Ultra scale-down concepts to address early stage process development challenges in integrated continuous bioprocessing

The benefits of continuous bioprocessing, e.g. accelerated process development and scale-up, reduced capital costs, and standardisation, could be achieved through facility automation, universal process architecture, and the alignment of operational structures for the development and manufacturing organisations [1]. Both control strategy and rational design of universal process architecture demand an understanding of the limits and interdependence of these unit operations, and knowledge on how these could be controlled to sustain desired product quality over long periods of time. For example, to effectively implement global process control, which coordinate feed flowrates, will require information as to the impact on product quality and operational efficiency of the range of flowrates on individual process equipment. One of the advantages of continuous processing is the potential for operating plants to serve clinical development by shortening plant operation. Could the same be used in early stage process development? How does this scale match process development goals which, apart from producing material to demonstrate feasibility of the process, have broader goals such as generating envelopes of performance and experimental data for process understanding? This presentation will initiate discussion on early stage bioprocess development needs when facilities are running integrated continuous processes and envisage how the process of technology transfer from development scale to operating scale might look. We will provide insights into the challenges encountered in designing scale-down mimics of continuous unit operations such as tangential flow filtration or TFF [2] and will illustrate ultra scale-down concepts [3] which could be used to understand unit operations within a continuous platform. TFF is a key unit operation that has been cited as having potential for upstream cell separation or clarification. In a previous work [2], we successfully demonstrated a microscale TFF platform which mimicked a typical bench-scale TFF, Pellicon 2TM (Merck Millipore) based on operating conditions. We obtained similar fluxes, transmissions of antibody fragments, total protein and DNA (unpublished). This was achieved with membrane area that is smaller by 100-fold and reduced feed material by at least 10-fold. We identified that fluid transfer is a key limitation in the reduction of feed since pump requirements for continuous flow dictate the minimum volume of material needed to run the equipment efficiently. Without compatible fluid transfer technologies, material requirement for scale-down, continuous equipment will still be in the litre-scale per experiment. For investigative studies, important to identify key process parameters and quality attributes, these amounts would be prohibitive and would require more resources and time. This highlights the need to re-consider the typical use of geometrical scale-down models to evaluate continuous unit operations and requires more thought on early stage development. Otherwise, we may only be moving the cost and risk of biomanufacturing from industrial scale to the bench scale of process development. The USD approach endeavors to understand the complex engineering environment within an individual unit operation by identifying key engineering parameters and determining the critical flow regime. This insight is then developed into USD technologies and techniques to mimic larger scale operation. The approach suits the requirements during the early stages of product development when the amount of material is scarce and information about the product or process is limited. First applied to continuous centrifugation with the USD centrifugation technique, the USD concept has been extended for other unit operations. The USD techniques were powerful in revealing process interactions. They facilitate Quality by Design and help define process control strategy by determining and quantifying critical processing parameters which control the critical process attributes. References: (1) Konstantinov KB, Cooney CL. White Paper on Continuous Bioprocessing. May 20–21, 2014 Continuous Manufacturing Symposium. Journal of Pharmaceutical Sciences. 2015;104(3):813-20; (2) Rayat ACME, Lye GJ, Micheletti M. A novel microscale crossflow device for the rapid evaluation of microfiltration processes. Journal of Membrane Science. 2014;452(0):284-93; (3) Rayat ACME, Chatel A, Hoare M, Lye GJ. Ultra scale-down approaches to enhance the creation of bioprocesses at scale: impacts of process shear stress and early recovery stages. Current Opinion in Chemical Engineering. 2016;14:150-7

A model for hypermedia learning environments based on electronic books

Designers of hypermedia learning environments could take advantage of a theoretical scheme which takes into account various kinds of learning activities and solves some of the problems associated with them. In this paper, we present a model which inherits a number of characteristics from hypermedia and electronic books. It can provide designers with the tools for creating hypermedia learning systems, by allowing the elements and functions involved in the definition of a specific application to be formally represented A practical example, CESAR, a hypermedia learning environment for hearing‐impaired children, is presented, and some conclusions derived from the use of the model are also shown

Screening of energy efficient technologies for industrial buildings' retrofit

This chapter discusses screening of energy efficient technologies for industrial buildings' retrofit

Next generation software environments : principles, problems, and research directions

The past decade has seen a burgeoning of research and development in software environments. Conferences have been devoted to the topic of practical environments, journal papers produced, and commercial systems sold. Given all the activity, one might expect a great deal of consensus on issues, approaches, and techniques. This is not the case, however. Indeed, the term "environment" is still used in a variety of conflicting ways. Nevertheless substantial progress has been made and we are at least nearing consensus on many critical issues.The purpose of this paper is to characterize environments, describe several important principles that have emerged in the last decade or so, note current open problems, and describe some approaches to these problems, with particular emphasis on the activities of one large-scale research program, the Arcadia project. Consideration is also given to two related topics: empirical evaluation and technology transition. That is, how can environments and their constituents be evaluated, and how can new developments be moved effectively into the production sector

Pilot-Scale Laboratory Instruction for ChE: the specific case of the Pilot-unit leading group

