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Peter Varunok1, Eric Lawitz2, Kimberly L Beavers3, Gary Matusow4, Ruby Leong5, Nathalie Lambert6, Coen Bernaards7, Jonathan Solsky5, Barbara J Brennan5, Cynthia Wat8, Anne Bertasso51Gastroenterology Associates, Poughkeepsie, NY, USA; 2Alamo Medical Research, San Antonio, TX, USA; 3Asheville Gastroenterology, Asheville, NC, USA; 4Gastroenterology Group, South Jersey, NJ, USA; 5Roche, Nutley, NJ, USA; 6Roche, Basel, Switzerland; 7Roche, San Francisco, CA, USA; 8Roche, Welwyn, UKBackground: Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device.Methods: In trial 1, 50 healthy adult subjects received one 180 µg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 µg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment.Results: In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0–168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin.Conclusion: These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle.Keywords: peginterferon alfa-2a, disposable autoinjector, hepatitis C, pharmacokinetics, user handling

A factory layout is designed to obtain a physical arrangement of different entities of a facility that most economically meets the required output, in terms of both quantity and quality. An optimum and good arrangement can make the flow of the material free from any interruption and will increase the productivity. New challenges to the manufacturing layout will occur when there is an increase in demand for customer-specific products, and an increasingly shorter product life cycle. Manufacturing companies that undergo production expansion to their current facilities without careful facilities planning, would in most situations, encounter many issues which could retard their overall operations. Due to ever reducing space in the plant, when a transfer is done, this causes tremendous pressure on its current facilities, causing several production bottlenecks and affecting productivity. The aim of this study is to develop a systematic integrated approach to re-configure its current layout to an optimum layout under this stochastic product demand. The approach is to select three key production optimization methodologies based on their individual strengths for the specific task required in developing this integrated approach. The development of this integrated approach takes into consideration the combination of these three key methodologies of the production optimization into a process flowchart, which are the Systematic Layout Planning (SLP), the Theory of Constraint (TOC), and the Discrete Event Simulation (DES). The step of developing the alternative layout is an integration of SLP with the TOC. The translated layouts were then validated by comparing the layout as it is (AS-IS) or the existing layout with the alternative layouts and analysed with the DES for the optimum layout in terms of productivity. The results from the case study revealed that Option 2 which was developed through this integrated approach is the optimum layout. Via this integrated approach, the throughput per hour of Option 2 improved by 15% over the existing layout and by 23% over the Option 1 layout. Total distance covered for the forklift movement with Option 2 shows a much lower distance travelled than the other two layouts. This study reveals the effectiveness of the developed integrated approach in developing the optimized layout with a better material flow strategy. [ABSTRACT FROM AUTHOR]