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Spencer D. Schaber

Bio: Spencer D. Schaber is an academic researcher from University of Edinburgh. The author has contributed to research in topics: Batch processing & Batch production. The author has an hindex of 1, co-authored 1 publications receiving 334 citations.

Papers
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01 Jan 2016
TL;DR: In this paper, the authors compared the costs of a dedicated continuous manufacturing process to synthesize an active pharmaceutical ingredient (API) and formulate it into tablets for a production scale of 2000 t of tablets per year, with raw material cost, production yield and API loading varied over broad ranges.
Abstract: The capital, operating, and overall costs of a dedicated continuous manufacturing process to synthesize an active pharmaceutical ingredient (API) and formulate it into tablets are estimated for a production scale of 2000 t of tablets per year, with raw material cost, production yield, and API loading varied over broad ranges. Costs are compared to batch production in a dedicated facility. Synthesis begins with a key organic intermediate three synthetic steps before the final API; results are given for key intermediate (KI) costs of $100 to $3000/kg, with drug loadings in the tablet of 10 and 50 wt %. The novel continuous process described here is being developed by an interdisciplinary team of 20 researchers. Since yields are not yet well-known, and continuous processes typically have better yields than batch ones, the overall yields of the continuous processes with recycling were set equal to that of the batch process. Without recycling, yields are 10% lower, but less equipment is required. The continuous process has not been built at large scale, so Wroth factors and other assumptions were used to estimate costs. Capital expenditures for continuous production were estimated to be 20 to 76% lower, depending on the drug loading, KI cost, and process chosen; operating expenditures were estimated to be between 40% lower and 9% higher. The novel continuous process with recycling coupled to a novel direct tablet formation process yields the best overall cost savings in each drug loading/KI price scenario: estimated savings range from 9 to 40%. Overall cost savings are also given assuming the yield in the continuous case is 10% above and 10% below that of the batch process. Even when yields in the continuous case are lower than in the batch case, savings can still be achieved because the labor, materials handling, CapEx, and other savings compensate.

374 citations


Cited by
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Journal ArticleDOI
01 Apr 2016-Science
TL;DR: An apparatus roughly the size of a household refrigerator is presented that can synthesize and purify pharmaceuticals under continuous-flow conditions, and the synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform is reported.
Abstract: Pharmaceutical manufacturing typically uses batch processing at multiple locations. Disadvantages of this approach include long production times and the potential for supply chain disruptions. As a preliminary demonstration of an alternative approach, we report here the continuous-flow synthesis and formulation of active pharmaceutical ingredients in a compact, reconfigurable manufacturing platform. Continuous end-to-end synthesis in the refrigerator-sized [1.0 meter (width) × 0.7 meter (length) × 1.8 meter (height)] system produces sufficient quantities per day to supply hundreds to thousands of oral or topical liquid doses of diphenhydramine hydrochloride, lidocaine hydrochloride, diazepam, and fluoxetine hydrochloride that meet U.S. Pharmacopeia standards. Underlying this flexible plug-and-play approach are substantial enabling advances in continuous-flow synthesis, complex multistep sequence telescoping, reaction engineering equipment, and real-time formulation.

679 citations

Journal ArticleDOI
TL;DR: The Food and Drug Administration (FDA) regulates pharmaceutical drug products to ensure a continuous supply of high-quality drugs in the USA as mentioned in this paper, where the FDA supports the implementation of continuous manufacturing using science-and risk-based approaches.
Abstract: The Food and Drug Administration (FDA) regulates pharmaceutical drug products to ensure a continuous supply of high-quality drugs in the USA. Continuous processing has a great deal of potential to address issues of agility, flexibility, cost, and robustness in the development of pharmaceutical manufacturing processes. Over the past decade, there have been significant advancements in science and engineering to support the implementation of continuous pharmaceutical manufacturing. These investments along with the adoption of the quality-by-design (QbD) paradigm for pharmaceutical development and the advancement of process analytical technology (PAT) for designing, analyzing, and controlling manufacturing have progressed the scientific and regulatory readiness for continuous manufacturing. The FDA supports the implementation of continuous manufacturing using science- and risk-based approaches.

598 citations

Journal ArticleDOI
TL;DR: The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug product in one integrated system.
Abstract: A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug product in one integrated system.

485 citations

Book ChapterDOI
01 Jan 2019
TL;DR: This review gives an overview of recent advances and current status of nanocrystals, especially with respect to the method of preparations, physicochemical characterizations, in vitro/in vivo performance, scale-up techniques and applications in the field of drug delivery for different tumor targeting.
Abstract: Nanotechnology-based drug delivery systems offer an unprecedented opportunity for tumor targeting. Nanocrystals are carrier-free crystalline nanosized solid drug particles. Due to high drug loading (as high as 100%), and being free of organic solvents or surfactants or polymers or solubilizing chemicals, nanocrystals have attracted great attention in the field of drug delivery for treatment of various cancers. Additionally, the hybrid or multifunctional nanocrystal has been extensively investigated for applications in experimental as well as clinical settings to improve delivery efficiency of therapeutic and diagnostic agents. This review gives an overview of recent advances and current status of nanocrystals, especially with respect to the method of preparations, physicochemical characterizations, in vitro/in vivo performance, scale-up techniques and applications in the field of drug delivery for different tumor targeting. Recently much attention has been given to multifunctional nanocrystals showing the capability to codeliver multiple components that target the drug delivery by surface functionalization, performing therapy as well as diagnosis. Preparative techniques like high-pressure homogenization, precipitation, and media milling have been known to show large-scale production of nanocrystals. High therapeutic applications of nanoparticles enable its administration through various routes like oral, parenteral, pulmonary, dermal, and ocular. Along with preparation and characterization, this review will dwell on the progress involved with multifunctional nanocrystals for cancer therapy and theranostics. Most available results in multifunctional nanocrystal targeting rely upon in vitro and animal models, which do not match the actual environment of the tumor in the body, which is one of the major obstacles. Other challenges faced when it comes to nanocrystals are scale-up and reproducibility. In addition, potential problems and possible future research directions for the advancement of newer techniques of multifunctional nanocrystals that make them highly suitable for tumor targeted are highlighted in this review.

246 citations

Journal ArticleDOI
TL;DR: This Review explores continuous flow biocatalysts with emphasis on new technology, enzymes, whole cells, co-factor recycling, and immobilization methods for the synthesis of pharmaceuticals, value-added chemicals, and materials.
Abstract: The continuous flow synthesis of active pharmaceutical ingredients, value-added chemicals, and materials has grown tremendously over the past ten years. This revolution in chemical manufacturing has resulted from innovations in both new methodology and technology. This field, however, has been predominantly focused on synthetic organic chemistry, and the use of biocatalysts in continuous flow systems is only now becoming popular. Although immobilized enzymes and whole cells in batch systems are common, their continuous flow counterparts have grown rapidly over the past two years. With continuous flow systems offering improved mixing, mass transfer, thermal control, pressurized processing, decreased variation, automation, process analytical technology, and in-line purification, the combination of biocatalysis and flow chemistry opens powerful new process windows. This Review explores continuous flow biocatalysts with emphasis on new technology, enzymes, whole cells, co-factor recycling, and immobilization methods for the synthesis of pharmaceuticals, value-added chemicals, and materials.

235 citations