Notes

Fat Metabolic process and Ferroptosis.
Relative potency assays for biological therapeutics require statistical evaluation to demonstrate similarity between the dose response curves of a reference standard and the test samples. We developed an equivalence testing approach that can be utilized for the complete potency assay lifecycle, from early development until commercialization. This approach is based on the use of generic equivalence margins to enable equivalence testing at the beginning of assay development, when the body of assay specific data is still very limited. Generic equivalence margins for equivalence testing of four parameter logistic curve fits were established for bioassays and binding assays spanning a variety of designs, formats, and read-outs. We also established that equivalence testing using ratios of the reference standard and test sample is superior to equivalence testing using absolute differences. click here Based on a large body of historical data, generic equivalence margins were determined for the curve upper asymptote, slope, and dynamic range. Furthermore, we developed a roadmap to guide the implementation of generic or assay-specific margins to ensure the appropriate data analysis approach is being applied during the assay lifecycle.Liposomes are increasingly being investigated and implemented as injectable-drug delivery systems. The preferred method for sterilizing injectable drug formulations using liposomes is to use filtration. However, due to the size of liposomes and their physicochemical properties, this can be challenging with sterilizing grade filters rated at 0.2 μm. Filter validation studies with injectable liposomes have shown a higher likelihood of premature filter blocking and bacterial recovery compared to other parenteral drug types. Consequently, a greater understanding of the sterilizing filtration of liposomes is required so that appropriate decisions are made concerning the selection and validation of sterilizing grade filters for these applications. In this work, Lipoid S100 liposomes were produced using a microfluidization technique without any encapsulated drug (empty) to investigate their filtration through a polyethersulfone (PES) filter. In order to improve the sterilizing grade filtration of liposomes, optimization of both the filtration process and formulation characteristics is important. To show this, the effect of different filtration conditions/parameters (prefiltration, serial filtration, differential pressure, inlet pressure) and liposome characteristics such as size and size distribution on filtration were examined. For example, by decreasing the size of liposome from 179.0 to 127.3 nm, the volumetric throughput (L/m2) was increased by more than 40-fold. Or by increasing the differential pressure, the volumetric throughput was improved significantly by more than 18-fold (0.7-4.1 bar) and in another experiment by more than 10-fold (0.3-2.1 bar). In addition, the benefit of using higher differential pressure on liposome transmission through various sterilizing grade membranes is shown.Drug shortages are a severe threat to human health and life. The situation in the U.S. even became this critical, that FDA formed a task force in 2018 in order to identify root causes and potential solutions [1]. Manufacturing issues, including rejects and disruptions during fill & finish processes, are a main root cause for inefficient drug manufacturing and resulting delays within the supply chain [2, 3]. This is of particular relevance as the standard pharmaceutical vial filling process can introduce various damages to containers starting from cosmetic defects as scratches or abrasions to fatal events like glass breakage [4]. To overcome the occurrence of undesirable interventions, (e.g. breakage from introduced damages), SCHOTT developed the EVERIC™ smooth vial. It is characterized by a coated outer surface in such a way that the excellent pristine properties of a produced glass surface are preserved. To this, the glass-to-glass friction is reduced and sustainable to different environmental conditions cauffects affecting the machinability.People as a Contamination Source in Pharmaceutical Cleanrooms -Source Strengths and Calculated Concentrations of Airborne Contaminants BENGT LJUNGQVIST AND BERIT REINMÜLLER Building Services Engineering, Chalmers University of Technology, Göteborg, Sweden Corresponding author Berit Reinmüller, Building Services Engineering, Architecture and Civil Engineering, Chalmers University of Technology, SE SE-41296 Göteborg, Sweden e-mail [email protected] ABSTRACT Results are presented from studies performed in a test chamber on cleanroom garments used, laundered, and sterilized (autoclaved 20 minutes at 121°C), 50, 60, and 70 times, and garments used, laundered, and sterilized with a prolonged autoclave cycle 50 times. The source strength is described as the mean value of the number per second of airborne particles and aerobic CFU, respectively, emitted from one person dressed in the system to be evaluated. Results from body-box tests have been used to calculate theoretical expected concentrations of airborne aerobic CFU and particles (≥0.5µm) in cleanrooms with different number of people present, and at different airflows (m3/s.). Theoretical expected concentrations of airborne aerobic CFU are often below the detection level of traditional measuring equipment. .Do changes to ISO 9001 from the 2008 version to the 2015 version warrant revision of ICH Q10? Or does ICH Q10 still meet the ISO 9001 principles? In 2008, the International Conference on Harmonization (ICH) issued guideline ICH Q10, describing a model for a Pharmaceutical Quality System (PQS) that can be implemented throughout the different stages of a product life cycle. Explicitly, the guideline was not intended to create any new expectations beyond the existing regulatory requirements. ICH Q10 was founded on principles established by the International Organization for Standardization (ISO) describing a model for the structure of a Quality Management System (QMS). From 1987 these principles had been codified in the ISO 9000 series of quality standards, for example, as revised in ISO 9001 2008. ICH Q10 also incorporated applicable Good Manufacturing Practice (GMP) regulations and complemented the existing ICH Q8 ″Pharmaceutical Development″ and ICH Q9 ″Quality Risk Management″ guidelines. ICH Q10 represents a harmonized model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle.
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