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Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
BRAZILIAN REGULATORY AFFAIRS IN HERBAL
MEDICINE
Alessandro Ferreira do NascimentoBrazilian Health Surveillance Agency (ANVISA)
29 September 2007
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Herbal drug preparations – extracts, tinctures, fatty or essential oils or resins prepared from herbal drugs, and preparations whose production involves a fractionation, purification, or concentration process. It is characterized by reproducibility and quality constancy.
Medicinal plants –Those capable of alleviatingor curing diseases, and have a tradicional use as a medicine within a population or community.
Definitions
Herbal drugs – plants or plant parts that havebeen conserved for storage by drying andstabilization.
Fonte: RDC 48/04
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
PHYTOMEDICINES
� Phytomedicines are drugs obtained by using exclusively herbal drug derivatives as active ingredients, characterized by the knowledge of efficacy and risks of its use, as well as for its quality constancy.
� Phytomedicines are regulated in Brazil as conventional drugs. They have to meet similar quality, safety and efficacy criteria required by ANVISA for all drugs.
Fonte: RDC 48/04
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
WhatWhat is is NOTNOT consideredconsidered PhytomedicinesPhytomedicines in in BrazilBrazil??
Tea
Herbal powder
Homeopathy
Plants
Parts of plantsIsolated compounds
Fonte: RDC 48/04
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
How are these products regulated?
� Isolated compounds – GPBEN, GEMES, GEMEG.� Plants, Plant parts – GGALI.� Cosmetics– GGCOS.� Teas – GGALI
Law 5.991/73“Art. 7º “The dispensation of medicinal plants is private of the
drugstores and “ervanarias”, considering the appropriate packaging and the botanical classification.
XII - Ervanaria – establishment that accomplishes dispensation of medicinal plants.”
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Pharmaceutical industry, public (official) or private laboratory, with Sanitary Licence and Good Manufacturing Practice and Quality Control (GMP Certificate).
Who is allowed to manufacture Phytomedicines?
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Regulatory Process of Fitomedicines in Brazil
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Port. 22/67 SNFMF
Port. 06/95 SVS
RDC 17/00 ANVISA
RDC 48/2004 ANVISA
Identity
Quality
Efficacy
Safety
Plantassociations
Tradition /History of use
Simplified Register list
Literature on the product
1967 1995 2000 2004
Package insertsLabeling
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Main guidelines on Phytomedicine registration: RDC 48/04
Important consideration related to the definitionImportant consideration related to the definition
Neither plants or plant parts are object of registration as phytomedicines.We do not register herbal drugs as medicines!
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Main guideline on Phytomedicines registration: RDC 48/04
�These guidelines include medicines whose active ingredients are derived exclusively from herbal drugs (oil, extract, tincture).
� They refer to the entire process of controlling the quality of herbal drug, herbal drugs preparations, excipients and the manufacturing process.
�There are requirements for chemical standardization referring to the control of a particular marker compound or group of compounds.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Main guidelines on Phytomedicines registration: RDC 48/04
Legal documents
Efficacy/safety Quality control
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Legal documents
� Sanitary surveillance inspection fee;
� Sanitary Licence;
� Technical responsibility certificate issued by the Regional Pharmacy Council;
� GMP;
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Legal Documents
� Package insert;
� Labeling (primary and secondary packaging);
� Expiry date;
� Manufacturing formula;
� Detailed description of all stages in the manufacturing process;
� Control methodology during the manufacturing process.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Quality control
� Control of herbal drug and herbal drug preparation (Identification tests, purity tests, qualitative and quantitative analyses of constituents with known therapeutic activity and/or of markers or characteristic chemical compounds);
� Control tests on final product: analysis method and specifications. Qualitative and quantitative analyses based on phytochemical markers.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
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ChromatographicProfile to 280 nm
Quality Control
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Safety and efficacy
� Efficacy and safety can be validated through ethnopharmacological surveys, scientific publications or pre-clinic and clinic pharmacological studies.
� Safety must also be determined by tests that prove the identity of the plant and the absence of contaminants.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
There are four ways to ensuresafety and efficacy:
1. Simplified Register list (RE 89/04);2. Literature on the product and the relevant literature (RE 88/04);3. Report of therapeutic testing, drafted and submitted in
accordance with the sequence required by RE 90/04 (pre-clinical) and by the National Health Council (clinical trials);
4. Etnopharmacological data;
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
RE 89/04 1. Simplified Register list – 34 plants
� Scientific literature, including clinical trials;
� Safety and efficacy established;
� Acquired experience in the registration;
� It is not necessary to validate therapeutic indication and safety.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
1. RE 89/04 - Simplified Register list
Scientific/Latin Name .............................. Maytenus ilicifolia Mart. ex Reiss.
