References of "Lebrun, Pierre"
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See detailValidation des méthodes analytiques: Approche basée sur l'erreur totale
Ziemons, Eric ULg; Hubert, Cédric ULg; Marini Djang'Eing'A, Roland ULg et al

Scientific conference (2015, May 12)

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See detailDesign Space for Analytical Methods: Why ? What ? How ?
Rozet, Eric ULg; Debrus, Benjamin ULg; Lebrun, Pierre ULg et al

Conference (2015, January 22)

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See detailFighting Poor Quality Medicines: Develop-ment, Transfer and Validation of Generic HPLC Methods for Analyzing two WHO Recommended Antimalarial Tablets
Mbinze Kindenge, Jérémie; Yemoa, Achille; Lebrun, Pierre ULg et al

in American Journal of Analytical Chemistry (2015), 6

As serious but neglected public health problems, poor quality medicines, i.e. for antimalarial medicines, urged to be fought. One of the approaches is to consider the analytical chemistry and separative ... [more ▼]

As serious but neglected public health problems, poor quality medicines, i.e. for antimalarial medicines, urged to be fought. One of the approaches is to consider the analytical chemistry and separative techniques. In this study, a generic liquid chromatographic method was firstly devel-oped for the purpose of screening 8 antimalarial active ingredients, namely amodiaquine (AQ), piperaquine (PPQ), sulfalene (SL), pyrimethamine (PM), lumefantrine (LF), artesunate (AS), artemether (AM) and dihydroartemisinine (DHA) by applying DoE/DS optimization strategy. Since the method was not totally satisfying in terms of peak separation, further experiments were undergone applying the same development strategy while splitting the 8 ingredients into five groups. Excellent prediction was observed prior to correlation between retention times of predicted and observed separation conditions. Then, a successful geometric transfer was realized to reduce the analysis time focusing on the simultaneous quantification of two WHO's recommended ACTs in anti-malarial fixed-dose combination (AM-LF and AS-AQ) in tablets. The optimal separation was achieved using an isocratic elution of methanol-ammonium formate buffer (pH 2.8; 10mM) (82.5: 17.5, v/v) at 0.6ml/min through a C18 column (100mm×3.5mm, 3.5 μm) thermostated at 25°C. After a successful validation stage based on the total error approach, the method was applied to determine the content of AM/LF or AS/AQ in seven brands of antimalarial tablets currently marketed in West, Central and East Africa. Satisfying results were obtained compared to the claimed contents. [less ▲]

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See detailTowards a full integration of optimization and validation phases: An Analytical-Quality-by-Design approach
Hubert, Cédric ULg; Houari, Sabah ULg; Rozet, Eric ULg et al

in Journal of Chromatography. A (2015)

When using an analytical method, defining an Analytical Target Profile (ATP) focused on quantitative performance represents a key input, and this will drive the method development process. In this context ... [more ▼]

When using an analytical method, defining an Analytical Target Profile (ATP) focused on quantitative performance represents a key input, and this will drive the method development process. In this context, two case studies were selected in order to demonstrate the potential of a Quality-by-Design (QbD) strategy when applied to two specific phases of the method lifecycle: the pre-validation study and the validation step. The first case study focused on the improvement of a Liquid Chromatography (LC) coupled to Mass Spectrometry (MS) stability-indicating method by the means of the QbD concept. The Design of Experiments (DoE) conducted during the optimization step (i.e. determination of the qualitative Design Space (DS)) was performed a posteriori. Additional experiments were performed in order to simultaneously conduct the pre-validation study to assist in defining the DoE to be conducted during the formal validation step. This predicted protocol was compared to the one used during the formal validation. A second case study based on the LC/MS-MS determination of glucosamine and galactosamine in human plasma was considered in order to illustrate an innovative strategy allowing the QbD methodology to be incorporated during the validation phase. An operational space, defined by the qualitative DS, was considered during the validation process rather than a specific set of working conditions as conventionally performed. Results of all the validation parameters conventionally studied were compared to those obtained with this innovative approach for glucosamine and galactosamine. Using this strategy, qualitative and quantitative information were obtained. Consequently, an analyst using this approach would be able to select with great confidence several working conditions within the operational space rather than a given condition for the routine use of the method. This innovative strategy combines both a learning process and a thorough assessment of the risk involved. [less ▲]

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See detailA quality by design approach for longitudinal quality attributes
Lebrun, Pierre ULg; Giacoletti, Katherine; Scherder, Tara et al

in Journal of Biopharmaceutical Statistics (2015), 25

The concept of quality by design (QbD) as published in ICH-Q8 is currently one of the most recurrent topics in the pharmaceutical literature. This guideline recommends the use of information and prior ... [more ▼]

