WHOguidelinesforqualityassessmentofHerbaldrugs-R.pptx

Herbal Drug Technology

1. RRRRRRRRRRRRNJNBKMNLKGR WHO GUIDELINES IN QUALITY ASSESSMENT OF HERBAL DRUGS Dr Prasanth B HOD , Pharmacognosy St James’ College of Pharmaceutical Sciences, Chalakudy

2. 2 Content s: Introduction Objective Assessment of Quality Safety Efficacy Intended use Product information for the consumer Utilization of guidelines C onclusion

3. 3 Introdu c t i on: For the purpose of these guidelines “Herbal medicine” should be regarded as : Finished,labelled medicinal products that ,contain as active ingredient aerial or underground parts of plants, or other plant material or combinations there of, whether in the crude state or as plant preparations Plant material include juices, gums, fatty oils, essential oils and any other substances of this nature.Herbal medicines may contain excipients in addition to the active ingredients. Medicines containing plant material combined with chemically defined,isolated constituents of plants, are not considered to be herbal medicine.

4. Exceptionally, in some countries herbal medicines may also contain, by tradition, natural organic or inorganic active ingredients which are not of plant origin. The past decade has seen a significant increase in the use of herbal medicines . As a result of WHO’s promotion of traditional medicines , countries have been seeking the assistance of WHO in identifying safe and effective herbal medicines for use in national health care system. In both developed and developing countries, consumers and health care providers need to be supplied with up-to-date and authoritative information on the beneficial properties and possible harm full effects ,of all herbal medicines.

5. 5 Obje c tiv e : To define basic criteria for the evaluation of quality,safety and efficacy of herbal medicines and there by to assist national regulatory authorities,scientific organisations and manufacturers to under take an assessment of the documentation or submission in respect of such products. As a general rule in this assessment, traditional experience means long term use as well as the medical , historical and ethonological background of those products shall be taken.

6. 6 Assessment of Quality,Safety and Efficacy and Intended use : Pharmaceutical assessment: T his part should cover all important aspects of the quality assessment of herbal medicines.However,if a pharmacopoeia monograph exists it should be sufficient to make reference to this monograph. If no such monograph is avaliable, a mo n ograph must be supplied and should be set out in the same way as in an official pharmacopoeia. All procedures should be in accordance with Good Manufacturing Practices [GMP]. Crude plant material: The botanical definition,including genus,species and authority should be given to ensure correct identification of a plant.A definition and description of the part of the plant from which the medicine is made ( eg;leaf,flower,root ) has to be provided as well as an indication as to whether fresh, dried or traditionally processed material is used.

7. The active and characteristics constituents should be specified and if,possible , content limits should be defined. Foriegn matter,impurities and microbial content should be defined or limited. V oucher specimen,representing each lot of plant material processed,should be authenticated by a qualified botanist and should be store for at least a ten year period. A lot number should be assigned and this should appear on the product label.

8. WHO documents and publications relating to the quality assurance of herbal medicines with regard to safety should include the following steps: 1. Authentication (Stage of collection, parts of the plant collected, regional status, botanical identity like phytomorphology , microscopical and histological analysis, taxonomical identity, etc.) 2. Foreign matter (herbs collected should be free from soil, insect parts or animal excreta, etc.) 3. Organoleptic evaluation (sensory characters – taste, appearance, odor, feel of the drug, etc.) 4. Tissues of diagnostic importance present in the drug powder. 5. Ash values and extractive values. 6. Volatile matter 7. Moisture content determination

9. 8. Chromatographic and spectroscopic evaluation. TLC, HPTLC, HPLC methods will provide qualitative and semi quantitative information about the main active constituents present in the crude drug as chemical markers in the TLC fingerprint evaluation of herbals (FEH). The quality of the drug can also be assessed on the basis of the chromatographic fingerprint. 9. Determination of heavy metals – e.g. cadmium, lead, arsenic, etc. 10. Pesticide residue – WHO and FAO (Food and Agricultural Organization) set limits of pesticides, which are usually present in the herbs. These pesticides are mixed with the herbs during the time of cultivation. Mainly pesticides like DDT, BHC, toxaphene, aldrin cause serious side-effects in human beings if the crude drugs are mixed with these agents.

10. 11. Microbial contamination – usually medicinal plants containing bacteria and molds are coming from soil and atmosphere. Analysis of the limits of E. coli and molds clearly throws light towards the harvesting and production practices. The substance known as afflatoxins will produce serious side-effects if consumed along with the crude drugs. Afflatoxins should be completely removed or should not be present.

11. Microbial tests should be applied to starting plant materials, intermediate and fi nished products where necessary. Enterobacteria and certain other Gram-negative bacteria Escherichia coli, Salmonella and Staphylococcus aureus are included as target strains of the test. The conditions of the tests for microbial contamination are designed to minimize accidental contamination of the materials being examined and the precautions taken must not adversely affect any microorganisms that could be revealed.

