A risk-based framework to manage single-use systems over lifecycle: Design, cleaning, operation, ongoing process verification

Using a formal risk management approach, SU systems (SUSs) and classical stainless steel-based systems (CSSs) are examined in detail. The risk assessment steps include: identification, analysis, mitigation and reevaluation/verification of risks over lifecycle. Adequate risk tools are used for each step. Failure modes specific of each type of system, are considered. The scientific background described in BPOG’s Guidelines on extractables (2014) and leachables (Jan.2017) for SUSs is built in, together with other authoritative sources for both types of systems. The risk quantitation, profiling and the holistic risk visualization for both technology platforms, allows companies with stainless steel only fermentation capacity and those with a mix of both technologies, to consider how to best evolve their capacity, when potential impacts on product quality and patient safety are taken into account. In addition to allowing the relative benchmarking of both technology platforms, comparisons over lifecycle of a specific platform are made possible by our approach, enabling companies to retain a complete picture of all their risk-based decisions and very detailed knowledge about their assets performance. The knowledge management component proposed is unique and supports several business processes and also decisions a company needs to justify before authorities. Our talk provides an insightful discussion of SUSs, using state-of-the-art risk-based and knowledge management tools, illustrated by examples on Design, Cleaning, Operation and Ongoing Process Verification, focusing on risks to quality and safety

Finite-Fault Rupture Detector (FinDer): Going Real-Time in Californian ShakeAlert Warning System

Rapid detection of local and regional earthquakes and issuance of fast alerts for impending shaking is considered beneficial to save lives, reduce losses, and shorten recovery times after destructive events (Allen et al., 2009). Over the last two decades, several countries have built operational earthquake early warning (EEW) systems, including Japan (Hoshiba et al., 2008), Mexico (Espinosa-Aranda et al., 1995), Romania (Mărmureanu et al., 2011), Turkey (Erdik et al., 2003), Taiwan (Hsiao et al., 2011), and China (Peng et al., 2011). Other countries, such as the United States (Böse, Allen, et al., 2013), Italy (Satriano et al., 2011), and Switzerland (Behr et al., 2015), are currently developing systems or evaluating algorithms in their seismic real-time networks

Comparability and similarity protocols for biotechnology products

Over lifecycle, from development through all industrialization stages and then over manufacturing history across multiple sites, a biotechnology product must show very high levels of quality consistency, as that is a pre-requisite for safety and efficacy to patients (cf. ICH Q5E, 2004). Recently, FDA defined different levels of similarity (Draft Guidance, May 2014, “Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product”) namely the concepts of (1) “highly similar with fingerprint-like similarity” and that of (2) “residual uncertainty” in regard to similarity. Here we present a new approach to combine whole analytical domains from different techniques used in comparability protocols (to support change management for same product and process) that also is applicable to assess similarity in biocomparability investigations. Our approach ensures much higher levels of confidence in Comparability Protocols by not overlooking differences that might be unnoticed or overlooked due to incomplete prior-knowledge in regards to methods used and attributes considered. Our approach can (a) detect very small differences, (b) establish therefore the exact level of comparability / similarity and (c) provides a sound statistical foundation to assess residual uncertainties. We will illustrate our approach on reference products over their lifecycle and to compare reference with putatively similar products. The outcome of assessments (a) through (c) can then be linked to pharmacological performance or both types of biotechnology products, and support regulatory or other decisions related to managing filings

Integrating analysis with process control for continuous bioprocessing: Extending the lifecycle concept to process analytical technologies

The most notable trends in the use of PAT tools in bioprocessing nowadays are: (1) the combined use of multiple tools to a product & process and (2) that information fusion provides a better process estimation and product quality knowledge foundation than the use classical use of one analytical method The lifecycle management aspects of validation launched by FDA in its 2011 Validation Guidance, arrived - through ICH Q11 (2012) and the forth coming ICH Q12 (2017), to all aspects of development, qualification and commercial manufacturing of large molecule drug substances. For continuous bioprocessing that challenges are significantly different and more complex than for batch processing of small molecules. The homeostasis state that are targeted for most continuous bioprocesses, puts specific requirements in each individual PAT tool chosen and in their combined use over lifecycle. Here, using case-studies, a discussion is done of specific challenges at each of the three stages of lifecycle, about how and when the shift is made from understanding (acquiring data & information) to enhanced bioprocess control (knowledge-based decisions) to realize product quality by design (predictive product quality). Finally, we show how platform knowledge can be managed across multiple products for a company’s own portfolio benefit, through aggregation and high-level visualization of multiple PAT projects

