QC Testing Research Articles

A-308 Placental Growth Factor Kryptor Immunoassay Reveals Quality Control Imprecision and Drift

Abstract Background The utility and value of determining the soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio for predicting the likelihood of progression to pre-eclampsia in pregnant women admitted with hypertension are increasingly becoming widely recognized. A key finding of the multi-center PRAECIS trial (NEJM Evid 2022;1(12)) is the observation that sFlt-1/PlGF ratios ≥ 40 correlate with higher risk for adverse maternal outcomes. The sFlt-1 and PlGF immunoassays performed on the ThermoFisher Scientific B·R·A·H·M·S Kryptor autoanalyzer became the first FDA-approved tests in 2023 for determining sFlt-1/PlGF ratio. In this study, an evaluation of the analytical performance of the sFlt-1 and PlGF KRYPTOR immunoassays was performed, which included analyte measuring range (AMR), accuracy, precision, and stability studies. Methods Calibration and QC materials (consisting of lyophilized recombinant human proteins), test reagents and solutions, and consumables were purchased and provided by ThermoFisher Scientific. Analytical runs were performed according to vendor’s instructions by trained medical laboratory scientists. Between-day precision of our two instruments for both immunoassays was assessed by assaying all three levels of sFlt-1 and PlGF QC materials, as well as patient serum pools with low PlGF concentration, once to twice daily for multiple consecutive days. Results While the analytical performance of the sFlt-1 immunoassay was robust and performed according to expectation (within-day CV <1% and between-day CV <3%), the PlGF immunoassay was surprisingly less reliable. Imprecision and inaccuracy of the PlGF immunoassay at the low end of its analytical measurement range was reflected by both sporadically out-of-control between-day measurements of all three QC levels (with target ranges of 24 - 36 pg/mL, 80 - 120 pg/mL, and 320 - 480 pg/mL), as well as slow downward drifts of particularly the low level QC material. In one instance, a downtrend was observed from 28 pg/mL to 14 pg/mL over 6 days, even with fresh reagents, solutions, and calibration. Such shortened stability of the PlGF assay does not meet the vendor’s claims of calibration stability of 15 days and onboard kit stability of 29 days. Using vendor’s provided material, the AMR of both sFlt-1 and PlGF were adequately verified and showed excellent linearity (r2> 0.99). Conclusions Despite low level QC imprecision and drift, the sFlt-1/PlGF ratios determined using the B·R·A·H·M·S Kryptor analyzers are acceptable for clinical use but with the caveat that we will perform batch testing with bracketing QCs and conduct stringent QC monitoring, frequent calibrations, and reduce the onboard kit stability as defined by ThermoFisher Scientific. Our findings serve as a reminder that FDA approval does not preclude thorough verification studies of any assay prior to implementation for clinical use.

Measurement of computed tomography modulation transfer function with a novel polymethyl methacrylate phantom.

A novel phantom for measuring the 10% and 50% values of the modulation transfer function (MTF) for computed tomography scanners (CT) was investigated. The phantom was constructed by drilling rows of holes of different sizes and frequencies into a small block of polymethyl methacrylate (PMMA). The MTF at a given frequency was determined from the ratio of the range of Hounsfield units within the rows of holes at different frequencies, and the difference in Hounsfield units between air and PMMA. A MTF curve was plotted from measurements at different frequencies and the 10% and 50% MTF values were obtained from a cubic spline interpolation. The MTF results obtained with the drilled hole phantom method were compared to a conventional method - using a thin wire and Spice-CT ImageJ Plugin- and with identical acquisition and reconstruction parameters. The drilled hole phantom measured the 50% MTF with reasonable accuracy but underestimated the 10% MTF by 8.2% on average. MTF measurements were reproducible for repeated image acquisitions and with different users analysing the images, and the phantom was able to accurately measure the change in MTF when measured on images using different reconstruction kernels. The tool may find application as a cheap, easy to use method for routine QC testing of CT scanners.

