Journal of Ethnopharmacology 66 (1999) 51 – 55

New rules for phytopharmaceutical drug registration in Brazil

P.R. Petrovick 1,a,*, L.C. Marques b, I.C. De Paula a

a
Laboratory of Galenical De6elopment, Graduate Course of Pharmaceutical Sciences, College of Pharmacy,
Rio Grande do Sul Uni6ersity, A6. Ipiranga 2752, 90610 -000, Porto Alegre, RS, Brazil
b
Department of Pharmacy, State Uni6ersity of Maringá, A6. Colombo 5790, Campus Uni6ersitário, 87020 -900, Maringá, PR, Brazil

Received 18 May 1998; received in revised form 29 June 1998; accepted 17 August 1998

Abstract

Although it is among the ten largest pharmaceutical markets in the world and has the most diverse flora, few efforts
have been made in Brazil in order to assure legal rules, which are able to provide phytotherapeutical products with
efficacy, safety and constant quality. Only in the last 3 years has the Ministry of Health convened an expert
commission to evaluate the existent legal requirements for such products and to provide modern and effective
legislation. The results of this work and the consequences of its implementation are discussed in this article. © 1999
Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Phytopharmaceutical; Legislation; Brazil

1. Introduction Such medicinal plants have, however, long been

Despite the rich Brazilian flora, which repre-
sents more than 20% of the plant species known
in the world, little has been done in Brazil to
study their potential as source of new drug
molecules or as raw materials for pharmaceutical
preparations.
* Corresponding author.
E-mail: prpetrov@farmacia.ufrgs.br
1
P.R. Petrovick and L.C. Marques are members of the
Expert Committee for Phytotherapeuticals, Federal Health
Agency, Ministry of Health, Brazil.
used in the treatment of various diseases and this
folk knowledge has been perpetuated along the
generations. The use of Brazilian medicinal plants
by the indigenous peoples was described by the
Portuguese discoverers in 1500. In the middle of
the XVI century, during the occupation of the
Brazilian Northeast by the Dutch, the physician
William Pies from the Occidental Indian Com-
pany, described the use of Ipecac, Jaborandi and
Tobacco (Gottlieb and Mors, 1979). After the
industrialisation era, the new-born original Brazil-
ian industry began the manufacture of phytother-

