21.03.2014 |

LOGFILE No. 12/2013 - The Brazilian GMP Guideline

The Brazilian GMP Guideline

By Dr. Hans H. Schicht

National and international companies manufacturing pharmaceutical drugs, vaccines and related products in Brazil are, of course, subject to inspection by officials from ANVISA (Agência Nacional de Vigilância Sanitária, 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 products in Brazil. Such inspections are based on the Brazilian GMP guidelines the latest edition of which was published as Resolution 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 municipalities) is responsible. This was a novelty: earlier 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 Único de Saúde (SUS) which can be translated as Single Health System. It is one of the most extensive public health systems in the world: with SUS, the entire Brazilian population - 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 Farmácias 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, efficacy 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 suppliers was established; price reductions resulted 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 quality 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: GMP for pharmaceutical products:main principles - 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 bodies.

One important peculiarity deserves mention: Whereas WHO uses the term "should" for the individual determinations, in agreement with the general practice in the standardization and guidelines literature, the ANVISA guidelines give preference to "must" determinations.

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 differing from those in the WHO GMP guideline are addressed. This compilation is not complete but only focuses on a few topics. For more detailed information please find a 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 requirements are established regarding manufacturing medicinal products in Brazil and outside the country for the local market. Methods not addressed in RDC 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 authorities. Occupational health topics and environmental safety are, as a rule, not addressed; however, manufacturers must guarantee worker safety and take the necessary 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 chapters are identical. Regarding the subject matter presented in each chapter, it is, however, structured differently. The Brazilian 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 required.

One difference is regarding the "technically responsible person". This function is required by law for all industrial companies operating in Brazil. Its range of responsibilities 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 specification must be investigated and actions according to the CAPA procedure must be taken.

Title III: Sterile products

This Title follows very closely the corresponding WHO determinations and guidelines published in 2002. WHO has since substituted them with a new edition published in 2010. Two topics (isolator technology, blow/fill/seal technology) have been added in RDC 17/2010 to the original WHO text. These have been reproduced, 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 exceptions 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 electronic 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 presently in force. Determinations are established for herbal medicines only, combination products with those of animal or mineral origin are not addressed. An appropriate quality assurance system must be in place, prime materials require adequate control, and processes as well as methodologies must be validated. Herbal raw material derivatives containing genetically modified 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 which, on its part, is compatible with EU GMP guidelines, it offers sound GMP guidance without surprises.

References

[1] Ministério de Saúde, Agência Nacional de Vigilância Sanitária ANVISA, Resolução RDC No 17, de 16 de abril de 2010: Boas Práticas de Fabricação 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

 

 
 

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