Paying for What You Get—Restitution Recovery for Breach of Contract

This article begins with a brief discussion of restitution as a remedy for breach of contract under the Restatement (Second) of Contracts. It then discusses the changes the Restatement of Restitution adopts and the reasons for the changes. Next, it discusses why the changes have not only failed to achieve the goal of clarifying the “prevailing confusion” related to restitution and breach of contract, but have at times created more confusion. It then explains that contract and restitution principles are not only not in tension relative to restitution for breach of contract, but in fact support such a recovery

Song Of The Brook

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Brillouin Light Scattering Measurement of the Elastic Properties of Aligned Multilamella Lipid Samples

Brillouin measurements of the elastic properties are presented for aligned multilamella samples of both pure dipalmitoyl phosphatidylcholine at various temperatures and water concentrations and for the same compound containing 33 mol% cholesterol at various temperatures and two water concentrations. For pure dipalmitoyl phosphatidylcholine the elastic moduli change significantly at the gel transition and the modulus for area compression of individual bilayers is inferred to be an order of magnitude larger below the gel transformation than above. The presence of cholesterol is shown to influence the elastic behavior of dipalmitoyl phosphatidylcholine.Engineering and Applied Science

Successful scale up of an intensified perfusion process to clinical and commercial scales

An intensified perfusion process for production of a therapeutic monoclonal antibody was developed and scaled to 100 L clinical and 500 L commercial scales. The baseline process was developed in 10 L benchtop bioreactors with stainless steel alternating tangential flow (ATF) cell retention systems. The process consisted of a 12 day growth phase followed by a 48 day harvest phase. Cell densities of \u3e120 Mvc/mL were sustained with high culture viability. Productivities of \u3e3 g/L·d were maintained throughout the harvest phase. The process was successfully scaled up to a 100 L single use bioreactor with dual ATF6 filters for clinical manufacturing. To verify that the process would perform similarly at commercial manufacturing scale, a proof of concept run was conducted in a 500 L single use bioreactor with dual ATF10 filters. Biomass concentration, culture viability, and productivity were comparable across scales. A full 60 day campaign in a 500 L bioreactor would generate over 70 kg of product in the clarified harvest. These studies demonstrate that intensified perfusion processes developed in benchtop bioreactors can be successfully reproduced at scales relevant for manufacturing

Toward development of continuous bioprocesses: Comparison of fed-batch and perfusion upstream production processes in early development

Continuous Processing is an exciting development in the field of bioprocessing. The potential for quick response to market demands, decrease in infrastructure, increased flexibility and consistent product quality has resulted in a growing interest in Continuous Processing for production of all types of protein drugs (high or low volume, stable or unstable). Sanofi is developing a novel Integrated Continuous Manufacturing platform for biologics that utilizes an upstream perfusion process. While cell culture perfusion processes offer substantial benefits for commercial biologics production, implementation may present challenges in early development, where speed to first in man studies is critical. Here we present a comparison of candidate Phase I fed-batch and perfusion processes resulting from our upstream development work for a monoclonal antibody. The report focuses on process productivity, product quality attributes, and development timelines. Assessment of the advantages and challenges for both processes informs strategy for Continuous Process platform developmen

Leveraging Sanofi intensified ICB platform to enable early process development for a labile and hard-to-express molecule

Within the biopharmaceutics industry, tremendous progress has been made in the implementation of early development antibody platforms to achieve high volumetric productivity and consistent product quality for novel therapies. More recently, development of new modalities provide opportunities for advancing exciting new therapeutic possibilities. However, many of these modalities present new upstream and downstream development challenges, e.g., low expression, labile molecules, low recovery, and unreliable product quality. The resulting additional development requirements increase the timelines for demonstrating Proof of Concept and may even prohibit certain therapeutic candidates from reaching the clinic at all. The Sanofi ICB platform provides opportunities to increase productivity and improve product quality, enabling manufacture of new entities previously inaccessible. Here, we present a case study of such a situation, in which the ICB platform is applied to an early-stage, labile, hard to express molecule produced from non-CHO mammalian cells. A combination of upstream and downstream high-throughput technologies have been incorporated to rapidly define a process sufficient for first-in-human studies. Process intensification enables adequate material generation within an acceptable number of batches for both development and clinical manufacturing. This case study demonstrates the strategy of using intensified perfusion platform for non-antibody modalities to support a diverse portfolio for our evolving industry