BPOG model solvent comparison for extractables testing for single use systems

Regulatory guidance requires an extractables based evaluation for drug manufacturing processes. Concerns about the increasing use of hyrbrid and fully single use systems in manufacturing processes and what they may contribute the bulk drug substance and final drug product has highlighted the need for thorough risk assessments and safety evaluations. Awareness of the risk each unit operation represents a strategy to deal with the risk is crucial. An outline of a manufacturing process will be presented along with each unit operations potential risk. This discussion will define an extractables testing strategy based upon the Biophorum Operations Group (BPOG) Extractables Protocol for the highest risk process step - sterilizing filtration in a point of use filling line application that is in direct contact with drug product. Analytical results from multiple methods for six model solvent streams will be shown: water, 0.5N NaOH, 0.1 M Phosphoric Acid, 50% Denatured Ethanol/ 50% Water mixture, 1% Polysorbate 80 and 5M NaCL; using time points of \u3c30 \u3eminutes, 24 hours and 7 days. A comparison of the compounds identified by each method, solvent and time point will presented. The extractables data from the sterilizing grade filter will be used to perform a patient safety evaluation for a typical process and a representative drug product. The calculated extractables concentration per dose will be compared to the Permissible Daily Exposure (PDE) level for individual compounds

The Institute of Archaeology & Siegfried H. Horn Museum Newsletter Volume 41.1

William Shea Dies, Karen Shea, Rebecca Shea Erdelyi, Gerhard Pfandl, and Paul J. Ray, Jr. Al-Maktába: The Bookstore Random Surveyhttps://digitalcommons.andrews.edu/iaham-news/1081/thumbnail.jp

The practical application of BPOG E&L protocols to viral clearance filters

Regulatory guidance advocates virus control at various stages of the drug manufacturing process and directs that you test the capacity of the process to remove or inactivate virus. Patient safety concerns require you to determine what impurities may be added by the virus control steps you implement. While the application of a standardized approach to identifying and quantifying the extractables from these steps has benefits when making comparisons, choices have to be made when developing the protocol that take into account the characteristics of the clearance device and use conditions This presentation will illustrate the practical implementation of standardized extractables method on an industry leading viral clearance technology by explaining the rational for the selection of extraction solvents; extraction conditions and sampling points. Data generated during the study will be presented as well as lessons learned in implementing the new protocol

Risk-based qualification of X-ray sterilization for single-use systems

The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation warrants consideration as an alternate sterilization technology. X-ray irradiation offers better penetration characteristics, improved dose uniformity ratio (DUR), and less environmental impact when compared to other sterilization modalities. We will share a risk based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization modalities

Evaluation of pupil performance in an art ability test.

Thesis (ED.M.)--Boston Universit

Adopting a fully single-use process to improve speed to clinic: A leachables case study

The implementation of single-use technologies for pharmaceutical product development continues to gain momentum; this trend is due to the advantages of increased flexibility, speed of implementation and lower capital investment In particular, they are seen as a means to accelerate the production of material for clinical trials. However, a primary concern regarding the use of such technologies is the impact leachables on patient safety in the final drug substance. Typically this concern is addressed through a patient safety evaluation utilizing extractable substances data based on model solvent extractions and from individual components and devices. However, little if any data has been published where leachables are evaluated under actual process conditions through a complete single-use clinical-scale process train. We have addressed this by completing a pilot scale 100 L “mock” mAb production and purification where the cells, and hence mAb protein, are absent but where the bioreactor was run for the normal duration with cell culture media and feeds, and the DSP train utilized all the standard process devices, buffers, conditions, and procedures. Data will be presented on the leachables profile throughout the entire production process the result of a patient safety evaluation conducted on the bulk drug substance after storage

Static vs. dynamic extraction – Comparing best practice for Single Use Technology

Which is the more discriminating method for single use technology– static or dynamic extraction? Discussion among industry groups and subject matter experts has been intense. However, very little data exist comparing the two techniques. This presentation will present the findings of a side-by-side study that compares the extractables generated from gamma irradiated 10” filters using each technique. The discussion will compare and contrast the profiles of the total organic carbon (TOC), volatile organic compounds (VOCs), semi-volatile organic compounds (SVOCs), pH, and metals extracted. The discussion will compare the profiles with time for each technique for each analysis, as well as summarize the pros and cons of each technique

Laser Light Sheet Flow Visualization of the Space Launch System Booster Separation Test

Planar flow visualizations were obtained in a wind tunnel test in the NASA Langley Research Centers Unitary Plan Wind Tunnel using the laser-light-sheet method. This method uses a laser to illuminate fine particles generated in the wind tunnel to visualize flow structures. The test article was designed to simulate the separation of the two solid rocket boosters (SRBs) from the core stage of the NASA Space Launch System (SLS) at Mach 4 using a scale model. The test was run on of the SLS Block 1B Cargo (27005) configuration and the SLS Block 1B Crew (28005) configuration. Planar flow visualization was obtained only on the crew configuration. Air at pressures up to 1500 psi was used to simulate plumes from the booster separation motors (BSMs) located at the nose, and aft skirt of the two boosters. The facility free stream was seeded with water vapor, which condensed and froze into small ice crystals in the tunnel nozzle expansion. A continuous wave green (532 nm) laser sheet was used to illuminate the ice crystals, and the resulting Mie-scattered light was collected with a camera. The resulting images clearly identify shock waves and other flow features including BSM plume shapes. Measurements were acquired for different BSM pressures and booster separation locations