An Update of the Brazilian Regulatory Bioequivalence Recommendations for Approval of Generic Topical Dermatological Drug Products

Soares, Kelen Carine Costa; Santos, Gustavo Mendes Lima; Gelfuso, Guilherme M.

doi:10.1208/s12248-015-9801-1

Cited by 5 publications

(5 citation statements)

References 2 publications

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“…23 Therefore, only in vitro studies are required for registration of all generic topical dermatologic drug products, including those containing corticosteroids. 18 Hence, the assumption that the entry of topical products in the Brazilian market is facilitated seems to be valid.…”

Section: Discussionmentioning

confidence: 99%

“…According to ANVISA Resolution RE n. 1170 (December 19, 2006), pharmacodynamic endpoints are not required for any topical dosage form, 22 while the FDA in the US may require comparative clinical trails or bioequivalence studies according to specific guidances, including bioequivalence studies with pharmacokinetic or pharmacodynamic endpoints, like the vasoconstrictor assay, also known as the human skin blanching assay, for the study of dermatologic corticosteroids. 18,21 Still, according to ANVISA Resolution RDC n. 37 (August 3, 2011), topical medicines, that is, those not intended for systemic effects, are granted a biowaiver if the generic product contains the same active ingredient, in the same concentration as that of the reference product (pharmaceutical equivalents), and the generic product contains excipients that have the same function as those of the reference formulation. 23 Therefore, only in vitro studies are required for registration of all generic topical dermatologic drug products, including those containing corticosteroids.…”

Section: Discussionmentioning

confidence: 99%

“…Comparing the registration requirements for generic topical dermatologic drug products of the Brazilian Health Surveillance Agency (ANVISA) and the FDA, for example, it can be seen that while the former requires only in vitro studies, the latter has specific guidances for bioequivalence. 18 Thus, a hasty analysis may lead to the conclusion that, as the entry of generic topical drug products in the Brazilian market are facilitated, more topical drug products will be available, fulfilling patients' demands and hampering innovation. Yet, after almost 20 years of the politic of generic drugs, as some studies show, innovation within Brazilian firms has increased, even though on a small scale, with more investments in internal R&D. 19,20 On the other hand, in the US, where the registration requirements of generic drug products are more strict, there is a general perception that there have been relatively fewer generics available for dermatologic use, affecting the population with lower purchasing power.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regulatory Requirements and Innovation: A Comparison of the Dermatologic Antifungal Drug Product Markets in Brazil and United States

Kollross¹,

Cunha-Filho

Gelfuso

2019

Ther Innov Regul Sci

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Background: Development of novel dermatological topical products for the treatment of cutaneous fungal infections is a constant necessity, especially in developing countries. Through public health policies, many developing countries have facilitated in the last decades the entry of generic products, which can be superficially seen as a threat to innovation. To verify whether regulatory requirements, or the waiving of some requirements, could have an impact on innovation, we performed a detailed technical comparison of the dermatologic antifungal markets of Brazil and of the United States, taking Brazil as an example of a developing country with more lenient requirements regarding the registration of generic topical drug products. Methods: The official databank of ANVISA (DATAVISA) and of US Food and Drug Administration (Orange Book) were assessed for valid topical dermatological antifungal drug products registered. Results: The Brazilian market has a greater number of registered drug products encompassing a greater variety of drug substances than the US, but the latter comprises more products with novel technologies. In both countries, cream was the predominant dosage form and imidazoles were the major substance group. Ketoconazole was the lead active substance in Brazil and ciclopirox was the lead drug in the US. Generic products dominated both markets. Conclusions: Despite the great number of registered products, the Brazilian market lacks the latest technologies, reflecting that the ease of generics registration is not accompanied by innovation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulatory Requirements and Innovation: A Comparison of the Dermatologic Antifungal Drug Product Markets in Brazil and United States

Kollross¹,

Cunha-Filho

Gelfuso

2019

Ther Innov Regul Sci

Self Cite

View full text Add to dashboard Cite

show abstract

“…Data content of quality, safety, and efficacy to be presented to ANVISA ( Table 2 ) are very similar to that required by Common Technical Documentation (CTD) established by ICH and World Health Organization [ 22 – 26 ]. Hence, ANVISA regulations are being developed in consonance with international regulatory authorities.…”

Section: Discussionmentioning

confidence: 99%

Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA)

Carmo

Piras²,

Rocha³

et al. 2017

BioMed Research International

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Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products.

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“…In 2003, Japan's National Institute of Health Sciences published a guideline that made provisions to include TS for BE studies of generic products for topical use (26). Other countries that accepted TS for BE assessment of topical products included South Africa (27) and Brazil (28) until recently when the European Medicines Agency (EMA) published a draft guideline on quality and equivalence of topical products in 2018 (29). More recently, a new FDA draft guidance has been published, whose objective is to facilitate the development and approval of generic products (30).…”

Section: Introductionmentioning

confidence: 99%

Application of a dermatopharmacokinetic (DPK) method for bioequivalence assessment of topical metronidazole creams

Rath¹,

Ramanah²,

Bon³

et al. 2020

J Pharm Pharm Sci

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Purpose: The main aim of the current research was to develop and apply a dermatopharmacokinetic (DPK) approach for the bioequivalence assessment of metronidazole (MTZ) topical cream products, indicated in the treatment of rosacea. Methods: A DPK methodology using tape stripping (TS) technique was developed by investigating the factors that may influence the TS results viz. tapes, dose durations, number of tapes to be used, pressure application, dose applied and gravimetric analysis of the tapes. An initial dose duration study was performed on 6 healthy participants to determine an appropriate application time duration using the Emax model. The SC thickness was normalised between participants using TEWL measurements. A pivotal study was conducted using both the arms of 10 healthy human participants to demonstrate the ability of the TS method for bioequivalence assessment by comparing the reference product to itself as a positive control and including products with higher and lower strengths of MTZ to serve as negative controls in order to confirm bioinequivalence. Results: Whereas the reference was found to be bioequivalent when compared to itself, the creams containing 0.56% and 0.95% MTZ (negative controls) were not bioequivalent (bioinequivalent). Furthermore, another product containing 0.75% MTZ was also assessed and was found to be bioequivalent to the reference product. In addition, the use of both forearms of each participant offered an important advantage of significantly reducing the number of human subjects required to demonstrate BE with a high statistical power of > 80%. Conclusion: The data obtained provides compelling evidence that the developed TS method has the potential to be a cost-effective surrogate alternative for lengthy and expensive clinical trials. Consequently, its application can facilitate faster development of generic products which would, in turn, lower the economic burden of healthcare.

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An Update of the Brazilian Regulatory Bioequivalence Recommendations for Approval of Generic Topical Dermatological Drug Products

Cited by 5 publications

References 2 publications

Regulatory Requirements and Innovation: A Comparison of the Dermatologic Antifungal Drug Product Markets in Brazil and United States

Regulatory Requirements and Innovation: A Comparison of the Dermatologic Antifungal Drug Product Markets in Brazil and United States

Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA)

Application of a dermatopharmacokinetic (DPK) method for bioequivalence assessment of topical metronidazole creams

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