Sherwin Shang - Academia.edu (original) (raw)
Papers by Sherwin Shang
Development of Biopharmaceutical Drug-Device Products, 2020
Launching a new or improvement to a combination product can bring the patient satisfaction and co... more Launching a new or improvement to a combination product can bring the patient satisfaction and confirmation but also the potential for an unexpected surprise as they may not be familiar with the combination product or changes made to the on-market product. In addition to planned changes, normal variation in combination product constituent parts may be perceived as a difference to the user and impact their experience with the product. These types of use experiences come back in the form of customer appreciation, complaints, and/or testimonies, through direct access via company product support channels, social media, as well as health care givers. In this chapter, lessons learned from the launch and sustaining engineering of the Humira Autoinjector will be discussed, including examples of design/process improvements based on an understanding of the key functional attributes of the design and constituent parts required to deliver robust autoinjector performance.
A key feature for medical products is the need to sterilize products prior to release. However, t... more A key feature for medical products is the need to sterilize products prior to release. However, the radiation dose, which disrupts DNA sequences in bioburdens, can also damage and alter polymer properties in substantial ways. Contrary to known degradations, there are also property enhancements through irradiation. In this presentation, both property degradation and enhancement will be illustrated with actual examples.
We have applied thermal, mechanical, and rheological techniques in the product development for me... more We have applied thermal, mechanical, and rheological techniques in the product development for medical elastomers with success. In this presentation, examples of actual product application will be used to illustrate the utility of these techniques and to demonstrate the derived information that was used in developing successful elastomeric related medical products.
A mechanistic model of a freeze-thaw process for a small fill volume (10s of mL) of drug product ... more A mechanistic model of a freeze-thaw process for a small fill volume (10s of mL) of drug product in a primary package such as a glass cartridge with a stopper is developed based on the analytical solution of the lumped capacitance heat transfer equation. The model uses the heat transfer coefficient for a given package calibrated from data analysis of thermal history for the initial liquid cooling; it is applied to predict the freezing and thawing for different ambient temperatures and variability in the heat transfer coefficient. The predicted time to reach a specified temperature below the freezing point agrees with experimental measurements within 10–15%. The freeze-thaw temperature data for a 20 mL cartridge with 15 mL fill volume obtained using a temperature-controlled chamber at various ambient temperatures ranging from −23.5 C in the freezing stage to +4.7 C for the thawing stage and +60 C for the thermal aging stage have been used to estimate the heat transfer coefficient of ...
L'invention decrit des systemes, des dispositifs et des procedes ameliores de therapie par fl... more L'invention decrit des systemes, des dispositifs et des procedes ameliores de therapie par fluide medical utilisant des cassettes. Un premier aspect decrit divers materiaux de tubes de pompe peristaltique. L'invention decrit egalement des materiaux de cassettes et de membranes, des configurations et des ameliorations de fabrication. Divers aspects de l'invention comprennent: un procede et un dispositif de detection et de correction de la hauteur de tete; un procede et un dispositif de melange; un procede et un dispositif de mesure du pH; des procedes et des dispositifs de detection et d'elimination de l'air; un dispositif et un procede d'amorcage actif; ainsi qu'un procede et un dispositif d'amelioration de la precision volumetrique.
AAPS PharmSciTech, 2021
The mixing of stratified miscible fluids with widely different material properties is a common st... more The mixing of stratified miscible fluids with widely different material properties is a common step in biopharmaceutical manufacturing processes. Differences between the fluid densities and viscosities, however, can lead to order-of-magnitude increase in blend times relative to the blending of single-fluid systems. Moreover, the mixing performance in two-fluid systems can be strongly dependent on the Richardson number defined as the ratio of fluid buoyancy to fluid inertia. In this work, we combine lattice Boltzmann transport algorithms with graphics card-based computing hardware to build accelerated digital twins of a physical mixing tanks. The digital twins are designed to predict real-time fluid mechanics with a fidelity that rivals experimental characterization at orders-of-magnitude less cost than physical testing. After validating the twins against measured single- and multi-fluid mixing data, we use them to explore the physics governing fluid blending in stratified two-fluid systems. We use output from the twins to provide general guidance on stratified two-fluid mixing processes, as well as guidance for building such models for other types of physical systems.
AAPS PharmSciTech, 2019
Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a us... more Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a useful tool in understanding and optimizing of the process, developing an operating design space following the quality-by-design principle, and justifying occasional process deviations during routine manufacturing. The steady-state model relies on two critical parameters, namely, the vial heat transfer coefficient, K v , and the cake resistance, R p. The classical gravimetric method used to measure K v is tedious, time-and resourceconsuming, and can be challenging and costly for commercial scale dryers. This study proposes a new approach to extract both K v and R p directly from an experimental run (e.g., temperature and Pirani profiles). The new methodology is demonstrated using 5% w/v mannitol model system. The values of K v obtained using this method are comparable to those measured using the classic gravimetric method. Application of the proposed approach to process scale-up and technology transfer is illustrated using a case study. The new approach makes the steady-state model a simple and reliable tool for model parameterization, thus maximizes its capability and is particularly beneficial for transfer products from lab/pilot to commercial manufacturing.