Brazil: innovation and development

October 2012 Series editor: David Everatt Published by the Gauteng City-Region ObservatoryThis essay discusses recent developments in Brazil´s innovation policies. These policies are part of a long-term developmental process and the current search for a new national configuration of policies and instruments capable of steering Brazil in the midst of globalisation and economic systems that have knowledge as their backbone. Industrialisation became the main source of inspiration as a means of attaining social evolution in countries like Brazil, South Africa, India, Mexico, Argentina and South Korea, to name a few; and in a sense this remains true today. These roots have marked state institutions and underscore the modus operandi of government planners. Brazil´s prospects for overcoming poverty, inequality and the burden of late development can be described as a process of attaining a better balance between earlier achievements and the current process of institution-building aimed at providing Brazil with the policies and instruments to support innovation as a means of achieving social and economic development.written by Glauco Arbix (Observatory for Innovation and Competitiveness, Institute of Advanced Studies University of São Paulo, Brazil) et al for GCR

ORGANIZATIONAL PERFORMANCE MEASUREMENT AND EVALUATION SYSTEMS IN SMEs: THE CASE OF THE TRANSFORMING INDUSTRY IN PORTUGAL

The competitiveness of organizations depends, among other things, of their performance levels. For such, it is vitally important that they have a measurement and evaluation system that, from a set of indicators, provides them reliable information to reflect their goals and evaluate their performances. The aims of this study are: (i) to identify the most discussed approaches in the literature to evaluate the organizational performance, and (ii) to carry out a diagnosis of how small and medium enterprises with economic activity in Portugal measure and operationalize the evaluation of their performance. To meet the objectives of the study, we proceeded to the analysis of published studies in scientific journals and conducted twelve interviews in SMEs. The results indicate that, in addition to the majority of the studied organizations not having a formal process of their strategy, they also do not measure their results in an integrated system that would allow them to make an evaluation according to their strategic goals

Keck Interferometer nuller update

The Keck Interferometer combines the two 10 m Keck telescopes as a long baseline interferometer, funded by NASA, as a joint development among the Jet Propulsion Laboratory, the W. M. Keck Observatory, and the Michelson Science Center. Since 2004, it has offered an H- and K-band fringe visibility mode through the Keck TAC process. Recently this mode has been upgraded with the addition of a grism for higher spectral resolution. The 10 um nulling mode, for which first nulling data were collected in 2005, completed the bulk of its engineering development in 2007. At the end of 2007, three teams were chosen in response to a nuller key science call to perform a survey of nearby stars for exozodiacal dust. This key science observation program began in Feb. 2008. Under NSF funding, Keck Observatory is leading development of ASTRA, a project to add dual-star capability for high sensitivity observations and dual-star astrometry. We review recent activity at the Keck Interferometer, with an emphasis on the nuller development

A CF3I-based SDD Prototype for Spin-independent Dark Matter Searches

The application of Superheated Droplet Detectors (SDDs) to dark matter searches has so far been confined to the light nuclei refrigerants C2ClF5 and C4F10 (SIMPLE and PICASSO, respectively), with a principle sensitivity to spin-dependent interactions. Given the competitive results of these devices, as a result of their intrinsic insensitivity to backgrounds, we have developed a prototype trifluoroiodomethane (CF3I)-loaded SDD with increased sensitivity to spin-independent interactions as well. A low (0.102 kgd) exposure test operation of two high concentration, 1 liter devices is described, and the results compared with leading experiments in both spin-dependent and -independent sectors. Although competitive in both sectors when the difference in exposures is accounted for, a problem with fracturing of the detector gel must be addressed before significantly larger exposures can be envisioned.Comment: revised and updated; accepted Astrop. Phy

First Results of the Phase II SIMPLE Dark Matter Search

We report results of a 14.1 kgd measurement with 15 superheated droplet detectors of total active mass 0.208 kg, comprising the first stage of a 30 kgd Phase II experiment. In combination with the results of the neutron-spin sensitive XENON10 experiment, these results yield a limit of |a_p| < 0.32 for M_W = 50 GeV/c2 on the spin-dependent sector of weakly interacting massive particle-nucleus interactions with a 50% reduction in the previously allowed region of the phase space formerly defined by XENON, KIMS and PICASSO. In the spin-independent sector, a limit of 2.3x10-5 pb at M_W = 45 GeV/c2 is obtained.Comment: 4 pages, 4 figures; PRL-accepted version with corrected SI contour (Fig. 4