Who guidelines

Anuradha singh Associate professor Sanskar college of Pharmacy,Ghaziabad,UP

1. WHO Guidelines for the Assessment of Herbal
medicines
Safetyisafundamentalprincipleintheprovisionof
herbalmedicinesandherbalproductsforhealthcare,
andacriticalcomponentofqualitycontrol.
Theseguidelinesprovidepractical,technicalguidance
formonitoringthesafetyofherbalmedicineswithin
pharmacovigilancesystems.
Theguidelinesweredevelopedwiththeviewthat,
withincurrentpharmacovigilancesystems,
monitoringofthesafetyofmedicinesshouldbe
enhancedandbroadenedinwaysthatwillallowthe
successfulmonitoringofherbalmedicines

2. PROBLEMS
Amongconsumers,thereisawidespread
misconceptionthat“natural”alwaysmeans
“safe”,andacommonbeliefthatremediesfrom
naturaloriginareharmlessandcarrynorisk.
However,somemedicinalplantsareinherently
toxic.
Herbalmedicinesareexpectedtohaveside
effects,whichmaybeofanadversenature.
Someadverseeventsreportedinassociationwith
herbalproductsareattributabletoproblemsof
quality.

3. Terms relating to herbal medicines
•Herbs-Herbsincludecrudeplantmaterialsuchasleaves,flowers,
fruit,seeds,stems,wood,bark,roots,rhizomesorotherplantparts,
whichmaybeentire,fragmentedorpowdered.
•Herbalmaterials-Herbalmaterialsareeitherwholeplantsorpartsof
medicinalplantsinthecrudestate.Theyincludeherbs,freshjuices,
gums,fixedoils,essentialoils,resinsanddrypowdersofherbs.
•Herbalpreparations-Herbalpreparationsarethebasisforfinished
herbalproductsandmayincludecomminutedorpowderedherbal
materials,orextracts,tincturesandfattyoils,expressedjuicesand
processedexudatesofherbalmaterials.Theyareproducedwiththe
aidofextraction,distillation,expression,fractionation,purification,
concentration,fermentationorotherphysicalorbiologicalprocesses.

4. •Medicinal plant A plant, either growing wild or
cultivated, used for its medicinal purposes.
•Finished herbal products or herbal medicinal
products-
Medicinal products containing as active
substances exclusively herbal drugs or herbal drug
preparations. They may consist of herbal
preparations made from one or more herbs. If
more than one herb is used, the term mixed
herbal product can also be used.

5. Terms relating to contaminants and residues in herbal medicines
•Contamination-Theundesiredintroductionofimpuritiesofa
chemicalormicrobiologicalnature,orofforeignmatter,intooronto
astartingmaterial,intermediateproductorfinishedherbalproduct
duringproduction,sampling,packagingorrepackaging,storageor
transport.
•Cross-contamination-Thecontaminationofastartingmaterial,
intermediateproductorfinishedproductwithanotherstarting
materialorproductduringproduction.
•Foreign matter -Material consisting of any or all of the following:
•Parts of the medicinal plant material or materials other than those
named with the limits specified for the plant material concerned;any
organism, part or product of an organism, other than that named in
the specification and description of the plant material concerned;
mineral admixtures such as soil, stones, sand, and dust; and glass,
metal and plastics or any other extraneous materials. These may be
loose or adhering to these medicinal plant materials.

6. •Acceptable daily intake (ADI) of a chemical
•The estimated maximum amount of an agent, expressed on a body mass
basis, to which an individual in a (sub)population may be exposed daily over
his or Introduction her lifetime without appreciable health risk.
•Acceptableresiduelevel(ARL)
•TheARLisgiveninmgofpesticideperkgofmedicinalplantmaterialand
canbecalculatedfromthemaximumacceptabledailyintake(ADI)ofthe
pesticideforhumans,asrecommendedbyFAOandWHO,andthemean
dailyintake(MDI)ofthemedicinalplantmaterial.
•Acute reference dose (ARD)
•The acute reference dose of a chemical is an estimate of the amount
of a substance, normally expressed on a body-weight basis, that can
be ingested in a period of 24 hours or less without appreciable health
risk to the consumer on the basis of all known facts at the time of the
evaluation.

7. •Extraneous maximum residue limit (EMRL)
•Apesticideresidueoracontaminantarisingfromenvironmentalsources
(includingformeragriculturaluses)otherthantheuseofapesticideor
contaminantsubstanceorindirectlyontheherbalmedicine.Theconcentration
isexpressedinmilligramsofpesticideresidueorcontaminantperkilogramof
theherbalmedicine.
•Maximum residue limit (MRL) -The MRL is the maximum concentration
of a pesticide residue (expressed as mg/kg).
•Permitted daily exposure
•The term “permitted daily exposure” (PDE) is defined, in the ICH
guidelines, as a pharmaceutically acceptable intake of residual
solvents to avoid confusion of differing ADIs for the same
substance.
•Persistent organic pollutants (POPs)
•Persistent organic pollutants (POPs) are chemical substances that
persist in the environment, bioaccumulatethrough the food web and
pose a risk of causing adverse effects to human health and the
environment

8. •Pesticide-Pesticidesaredefinedasanysubstanceintendedfor
preventing,destroying,attracting,repelling,orcontrollinganypest
includingunwantedspeciesofplantsoranimalsduringproduction,
storage,transport,distributionandprocessing.
•Tolerable intake (TI) –Tolerable intake is defined as an estimate of
the intake of a substance over a lifetime that is considered to be
without appreciable health risk.
•Residual solvents
•These are residues of organic solvents that are used or produced in
the manufacture of and processing of herbal preparations/products.
Solvents are classified by the ICH-
•class 1 (solvents to be avoided such as benzene);
•class 2 (limited toxic potential such as methanol or hexane); and
•3 (low toxic potential such as ethanol).