Common Name ...................................... Espinheira-Santa
Parts of the plant .................................... Leaves
Constituents with known therapeutic activity/Markers ................... Tannins
Herbal drug preparation ........................ Extracts, tinctures
Uses.................................................... Dyspepsia, gastric ulcers complementary treatment.
Daily Dosage............................................ 60 - 90 mg tannins
Administration......................................... Oral
Restrictions of use................................... OTC
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Other plants in the list:
Ginkgo biloba
Valeriana officinalis
Mykania glomerata
Aloe vera
Calendula officinalis
1. RE 89/04 - Simplified Register list
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
2. Bibliography on the product and the relevantliterature - RE 88/04
� Reach 6 points to validate use safety and therapeuticalindications;
� The therapeutic indications and dosage should be the same found in the literature;
� In the case of associations, the literature must refer to the final product and not to each component separately.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
2. Bibliography on the product and the relevantliterature - RE 88/04
GRUPO I:1. Blumenthal, M. The complete german commission E monographs -Therapeutic guide to herbal medicines ouBlumenthal, M.; Goldberg, A.; Brinckmann, J. Herbal medicine - Expandedcommission E monographs. 2- WHO monographs on selected medicinal plants. 3- ESCOP-European Scientific Cooperative on Phytotherapy. Monographs on themedicinal uses of plant drugs. 4- American Herbal Pharmacopoea and Therapeutic Compendium –Monografias.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
2. Bibliography on the product and the relevantliterature - RE 88/04
GRUPO II:5- Bradley, P.R. British herbal compendium - A handbook of scientific informationon widely used plant drugs.6. Les médicaments à base de plantes. Paris: Agence du Medicament. 7- Monografias - contendo informações etnofarmacológicas, dados químicos e dados de estudos pré-clínicos e clínicos, realizadas por pesquisadores credenciados pelo CNPq ou equivalente.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
2. Bibliography on the product and the relevantliterature - RE 88/04
GRUPO III:8 - Hacia una farmacopea caribeña (TRAMIL 7). 9- Disposición n.º 2673. Ministerio de la Salud y Acción Social, Secretaria de Política y Regulación de Salud, ANMAT. 10- GARCIA, A.A. Vademecum de prescripción-plantas medicinales. 11- Newall, C.A.; Anderson, L.A.; PhiLlipson, J.D. Herbal medicines-a guide for health-care professionals.12- PDR for herbal medicines. 13- Matos, F.J. Farmácias vivas: sistema de utilização de plantas medicinais projetado para pequenas comunidades. 14- Gupta, M.P. 270 plantas medicinales iberoamericanas. 15 - ALONSO, J.R. Tratado de fitomedicina-bases clínicas e farmacológicas.16- Simões, C.M.O.; Schenkel, E.P.; GOSMANN, G.; MELLO, J.C.P. de; Mentz, L.A.; Petrovick, P.R. Farmacognosia-da planta ao medicamento. 17- LOGGIA, R.D. Piante officinali per infusi e tisane-um manuale su basiscientifiche per farmacisti e medici.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
� Proof of safety use (pre-clinic and clinical toxicology) and of therapeutic effectiveness (pre-clinic and clinical pharmacology) of the phytomedicine.
� A standardized extract should be used;
3. Report of therapeutic testing, drafted and submitted in accordance with the sequence required by RE 90/04 (pre-clinical) and by the National Health
Council (clinical trials);
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
4. Ethnopharmacological data
� Evaluated in agreement with established criteria:- episodic indication of use or for short periods of time; - coherence regarding the proposed therapeutic indications; - absence of poisonous risk to the user; - absence of groups or poisonous chemical substances; - proofs of use for a period over 20 years.
�There is no registration under these criteria to the date.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Other guidelines on Phytomedicines registration
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Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
�There are approximately 400 phytomedicinesregistered, based on approximately 60 medical plants, being 9 of them native.
�Most registered products are based on the plants: Ginkgo biloba, Aesculus hippocastanum, Panaxginseng, Senna alexandrina, Peumus boldus, Cynarascolymus, Passiflora incarnata, Valeriana officinalisand Arnica montana. Such species are mentioned in the RE 89/04.
Agência Nacionalde Vigilância Sanitária www.anvisa.gov.br
Perspectives
� Registration of herbal medicinal teas as therapeutic auxiliaries;
� Elaboration of official monographies;
� Standardization of package inserts;
� Electronic registration.