This paper presents an original approach for Chemical Engineering laboratory teaching that is currently applied at INP-ENSIACET (France). This approach, referred to as "pilot-unit leading group" is based on a partial management of the laboratories by the students themselves who become temporarily in charge of one specific laboratory. In addition to meeting the classical pedagogic requirements of the laboratories, this teaching method allows the students to actively experience technical project management

Panama City Fisheries Resources Office: FY 2003 Annual Report

HIGHLIGHTS FOR FY 2003 1. Continued a 3-year threatened Gulf sturgeon population estimate in the Escambia River, Florida and conducted presence-absence surveys in 4 other Florida river systems and 1 bay. 2. Five juvenile Gulf sturgeon collected, near the mouth of the Choctawhatchee River, Florida, were equipped with sonic tags and monitored while over-wintering in Choctawhatchee Bay. 3. Continued to examine Gulf sturgeon marine habitat use. 4. Implemented Gulf Striped Bass Restoration Plan by coordinating the 20th Annual Morone Workshop, leading the technical committee, transporting broodfish, and coordinating the stocking on the Apalachicola-Chattahoochee-Flint (ACF) river system. 5. Over 73,000 Phase II Gulf striped bass were marked with sequential coded wire tags and stocked in the Apalachicola River. Post-stocking evaluations were conducted at 31 sites. 6. Three stream fisheries assessment s were completed to evaluate the fish community at sites slated for habitat restoration by the Partners for Fish and Wildlife Program (PFW). 7. PFW program identified restoration needs and opportunities for 10 areas. 8. Developed an Unpaved Road Evaluation Handbook. 9. Completed restoration of Chipola River Greenway, Seibenhener Streambank Restoration, Blackwater River State Forest, and Anderson Property. 10. Assessments for fluvial geomorphic conditions for design criteria were completed for 3 projects. 11. Geomorphology in Florida streams initiated development of Rosgen regional curves for Northwest Florida for use by the Florida Department of Transportation. 12. Developed a Memorandum of Understanding between partners for enhancing, protecting, and restoring stream, wetland, and upland habitat in northwest Florida 13. Completed aquatic fauna and fish surveys with new emphasis on integration of data from reach level into watershed and landscape scale and keeping database current. 14. Compliance based sampling of impaired waterbodies on Eglin Air Force Base in conjunction with Florida Department of Environmental Protection for Total Maximum Daily Load development support. 15. Surveyed 20 sites for the federally endangered Okaloosa darter, provided habitat descriptions, worked with partners to implement key recovery tasks and set priorities for restoration. 16. Worked with partners to develop a freshwater mussel survey protocol to provide standard operating procedures for establishing the presence/absence of federally listed mussel species within a Federal project area. 17. GIS database was created to identify all known freshwater mussel records from the northeast Gulf ecosystem. 18. Completed recovery plan for seven freshwater mussels and drafted candidate elevation package for seven additional mussels. Developed proposals to implement recovery plan. 19. Worked with Corps of Engineers and State partners to develop improved reservoir operating policies to benefit both riverine and reservoir fisheries for the ACF river system. 20. Multiple outreach projects were completed to detail aquatic resources conservation opportunities. 21. Multiple stream restoration and watershed management projects initiated or completed (see Appendix A)

Learning from Evaluation

{Excerpt} Evaluation serves two main purposes: accountability and learning. Development agencies have tended to prioritize the first, and given responsibility for that to centralized units. But evaluation for learning is the area where observers find the greatest need today and tomorrow. Because the range of types (not to mention levels) of learningis broad, organizations have, from the early days, followed a division-of-labor approach to ascribing responsibility for learning. Typically, responsibility is vested in a policy (or research) unit to allow managers to focus on decision making while other organizational constituents generate information and execute plans. Without doubt, this has encouraged compartmentalization of whatever learning is generated. What is more, since organizational constituents operate in different cultures to meet different priorities, each questions the value added by the arrangement

A review of data visualization: opportunities in manufacturing sequence management.

Data visualization now benefits from developments in technologies that offer innovative ways of presenting complex data. Potentially these have widespread application in communicating the complex information domains typical of manufacturing sequence management environments for global enterprises. In this paper the authors review the visualization functionalities, techniques and applications reported in literature, map these to manufacturing sequence information presentation requirements and identify the opportunities available and likely development paths. Current leading-edge practice in dynamic updating and communication with suppliers is not being exploited in manufacturing sequence management; it could provide significant benefits to manufacturing business. In the context of global manufacturing operations and broad-based user communities with differing needs served by common data sets, tool functionality is generally ahead of user application

Applications of lean thinking: a briefing document

This report has been put together by the Health and Care Infrastructure Research and Innovation Centre (HaCIRIC) at the University of Salford for the Department of Health. The need for the report grew out of two main simple questions, o Is Lean applicable in sectors other than manufacturing? o Can the service delivery sector learn from the success of lean in manufacturing and realise the benefits of its implementation?The aim of the report is to list together examples of lean thinking as it is evidenced in the public and private service sector. Following a review of various sources a catalogue of evidence is put together in an organised manner which demonstrates that Lean principles and techniques, when applied rigorously and throughout an entire organization/unit, they can have a positive impact on productivity, cost, quality, and timely delivery of services