6 research outputs found

    Oxidatie van omvangrijke biomoleculen over MCM-41

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    Available from KULeuven, Campusbib. Exacte Wetenschappen, Celestijnenlaan 300A, 3001 Heverlee, Belgium / UCL - Université Catholique de LouvainSIGLEBEBelgiu

    Continuous twin screw granulation : impact of microcrystalline cellulose batch-to-batch variability during granulation and drying : a QbD approach

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    Despite significant advances in the research domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent mitigation of the impact of this variability on the manufacturing process and drug product was recently stressed in the Draft Guidance for Industry on Quality Considerations for Continuous Manufacturing by the U.S. Food and Drug Administration (FDA). Therefore, this study assessed the impact of microcrystalline cellulose (MCC) batch-to-batch variability and process settings in a continuous twin screw wet granulation and semi-continuous drying line. Based on extensive raw material characterization and subsequent principal component analysis, raw material variability was quantitatively introduced in the design of experiments approach by means of t1 and t2 scores. L/S ratio had a larger effect on critical granule attributes and processability than screw speed and drying time. A large impact of the t1 and t2 scores was found, indicating the importance of raw material attributes. For the studied formulation, it was concluded that MCC batches with a low water binding capacity, low moisture content and high bulk density generated granules with the most desirable quality attributes. Additionally, an innovative and quantitative approach towards mitigating batch-to-batch variability of raw materials was proposed, which is also applicable for additional excipients and APIs

    Nitrosamine Risk Assessments in Oligonucleotides

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    EMA, FDA and other regulatory agencies expect that all pharmaceutical products be assessed for the potential presence of N-nitrosoamine (nitrosamine) impurities. This white paper addresses general considerations for nitrosamine risk assessments of oligonucleotide products. The authors propose a general risk assessment platform which should facilitate safe, consistent development of new treatments and alignment with regulators. The European Pharma Oligonucleotide Consortium (EPOC)1 is a collaboration among multiple pharma companies with the aim of sharing chemistry, manufacturing, and controls (CMC) knowledge as well as strategies to enable harmonization of oligonucleotide development and commercialization. The objective of the consortium is to publish science-based recommendations for the development of oligonucleotide therapeutics in a series of technical and regulatory white papers, drawing on its collective subject matter expertise and complementing that in the literature and guidelines. This public body of prior knowledge endeavours to serve as a reference for industry practice and help establish development principles for oligonucleotides. The consortium aims at being proactive and inclusive, and it anticipates initiating wider discussion on oligonucleotide CMC practice and policy, thus expediting access to these potentially life changing medicines

    A multivariate raw material property database to facilitate drug product development and enable in-silico design of pharmaceutical dry powder processes

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    In current study a holistic material characterization approach was proposed and an extensive raw material property database was developed including a wide variety of APIs and excipients with different functionalities. In total 55 different materials were characterized and described by over 100 raw material descriptors related to particle size and shape distribution, specific surface area, bulk, tapped and true density, compressibility, electrostatic charge, moisture content, hygroscopicity, permeability, flowability and wall friction. Principal component analysis (PCA) was applied to reveal similarities and dissimilarities between materials and to identify overarching properties. The developed PCA model allows to rationalize the number of critical characterization techniques in routine characterization and to identify surrogates for use during early drug product development stages when limited amounts of active pharmaceutical ingredients are available. Additionally, the developed database will be the basis to build predictive models for in silico process and formulation development based on (a selection of) property descriptors
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