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Methanol-assisted Secondary Drying to Accelerate Residual Solvent Removal in Spray-dried Polymers

Drug candidates with low aqueous solubility require bioavailability enhancement techniques to enable oral delivery. Spray drying has been used to manufacture amorphous solid dispersions with enhanced oral bioavailability, resulting in over a dozen commercial products and many more in clinical trials. After spray drying is used to convert a liquid feed to a solid powder, residual solvent remains in the product, which must be removed to meet ICH safety specifications. The process of residual solvent removal is called secondary drying. Typical secondary drying techniques, such as drying in the presence of water vapor or vacuum drying often suffice. Some spray-dried materials are more challenging, requiring 24 hours or longer to secondary dry at typical conditions. This work introduces methanol-assisted secondary drying, a technique which can be used to accelerate residual solvent removal from spray-dried products.
Authors: Dr. Kimberly Shepard
Publish Date: 05-Nov-2020

Rapid Fire Presentation: Measuring Lipolytic Activity in Biologics Drug Substance and Drug Product

Polysorbate degradation is discussed being oxidatively and hydrolytically, via lipolytic activity of enzymes (Lipases) in HCP. We developed an analytical assay to detect and measure lipolytic activity in biopharmaceutical partly purified DS, drug substance (DS) and drug product (DP). The assay was optimized by variation of key parameters. The assay can support the optimization of the downstream purification process in order to remove HCPs with lipolytic activity. Furthermore it can be used to measure lipolytic activity in DS / DP samples and support root cause investigations related to polysorbate degradation. To learn more, download our rapid-fire presentation.
Authors: Andreas Zerr
Publish Date: 03-Nov-2020

Addressing Manufacturing Challenges for Commercialization of iPSC-Based Therapies

Abstract: The development of reprogramming technology to generate human induced pluripotent stem cells (iPSCs) has tremendously influenced the field of regenerative medicine and clinical therapeutics where curative cell replacement therapies can be used in the treatment of devastating diseases such as Parkinson’s disease (PD) and diabetes. In order to commercialize these therapies to treat a large number of individuals, it is important to demonstrate the safety and efficacy of these therapies and ensure that the manufacturing process for iPSC-derived functional cells can be industrialized at an affordable cost. However, there are a number of manufacturing obstacles that need to be addressed in order to meet this vision. It is important to note that the manufacturing process for generation of iPSC-derived specialized cells is relatively long and fairly complex and requires differentiation of high-quality iPSCs into specialized cells in a controlled manner. In this chapter, we have summarized our efforts to address the main challenges present in the industrialization of iPSC-derived cell therapy products with focus on the development of a current Good Manufacturing Practice (cGMP)-compliant iPSC manufacturing process, a comprehensive iPSC characterization platform, long-term stability of cGMP compliant iPSCs, and innovative technologies to address some of the scale-up challenges in establishment of iPSC processing in 3D computer-controlled bioreactors. 
Authors: Mehdi Dashtban, Krishna Morgan Panchalingam, Mehdi Shafa and Behnam Ahmadian Baghbaderani
Publish Date: 02-Nov-2020

Rapid Fire Presentation: Polysorbate in Biologics – Understanding Degradation by Applying Proper Analytics

Polysorbates are excipients in biopharmaceutical formulations that protect the therapeutic proteins from interfacial stress. The biopharmaceutical industry currently phases a problem due to observed degradation - oxidatively and hydrolytically - of polysorbate in drug product formulations, leading to increased formation of sub-visible and visible particles and to a potential loss of protecting propensity of the surfactant. Interestingly, mitigation of the effects observed in drug product often can be provided already during drug substance manufacturing and compounding. However, a proper analytical toolbox is necessary to spot polysorbate degradation at an early stage and to differentiate the degradation mechanisms. In this work, we present an optimized analytical toolbox to control polysorbate quantity and quality. Additionally we present analytical strategies to be applied for root cause investigations once polysorbate degradation is observed. To learn more, download our presentation.
Authors: Dr. Michael Jahn
Publish Date: 02-Nov-2020

Rapid Fire Presentation: in vivo Protein Stability - What Happens After Administration?

