Quality and equivalence of topical products: A critical appraisal

Miranda, Margarida; Cardoso, Catarina; Vitorino, Carla

doi:10.1016/j.ejps.2019.105082

Cited by 12 publications

(20 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As outlined in the draft guideline on the quality and equivalence of topical products, a patient-focused approach should be envisioned while developing a product [ 21 , 22 ]. Therefore, as previously mentioned, aspects such as patient acceptability, highly influenced by rheological attributes, should be primary concerns when developing a product.…”

Section: Introductionmentioning

confidence: 99%

“…EMA draft guideline proposes, as an alternative to clinical endpoint studies, a modular framework for equivalence demonstration in topical generic products. Accordingly, for a product to apply, extended pharmaceutical equivalence criteria must be fulfilled: (i) qualitative, quantitative and microstructure sameness (Q1, Q2, Q3, respectively) towards the reference product; (ii) product performance (Q4) mainly supported by in vitro release testing; and, finally, (iii) if the test product regards a complex dosage form, equivalence regarding the efficacy profile should be supported through in vitro permeation or dermatopharmacokinetic studies [ 22 , 23 ]. In this context, microstructure equivalence demonstration is a cornerstone for bioequivalence assessment of topical generic products.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

Simões

Miranda

Cardoso³

et al. 2020

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

The increasing demand for product and process understanding as an active pursuit in the quality guideline Q8 and, more recently, on the draft guideline on quality and equivalence of topical products, has unveiled the tremendous potential of rheology methods as a tool for microstructure characterization of topical semisolid dosage forms. Accordingly, procedure standardization is a dire need. This work aimed at developing and validating a methodology tutorial for rheology analysis. A 1% hydrocortisone cream was used as model cream formulation. Through a risk assessment analysis, the impact of selected critical method variables (geometry, temperature and application mode) was estimated in a broad range of rheological critical analytical attributes—zero-shear viscosity, upper-shear thinning viscosity, lower-shear thinning viscosity, infinite-shear viscosity, rotational yield point, thixotropic relative area, linear viscoelastic region, oscillatory yield point, storage modulus, loss modulus, and loss tangent. The proposed validation of the approach included the rheometer qualification, followed by the validation of numerous operational critical parameters regarding a rheology profile acquisition. The thixotropic relative area, oscillatory yield point, flow point and viscosity related endpoints proved to be highly sensitive and discriminatory parameters. This rationale provided a standard framework for the development of a reliable and robust rheology profile acquisition.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

Simões

Miranda

Cardoso³

et al. 2020

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since the excipients in the comparator product are listed in the patient information leaflet, establishing the Q1 sameness seems to be relatively simple. On the other hand, in order to achieve Q2 sameness, reverse engineering of the comparator product needs to be performed, applying appropriate and validated analytical methods [ 2 , 15 ]. However, due to patent pending or undesirable quality outcome, manufacturers of generic semisolid products are sometimes compelled to modify the formulation composition of the comparator product, and consequently, accomplishing the Q1/Q2 sameness could be a quite challenging task [ 15 , 17 ].…”

Section: Demonstration Of Extended Pharmaceutical Equivalence Of Topical Semisolid Drug Productsmentioning

confidence: 99%

“…On the other hand, in order to achieve Q2 sameness, reverse engineering of the comparator product needs to be performed, applying appropriate and validated analytical methods [ 2 , 15 ]. However, due to patent pending or undesirable quality outcome, manufacturers of generic semisolid products are sometimes compelled to modify the formulation composition of the comparator product, and consequently, accomplishing the Q1/Q2 sameness could be a quite challenging task [ 15 , 17 ]. Additionally, as stated in EMA draft guideline, not only formulation composition, but also, the grade of the excipients should be the same, due to its significant impact on the product quality and performance [ 15 , 18 , 19 ].…”

Section: Demonstration Of Extended Pharmaceutical Equivalence Of Topical Semisolid Drug Productsmentioning

confidence: 99%

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

2021

View full text Add to dashboard Cite

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches.

show abstract

“…The release profile provides useful information on the pharmaceutical performance characteristics of topical products, including nanotechnology-based formulations, since the API must be released before it becomes bioavailable in the skin. Moreover, from both scientific and regulatory perspectives, IVRT methods are responsive to product microstructure, making them a useful tool to assess product similarity [4,[39][40][41].…”

Section: Ivrtmentioning

confidence: 99%

Fast Screening Methods for the Analysis of Topical Drug Products

Miranda

Cardoso²,

Vitorino

2020

Processes

Self Cite

View full text Add to dashboard Cite

Considering the recent regulatory requirements, the overall importance of in vitro release testing (IVRT) methods regarding topical product development is undeniable, especially when addressing particulate systems. For each IVRT study, several hundreds of samples are generated. Therefore, developing rapid reversed-phase high-performance liquid chromatography (RP-HPLC) methods, able to provide a real-time drug analysis of IVRT samples, is a priority. In this study, eight topical complex drug products exhibiting distinct physicochemical profiles were considered. RP-HPLC methods were developed and fully validated. Chromatographic separations were achieved on a XBridgeTM C18 (5 µm particle size, 150 mm × 2.1 mm), or alternatively on a LiChrospher® 100 RP-18 (5 µm particle size, 125 mm × 4.6 mm) at 30 °C, under isocratic conditions using UV detection at specific wavelengths. According to the physicochemical characteristics of each drug, different mobile phases were selected. Irrespective of the drug (hydrocortisone, etofenamate, bifonazole, clotrimazole, acyclovir, tioconazole, clobetasol, and diclofenac) and formulation, retention time values did not exceed 6.5 min. All methods were linear, specific, precise, and accurate at the intraday and interday levels, robust, and stable. These were successfully applied to establish product-specific IVRT profiles, thus providing a key database useful for topical pharmaceutical manufacturers.

show abstract

Quality and equivalence of topical products: A critical appraisal

Cited by 12 publications

References 24 publications

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

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

Fast Screening Methods for the Analysis of Topical Drug Products

Contact Info

Product

Resources

About