10. ACTIONS REQUIRED For the safety of
those using herbal medicines
•Four complementary actions are needed:
•Clear identification of the nature of adverse events
•Management of the risks
•Institution of measure to prevent adverse events
•Good communication of the risks and benefits of
herbal medicines

11. WHO Guidelines for the Assessment of Herbal
medicines
In1991,theDirector-GeneralofWHO,inareporttotheForty-fourth
WorldHealthAssembly,emphasizedthegreatimportanceofmedicinal
plantstothehealthofindividualandcommunities.
ThisWHOguidelinespresentgeneralconsiderationonpotentially
hazardouscontaminantsandresiduesinherbalmedicinesandinclude
guidingprinciplesofassessingqualityofherbalmedicines,intermsof
majorcontaminantsandresidues.Italsorecommendsanalytical
methodsforqualitativeandquantitativedeterminationofsuch
contaminantsandresidues.
Withinoverallcontextofqualityassurance,theseguidelinesintendedto
providegeneraltechnicalguidancetoMemberStatesinassessing
qualityrelatingtosafetyofherbalmaterialsandproductsclassifiedas
medicines,withregardstomajorandcommoncontaminantsand
residues.

12. The objectives of these guidelines are
to provide:
•guidingprinciplesforassessingthequalityin
relationtothesafetyofherbalmedicines,with
specificreferencetocontaminantsandresidues;
•modelcriteriaforuseinidentifyingpossible
contaminantsandresidues;
•examplesofmethodsandtechniques;and
•examplesofpracticaltechnicalproceduresfor
controllingthequalityoffinishedherbalproducts.
•Thescopeoftheseguidelinesdoesnotcover
issuesofadulterationofherbalmedicinesand/or
counterfeitproducts.

13. Inthepursuitoftheabove-mentionedobjectives,theseguidelinesshouldberead
togetherwiththeotherWHOdocumentsandpublicationsrelatingtothequality
assurance of herbal medicines with regard to
safety,forexample
•• Quality control methods for medicinal plant materials (2)
•• Good agricultural and collection practices (GACP) for medicinal plants (3)
•• International pharmacopoeia, 4th ed. (4, 5)
•WHO guidelines for assessing quality of herbal medicines with reference to
contaminants and residues (3)
•• Good manufacturing practices: main principles for pharmaceutical products (6)
•• Good manufacturing practices: supplementary guidelines for the manufacture of
herbal medicinal products (7)
•• Guide to good storage practices for pharmaceuticals (8)
•• Good trade and distribution practices (GTDP) for pharmaceutical starting
materials (9)
•• General guidelines for methodologies on research and evaluation of traditional
•medicine (10)
•• Guidelines for assessment of herbal medicines (11)
•• WHO monographs on selected medicinal plants (12, 13).

14. Guiding principles for assessing safety of herbal medicines
with reference to contaminants and residues
•1.Arsenic and toxic metals
•In general quantitative test & limit tests accurately
determine the concentrations of toxic metals in the
form of impurities & contaiminants.
•In general, if the heavy metals burden of the herbal
material is unknown, it is suggested that it has to be
determined qualitatively & quantitatively on several
batches.

15. 2.Determination of radioactive
contaiminants
•Due to severe nuclear accidents, the environment
may be contaminated with airborne radioactive
material. These may deposited on plants.
•Their concentration & type can be determined by
radiation monitoring laboratories of most of the
WHO member state.
•This can also be done by International Atomic
Energy Agency (IAEA).

16. Determination of Aflatoxins
•Aflatoxinsare poisonous carcinogens and mutagens that
are produced by certain molds (Aspergillusflavusand
Aspergillusparasiticus) which grow in soil, decaying
vegetation, hay, and grains.
•The member state adapt Good Practices for national
pharmaceutical control laboratories & GMP accordingly.
•Only products having history of aflatoxincontaimination
needs to be tested.

17. Determination of Microbiological contaminants
•Herbs and herbal materials normally carry a large number of
bacteria and moulds,oftenoriginating in soil or derived from
manure.
•Current practices of harvesting, production, transportation and
storage may cause additional contamination and microbial
growth.
•Microorganisms may result from failure to control the moisture
levels of herbal medicines during transportation and storage,as
well as from failure to control the temperatures of liquid forms
and finished herbal products. The presence of Escherichia coli,
Salmonella spp. and moulds may indicate poor quality of
production and harvesting practices.
•This should be controlled by implementing best practice
guidelines such as GACP and GMP.
•(Good agricultural and collection practices)