1. LOGFILE No. 12 / May 2013 Maas & Peither AG GMP Publishing http://www.gmp-publishing.com/ 2013 Maas & Peither AG GMP Publishing, Germany, all rights reserved Page 1/3 The Brazilian GMP Guideline By Dr. Hans H. Schicht National and international companies man- ufacturing pharmaceutical drugs, vaccines and related products in Brazil are, of course, subject to inspection by officials from ANVI- SA (Agncia Nacional de Vigilncia Sanitria, the National Health Surveillance Agency). In recent years, ANVISA inspectors have, in increasing scale, also been encountered outside of Brazil, focussing their efforts on enterprises marketing pharmaceutical prod- ucts in Brazil. Such inspections are based on the Brazilian GMP guidelines the latest edition of which was published as Resolu- tion Anvisa RDC No 17 dated 16 April 2010 in Portuguese [1]. Since then, an official English translation has also been published by ANVISA [2]. Point of departure for GMP in Brazil The newly elaborated Brazilian Federal Constitution of 1988 determined health to be a public right for which government on all levels (federation, states, and municipali- ties) is responsible. This was a novelty: earli- er on, only persons formally contracted by an employer plus their direct dependents as well as pensioners with accumulated 30 years of formally contracted employment had access to the public health system. Legislation established, in 1990, the Sistema nico de Sade (SUS) which can be translat- ed as Single Health System. It is one of the most extensive public health systems in the world: with SUS, the entire Brazilian popula- tion - now passing the level of 200 million - obtained access to the public health system, i.e. to medical treatment, health stations and hospitals, laboratory services, blood centers, as well as to preventive actions such as vaccination campaigns - all free of charge. A special system of pharmacies was created in this context, the Farmcias Populares, serving exclusively people with low income. They offer a basic selection of essential medicines, with focus on generics, either free of charge or at low cost. Presently, most drug stores in Brazil are affiliated to this system and operate a specific sector for providing this service. With the introduction of SUS, the Brazilian government became the biggest purchaser of medicines in the country. In order to assure security, efficiency and quality of the medicines sold through the SUS system as well as through all the other pharmacies, the implementation of GMP principles became inevitable. Introducing GMP had a most welcome side effect: all suppliers were required to meet uniform quality standards with the consequence that a fair point of departure for competition between suppli- ers was established; price reductions result- ed as a consequence. Introducing GMP to Brazil Brazil is a member of the World Health Organization (WHO). As such, it is obliged to incorporate the WHO pharmaceutical quali- ty assurance guidance into its national health legislation system without major deviations. The first Brazilian GMP guideline was published in 1995. The present edition, RDC no. 17/2010, is derived from the 2003 edition of the basic WHO GMP guide: Main principles for pharmaceutical products - Quality management in the drug industry: philosophy and essential elements. Some segments of RDC 17/2010, however, are based upon more recent WHO guidances, or upon guidance from other regulatory bod- ies. One important peculiarity deserves mention: Whereas WHO uses the term "should" for the individual determinations, in agreement with the general practice in the standardiza- tion and guidelines literature, the ANVISA guidelines give preference to "must" de- terminations. GMP guidelines on related topics have also been published by ANVISA, e.g. for active pharmaceutical ingredients and for the preparation of individual prescriptions in healthcare pharmacies. In the following, only determinations differ- ing from those in the WHO GMP guideline are addressed. This compilation is not com- plete but only focuses on a few topics. For more detailed information please find a

