BRAZILIAN REGULATORY AFFAIRS IN HERBAL MEDICINE

Transcrição

1 BRAZILIAN REGULATORY AFFAIRS IN HERBAL MEDICINE Alessandro Ferreira do Nascimento Brazilian Health Surveillance Agency (ANVISA) 29 September 2007

2 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. Fonte: RDC 48/04

3 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

4 What is NOT considered Phytomedicines in Brazil? Tea Herbal powder Plants Isolated compounds Homeopathy Parts of plants Fonte: RDC 48/04

5 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.

6 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).

7 Regulatory Process of Fitomedicines in Brazil

8 Port. 22/67 SNFMF Port. 06/95 SVS RDC 17/00 ANVISA RDC 48/2004 ANVISA Identity Quality Efficacy Safety Plant associations Package inserts Labeling Tradition /History of use Simplified Register list Literature on the product

9 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!

10 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.

11 Main guidelines on Phytomedicines registration: RDC 48/04 Legal documents Efficacy/safety Quality control

12 Legal documents Sanitary surveillance inspection fee; Sanitary Licence; Technical responsibility certificate issued by the Regional Pharmacy Council; GMP;

13 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.

14 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.

15 Quality Control Chromatographic Profile to 280 nm

16 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.

17 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;

18 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.

19 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 mg tannins Administration... Oral Restrictions of use... OTC

20 1. RE 89/04 - Simplified Register list Other plants in the list: Ginkgo biloba Valeriana officinalis Mykania glomerata Aloe vera Calendula officinalis

21 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.

22 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.

23 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.

24 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 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 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 basi scientifiche per farmacisti e medici.

25 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;

26 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.

27 Other guidelines on Phytomedicines registration! " # $"% -./(( & $'() * +,

28 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 the RE 89/04.

29 Perspectives Registration of herbal medicinal teas as therapeutic auxiliaries; Elaboration of official monographies; Standardization of package inserts; Electronic registration.

30 Thank you!