Legislation
Decree

Decree nº 3.675, of November 28, 2000
PUBLISHED ON NOVEMBER 29, 2000 IN THE D.O.U. (THE OFFICIAL JOURNAL OF THE UNION)

THE PRESIDENT OF THE REPUBLIC, by using his prerogatives which have been provided by the Constitution - item 84, sub-item 4, and having regard for the Law nr. 9,787, of February 10,1999,

DECREES:

Item 1. During a period of one year, starting at the date this decree is in force, the Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency) may grant special files for generic medicines, aiming at stimulating their adoption and utilization in the Country.
Sole sub-item. A special file will be effective for one year, starting at the date of the announcement of the product's file in the D.O.U.

Item 2. The special file will be granted only for products already filed as generic medicines for human use, by one of the following health authorities:
I - Food and Drug Administration (USA);
II - Health Canada - Therapeutic Products Directorate; or
III - The European Agency for the Evaluation of Medicinal Products.

Item 3. For the application of every generic medicine, it is mandatory to present the assays that support:
I - its pharmaceutical equivalence and bioequivalence versus the reference drug, produced locally by the reference manufacturer or by the licensee manufacturer; and
II - that the medicine has been utilized in the same dosage, shape, size, weight and consistent dissolution profile, in relation to the national reference drug.
Sole sub-item. When the reference medicine utilized in such assays is not the one produced by the local reference manufacturer, or by the licensee manufacturer, the generic medicine should be pharmaceutically equivalent to the national reference medicine, containing the same drug, with the same dosage and the same pharmaceutical form.

Item 4. A special file will be converted into file, since the generic medicine accomplishes the technical guidelines demanded by the Diretoria Colegiada da Agência Nacional de Vigilância Sanitária (Board of the National Health Surveillance Agency), as determined by the Law nr. 9,787, item 2, of February 10, 1999, or since the generic medicine has been submitted to the assays of pharmaceutical equivalence and bioequivalence versus the national reference medicine.

Item 5. The special file, which was granted under the terms of this Decree, will be canceled if:
I - forty five days after the date the official announcement of the product's file, the product is not yet available at the pharmacies all over the Country, or the product is not available in a quantity sufficient to supply the needs of the relevant population;
II - eight months after the date of the official announcement of the product's file, the necessary measures to produce the product locally have not yet been taken.

Item 6. The legal and the technical documentation that is required to apply for the special file are listed on the Annex form of this Decree.

Item 7. This Decree is to be in force on January 2, 2001.

Brasília, November 28, 2000; 179th of Independence and 112th of Republic.

FERNANDO HENRIQUE CARDOSO
José Serra

ANNEX

REQUIRED DOCUMENTS FOR THE SPECIAL FILE OF IMPORTED GENERIC MEDICINES.

I - Legal aspects

a) The Company which is Responsible for Importing
1. Payment receipt of file tariff (both, original and copy), duly authenticated;
2. Copy of the official document that enables the company to function, or the updated Health Certificate;
3. Copy of the company Functioning Permission, as published in the D.O.U.;
4. Certificate of Technical Responsibility delivered by the Conselho Regional de Farmácia (Regional Pharmacy Board); and
5. Certificate of Good Manufacturing Practices and Control, delivered by the Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency), when the importing company participates in any stage of the manufacturing process.

b) The Manufacturing Company
1. Certificate of Good Manufacturing Practices and Control (BPFC/GMP), delivered by the health authority of the country where the product was first filed: Canada (Health Canada Therapeutic Products Directorate), USA (FDA - Food and Drug Administration) or EMEA (The European Agency for the Evaluation of Medical Products);
2. File Certificate of Generic Medicine, delivered by one or more health authorities: Canada (Health Canada Therapeutic Products Directorate), USA (FDA - Food and Drug Administration) or EMEA (The European Agency for the Evaluation of Medical Products);
3. The above mentioned certificates in items a and b, must be presented accompanied by their officially authorized portuguese versions.

II - Technical Aspects
Forms FP1 and FP2

III - Technical Report
a) Manufacturing aspects
1. Complete formula of the medicine, regarding all presentations, and the role of each component;
2. If the product is to be packed in Brazil, the primary packing materials must be identified by their specifications, and compared with those materials utilized in the country where the product was manufactured, provided the studies on the stability tests for Zone IV.

b) Quality Control Aspects
1. Complete specification of the medicine, indicating the utilized monograph, regarding the post-marketing studies;
2. Analytical methods undertaken, indicating the utilized monograph, regarding the post-marketing studies;
3. Original certificate of the reference medicine, that has been utilized for the pharmaceutical equivalence and bioequivalence assays were carried out;
4. In addition to the certificate of the pharmaceutical equivalence, the applying company should present a comparative study on dissolution profile, versus the national reference medicine, by utilizing the factors 12 and 12, when the reference drug utilized in the assays is not produced by the reference manufacturer, or by the licensee manufacturer; likewise, if relevant, the in-vitro/in-vivo correlation assays should be presented, as well as the rationale to undertake them.

IV - Labeling and package insert aspects

The texts of labeling and package insert must comply with those of the national reference, and they should be in agreement with the law in force; the texts should be provided in diskette and in two printed copies written in portuguese.