0378-8741/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.
PII: S0378-8741(98)00149-4
52 P.R. Petro6ick et al. / Journal of Ethnopharmacology 66 (1999) 51–55
apeuticals based on traditional information and
formulations, and reached its production apex in
the forties. This decade also saw the establish-
ment of the foreign chemical and pharmaceuti-
cal industry in the country. From this moment
on, synthetic drugs from international pharma-
ceutical laboratories have dominated the market.
Following the actual globalisation tendency,
Brazil has also sought for alternative drug
sources.
Nowadays, the Brazilian pharmaceutical in-
dustry has a U$9 billion market, and is, there-
fore, among the 10th largest in the world.
Around 30% of the marketed drugs registered
by the Federal Health Office are classified as
Phytopharmaceutical, representing 20 – 25% of
the local pharmaceutical market (Petrovick,
1996). In addition Brazil exports considerable
quantities of medicinal plants, extracts and iso-
lated substances, reaching the value of U$22
million per year (Sharapin, 1996).
Despite their importance, 70% of the phy-
topharmaceutical resources have not been suffi-
ciently studied, in order to provide the necessary
confirmation of their efficacy and safety, as ev-
ery medicine actually demands. For many years,
in fact, such products were marketed without
clear legal registration rules by the Brazilian
Government.
2. Historical background
The legal requirements for registration and
market authorisation of phytopharmaceuticals in
Brazil began with decree 19606 in 1931 (Bijos
and Pilar, 1964a,b), which stated that such
drugs were pharmacopoeial preparations, mainly
‘magistrally prepared drugs, easily processed’
and therefore, exempted from legal registration.
Later, in 1946, decree 20397 (Bijos and Pilar,
1964a,b) expanded their class, allowing the ex-
emption of products which demonstrated suffi-
cient similarity to those pharmacopoeial
phytopharmaceutical products. This shielded the
national industry from competitive international
pharmaceutical industries, which invested deeply
in technological development of new drugs and
products.
The thalidomide event, in the 1960s, resulted
in directive n. 22, published by the Federal
Health Office for Pharmacy and Medicine
(SNFMF) in 1967 (Brazil, 1967). This directive
maintained the pharmacopoeial drug classifica-
tion, mentioning them clearly in the document,
and advising the producers to annex copies of
the corresponding phamacopoeial monographs
to registration applications, so as to impart a
‘scientific’ quality to these products.
Law 6360, from 1976 (CFF, 1996), was ap-
plied for modern drug registration and evalua-
tion, but no mention was made of
phytopharmaceuticals, apart from the article
which made their exemption from registration
an official act. This was a terrible mistake since
from that moment on, pharmaceutical dosage
forms containing pharmacopoeial vegetable raw
material mixed with other substances were also
exempted from formal registration. Decree
79094 in 1977 regulated Law 6360 (CFF, 1996),
but made no mention of phytopharmaceuticals.
Directive n. 19 in 1981 (Brazil, 1981), published
by the Brazilian Drug Division (DIMED) of the
Federal Health Agency (SVS), created addition-
ally the expression ‘natural product’ to designate
those medicines prepared from plants. A misun-
derstanding of this expression resulted in im-
proper advertisement in the media, such as, that
natural products ‘are harmless to the health be-
cause they come from nature’. Only in 1991, as
a consequence of its prohibition in Germany,
was the plant Symphytum officinale, widely used
by the population for oral administration and
supported by TV-programs, banned from the
Brazilian market (Brazil, 1992).
It is interesting also to relate that two direc-
tives, n. 19 and 32 in 1986 (Brazil, 1986a,b),
published by the Federal Health Agency-SVS,
differentiated between plants used for nutritional
and therapeutic purposes. The first one would,
from that moment on, be registered by the
Food Division of the SVS, and could not con-
tain any therapeutic claims in the secondary
packaging, labels and insert.
 P.R. Petro6ick et al. / Journal of Ethnopharmacology 66 (1999) 51–55
3. Present situation
The Health Ministry, influenced by earlier
World Health Organisation directives from some
years before (WHO, 1991), in 1994 convened an
expert commission (Brazil, 1994) to evaluate the
phytopharmaceutical situation in the country. In
October 1994, the Commission presented directive
proposal n. 12,3 published by the SVS, to regulate
the phytopharmaceutical product registration.
