References of "Hubert, Cédric"
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See detailGestion du risque associé au cycle de vie des méthodes analytiques : Applications aux molécules de faibles poids moléculaires analysées par Spectrométrie de Masse
Hubert, Cédric ULg

Doctoral thesis (2015)

Analytical method lifecycle is composed of several steps, but always starts with a question defining the problem. Analytical method performances are consequently specified by the analyst trough the ... [more ▼]

Analytical method lifecycle is composed of several steps, but always starts with a question defining the problem. Analytical method performances are consequently specified by the analyst trough the definition of the “Analytical Target Profile (ATP)”, as proposed by the regulatory bodies. Subsequent steps (namely the development and validation steps) then take place, followed by routine use of the analytical procedure. In the specific context of the pharmaceutical industry, regulatory authorities have recently imposed the assessment and management of risk throughout the entire product lifecycle. This includes the analytical procedure and consequently its own lifecycle. Working in this context, our concerns were initially focused on the validation step of the method lifecycle. Indeed, the objective of analytical method validation is to demonstrate that this method is suited for quantifying the target analytes with an established and suitable level of accuracy, as defined by the “ATP”. This is sometimes called the “fit-for-future-purpose” concept. In the course of this study we have experimentally confirmed that a decision regarding the validity of a method based on prediction can be achieved by using the “β-expectation tolerance interval” (accuracy profile) as a decision tool. Indeed, it seemed essential to demonstrate the capability of this approach to manage a part of the analytical risk before addressing the development step. Typically this step of the analytical procedure lifecycle is addressed using a “Changing One Separate Factor a Time (COST)” approach (also known as the “Quality-by-Testing (QbT)” approach). By means of a complex case study, and considering validation of the method through the accuracy profile, we have shown that this strategy can lead to a suitable method for assessing the risk of routine use, even where the experimental domain is not examined. In order to consider an experimental domain rather than a set of specific experimental conditions during the development phase, we have evaluated a multivariate approach: the “Quality-by-Design (QbD)” strategy. This strategy allows the definition of a “Design Space (DS)” by means of design of experiments (DoE). This DS, computed considering critical method parameters, allows the analyst to focus on the main objective of an analytical method: obtaining reliable results using a robust method. A comparative study of the QbT versus QbD approach was performed. In the course of this study, the benefits of the QbD strategy in terms of managing the qualitative part of the analytical risk were highlighted. Finally, we have focused our research on the development of a global strategy allowing the unification of the development and validation phases in a single step. With this innovative approach, we are the first to propose a strategy allowing the management of global analytical risk (i.e., both qualitative and quantitative risk). Indeed, we have demonstrated that it is possible to validate an experimental domain by means of the accuracy profile. With this innovative strategy, the DS is no longer simply the place where qualitative performances are obtained, but also the space where quantitative performances of the analytical procedure are assessed and managed. In conclusion, during this thesis, we have confirmed the predictive capabilities of the accuracy profile. Moreover, we have highlighted the benefits of a QbD strategy in terms of risk management. We have also demonstrated that this methodology can be used as a learning tool, facilitating the continuous improvement of the analytical procedure. Furthermore, with the innovative strategy presented during the latter part of this work, we have demonstrated that qualitative and quantitative risk can be assessed and managed throughout the entire analytical method lifecycle. [less ▲]

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See detailA simple approach for ultrasensitive detection of bisphenols by multiplexed surface-enhanced Raman scattering
De Bleye, Charlotte ULg; Dumont, Elodie ULg; Hubert, Cédric ULg et al

in Analytica Chimica Acta (2015), 888

Bisphenol A (BPA) is well known for its use in plastic manufacture and thermal paper production despite its risk of health toxicity as an endocrine disruptor in humans. Since the publication of new ... [more ▼]

Bisphenol A (BPA) is well known for its use in plastic manufacture and thermal paper production despite its risk of health toxicity as an endocrine disruptor in humans. Since the publication of new legislation regarding the use of BPA, manufacturers have begun to replace BPA with other phenolic molecules such as bisphenol F (BPF) and bisphenol B (BPB), but there are no guarantees regarding the health safety of these compounds at this time. In this context, a very simple, cheap and fast surface-enhanced Raman scattering (SERS) method was developed for the sensitive detection of these molecules in spiked tap water solutions. Silver nanoparticles were used as SERS substrates. An original strategy was employed to circumvent the issue of the affinity of bisphenols for metallic surfaces and the silver nanoparticles surface was functionalized using pyridine in order to improve again the sensitivity of the detection. Semi-quantitative detections were performed in tap water solutions at a concentrations range from 0.25 to 20 µg L-1 for BPA and BPB and from 5 to 100 µg L-1 for BPF. Moreover, a feasibility study for performing a multiplex-SERS detection of these molecules was also performed before successfully implementing the developed SERS method on real samples. [less ▲]

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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 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 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 detailUsefulness of capability indices in the framework of analytical methods validation
Bouabidi, Abderrahim ULg; Ziemons, Eric ULg; Marini Djang'Eing'A, Roland ULg et al

in Analytica Chimica Acta (2012), 714

Analytical methods capability evaluation can be a useful methodology to assess the fitness of purpose of these methods for their future routine application. However, care on how to compute the capability ... [more ▼]

Analytical methods capability evaluation can be a useful methodology to assess the fitness of purpose of these methods for their future routine application. However, care on how to compute the capability indices has to be made. Indeed, the commonly used formulas to compute capability indices such as Cpk, will highly overestimate the true capability of the methods. Especially during methods validation or transfer, there are only few experiments performed and, using in these situations the commonly applied capability indices to declare a method as valid or as transferable to a receiving laboratory will conduct to inadequate decisions. In this work, an improved capability index, namely Cpk-tol and the corresponding estimator of proportion of non conforming results ( ) has been proposed. Through Monte-Carlo simulations, they have been shown to greatly increase the estimation of analytical methods capability in particular in low sample size situations as encountered during methods validation or transfer. Additionally, the usefulness of this capability index has been illustrated through several case studies covering applications commonly encountered in the pharmaceutical industry. Finally a methodology to determine the optimal sample size required to validate analytical methods is also given using the proposed capability metric. [less ▲]

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See detailHigh Throughput determination of Levonorgestrel in human plasma using a Sensitive LC-MS/MS method
Hubert, Cédric ULg; Streel, Bruno; Sibenaler, Renilde et al

Poster (2011, June 19)

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See detailProtocole d'essai LC/MS - P001 - V01
Hubert, Cédric ULg; Ziemons, Eric ULg; Hubert, Philippe ULg

Report (2011)

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See detailComparison between new and old excipients
Hubert, Cédric ULg; Ziemons, Eric ULg; Hubert, Philippe ULg

Report (2011)

Detailed reference viewed: 21 (5 ULg)