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This article describes regulatory approaches for approval of 'generic' orally inhaled drug products (OIDPs) in the United States, European Union, Brazil, China and India. While registration of a generic OIDP in any given market may require some documentation of the formulation and device similarity to the 'original' product as well as comparative testing of in vitro characteristics and in vivo performance, the specific documentation approaches, tests and acceptance criteria vary by the country. This divergence is due to several factors, including unique cultural, historical, legal and economic circumstances of each region; the diverse healthcare and regulatory systems; the different definitions of key terms such as 'generic' and 'reference' drug; the acknowledged absence of in vitro in vivo correlations for OIDPs; and the scientific and statistical issues related to OIDP testing (such as how best to account for the batch-to-batch variability of the Reference product, whether to use average bioequivalence or population bioequivalence in the statistical analysis of results, whether to use healthy volunteers or patients for pharmacokinetic studies, and which pharmacodynamic or clinical end-points should be used). As a result of this discrepancy, there are ample opportunities for the regulatory and scientific communities around the world to collaborate in developing more consistent, better aligned, science-based approaches. Moving in that direction will require both further research and further open discussion of the pros and cons of various approaches. [ABSTRACT FROM AUTHOR]

The presentations at the Orlando Inhalation Conference on pharmacokinetic (PK) studies indicated that PK is the most sensitive methodology for detecting formulation differences of oral inhaled drug products (OIDPs) that have negligible gastrointestinal bioavailability or for which oral absorption can be prevented (e.g., ingestion of charcoal). PK studies, therefore, may represent the most appropriate methodology for assessing local and systemic bioequivalence (BE). It was believed by many (but not all participants) that potential differences between formulations are more likely to be detected in healthy adult volunteers, as variability is reduced while deposition to peripheral areas is not restricted. A study design allowing assessment and statistical consideration of intra-subject and inter-batch variability within the evaluation of BE studies was suggested, while optimal inhalation technique during PK studies should be enforced to decrease variability. Depending on the drug and in vitro method, in vitro tests may not detect differences in PK parameters. Harmonization of BE testing requirements among different countries should be encouraged to improve global availability of low cost OIDPs and decrease industry burden. [ABSTRACT FROM AUTHOR]

This note aims to clarify the Brazilian regulatory bioequivalence recommendations for approval of generic topical dermatological drug products, since the legal framework of the 'Brazilian Health Surveillance Agency' (ANVISA) is only available in Portuguese. According to Resolutions RE n. 1170 (December 19th 2006) and RDC n. 37 (August 3rd 2011) in Brazil, only in vitro studies are required for registration of generic topical dermatological drug products. Current Regulatory Agenda of ANVISA, which contains possible future resolutions to be revised over 2015-2016, includes a discussion on biowaiver requirements and on possible in vitro and in vivo comparability tests for these products. [ABSTRACT FROM AUTHOR]