The premises of this proposal had been based on
the German (Keller, 1991) and French (Artiges,
1991) regulations as well as the WHO directives,
and a determined period of time allowed the
organised society to present suggestions and com-
ments. The revised proposal was incorporated
into directive n. 6, issued by SVS in 1995 (Brazil,
1995), which finally established the legal require-
ments for the phytopharmaceutical drug registra-
tion in Brazil.
4. Directive n. 6
This directive tries to adapt the internationally
accepted concept of drugs to phytopharmaceutical
products, intending the modernisation and ade-
quacy of definitions and quality requirements.
4.1. Legal definitions
A phytopharmaceutical product is a processed
drug containing as active ingredients exclusively
plant material and/or vegetable drug prepara-
tions. Isolated active substances, whether of veg-
etable origin or not, cannot be added to such
preparations. They are intended to treat, cure,
alleviate, prevent and diagnose diseases, restoring,
correcting, influencing or modifying physiological
conditions in human beings. It is the final product
inside its labelled package. Pharmaceutical excipi-
ents, accepted by the SVS Division, can be used in
their preparation (Petrovick et al., 1997).
Vegetable raw material includes the fresh plant,
the vegetable drug or any elaborated preparation
thereof, used as an intermediate component in the
preparation of phytopharmaceutical products.
53
4.2. About manufacturing and marketing
The legal requirements demand complete docu-
mentation of efficacy, safety and constant defined
quality as a condition for the registration of phy-
topharmaceutical products.
4.3. Quality control guidelines
The directive specifies the quality characteristics
and some general assays for:
“ raw material, depending on whether it is a drug
or a preparation thereof (botanical and
physico-chemical identification, foreign materi-
als, microbial and chemical contamination, and
quantitative analysis, etc);
“ intermediate process products have to present a
complete pharmaceutical and analytical docu-
mentation, proving the maintenance and assur-
ance of their quality;
“ for finished products quality control data and
assessment methods are requested, as well as
efficacy and safety test results in humans, in
conformity with the guidelines of directive 116
published by SVS (Brazil, 1996). Scientific doc-
umentation from the literature may be submit-
ted, instead of controlled clinical trials or
animal tests, if they already exist for the pro-
posed preparation.
4.4. New and old phytopharmaceutical products
The legal code differs between new and old
products, giving the later ones 5 or 10 years for
the assessment of safety and efficacy, respectively.
5. Directive n. 116
In order to regulate pharmacological and toxi-
cological tests, directive 116 (Brazil, 1996) re-
quires detailed information about pre-clinical and
clinical test performances. This directive was elab-
orated with the support of the Brazilian Academy
of Sciences and was in conformity with the Brazil-
ian guidelines for biological testing of drugs
(Brazil, 1988), World Health Organisation guideli-
nes (WHO, 1993), EEC directives and the GCP-
Good Clinical Practice (WHO, 1992).
54 P.R. Petro6ick et al. / Journal of Ethnopharmacology 66 (1999) 51–55
6. Goals
According to the Brazilian legislators, the main
objectives of the new code to be attained by its
implementation, aim at:
“ the safe utilisation of phytopharmaceuticals by
the population, including them in the govern-
mental healthcare programs;
“ improvement of scientific skill in the pharma-
cological, toxicological, analytical and techno-
logical fields;
“ interaction between research centres, Universi-
ties and Industries, and;
“ development of new phytopharmaceutical
products.
7. Practical problems and consequences
As previously stated, the Brazilian pharmaceu-
tical industry changed little over the last four
decades. For this reason, their manufacturing pro-
cedures are still old fashioned, invoking requiring
large financial investments in order to install the
new rules of quality production. Consequently,
the Brazilian Government is facing great resis-
tance from these industries, and the hope lies in
recent agreements between the Federal Health
Office, the scientific society and industrial phar-
macists and Pharmaceutical Industry
Associations.
Another obstacle is the limited number of re-
search institutions and centres qualified to per-
form all the clinical trials and the extensive list of
plants, for which chemical, botanical, agronomi-
