Old active ingredients in new medicinal products: is the regulatory path coherent with patients’ expectations?

Abstract

The knowledge of the different regulatory pathways for marketing authorization can be useful to set up the most appropriate strategies to rationalize the medicament development and to assure the economic sustainability for payers.

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

“…Drug concentration in the receptor medium should not exceed 30% of its maximum solubility in the receptor medium [14] Linearity, precision and reproducibility The R 2 value of the in vitro release rate (IVRR) (slope) should be calculated across the sampling times throughout the IVRT study duration, for three IVRT runs with a set of six [44] or 12 [12] diffusion cells on 3 different days. Precision and reproducibility should be assessed from intra-/inter-run data analysis.…”

“…The information on qualitative/quantitative composition and microstructure of the semisolid products being compared represents the basis for rational selection of relevant in vitro/in vivo product performance measures for the determination of bioequivalence [ 5 , 9 , 10 , 11 ]. As a result, within the last few years, both European and American regulatory authorities have been advancing regulation relevant to topical generic products, accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment [ 12 ]. From 2012, U.S. Food and Drug Administration (FDA) has continuously published non-binding, product-specific guidelines for generic product development, to identify the appropriate methodology for developing drugs and generating evidence needed to support abbreviated new drug application (ANDA) approval [ 13 ].…”

Design and development of topical liposomal formulations in a regulatory perspective

“…Based on their intrinsic features of the formulation and the absorption route, the topically applied liposomal products are classifiable as non-biological complex drugs [ 20 ]. As other complex formulations, small changes in the critical quality attributes (CQA) have a substantial impact on the performance of in vivo and, therefore, an in-depth evaluation should be mandatory for driving the pharmaceutical development based on the target product profile (TPP) of the finished product [ 22 ]. Thus, as above mentioned, deep characterization of chemical features of excipients and their possible interactions with the drug is required for quality purposes in the definition of formulation space which can be rationalized with the help of Quality-by-Design (QbD) [ 29 , 30 ].…”

“…Secondly, their technological peculiarities led the regulatory authorities to consider them as non-biological complex drugs and to put in place specific and more stringent guidelines for assessing their benefit/risk balance [ 21 ]. Finally, when major post-marketing variations are required, the complexity of the formulation and the topical application limit the adoption of bioequivalence studies to assess the clinical equivalence of two products, requiring more expensive clinical trials [ 22 ].…”

How Do Hospital Pharmacists Approach Substitution of Nanomedicines? Insights from a Qualitative Pilot Study and a Quantitative Market Research Analysis in Five European Countries

“…The hybrid pathway is designed for follow-on medicinal products for which the strict definition of a “generic” is not met, i.e., bioequivalence cannot be shown, or the product differs from the reference product in its pharmaceutical formulation, indication, strength or administration route [ 14 ]. Hybrid medicines are those whose authorization depends both on the original data for the reference product and on new clinical trial data for the follow-on product [ 11 , 13 ].…”