brazilian regulatory affairs in herbal … f nascimento.pdfbrazilian regulatory affairs in herbal...

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


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


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


WhatWhat is is NOTNOT consideredconsidered PhytomedicinesPhytomedicines in in BrazilBrazil??

Tea

Herbal powder

Homeopathy

Plants

Parts of plantsIsolated compounds

Fonte: RDC 48/04


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.”


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?


Regulatory Process of Fitomedicines in Brazil


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


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!


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.


Main guidelines on Phytomedicines registration: RDC 48/04

Legal documents

Efficacy/safety Quality control


Legal documents

� Sanitary surveillance inspection fee;

� Sanitary Licence;

� Technical responsibility certificate issued by the Regional Pharmacy Council;

� GMP;


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.


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.


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ChromatographicProfile to 280 nm

Quality Control


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.


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;


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.


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


Other plants in the list:

Ginkgo biloba

Valeriana officinalis

Mykania glomerata

Aloe vera

Calendula officinalis

1. RE 89/04 - Simplified Register list


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.



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.



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.



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.


� 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);


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.


Other guidelines on Phytomedicines registration

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�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.


Perspectives

� Registration of herbal medicinal teas as therapeutic auxiliaries;

� Elaboration of official monographies;

� Standardization of package inserts;

� Electronic registration.


Thank you!

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