Good Manufacturing Practice–compliant human induced pluripotent stem cells: from bench to putative clinical products

Background aimsFew human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic and autologous hiPSC-derived products. MethodsOur standard research protocol for hiPSCs production was adapted and translated into a GMP-compliant platform. In addition to the generation of GMP-compliant hiPSC, the platform entails the methodology for donor recruitment, consent and screening, donor material procurement, hiPSCs manufacture, in-process control, specific QC test validation, QC testing, product release, hiPSCs storage and stability testing. For platform validation, one test run and three production runs were performed. Highest-quality lines were selected to establish master cell banks (MCBs). ResultsTwo MCBs were successfully released under GMP conditions. They demonstrated safety (sterility, negative mycoplasma, endotoxins <5.0 EU/mL and negative adventitious agents), cell identity (>75% of cells expressing markers of undifferentiated state, identical STR profile, normal karyotype in >20 metaphases), purity (negative residual vectors and no plasmid integration in the genome) and potency (expression of at least two of the three markers for each of the three germ layers). In addition, directed differentiation to somitoids (skeletal muscle precursors) and six potential clinical products from all three germ layers was achieved: pancreatic islets (endoderm), kidney organoids and cardiomyocytes (mesoderm), and keratinocytes, GABAergic interneurons and inner-ear organoids (ectoderm). ConclusionsWe successfully developed and validated a platform for generating GMP-compliant hiPSC lines. The two MCBs released were shown to differentiate into clinical products relevant for our own and other regenerative medicine interests.

P‐BT‐1 | What to Expect When You Request Post‐Thaw Segment QC Testing on a Cord Blood Unit?

P‐BT‐1 | What to Expect When You Request Post‐Thaw Segment QC Testing on a Cord Blood Unit?

B-090 Evaluation of Clinical Serology Assays Through the Development of Linearity Materials for aHBs IgG, Rubella IgG, and Toxoplasma IgG

Abstract Background The human body produces immunoglobulin antibodies as a response to various viruses, bacteria, and pathogens. Automated antibody assays, developed to detect immune response or infectious state, are typically qualitative or semi-quantitative where a positive or negative designation is reported out based on a comparison of signal intensity from the chemical reaction and a predetermined signal to cut-off ratio. In these assays the result is not suggestive of a concentration but rather the strength of the antibody antigen avidity. Use of daily QC, in conjunction with linearity materials, can be used to monitor the performance of these assays. Although the signal response may be linear, serological assays can show variability due to the assay’s antigen specificity to the antibodies present in the sample and the antibody heterogeneity within the samples. Understanding these variables is crucial in interpreting patient and control results, as well as developing controls and linearity material to meet the needs of regulatory requirements for clinical testing. Methods Evaluation of high and low titer patient samples was carried out across multiple platforms including the Roche cobas®, Abbott Alinity, Ortho Vitros, and Siemens Centaur, where applicable, for analyte recovery of aHBs IgG, Toxoplasma IgG and Rubella IgG. These patient samples were then used to evaluate the linear response across the analyzer measuring range using equal delta admixtures, as well as serial dilution studies. Results The serology assays tested here, for Rubella IgG, show a significant difference in recovery of approximately 50% when comparing a 60% diluted patient sample run across multiple platforms. Results vary at both the low and high end of the assays. The linearity of aHBs IgG assays and linear variability in the Rubella IgG and Toxoplasma IgG assays is demonstrated via equal delta analysis. These results demonstrate the incongruity in results within a patient sample, likely due to the heterogeneity of antibodies in the patient samples and the non-linear dilution effect this can cause. Conclusion Since serology assays are based on antigen antibody avidity, patient pools taken from recently infected patients, while ideal low positives, can be variable lot to lot and assay to assay as the antibodies are not matured and contain a mix of IgG and IgM, decreasing avidity. Lot to lot variability is decreased in third party controls and linearity materials such as VALIDATE by diluting high titer patient samples or by using recombinant antibodies. Laboratories must set their own acceptance criteria for daily QC and calibration verification linearity testing, keeping in mind inherent assay variability and variability in the controls themselves. It is important to keep in mind that in-kit controls and linearity materials are typically optimized for that specific lot of reagent and calibrators and that although they may be required as part of the manufacture’s IFUs, use of a third-party quality control and linearity material in conjunction with the in-kit controls can help to ensure laboratories are monitoring the assay for changes over time and allows for comparison against peer data when determining clinical significance of assay performance.