2. LOGFILE No. 12 / May 2013 Maas & Peither AG GMP Publishing http://www.gmp-publishing.com/ 2013 Maas & Peither AG GMP Publishing, Germany, all rights reserved Page 2/3 comprehensive version of the article along with the Brazilian GMPs in our next Update for the GMP MANUAL. A brief summary Title I: Initial provisions This chapter defines the scope and purpose of RDC 17/2010. Minimum GMP require- ments are established regarding manufac- turing medicinal products in Brazil and outside the country for the local market. Methods not addressed in BPC 17/2010 resulting from technical progress or the specific requirements of given products are permitted to be adopted, provided they are validated and do not prejudice the quality of the product. Medicinal products are subject to registration and may be produced only by manufacturers duly licensed and authorized; these companies are regularly inspected by the responsible national au- thorities. Occupational health topics and environmental safety are, as a rule, not addressed; however, manufacturers must guarantee worker safety and take the nec- essary steps for environmental protection. Title II: Quality management This Title follows closely the corresponding general WHO GMP guideline: the structure and its subdivision into a total of 17 chap- ters are identical. Regarding the subject matter presented in each chapter, it is, however, structured differently. The Brazili- an guideline is written in the style of the legal document which it is: each Article focusses on a single determination which can be numerically referred to in inspection reports and subsequently enforced if re- quired. One difference is regarding the "technically responsible person". This function is re- quired by law for all industrial companies operating in Brazil. Its range of responsibili- ties goes beyond that of the "authorized person" in the WHO and the "qualified person" in the EU GMP guidance. Title II requires complaints regarding falsified products and stolen cargo to be notified to the responsible health authorities. Starting and intermediate materials out of specifica- tion must be investigated and actions ac- cording to the CAPA procedure must be taken. Title III: Sterile products This Title follows very closely the corre- sponding WHO determinations published in 2002. WHO has since substituted them with a new edition published in 2010. Two topics (isolator technology, blow/fill/seal technolo- gy) have been added in RDC 17/2010 to the original WHO text. These have been repro- duced, without any change, from the 2008 edition of Annex 1 to the EU GMP guide. Regarding terminally sterilized products, RDC 17/2010 is stricter than WHO: high risk operations must be performed in grade C conditions. Garments of persons working in grade A/B areas must be changed after each work session. Contrary to WHO, no excep- tions are foreseen. Title VII: Computer information systems The original EU GMP guidance established in Annex 11 has served as base for this Title. The concepts of risk management and elec- tronic signatures are not addressed. For the validation of computerized systems, an exhaustive guide has been prepared by ANVISA in co-operation with professionals from the Brazilian Chapter of ISPE - the International Society of Pharmaceutical Engineers. Title VIII: Herbal medicines This Title is based upon the corresponding WHO guidance published in 2006 and pres- ently in force. Determinations are estab- lished for herbal medicines only, combina- tion products with those of animal or min- eral origin are not addressed. An appropri- ate quality assurance system must be in place, prime materials require adequate control, and processes as well as methodol- ogies must be validated. Herbal raw materi- al derivatives containing genetically modi- fied organisms must comply with the specific standards in force. Conclusion The Brazilian GMP guideline RDC 17/2010 for medicinal products comprises not only the generally applicable GMP stipulations, but also covers a number of additional topics such as sterile, biological and herbal products, water for pharmaceutical use as well as qualification and validation. Based upon corresponding WHO GMP guidance 3. LOGFILE No. 12 / May 2013 Maas & Peither AG GMP Publishing http://www.gmp-publishing.com/ 2013 Maas & Peither AG GMP Publishing, Germany, all rights reserved Page 3/3 which, on its part, is compatible with EU GMP guidelines, it offers sound GMP guid- ance without surprises. References [1] Ministrio de Sade, Agncia Nacional de Vigilncia Sanitria ANVISA, Resoluo RDC No 17, de 16 de abril de 2010: Boas Prticas de Fabricao de medicamentos (Ministry of Health, National Health Surveillance Agency, Resolution RDC No 17 of 16.04.2010: Good practices of manufacturing medicinal products). [2] ANVISA Resolution RDC No 17 of 16.04.10: Good practices of medicament manufacturing (offizielle englischsprachige Ausgabe). Author: Dr. Hans H. Schicht Contamination Control Consulting Langwisstrasse 5 8126 Zumikon Switzerland GMP MANUAL Online Good Manufacturing Practice & Implementation GMP in Practice: written by internationally renowned industry experts. GMP Regulations: the most important GMP regulations. Your benefits full text search copy and paste function print options For a free 14 days trial contact: Ms Annette Crawford annette.crawford@gmp-publishing.com