Brazil experience with

regulation of herbal medicinal

products
Brazilian Health Surveillance Agency (ANVISA)
27 September 2007

Definitions
Medicinal plants Those capable of alleviating or curing
diseases, and have a tradicional use as a medicine within a
population or community.
Herbal drugs plants or plant parts that have
been conserved for storage by drying and
stabilization.
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.

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.

What is NOT considered Phytomedicines in Brazil?

Herbal powder
Plants

Tea

Isolated compounds

Homeopathy

Parts of plants

How are these products regulated?

Isolated compounds GPBEN, GEMES, GEMEG.
Plants, Plant parts GGALI.
Cosmetics GGCOS.
Teas GGALI
Law 5.991/73
Art. 7 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.

Who is allowed to manufacture Phytomedicines?

Pharmaceutical industry, public (official) or private laboratory,
with Sanitary Licence and Good Manufacturing Practice and
Quality Control (GMP Certificate).

An overview of Phytomedicine guidelines in Brazil

1967
Port. 22/67
SNFMF

1995
Port. 06/95
SVS

2000

2004

RDC 17/00
ANVISA

RDC 48/2004
ANVISA

Identity
Quality
Efficacy
Safety
Plant
associations

Tradition /History of use

Package inserts
Labeling

Simplified Register list

Literature on the product

Main guidelines on Phytomedicine registration:

RDC 48/04
Important 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.

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 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);
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

1. RE 89/04 - Simplified Register list

Scientific/Latin Name.............................. Hypericum perforatum L.
Common Name...................................... Hiprico
Parts of the plant ................................. Aerial part
Constituents with known therapeutic activity/Markers.................... hypericin
Herbal drug preparation........................ Extracts, tinctures
Uses......................................................... Light to moderate depressive states.
Daily Dosage ........................................... 0.9 2.7 mg of hypericin
Administration ........................................ Oral
Restrictions of use................................... Prescription only

1. RE 89/04 - Simplified Register list

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

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.

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.

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 mdicaments base de plantes. Paris: Agence du Medicament.
7- Monografias - contendo informaes etnofarmacolgicas, dados qumicos e
dados de estudos pr-clnicos e clnicos, realizadas por pesquisadores
credenciados pelo CNPq ou equivalente.

2. Bibliography on the product and the relevant

literature - RE 88/04
GRUPO III:
8 - Hacia una farmacopea caribea (TRAMIL 7).
9- Disposicin n. 2673. Ministerio de la Salud y Accin Social, Secretaria de
Poltica y Regulacin de Salud, ANMAT.
10- GARCIA, A.A. Vademecum de prescripcin-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. Farmcias vivas: sistema de utilizao de plantas medicinais
projetado para pequenas comunidades.
14- Gupta, M.P. 270 plantas medicinales iberoamericanas. 15 - ALONSO, J.R.
Tratado de fitomedicina-bases clnicas e farmacolgicas.
16- Simes, 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 basi
scientifiche per farmacisti e medici.

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);
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;

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

RDC 140/03 e
Port.110/97
(Package inserts)
RDC 333/03
(Labeling)

Law 6360/76

RE 88/04
Literature

RE 89/04
Simplified registration
RDC 48/04
(Registration)

RE 90/04
Pre-clinical studies

RE 01/05
(Stability)
RE 91/04
Post registration
RDC 138/03
GITE/prescription

RE 899/03
(Validation)

RDC 102/00
Advertising

 We do not have a complete list with the phytomedicines

registered in Brazil, due to the high dinamics of the process.
There are aproximately 400 phytomedicines registered, based
on aproximately 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 the RE 89/04.

Perspectives
Registration
auxilliaries;

of

herbal

medicinal

Elaboration of official monographies;

Standardization of package inserts;
Electronic registration.

teas

as

therapeutic

Thank you!

gmefh@anvisa.gov.br