12. 12. Radioactive contamination – Microbial growth in herbals are usually avoided by irradiation. This process may sterilize the plant material but the radioactivity hazard should be taken into account. The radioactivity of the plant samples should be checked accordingly to the guidelines of International Atomic Energy (IAE) in Vienna and that of WHO

13. The quality of the raw materials can be tested according to the following format: • Name of the drug (English, Regional names, Exact botanical nomenclature) • Part of the plant used • Area of collection • Distribution details • Season of Crop • Time and year of collection • Pesticide and insecticides • Condition of the drug (fresh or dry) • Form of the drug (powdered or intact or cuttings like etc.

14. In order to obtain quality oriented herbal products care should be taken right from the proper identification of plants; season and area of collection, extraction, isolation and verification process. Chemical and instrumental analyses are routinely used for analyzing synthetic drugs to confirm its authenticity

15. 15 Plant Preparations : Plant preparation should include powdered plant materials, extracts,tintures,fatty or essential oils,expressed juices and preparations whose production involves a fractionation, purification or concentration process.The manufacturing process should be described in detail.If any other substance is added during the manufacture,to adjust the plant preparation to a certain level of active or characteristic constituents or for any other purpose,the added substsnce should be mentioned in the procedure description. A method for identification, and where possible assay of plant preparation should be added.If the identification of an active principle is not possible,it should be sufficient to identify a characteristic substance or mixture of substances (eg;chromatographic fingerprint) to ensure consistent quality of preparation

16. 16 Finished products : However the scene is different especially for polyherbal formulation, as there is no chemical or analytical methods available. The herbal formulations in general can be standardized schematically as to formulate the medicament using raw materials collected from different localities and a comparative chemical efficacy of different batches of formulation are to be observed. The preparation with better clinical efficacy are to be selected. After all the routine physical, chemical and pharmacological parameters are to be checked for all the batches to select the final finished product and to validate the whole manufacturing process. The manufacturing procedure and formula including the amount of excipients should be described in detail.

17. A method of identification,and where possible quantification,of the plant material in the finished product should be defined. If the identification of an active principle is not possible,it should be sufficient to identify a characteristic substsance or mixture of substance ( eg,chromatographic fingerprinting) to ensure consistent quality of the product. For important finished produts, confirmation of regulatory status in the country of the origin should be required;the WHO certification scheme on the quality of the pharmaceutical products moving in International Commerce should be applied.

18. 18 Stability: The physicsal and chemical stability of the product in the final marketing container should be tested under defined storage conditions and the shelf-life should be established. Safety assessment: This part should cover all the relavent aspects of the safety assessment of a medicinal product has been traditionally used with out demonstrated harm and no specific restrictive regulatory action should be undertaken unless new evidence demands a revised risk-benefit assessment. Toxicological studies: If any toxicological studies are available, they should be part of the assessment .If a toxicological risk is known, toxicity data have to be submited.Risk assessment, whether it is independent of dose (eg,special danger allergies) ,or whether it is a function of dose should be documented.

19. 19 Assessment of Efficacy and Intended use: This part should cover all the important aspects of efficacy assessment. A review of the relavent literature should be carried out and copies provided of the original articles or proper references to them. Activity: The pharmocological and clinical effects of the active ingredients and,if known,their constituents with therapeutic activity shoud be specified or described. Evidence required to support indications: The indications for the use of medicine should be specified.In the case of traditional medicines,the requrements for proof of efficacy shall depend on the kind of indication.

20. 20 Combination products: As many herbal remedies consist of a combination of several active ingredients, and as experience on the use of traditional remedies is often based on he combination of products . In assessment there should be differentiation between old and new combinations products. Identical requrements for the assessment of old and new combinations would result in an appropriate assessment of certain traditional medicines. In the case of traditionally used combination products,the documentation of traditional use and experience may serve for documentation of efficacy. In ordeer to justify the efficacy of a new ingredient and its positive effect on the total combination,clinical studies may be reqired.

21. 21 Product Information for the Consumer: The labelling of the products and the package insert should be understandable to the consumer/patient. The package informstion should cover all necessary information on the proper use of product. The following elements of information usually suffice: Name of the product Quantitave list of active ingredient Dosage form Indications D osage (if appropriate,specified for children and the elderly) M ode of administration D uration of use M ajor adverse effects,if any O ver dosage information C ontraindication,warnings,precautions and major drug indications U se during pregnancy and lactation E xpiry date L ot number H older of the marketing authorisation

22. 22 Identification of the active ingredient by the latin botanical name,in addition to the common name in the language of preference of national regulatory authority is recommended. Promotion: Advertisements and other promotional activities to health personnel and the lay public should be fully consistent with the approved package information. Utilization of guidelines: WHO guidelines for the assessment of herbal medicines are intended to facilitate the work to a carried out by regulatory authority, scientific bodies and industry in the development , and assessment and registration of such products. The effective regulation and control of herbal medicines moving in international commerce also require close liaison with appropriate national institutions that are able to keep under regular review all aspects of their production and use , as well as to conduct or sponser evaluative studies of their efficacy,toxicity,safety,acceptability, cost and relative value compared with other drugs used in modern medicine.

23. 23 Conc l usion: All the Herbal based industries should meet specification and requirements of herbal drugs and formulations as per the WHO guidelines to attain the quality,safety and efficacy.

24. 24 References: GUIDELINES FOR THE ASSESSMENT OF HERBAL MEDICINES [Programme on traditional medicines WHO Geneva,1991]

25. 25 THANK YOU