Spectrophotometric method development and validation for determination of pazopanib in the bulk and the formulation

The present work is performed on analytical method development with its latter validation study of a simple and accurate UV-Visible spectrophotometric method for the content determination of the Pazopanib HCl (PAZ). The optimum conditions and solvent selection for the analysis of the drug were established. Absorption maxima (λmax) taken for the analysis was 267nm in the purposed medium. Calibration curve was obtained and plotted against the observed values. Validation of the method was performed as per the current ICH guidelines for linearity, accuracy, precision, LOD and LOQ. The method is simple, accurate, sensitive, precise and reproducible. The method can be used in IPQC and QC testing on a commercial stage as well as in small scale labs, as the method is economical and cheap. The analysis is done on UV-Visible spectrophotometer which is easily available in every institute or in small labs as well.

Evaluation of an alternative method for determination of Protective Dose50 of Classical swine fever vaccines

Classical Swine Fever (CSF) is still one of the most economically important viral diseases of pigs. The disease is controlled by vaccination in the endemic countries. Hence, availability or supply of efficacious and potent vaccine in the field settings is of utmost importance. Currently, as per requirement of any Pharmacopoea, a CSF vaccine must contain 100 PD50/dose which is determined by vaccinating pigs at 1/40th and 1/160th dilution of each dose followed by virulent challenge at 28 days post vaccination (dpv). Here, the control and the unprotected groups succumb to disease and need to be euthanized. Moreover, such challenge experiments are not feasible for each batch of the vaccine. In this communication, an alternate method of PD50 dose calculation of live-attenuated CSF vaccines by measuring Serum Neutralizing Titre i.e Fluorescent Antibody Virus Neutralization (FAVN) titre of the vaccinated pigs at 28 dpv was established. This alternative method do not require the vaccinated pigs to be challenged. Serum samples, generated out of QC testing of eight batches of CSF vaccines in the laboratory, were tested and found that pigs having FAVN titre ≥10 were protected against challenge. Initially this test was optimized in serum samples of 12 animals and then validated with another 56 serum samples. It was found that the alternate method is 100% correlating with the challenge experiment. Thus, based on FAVN titre of the vaccinated animal serum, it can be predicted whether the pigs would or would not come through the challenge infection. Using the predicted status (protected/succumbed), PD50 can be calculated by applying Reed and Muench formula, hence alternate method can be used as routine QC test for potency of CSF vaccines. The newly developed assay was specific since no signal was observed in controls.

Comparison of 3 Diagnostic Tests for the Detection of Giardia and Cryptosporidium spp. in Asymptomatic Dogs (Canis lupis familiaris).

After detecting Giardia and Cryptosporidium infections and coinfections in 2 litters of puppies in our vivarium, our team realized that we needed a simple, quick, and economical point-of-care test for concurrent screening of asymptomatic dogs for both organisms. Periodic screening of colony dogs and of all dogs introduced into a colony can prevent the spread of Giardia and Cryptosporidium to immunologically naïve animals and help keep staff safe from these zoonotic organisms. To compare methods for diagnosing Giardia and Cryptosporidium spp. in dogs, we used a convenience sampling of feces from 2 populations of dogs; samples were tested with a lateral-flow assay (QC), a commercially available direct fluorescent assay (DFA), and an inhouse PCR test using established primers. QC results were analyzed in 2 ways: 1) relative to a reference standard that permitted comparative interpretation of DFA and PCR results; and 2) using Bayesian analysis for comparison independent of a reference standard. The QC test showed good specificity for the detection of Giardia according to both the reference standard (95%) and the Bayesian analysis (98%). Similarly, specificity of the QC for the detection of Cryptosporidium was 95% according to the reference standard and 97% according to Bayesian analysis. However, the sensitivity of the QC test was much lower for both Giardia (reference standard, 38%; Bayesian analysis, 48%) and Cryptosporidium (25% and 40%, respectively). This study demonstrates that the QC test can be used to detect both Giardia and Cryptosporidium in dogs and that positive results can be accepted with confidence, whereas negative tests should be confirmed through secondary testing methods.

