL OBTAINED                 23#                     39                   40
  AFTER TREATMENT


#EXTRACTS     AND TINCTURES                                     19                   26


#FIXED   OILS (Plants)                                                               20


#VOLATILE    OILS (Aromatic Plants)                                                  30*


Total                                   96                      164                  249
    * For the forthcoming volume in 2007 EP may have nearly   100*   monographs on V.O.




 EUROPEAN SCIENTIFIC COOPERATIVE
        ON PHYTOTHERAPY


                     ESCOP – MONOGRAPHS

           60 IN 6 COLLECTIONS OF 10 EACH

     RECOMMENDED FOR USE TO SUPPORT
   DEMONSTRATION OF THE SAFETY AND EFFICACY
       OF MEDICINAL PLANT PRODUCT




                                                                                                      35
    GERMAN COMMISSION E MONOGRAPHS 1998

                        191 APPROVED
299 HERBS
                        108 UNAPPROVED

8     COMPONENT                        2 APPROVED
                                       6 UNAPPROVED
      CHARACTERISTICS
                                       67 APPROVED
8     FIXED COMBINATIONS                6 UNAPPROVED



8     EXPANDED COMMISSION E MONOGRAPHS HAVING
      IN-DEPTH OVERVIEW WITH CLINICAL DATA




        BRITISH HERBAL PHARMACOPOEIA

BRITISH HERBAL MEDICINE ASSOCIATION [BHMA] 1971

BHP
      FIRST EDITION        169 MONOGRPAHS
      SECOND EDITION       233 MONOGRPAHS


BHC (BRITISH HERBAL COMPENDIUM)
      84 MONOGRAPHS




                                                       36
          JAPANESE STANDARDS
       FOR HERBAL MEDICINES (J.S.H.M.)

JSHM MONOGRAPHS ON: 248 HERBAL MEDICINES

      165 FROM PHARMACOPOEIA OF JAPAN

       83 FROM JAPANESE HERBAL MEDICINE
       CODEX (JSHM)


    DESCRIPTIONS FOR INFORMATION AND
  NOT OFFICIAL STANDARDS FOR CONFORMITY




 THE UNITED STATES PHARMACOPOEIA AND
     THE NATIONAL FORMULARY USP-NF
  USP 30
           Herbal Drugs – 39; Herbal Preparations – 73
                  Herbal medicinal products - 25

 NF 2007

            Gums, fixed oils, essential oils, resins – 53
   “THE ADDITION OF THESE MONOGRAPHS IN THE USP-NF
   IS A RESULT OF PUBLIC PRESSURE FROM THE SOARING
              POPULARITY OF HERBAL DRUGS”




                                                            37
          PHARMACOPOEIA OF THE
         PEOPLE’S REPUBLIC OF CHINA
 CHINESE PHARMACOPOEIA 2000 IN 2 VOLUMES

               VOLUME I


992 MONOGRAPHS ON CHINESE MATERIA MEDICA AND
    TRADITIONAL CHINESE PATENT MEDICINES

              76   NEW ADMISSIONS

             248   REVISIONS




 AYURVEDIC PHARMACOPOEIA OF INDIA [API]

  ABOUT 1000 SINGLE DRUGS AND 8000 COMPOUND
  FORMULATIONS OF RECOGNIZED MERIT ARE USED
  IN INDIA.
  AYURVEDIC PHARMACOPOEIAL COMMITTEE [APC]
  TARGETED STUDY ON 600 SINGLE DRUGS.
  FIVE VOLUMES OF PART I OF API HAVE BEEN
  PUBLISHED.
                        API     VOL I       80
                        API     VOL II      78
                        API     VOL III     100
                        API     VOL IV      68
                        API     VOL V       84




                                                  38
Constraints

                                       Main Dependence on
                                          Wild Sources
                                                                  Herbal
                          Regulatory
                                                              Pharmacopoeia?
                           Aspects


              Adulteration and                                     Lack of Public
                Substitution           Constraints in              Test – houses
                                       Quality Control
                                                                    Lack of safety
             No Certification of                                  evaluation facility
               Raw Material


              Pharmacovigilance data                          Poor investment in
                  not collected                               R&D of Med. Plant
                                            Lack of Trained       products
                                              Manpower




Concluding Remarks
    African countries for Promoting Quality Herbal – Drugs in National Health -
                                      Care
  National Policy and planning strategies
  Methodology for assessing efficacy
  Regulatory mechanism & its implementation
  Quality control procedures by setting standards of RM, Production and product.
  Agro & Process technologies & sharing innovations among Caribbean islands
  Promoting cultivation
  Adopting GHP
  Human Resources Development – common training programmes
  Mechanism for regional co – operation
  Collation of exchange of information, regional databases on MAPs
  Herbal pharmacopoeia of the region
  Harmonization of regulations for promoting trade among the neighbouring countries
  Pooling of germplasm of rich biodiversity of MAPs in African countries




                                                                                        39

				
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