Knowledge of the stability of therapeutic proteins in vivo, or after administration to patients, is limited. This talk explains the relevance of in vitro studies to assess the stability of therapeutic proteins under simulating physiologic conditions. in vivo degradation of a therapeutic protein may alter treatment efficacy and/or patient safety. Moreover, in vitro studies can support the selection of better molecules in early stages of pharmaceutical development. In our study, we compared the physical stability of 8 different monoclonal antibodies (mAbs) in phosphate-buffered saline (PBS) and human serum. mAbs were characterized with respect to fragmentation, aggregation, and proteinaceous particle formation. To learn more, download our rapid fire presentation. 
Authors: Joachim Schuster
Publish Date: 02-Nov-2020

Rapid Fire Presentation: Modeling Phase Separation Risk During Spray Drying from Mixed Solvents

Low organic solubility compounds in need of bioavailability enhancement by spray drying are increasingly prevalent in many development pipelines. Using mixed aqueous/organic solvents is one way to improve organic solubility, thereby increasing process throughput, though this approach may impart phase separation risks by solvent enrichment during drying. Practical tools for predicting the impacts of mixed solvents on the properties and performance of spray-dried dispersions is an important gap in process and formulation development. This work presents a model for droplet drying and phase behavior in a four-component system, incorporating two different solvents. To learn more, download our rapid fire presentation.
Authors: Dr. Jonathan Cape
Publish Date: 29-Oct-2020

Rapid Fire Presentation: Processing Low Viscosity Products Using Liquid Filling and Banding Technology

Alongside the ability to formulate and deliver challenging poorly aqueous soluble APIs, liquid-filled capsule-based systems have a number of advantages. Lipid-based formulations can be formulated and manufactured in soft gel capsules or hard capsule shells. When developing a liquid-filled hard capsule, capsule selection is fundamental and needs to be assessed early on in the process, with a view to scale up to be performed. When enhancing bioavailability with lipid-based systems, a number of oils and surfactants are employed and often these materials are of low viscosity. This rapid fire presentation focuses on the processing of such oils and scale up considerations.
Authors: Dr. Jenifer Mains
Publish Date: 29-Oct-2020

A Novel Architecture for High Drug-loaded Amorphous Solid Dispersion Tablets; Assessment of in vitro and in vivo Performance, Stability and Manufacturability

Amorphous solid dispersions (ASDs) can increase solubility and dissolution rate of poorly water soluble drugs. However, ASD dosage forms are often large or require multiple units to meet dose requirements due to incorporation of concentration-sustaining polymers (CSPs) in the formulation. To address this challenge, a high-loaded dosage form (HLDF) architecture for ASDs was developed, in which a drug is first spray-dried with a high glass transition temperature (Tg) dispersion polymer to facilitate high drug loading while maintaining physical stability. The ASD is then granulated with a CSP to extend supersaturation in solution. The HLDF approach differs from traditional ASD architectures in which the dispersion polymer inside the ASD has the dual purpose of maintaining physical stability and extending supersaturation in solution, thereby constraining the formulation and often resulting in low dosage form drug loading. The HLDF platform has the potential to reduce tablet mass by at least 40% while maintaining performance, stability and manufacturability. This presentation describes case studies highlighting the HLDF architecture, including physical stability, in vitro and in vivo performance and manufacturability.
Authors: Dr. Deanna Mudie
Publish Date: 28-Oct-2020

Liquid-Filled Capsules for Highly Potent Drug Compounds

Highly potent active pharmaceutical ingredients (HPAPIs) are an increasing portion of pharma and biotech pipelines. Because of their highly potent nature and the low dose for these compounds, occupational exposure and dose uniformity can be make the development pathway more difficult.  Read our Executive Summary to learn more about how liquid-filled hard capsules can improve a HPAPI compound’s development pathway.
Authors: Alyn McNaughton
Publish Date: 27-Oct-2020

Rapid Fire Presentation: Methanol-Assisted Secondary Drying to Accelerate Residual-Solvent Removal in Spray-Dried Polymers

In this presentation, we (1) identify the challenges associated with secondary drying of spray dried materials; (2) describe the experimental setup used to conduct methanol-assisted secondary drying; and (3) define the circumstances where methanol-assisted secondary drying can be beneficial to spray dried dispersion manufacturing.  To learn more, please download our slides.
Authors: Dr. Kimberly Shepard
Publish Date: 27-Oct-2020