The concept of quality by design (QbD) as published in ICH-Q8 is currently one of the most recurrent topics in the pharmaceutical literature. This guideline recommends the use of information and prior knowledge gathered during pharmaceutical development studies to provide a scientific rationale for the manufacturing process of a product and provide guarantee of future quality. This poses several challenges from a statistical standpoint and requires a shift in paradigm from traditional statistical practices. First, to provide “assurance of quality” of future lots implies the need to make predictions regarding the quality given past evidence and data. Second, the quality attributes described in the Q8 guidelines are not always a set of unique, independent measurements. In many cases, these criteria are com- plicated longitudinal data with successive acceptance criteria over a defined period of time. A common example is a dissolution profile for a modified or extended-release solid dosage form that must fall within acceptance limits at several time points. A Bayesian approach for longitudinal data obtained in various conditions of a design of experiment is provided to elegantly address the ICH-Q8 recommendation to provide assurance of quality and derive a scientifically sound design space. [less ▲]

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See detailAnalytical Procedure Validation and the Quality by Design Paradigm
Rozet, Eric ULg; Lebrun, Pierre ULg; Michiels, Jean-François et al

in Journal of Biopharmaceutical Statistics (2015), 25

Since the adoption of the ICH Q8 document concerning the development of pharmaceutical processes following a quality by design (QbD) approach, there have been many discussions on the opportunity for ... [more ▼]

Since the adoption of the ICH Q8 document concerning the development of pharmaceutical processes following a quality by design (QbD) approach, there have been many discussions on the opportunity for analytical procedure developments to follow a similar approach. While development and optimization of analytical procedure following QbD principles have been largely discussed and described, the place of analytical procedure validation in this framework has not been clarified. This article aims at showing that analytical procedure validation is fully integrated into the QbD paradigm and is an essential step in developing analytical procedures that are effectively fit for purpose. Adequate statistical methodologies have also their role to play: such as design of experiments, statistical modelling, and probabilistic statements. The outcome of analytical procedure validation is also an analytical procedure design space, and from it, control strategy can be set. [less ▲]

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See detailEvaluation of the quantitative performances of Supercritical Fluid Chromatography : from method development to validation
Dispas, Amandine ULg; Lebrun, Pierre ULg; Ziemons, Eric ULg et al

in Journal of Chromatography. A (2014), 1353(Method Validation), 78-88

Recently, the number of papers about SFC increased drastically but scientists did not truly focus their work on quantitative performances of this technique. In order to prove the potential of UHPSFC, the ... [more ▼]

Recently, the number of papers about SFC increased drastically but scientists did not truly focus their work on quantitative performances of this technique. In order to prove the potential of UHPSFC, the present work discussed about the different steps of the analytical life cycle of a method: from development to validation and application. Moreover, the UHPSFC quantitative performances were evaluated in comparison with UHPLC, which is the main technique used for quality control in the pharmaceutical industry and then could be considered as a reference. The methods were developed using Design Space strategy, leading to the optimization of robust method. In this context, when the Design Space optimization shows guarantee of quality, no more robustness study is required prior to the validation. Then, the methods were geometrically transferred in order to reduce the analysis time. The UHPSFC and UHPLC methods were validated based on the total error approach using accuracy profile. Even if UHPLC showed better precision and sensitivity, UHPSFC method is able to give accurate results in a dosing range larger than the 80–120% range required by the European Medicines Agency. Consequently, UHPSFC results are valid and could be used for the control of active substance in a finished pharmaceutical product. Finally, UHPSFC validated method was used to analyse real samples and gave similar results than the reference method (UHPLC). [less ▲]

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See detailMéthodes chromatographiques génériques de criblage pour lutter contre les médicaments de qualité inférieure
Habyalimana, Védaste; Kalenda Tshilombo, Nicodème; Dispas, Amandine ULg et al

in Spectra Analyse (2014), 43

Poor quality medicines are a danger and a threat to public health. In this context, several generic analytical methods have been developed to screen molecules of interest grouped by pharmacological class ... [more ▼]

Poor quality medicines are a danger and a threat to public health. In this context, several generic analytical methods have been developed to screen molecules of interest grouped by pharmacological class using an innovative strategy based on design of experiments followed in some cases by independent component analysis and calculation of design space. Once validated via the classical total error measurement approach, these methods were applied to quantify antimalarial, non-steroidal anti-inflammatory and antibiotic medicines. Alarming results regarding the dosage of these drugs widely used by people confirm the need to fight against this scourge. [less ▲]

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See detailImprovement of a stability-indicating method by Quality-by-Design versus Quality-by-Testing: A case of a learning process
Hubert, Cédric ULg; Lebrun, Pierre ULg; Houari, Sabah ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2014), 88