Development and clinical evaluation of an online automated quality control system for improving laboratory quality management

BackgroundWe developed an efficient online automated quality control (AUTO QC) system and tested its feasibility on automatic laboratory assembly lines. MethodsAUTO QC is based on developed quality control software (Smart QC) and designed adaptable consumables before. We applied the system to two assembly lines in our laboratory. Using third-party quality control samples, we evaluated the impact of the online AUTO QC system on out-of-control rate, biosecurity risk, turnaround time (TAT) and cost. ResultsAUTO QC significantly decreased the occurrence rate of the Westgard quality control rules 13S/22S/R4s and 12S, representing out-of-control and warning, respectively. The out-of-control rates were reduced by 58%, and the potential biosecurity risk of the samples decreased by 90%. The AUTO QC implementation also reduced the median TAT (by 7 min), the number of full-time employees and the cost of the quality control samples (by 45%). ConclusionsThe total laboratory AUTO QC system can improve the quality and stability of QC testing and reduce cost.

The Impact of RCEP on Dual Circulation and Greater Bay Area — From the Perspective of China’s Stock Market Conditions

&lt;p&gt;With the daily data from Nov 20, 2019 to Oct 31, 2022, this paper examines the dynamic nonlinear effects of RCEP on Dual Circulation and Greater Bay Area stock market from a quantile perspective. The rolling window quantile regressions detect the positive effects of RCEP on Dual Circulation and Greater Bay Area stock markets with significant time-varying characteristics. Meanwhile, QQ results show that the impacts from RCEP index are more significant under extreme conditions. In addition, we further use a nonparametric QC test to provide evidence on the predictive power of RCEP for Dual Circulation and Greater Bay Area with stock market.&lt;/p&gt;

Key priorities for cell &amp; gene therapy manufacturing evolution in 2023 &amp; beyond

David McCall,&#160;Commissioning Editor,BioInsights, spoke to David DiGiusto, Senior Vice President, Stem Cells and Regenerative Medicine, National ResilienceDavid DiGiusto is the Senior Vice President for Stem Cells and Regenerative Medicine at National Resilience. He has over 28 years of experience in the scientific, clinical and regulatory aspects of cells as therapeutic agents including the isolation, characterization and genetic modification of hematopoietic stem cells, T cells and regenerative medicine products for clinical applications. He has been instrumental in the creation of seven GMP compliant biologics manufacturing facilities and associated quality systems, production and QC testing programs. Under his direction, plasmid DNA, CAR-T cells, regulatory T cells, engineered stem cell grafts and gene modified hematopoietic stem cell products have been manufactured and released for use in Phase 1/2 clinical trials. David is a major contributor to first in human studies for Cancer and HIV Gene Therapy and has developed methods for assessing&#160;ex vivo&#160;stem cell manipulations using&#160;in vitro and&#160;in vivo&#160;models. David is a former member of the NIH recombinant DNA advisory committee (RAC) and an independent consultant to the Biotechnology industry.

Radiation protection measures of the radiological facilities in Kano metropolis, Nigeria

Abstract Introduction: The medical use of ionizing radiation contributes the largest amount of man-made radiation exposure and ranks second to natural background radiation. Adhering to the standard radiation protection measures minimizes radiation dose to patients, staff, and other public members. Aim: This study aimed to evaluate radiation protection measures in radiological facilities in the Kano metropolis, Nigeria. Materials and Methods: This was a cross-sectional study conducted in the Kano metropolis, Nigeria, between February 2021 and May 2021. A structured questionnaire was formulated. The measuring tool was validated by expert and experienced colleagues. The reliability of the measuring tool was tested using a pilot study, and Cronbach’s alpha reliability coefficient was found to be 0.815. A total of 101 respondents were recruited. These were the radiographers working in the functional radiological facilities. The obtained data were analyzed using SPSS software version 23.0, and P &lt;0.05 was considered statistically significant. Results: X-ray room design was sufficient in the majority of radiological facilities 67 (66.7%). Insufficient availability of personnel protective devices in 47 (46.9%) respondents was observed. The majority, 24 (23.9%) of the respondents, indicated poor utilization of personnel protective devices. There was insufficient registration and records of radiation safety measures 26 (26.0%). Only 48 (47.5%) respondents indicated the availability of a QA committee in their facility. Fifty-two (51.5%) of the respondents reported that they have medical physicists/engineers available to provide support within their department, while only 25 (25.7%) had radiation safety officers in their facilities. There was a weak negative correlation between lead aprons and lead rubber gloves with the level of staff training, respectively (r = −0.254, P = 0.010; r = −0.214, P = 0.031). Conclusion: There was sufficient X-ray room design in the Kano metropolis. An insufficient availability of personal protective devices, poor utilization, registration, and records of radiation safety measures was observed. There were inadequate QA committee and QC test in the majority of the radiological facilities. A weak negative correlation was observed between the use of lead aprons and lead rubber gloves with the level of staff training.