cal, pharmacological and toxicological studies are
required. The most disturbing problem is the inef-
fectiveness of Governmental Inspection Agencies.
The lack of a clear concept of ‘a long time used
product, without adverse reactions records’, as
appraised by the pharmaceutical industry to jus-
tify the safety of herbal drugs and products, and
of a nation-wide organised epidemiological system
are serious barriers to be also surmounted.
The new Brazilian legal code has awakened
other Latin American countries with respect to
the need for harmonisation of regional regulation
of phytopharmaceutical drugs, especially with re-
gard to the free trade union (MERCOSUL) be-
tween Brazil, Argentina, Paraguay and Uruguay
and the American free market area. The accep-
tance of such products by the members of the
European Union and their marketing authorisa-
tion in these countries (Artiges, 1991; Keller,
1991) depends on well documented minimal qual-
ity criteria, such as those established by WHO,
which are fulfilled by the new Brazilian
legislation.
Acknowledgements
The authors thank Dr Christine Gaillard for
critical comments and assistance in preparing the
manuscript.
References
Artiges, A., 1991. What are the legal requirements for the use
of phytopharmaceutical drugs in France? Journal of
Ethnopharmacology 32, 231 – 234.
Bijos, G.M., Pilar, O., 1964. Legislação Farmacêutica 1931 a
1964, Rio de Janeiro, São José, pp. 5 – 14.
Bijos, G.M., Pilar, O.@ 1964. Legislação Farmacêutica 1931 a
1964, Rio de Janeiro, São José, pp. 79 – 102.
Brazil, 1967. Portaria SNFMF n. 22 from 30.10.67, Diário
Oficial da União, 16. Nov. (Normative for the use of
phytotherapeutic preparations).
Brazil, 1981. Portaria DIMED n. 19 from 27.11.81., Diário
Oficial da União, 14. Dec. (Natural Product Preliminary
Approval).
Brazil, 1986. Portaria SNFMF n. 19 from 07.04.86. Diário
Oficial da União, 09. Apr. (Registration as food for herbs
and spices destined to the preparation of teas without
therapeutic indications).
Brazil, 1986. Portaria SNFMF n. 32 from 05.07.86. Diário,
Oficial da União, 11. Aug. (Distinguish herbs for dietary or
therapeutic purposes).
Brazil, 1988. Resolution n. 1 from 13.06.88, National Health
Council, Diário Oficial da União, 01. Jan., 1989. (Guideli-
nes for health research).
Brazil, 1992. Portaria SNVS n. 19 from 30.01.92. Diário
Oficial da União, 03. Feb. (Forbid the use of Symphytum
officinale L. for internal use).
Brazil, 1994 Portaria n. 31 from 04.04.94 Diário Oficial da
União, 08. Apr. (Constitution of the Expert Committee for
Phytopharmaceutic Products).
Brazil, 1995. Portaria SVS n. 6 from 31.01.95. Diário Oficial
da República Federativa do Brasil,. 06. Jan. (Normative
for the registration of phytotherapeutic products).
 P.R. Petro6ick et al. / Journal of Ethnopharmacology 66 (1999) 51–55
Brazil, 1996. Portaria SVS n. 116 from 08.08.96. Diário Oficial
da República Federativa do Brasil, 14. Aug. (Proposal for
toxicity and efficacy assessment from phytotherpic prod-
ucts).
CFF, 1996, Conselho Federal de Farmácia. A organização
jurı́dica da Profissão Farmacêutica (coletânea), Brası́lia-
DF.
Gottlieb, O.R., Mors, W.B., 1979. Planzenprophylaxe aus dem
Tropenwald Brasiliens. Unesco Kurier 20 (7), 35–36.
Keller, K., 1991. Legal Requirements for the use of phy-
topharmaceutical drugs in the Federal Republic of Ger-
many. Journal of Ethnopharmacology 32, 225–229.
Petrovick, P.R., 1996. Normatização da Indústria Fitofarma-
cêutica. In: 1a Reunión de Coordinación Internacional.
Programa Iberoamericano de Ciencia y Tecnologı́a para el
Desarrollo (CYTED). Red Iberoamericana de Productos
Fitofarmacéuticos (RIPROFITO), Sep. 28–Oct. 01, An-
tigua-Guatemala, pp. 91–93.
55
Petrovick, P.R., González Ortega, G., Bassani, V.L., 1997.
From a medicinal plant to a pharmaceutical dosage form.
A (still) long way for the Brazilian medicinal plants. Ciên-
cia e Cultura 49 (5/6), 364 – 369.
Sharapin, N., 1996. Normatização da Indústria Fitofarmacêu-
tica. In: 1a Reunión de Coordinación Internacional. Pro-
grama Iberoamericano de Ciencia y Tecnologı́a para el
Desarrollo (CYTED). Red Iberoamericana de Productos
Fitofarmacéuticos (RIPROFITO), 28 sep – 01 oct., An-
tigua-Guatemala, p.42 – 44.
WHO, 1991. Guidelines for the Assessment of Herbal
Medicines, World Health Organisation, Geneva.
WHO, 1992. Guidelines for Good Clinical Practice (GCP) for
trials on Pharmaceutical Products, World Health Organi-
sation Drug Information 6 (4), 170 – 188.
WHO, 1993. Regional Office for the Western Pacific, Research
Guidelines for Evaluating the Safety and Efficacy of
Herbal Medicines, World Health Organisation, Manila.