The understanding of the method is a major concern when developing a stability-indicating method and even more so when dealing with impurity assays from complex matrices. In the presented case study, a ... [more ▼]

The understanding of the method is a major concern when developing a stability-indicating method and even more so when dealing with impurity assays from complex matrices. In the presented case study, a Quality-by-Design approach was applied in order to optimize a routinely used method. An analytical issue occurring at the last stage of a long-term stability study involving unexpected impurities perturbing the monitoring of characterized impurities needed to be resolved. A compliant Quality-by-Design (QbD) methodology based on a Design of Experiments (DoE) approach was evaluated within the framework of a Liquid Chromatography (LC) method. This approach allows the investigation of Critical Process Parameters (CPPs), which have an impact on Critical Quality Attributes (CQAs) and, consequently, on LC selectivity. Using polynomial regression response modeling as well as Monte Carlo simulations for error propagation, Design Space (DS) was computed in order to determine robust working conditions for the developed stability-indicating method. This QbD compliant development was conducted in two phases allowing the use of the Design Space knowledge acquired during the first phase to define the experimental domain of the second phase, which constitutes a learning process. The selected working condition was then fully validated using accuracy profiles based on statistical tolerance intervals in order to evaluate the reliability of the results generated by this LC/ESI-MS stability-indicating method. A comparison was made between the traditional Quality-by-Testing (QbT) approach and the QbD strategy, highlighting the benefit of this QbD strategy in the case of an unexpected impurities issue. On this basis, the advantages of a systematic use of the QbD methodology were discussed. [less ▲]

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See detailQuantitative approaches based on Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Raman Chemical Imaging (SER-CI)
De Bleye, Charlotte ULg; Sacre, Pierre-Yves ULg; Dumont, Elodie ULg et al

Conference (2014, January 20)

Surface-enhanced Raman scattering (SERS), discovered in 1978, is a recent technique enabling to circumvent the main limitations of classical Raman spectroscopy by dramatically exalting the Raman ... [more ▼]

Surface-enhanced Raman scattering (SERS), discovered in 1978, is a recent technique enabling to circumvent the main limitations of classical Raman spectroscopy by dramatically exalting the Raman scattering of the target molecules which are adsorbed or very closed to metallic surfaces while reducing the fluorescence impact on spectra [1]. This technique combines the sensitivity of the fluorescence keeping the structural information of molecules obtained from the SERS spectrum [2]. This last point allows to implement multiplex analyses. Moreover, it is possible to perform Surface-enhanced Raman chemical imaging (SER-CI) analyses which enable to acquire a visual representation of samples combining spectral and spatial measurements. Therefore SERS could become an attractive technique in numerous fields such as pharmaceutical and biomedical research. In this context, the feasibility of developing quantitative approaches using SERS and SER-CI on a pharmaceutical model was studied. The aim was to develop methods allowing the quantification of 4-aminophenol (4-AP) in a pharmaceutical formulation based on paracetamol. 4-AP is the main impurity of paracetamol and is actively research because of its toxicity. This pharmaceutical model was first investigated using SERS and a quantitative method enabling to quantify 4-AP from 3 to15 µg/mL was developed and validated using the standard addition method as a calibration method [3]. From these results, the possibility of developing a quantitative approach using SER-CI was investigated. Tablets based on paracetamol comprising different concentrations of 4-AP were prepared. Different ways to cover the sample surface by the SERS substrate were tested and a homogeneity study was performed to improve the repeatability of SER-CI analyses. Different spectral intensity normalizations were also tested in order to optimize the SER-CI method. Finally, a quantitative approach using SER-CI was developed allowing the quantification of 4-AP from 0.025% to 0.2% (w/w) in paracetamol tablets [4]. This first quantitative approach could pave the way to quantitative analysis of small molecules using SER-CI in complex matrices. References [1] P.L. Stiles, J.A. Dieringer, N.C. Shah, R.P. Van Duyne, Annu. Rev. Anal. Chem. 1 (2008) 601-626. [2] R.F. Aroca, R.A. Alvarez-Puebla, N. Pieczonka, S. Sanchez-Cortez, J.V. Garcia-Ramos, Adv. Colloid Interface Sci. 116 (2005) 45-61. [3] C. De Bleye, E. Dumont, E. Rozet, P.-Y. Sacré, P.-F. Chavez, L. Netchacovitch, G. Piel, Ph. Hubert, E. Ziemons, Talanta 116 (2013) 899-905. [4] C. De Bleye, P.-Y. Sacré, E. Dumont, L. Netchacovitch, P.-F. Chavez, G. Piel, P. Lebrun, Ph. Hubert, E. Ziemons, J. Pharm. Biomed. Anal. (in Press) [less ▲]

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