QbD-Based Development and Validation of Novel Stability-Indicating Method for the Assay and Dissolution of Garenoxacin in Garenoxacin Tablets.

Garenoxacin mesylate is a novel des-fluoro(6) quinolone, approved and marketed for human use in Japan under the name Geninax. In this current work, a simple and stability-indicating method for the assay and dissolution of garenoxacin in garenoxacin tablets 200 mg was performed. New method developed for the particle size measurement of Garenoxacin mesylate Active Pharmaceutical Ingredient using Malvern 2000. A quality by design (QbD)-based stability-indicating assay method was developed using 0.1% (v/v) formic acid in water and methanol (70:30). Using a photodiode array detector the peak purity of the garenoxacin peak for all degradation samples was studied. The biopharmaceutical classification system (BCS) solubility of garenoxacin mesylate active pharmaceutical ingredient (API) was studied by a modified shake flask method. A dissolution test method was developed using 0.1 N hydrochloric acid as the medium, United State Pharmacopoeia apparatus-II (paddle), revolution per minute (rpm) 50, temperature 37 ± 0.5°C and time 30 min. Liquid paraffin was used as the dispersant in the particle size measurement of garenoxacin mesylate API using the Malvern Mastersizer-wet method. The QbD-based RP-HPLC method was stability-indicating, simple, precise, and accurate. The assay method was linear over 12.5 to 75 µg/mL at the detection wavelength of 280 nm. A UV-based method was developed and validated for the dissolution of garenoxacin 200 mg tablets and the method was found to be linear over 2.9 to 34.2 µg/mL at 280 nm. Based on data, the dissolution tolerance for garenoxacin 200 mg tablets was proposed as Q not less than 80% at time 30 min (% drug released with respect to label claim (Q). The effect of garenoxacin mesylate API particle size in the tablet dosage form was studied using particles of 92 µm and 220 µm [90% of the total particles are smaller than this size (D90)] and it was found that there was no impact on the in vitro dissolution profile. The reported stability-indicating assay and dissolution test methods can be used in regular QC testing of garenoxacin 200 mg tablets. The Malvern particle size wet dispersion measurement method developed and validated for garenoxacin mesylate API is simple and robust. A QbD based RP-HPLC method (using Design Expert Software version 11) was developed and studied peak purity of Garenoxacin peak using Photo Diode Array detector (for all degradation samples, control sample and standard solution) and the same method is validated following USP and ICH guidelines.LC-MS compatible volatile buffer solution is used in the preparation of the mobile phase for the novel stability-indicating RP-HPLC assay method.

Development of a compact test board for silicon sensors IV/CV characterization

To build silicon trackers of modern and future high-luminosity collider experiments, thousands of silicon strip modules have to be produced and tested. The modules in new trackers must reliably work usually during 5–10 years or more under harsh irradiation conditions, as it will be impossible to replace a failing module once installed inside the detector. It means that reliable and rigorous testing of strip modules and its components is mandatory. To sustain the production throughput we should be able to test several modules in parallel. For this reason a fast, reliable, scalable and cost effective production QC test bench has to be designed and implemented. For the CV and IV measurements of sensors and modules we are developing a low-cost (less than 500 €) integrated electronic board which will be scaled up to ten channels to measure DUTs in parallel. In the current work the design of the IV/CV board and the calibration procedure to increase the accuracy of the current and capacitance measurements, for which a special calibration dipole board based on tight tolerance capacitors and resistors has been designed, as well as future development plans are described.

HPLC-MS Analysis of Four Potential Genotoxic Impurities in Alogliptin Pharmaceutical Materials.