Development of Biopharmaceutical Drug-Device Products, 2020
Launching a new or improvement to a combination product can bring the patient satisfaction and co... more Launching a new or improvement to a combination product can bring the patient satisfaction and confirmation but also the potential for an unexpected surprise as they may not be familiar with the combination product or changes made to the on-market product. In addition to planned changes, normal variation in combination product constituent parts may be perceived as a difference to the user and impact their experience with the product. These types of use experiences come back in the form of customer appreciation, complaints, and/or testimonies, through direct access via company product support channels, social media, as well as health care givers. In this chapter, lessons learned from the launch and sustaining engineering of the Humira Autoinjector will be discussed, including examples of design/process improvements based on an understanding of the key functional attributes of the design and constituent parts required to deliver robust autoinjector performance.
A key feature for medical products is the need to sterilize products prior to release. However, t... more A key feature for medical products is the need to sterilize products prior to release. However, the radiation dose, which disrupts DNA sequences in bioburdens, can also damage and alter polymer properties in substantial ways. Contrary to known degradations, there are also property enhancements through irradiation. In this presentation, both property degradation and enhancement will be illustrated with actual examples.
We have applied thermal, mechanical, and rheological techniques in the product development for me... more We have applied thermal, mechanical, and rheological techniques in the product development for medical elastomers with success. In this presentation, examples of actual product application will be used to illustrate the utility of these techniques and to demonstrate the derived information that was used in developing successful elastomeric related medical products.
A mechanistic model of a freeze-thaw process for a small fill volume (10s of mL) of drug product ... more A mechanistic model of a freeze-thaw process for a small fill volume (10s of mL) of drug product in a primary package such as a glass cartridge with a stopper is developed based on the analytical solution of the lumped capacitance heat transfer equation. The model uses the heat transfer coefficient for a given package calibrated from data analysis of thermal history for the initial liquid cooling; it is applied to predict the freezing and thawing for different ambient temperatures and variability in the heat transfer coefficient. The predicted time to reach a specified temperature below the freezing point agrees with experimental measurements within 10–15%. The freeze-thaw temperature data for a 20 mL cartridge with 15 mL fill volume obtained using a temperature-controlled chamber at various ambient temperatures ranging from −23.5 C in the freezing stage to +4.7 C for the thawing stage and +60 C for the thermal aging stage have been used to estimate the heat transfer coefficient of ...
L'invention decrit des systemes, des dispositifs et des procedes ameliores de therapie par fl... more L'invention decrit des systemes, des dispositifs et des procedes ameliores de therapie par fluide medical utilisant des cassettes. Un premier aspect decrit divers materiaux de tubes de pompe peristaltique. L'invention decrit egalement des materiaux de cassettes et de membranes, des configurations et des ameliorations de fabrication. Divers aspects de l'invention comprennent: un procede et un dispositif de detection et de correction de la hauteur de tete; un procede et un dispositif de melange; un procede et un dispositif de mesure du pH; des procedes et des dispositifs de detection et d'elimination de l'air; un dispositif et un procede d'amorcage actif; ainsi qu'un procede et un dispositif d'amelioration de la precision volumetrique.
AAPS PharmSciTech, 2021
The mixing of stratified miscible fluids with widely different material properties is a common st... more The mixing of stratified miscible fluids with widely different material properties is a common step in biopharmaceutical manufacturing processes. Differences between the fluid densities and viscosities, however, can lead to order-of-magnitude increase in blend times relative to the blending of single-fluid systems. Moreover, the mixing performance in two-fluid systems can be strongly dependent on the Richardson number defined as the ratio of fluid buoyancy to fluid inertia. In this work, we combine lattice Boltzmann transport algorithms with graphics card-based computing hardware to build accelerated digital twins of a physical mixing tanks. The digital twins are designed to predict real-time fluid mechanics with a fidelity that rivals experimental characterization at orders-of-magnitude less cost than physical testing. After validating the twins against measured single- and multi-fluid mixing data, we use them to explore the physics governing fluid blending in stratified two-fluid systems. We use output from the twins to provide general guidance on stratified two-fluid mixing processes, as well as guidance for building such models for other types of physical systems.
AAPS PharmSciTech, 2019
Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a us... more Modeling of the lyophilization process, based on the steady-state heat and mass transfer, is a useful tool in understanding and optimizing of the process, developing an operating design space following the quality-by-design principle, and justifying occasional process deviations during routine manufacturing. The steady-state model relies on two critical parameters, namely, the vial heat transfer coefficient, K v , and the cake resistance, R p. The classical gravimetric method used to measure K v is tedious, time-and resourceconsuming, and can be challenging and costly for commercial scale dryers. This study proposes a new approach to extract both K v and R p directly from an experimental run (e.g., temperature and Pirani profiles). The new methodology is demonstrated using 5% w/v mannitol model system. The values of K v obtained using this method are comparable to those measured using the classic gravimetric method. Application of the proposed approach to process scale-up and technology transfer is illustrated using a case study. The new approach makes the steady-state model a simple and reliable tool for model parameterization, thus maximizes its capability and is particularly beneficial for transfer products from lab/pilot to commercial manufacturing.