Legislation
Resolution

Resolution - RE nº 481, of March 19, 2002
(Official Journal of 20/03/2002)

The Director of the Collegiate Board of Directors of the National Sanitary Surveillance Agency, in the use of the attributions vested in him under Administrative Rule 724, issued by the Director-Chairman, on October 10, 2000,

WHEREAS

paragraph 3 of article 111, of the Bylaws approved by Administrative Rule 593, of August 25, 2000, re-published in the Official Journal of the Union of December 22, 2000;
that the matter was submitted to the examination of the Collegiate Board of Directors, which approved the matter in a meeting held on March 13, 2002, decides:

Article 1 - To determine the publication of the "Guide for Exemption and Substitution of Bioequivalence Studies", attached.

Article 2 - This Resolution enters into force on the date of its publication.

GONZALO VECINA NETO

GUIDE FOR THE BIOEQUIVALENCE EXEMPTION AND STUDY SUBSTITUTION
1. THE FOLLOWING TYPES OF DRUG PRODUCTS ARE EXEMPT FROM THE BIOEQUIVALENCE STUDIES

1.2. drug products administered via parenteral route (intravenous, intramuscular, subcutaneous or intratecal), like the aqueous solutions containing the same drug , at the same concentration of the reference drug product and excipients of same function, with compatible concentration levels;

1.3. oral use solutions that contain the same drug , at the same of concentration of the reference drug product and that do not contain excipients that affect gastrointestinal motility or drug absorption;

1.4. powders for reconstitution that result in a solution that meets requirements (1.1) e (1.2);

1.5. gases;

1.6. otological and ophthalmic aqueous solutions containing the same drug , at the same concentration of the reference drug products and excipients of same function, with compatible concentration levels;

1.7. for topical use drug products, not meant for systemic effect, containing the same drug , at the same concentration of the reference drug product and excipients of the same function, with compatible concentration levels, meant for otological and ophthalmic use, presented in suspension form, the results of the pharmacodynamics studies supporting the therapeutic equivalence must be presented, but the pharmacodynamic study model must be previously approved by ANVISA;

1.8. inhalant drug products and nasal sprays assimilated with or without a device, presented in an aqueous solution and containing the same drug , at the same concentration of the reference drug product and excipients of same function, with compatible concentration levels;

1.9. oral use drug products whose drugs are not absorbed in the gastrointestinal tract.

2. CASES IN WHICH BIOEQUIVALENCE MAY BE SUBSTITUTED BY PHARMACEUTICAL EQUIVALENCE

2.1. in the case of immediate release generic drugs, with several dosages, same pharmaceutical characteristics and equivalent formulations, produced by the same manufacturer, at the same manufacturing site, the bioequivalence study must be undertaken with the highest dosage, the lower dosage ones being exempt from this study if the drug dissolution profiles, among all dosages, are comparable according to the GUIDE FOR DISSOLUTION TESTING OF ORAL SOLID IMMEDIATE RELEASE DOSAGE FORMS. If it is impossible to use the higher dosage in the bioequivalence study, this must be technically justified. This rule is applicable to the drugs that present linear pharmacodynamics in the therapeutic range;

2.2. drug products exempt from medical prescription, containing the drugs acetylsalicylic acid, paracetamol, dipyrone ou ibuprophen, in the solid dosage form, will be exempt from the bioequivalence study if the dissolution profile is comparable to the reference drug products, using the comparison criteria described in the GUIDE FOR DISSOLUTION TESTING OF ORAL SOLID IMMEDIATE RELEASE DOSAGE FORMS.

2.3. topical use drug products, with the exception of those foreseen in item 1.6, at the same level of concentration in relation to the reference drug product and excipients of same function, with compatible concentration levels.