Pyridine, 3-aminopyridine, 4-dimethylaminopyridine, and N, N-dimethylamine are reactive bases that may be used in the preparation of the pharmaceutical ingredient alogliptin (ALO). They are considered as potentially genotoxic impurities (PGIs) since they contain electrophilic functional groups. Therefore, they should be monitored at the allowed limits in ALO. The aim of this study was to develop a novel liquid chromatography-mass spectrometry (LC-MS) method to estimate quantities of pyridine, 3-aminopyridine, 4-dimethylaminopyridine, and N, N-dimethylaniline impurities in ALO drug material. The separation was performed on Kromasil CN (250 mm × 3.9 mm, 3.5 µm) column in reversed phase mode. The mobile phase was a mixture of water-methanol (55:45, v/v) containing 2.5 mM ammonium acetate and 0.1% formic acid. Impurities were detected by MS in selected ion monitoring mode at m/z = 80, 95, 122, and 123 for pyridine, 3-aminopyridine, N, N-dimethylaniline, and 4-dimethylaminopyridine, respectively. The flow rate of the method was 0.5 mL/min. The sensitivity of the method was excellent at levels much less than the allowed limits. The method had excellent linearity in the concentration ranges of Quantitation Limit (QL)-150% of allowed limits and coefficients of determination were above 0.9990. The recovery ratios were in the range of 93.56-110.28%. Results showed good linearity, precision, accuracy, sensitivity, selectivity, robustness, and solution stability. The studied method was applied to test two samples of raw materials and one sample of tablets. The method discussed here could be very useful for controlling potentially genotoxic impurities (PGIs) levels in ALO during its synthesis, and for QC testing of ALO raw materials before using them in the preparation of pharmaceutical products.

Technical Note: Volumetric coverage in breast tomosynthesis images — Phantom QC results from the TMIST study

In the reconstruction of volume breast images from x-ray projections in breast tomosynthesis, some tomographic systems truncate the image data presented to the radiologist such that a non-negligible amount of tissue may be missing from the breast image. QC tests were conducted to determine if this problem existed in imaging in the TMIST study. Test tools developed for TMIST containing small objects at known heights were used in routine weekly and annual QC testing of tomosynthesis units to assess the degree to which phantom material that was irradiated in imaging was excluded from the reconstructed image. Results from 318 tests on five system types from three manufacturers are reported. The presence and extent of this problem varied among system types. The cause was most frequently related to machine errors in the determination of breast thickness or to deflection of components during breast compression. In particular, the problem occurred when a compression paddle other than the one calibrated for tomosynthesis was used for the tests. This was also verified to have occurred in some clinical imaging. Missing volume can be avoided by intentionally reconstructing additional image slices above and below the presumed locations of the breast support and compression plate. A compression paddle which has been calibrated for tomosynthesis should be used both for clinical imaging and testing. The prevalence of this phenomenon suggests that more frequent testing for volume coverage may be advisable.

Development of a coherent framework for balanced mix design and production quality control and quality acceptance

Asphalt mixtures are becoming increasingly complex, and given ever-changing components of asphalt mixtures, both balanced mix design (BMD) and production quality control and quality acceptance (QC/QA) are critical to have a mixture performing well in the field. This paper established a coherent BMD/QC/QA framework that has four inter-connected components: (1) volumetric mix design and selection of multiple asphalt contents for mixture performance evaluation, (2) mixture performance evaluation at multiple asphalt contents and selection of the balanced asphalt content, (3) mixture performance verification at the balanced asphalt content, and (4) production QC/QA testing. One set of laboratory tests and associated acceptance criteria are recommended for the mixture performance evaluation and the production QC/QA testing and the other set for the mixture performance verification where DOTs can choose their preferred performance verification tests. Furthermore, two practical loose mixture aging protocols are developed, one for short-term aging used in the process of the volumetric mix design, the mixture performance evaluation, and the production QC/QA testing and the other for mid-term aging employed in the mixture performance verification. The recommended short-term aging protocol is to age the loose mixture in a force draft oven for 2 hrs at the mixture compaction temperature, while the mid-term aging protocol consists of three steps: (1) short-term aging, (2) 20 hrs loose mixture aging at 100 °C, and (3) reheating to for compaction. A case study is presented at the end of this paper to demonstrate the whole process of the framework including the actual plant production QC testing.

