Table 2.

Obligations of an application.

Area [6, 7]	Obligations [6, 7]	Comment
Administrative documentation	(i) Payment of health surveillance fee  (ii) GMP certification	The absence of fee payment, operating authorization, and GMP certification lead to marketing authorization refusal without substantive review [12]
	(iii) Operating authorization	A special operating authorization is necessary when controlled drugs are manipulated
	(iv) Sanitary permit
	(v) Petition forms
	(vi) Certificate of technical responsibility
	For imported drug products	For imported drug products, the absence of CPP and GMP certification causes marketing authorization refusal without substantive review [12]
	(i) Certificate of Pharmaceutical Product (CPP)
	(ii) GMP certification
	(iii) Importer quality control specifications
Production report	(i) Batch master record	Production report should be the standard one for production of either pilot or industrial batches
	(ii) Production process and equipment
	(iii) Industrial batch size
	(iv) Three pilot batches' record copies	Pilot batches records must have the same processes established on batch master record
Active pharmaceutical ingredient (API)	(i) Synthetic route	Describe starting material, solvents, and intermediates
	(ii) Analytical methods and specifications adopted	(i) Both API and drug product manufacturers have to present analytical method and specifications
		(ii) When a specific analytical method is not described in any official pharmacopeia accepted by ANVISA, it has to be validated [6, 7]
	(iii) API certificate of analysis	API certificate of analysis also has to be presented. Drug product manufacturer has to apply API certificates from the API batches used on drug product pilot batches [6, 7]
	(iv) Mainly impurities	Main impurities have to be monitored on quality control tests
	(v) Chirality data	Chiral forms may have different pharmacological effects. They are related to efficacy and safety of a drug product
	(vi) Polymorphism data	Polymorphism can affect solubility and dissolution rate of a drug product. It directly impacts bioavailability. API polymorphic forms have to be monitored until the expiration date, using proper analytical methods for physical characterization
	(vii) Stability and photostability studies	Stability studies must be performed in Brazilian climatic zone, IVb: 30°C ± 2°C; 75% ± 5%
Drug product quality control	(i) Analytical methods and specifications adopted	When a specific analytical method is not described in any official pharmacopeia accepted by ANVISA, it has to be validated [6, 7]
	(ii) Certificate of analysis of three pilot batches	(i) Methods must be specific. To prove specificity, forced degradation studies must be performed with the drug product
		(ii) Forced degradation studies are also important for prediction of possible compounds generated on stability studies, production process, and interaction between excipients and API
Drug product stability study	Stability study report from three pilot batches	(i) Stability indicating methods must be used to determine, with accuracy, the content of the drug product, degradation products, and other components, without any interfering species
		(ii) Methods must be validated
		(iii) Specification should be stablished according to drug product on analysis
Therapeutical equivalence	(i) Pharmaceutical equivalence	Pharmaceutical equivalence must compare drug product biobatch and reference drug product. Biobatch consists of the drug product batch used on bioequivalence studies
	(ii) Bioequivalence	Bioequivalence is an in vivo obligatory study which compares the bioavailability of a reference drug product and generic or similar drugs