BRAZILIAN REGULATORY AFFAIRS IN HERBAL MEDICINE

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Agência Nacional

de Vigilância Sanitária _{www.anvisa.gov.br}

BRAZILIAN REGULATORY

AFFAIRS IN HERBAL

MEDICINE

Alessandro Ferreira do Nascimento

Brazilian Health Surveillance Agency (ANVISA)

29 September 2007

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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

Medicinal plants –Those capable of alleviating

or curing diseases, and have a tradicional use as a medicine within a population or community.

Definitions

Herbal drugs – plants or plant parts that have

been conserved for storage by drying and stabilization.

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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.

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What

is

NOT

considered

Phytomedicines

in

Brazil

?

Tea Herbal powder Homeopathy Plants Parts of plants Isolated compounds

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How are these products regulated?

Isolated compounds

–

GPBEN, GEMES, GEMEG.

Plants, Plant parts

–

GGALI.

Cosmetics

–

GGCOS.

Teas

–

GGALI

Law 5.991/73

“

Art. 7

º “

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.

”

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Pharmaceutical industry, public (official) or private laboratory,

with Sanitary Licence and Good Manufacturing Practice and

Quality Control (GMP Certificate).

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Port. 22/67

SNFMF

Port. 06/95

SVS

RDC 17/00

ANVISA

RDC 48/2004

ANVISA

Identity Quality Efficacy Safety Plant associations

Tradition /History of use Simplified Register list Literature on the product

1967

1995

2000

2004

Package inserts Labeling

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Main guidelines on Phytomedicine registration: RDC

48/04

Important consideration related to the definition Important consideration related to the definition

Neither plants or plant parts are object of registration as phytomedicines.

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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.

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Main guidelines on Phytomedicines registration: RDC

48/04

Legal documents

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Legal documents

Sanitary surveillance inspection fee;

Sanitary Licence;

Technical responsibility certificate issued by the Regional

Pharmacy Council;

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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.

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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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Chromatographic Profile to 280 nm

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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.

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There are four ways to ensure

safety 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);

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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.

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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

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Other plants in the list: Ginkgo biloba Valeriana officinalis Mykania glomerata Aloe vera Calendula officinalis

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2. Bibliography on the product and the relevant

literature - RE 88/04

Reach 6 points to validate use safety and therapeutical indications;

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.

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2. Bibliography on the product and the relevant

literature - RE 88/04

GRUPO I:

1. Blumenthal, M. The complete german commission E monographs -Therapeutic guide to herbal medicines ou

Blumenthal, M.; Goldberg, A.; Brinckmann, J. Herbal medicine - Expanded commission E monographs.

2- WHO monographs on selected medicinal plants.

3- ESCOP-European Scientific Cooperative on Phytotherapy. Monographs on the medicinal uses of plant drugs.

4- American Herbal Pharmacopoea and Therapeutic Compendium – Monografias.

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2. Bibliography on the product and the relevant

literature - RE 88/04

GRUPO II:

5- Bradley, P.R. British herbal compendium - A handbook of scientific information on 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.

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2. Bibliography on the product and the relevant

literature - 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.

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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

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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.

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Other guidelines on Phytomedicines registration

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There are approximately 400 phytomedicines

registered, based on approximately 60 medical plants,

being 9 of them native.

Most registered products are based on the plants:

Ginkgo biloba, Aesculus hippocastanum, Panax

ginseng, Senna alexandrina, Peumus boldus, Cynara

scolymus, Passiflora incarnata, Valeriana officinalis

and Arnica montana. Such species are mentioned in

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Perspectives

Registration of herbal medicinal teas as therapeutic auxiliaries;

Elaboration of official monographies;

Standardization of package inserts;

Electronic registration.

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