Data-acquisition system developments for ATLAS pixel QA and QC test toward High-Luminosity LHC

In preparation for the High-luminosity LHC upgrade, the whole ATLAS inner tracker will be replaced by a new silicon detector tracker. The innermost region will be covered by silicon pixel detectors as a high density of produced particles is expected. To operate in such an environment, high-resolution sensors and a high-speed readout system are required. At the moment, the front-end readout chip prototype RD53A and a data acquisition system (the YARR system) based on a commercial FPGA board and dedicated software for quality assurance and quality control test have been developed. Due to the high density of sensor channels, the output speed from RD53A is at maximum 1.28 Gbps per line, sixteen times faster than the readout front-end chip currently used in the ATLAS pixel system. The data acquisition system needs to establish communication with 1.28 Gbps speed during the quality control tests, to validate the data acquisition path, and to optimize the procedure for data taking at high speed. From the quality control perspective this optimization allows to test large numbers of modules simultaneously exploiting the data acquisition speed reducing the time needed for the tests. Another challenging point is the novel concept of readout structure planned for the operation after installation. In High-luminosity LHC, large parts of the ATLAS data acquisition system infrastructure are going to be shared among all sub-detectors, using FELIX systems, while current ATLAS data acquisition systems are dedicated for each sub-detector. This means that all processes done in the present data acquisition system hardware need to be overhauled into software running on the new data acquisition system. To minimize the differences between the data acquisition system for operation and quality control test, we introduced the prototype FELIX system into the data acquisition path of the YARR system. In this proceeding, an established data acquisition structure for quality assurance and quality control test of the new pixel detector is introduced, and results from basic quality control tests of the pixel detector with the new readout chip are presented.

Validation protocol for current good manufacturing practices production of [15O]water for hybrid PET/MR studies

Oxygen-15 (O; t½ = 122.4 s) has been used for nuclear imaging experiments since the beginning of the field. With the advent of simultaneous hybrid PET/MR technology, [O]water has seen a resurgence and remains the gold standard method for quantitative blood flow studies. The short half-life presents a nontrivial challenge to applying current good manufacturing practices production methods to maintain patient safety. A two-vial production method was devised to ensure adequate mixing of [O]water vapour into buffered isotonic saline. For production validation, six batches of [O]water were prepared: sterility, quality control testing and four patient doses. The final dose also underwent quality tested. Routine quality control testing included the following: radiochemical identity and purity, radionuclidic identity and purity, appearance, pH, pyrogenicity, and filter integrity. Sterility was retrospectively confirmed. For validation, breakthrough Pt concentration was also measured. Consistent yields of 10-12 GBq (270-325 mCi) were obtained 3 min after bombardment. Overall, 26 [O]water batches underwent quality control testing under this protocol and all met or exceeded release specifications for clinical use. The multiple batch protocol proved to be a safe and effective means for producing [O]water. Furthermore, this protocol could be readily adapted by any facility attempting to produce [O]water for clinical studies. Compared with previous attempts at our site, the protocol outlined here was more consistent and reliable, improved production workflow and led to more available radioactivity for participant injection and QC testing.

HPTLC and UPLC-MS/MS Methods for Quality Control Analysis of Itrifal Formulations of Unani System of Medicine.

Ultra-performance LC (UPLC)-tandem MS (MS/MS) and high-performance TLC (HPTLC) assay methods were developed for chemical fingerprinting and quantitative analysis of bioactive constituents of a certain "Itrifal formulation," a traditional kind of Unani medicine. In the present investigation, HPTLC and UPLC-MS/MS methods were developed and validated for the detection and quantification of major metabolites present in itrifal formulation. The metabolites present in the formulation were separated using modern chromatographic techniques, and a quantitative analysis was performed. Analytical performance of the proposed HPTLC and UPLC-MS/MS methods was validated as per the defined guidelines with respect to linearity, accuracy, precision, robustness, and specificity. The developed UPLC-MS/MS and HPTLC methods were used for quantification of gallic acid, tannic acid, catechin, and quercetin. All four constituents were quantified by UPLC-MS/MS, while two constituents were quantified by HPTLC in the commercial itrifal formulation. The calibration plot was found to be linear, accurate, precise, robust, and specific for both HPTLC and UPLC-MS/MS. The present methods were successfully applied for analysis of the given markers in itrifal formulations. The same can be used for QC and stability testing of itrifal formulations.