QC Testing Research Articles

Identification and Characterization of Indole and Oxindole Alkaloids from Leaves of Mitragyna speciosa Korth Using Liquid Chromatography-Accurate QToF Mass Spectrometry.

Alkaloids have been reported to be the major physiologically active constituents in Mitragyna. An analytical method was developed to provide an alternative, fast method for characterization of alkaloids from various M. speciosa samples. The separation was achieved using an RP octylsilyl (C8) column, MS detection, and a water-acetonitrile with formic acid gradient as the mobile phase. Ultra-HPLC/quadrupole time-of-flight MS analysis and characterization were performed on 12 corynanthe-type indole/oxindole alkaloids obtained from the leaves of M. speciosa Korth. The indoles and oxindoles had an open E ring with or without substitution occurring at the C9 position. The full single mass spectrum of alkaloids showed a strong signal for the protonated molecule [M+H]+. The product ion spectrum of mitragynine type of alkaloids showed strong response at m/z=174.0901 suggestive of an ion containing an odd number of nitrogen atoms corresponding to formula C11H12NO, which is characteristic of indole alkaloids. A multivariate statistical analysis technique, principal component analysis, was used to show discrimination between the M. speciosa samples. The results indicated that the analytical method is suitable for QC testing of various Mitragyna commercial samples and can be used to evaluate market products purported to contain M. speciosa.

Internal quality control used for erythrocyte sedimentation rate (ESR) by australasian laboratories

Aim This study was performed as part of the investigation of the wide variation in results in the RCPAQAP Erythrocyte Sedimentation Rate (ESR) module with the aim of determining the types of internal quality control used for ESR by participating laboratories and whether this might contribute to the variation seen in the survey results. Methods A questionnaire was distributed to 483 laboratories participating in the RCPAQAP ESR module. Questions pertained to the type of laboratory, ESR method used, type of control and assessment of acceptable performance. Results 89% of labs performed internal QC for automated ESR methods compared with 47% for manual methods. A wide variety of practices were used. Most respondents reviewed their ESR EQA survey data in conjunction with their internal QC. Those who did not perform internal QC, in the traditional sense, for any or some of their ESR methods, stated other ways of assessing their ESR performance. Discussion and conclusion Variation in internal QC practices could contribute to variation in RCPAQAP ESR survey results. The RCPAQAP cannot mandate internal QC testing for ESRs, but all laboratories are encouraged to develop a suitable program and analyse performance and RCPAQAP survey results in conjunction with this.

The Precise Methods for the Measurement of Collimator Hole Angulation and Center of Rotation of SPECT by Adaptive Quality Control Phantom

The Adaptive Quality Control Phantom (AQCP) is a computer-controlled phantom which positions and moves a radioactive source in the Field of View (FOV) of an imaging nuclear medicine device on a definite path to produce a spatial distribution of gamma rays to perform QC Tests such as the Collimator Hole Angulation (CHA) and the Center of Rotation (COR) of Single Photon Emission Computer Tomography (SPECT). The collimator hole angulation for six collimators was measured using a point source and a computer-controlled cylindrical positioning system. In this method, the displacement of the image of a point source was examined as the AQCP was moving point source vertically away from the collimator face. The results of the high-accuracy measurement method of CHA show that the measurement accuracy for absolute angulation errors is better than ±0.024°. The Root Mean Square (RMS) of CHA for LEHR, LEHS and LEUHR collimators of SMV dual heads camera and LEGP, MEGP and HEGP of GE Millennium MG were evaluated to be 0.290°, 0.292°, 0.208°, 0.154°, 0.220° and 0.202°, respectively. It is to be added in this connection that the evaluated RMS of CHA for LEHR collimator with the distance variation from the collimator’s surface ±1 mm has been varied ±0.04 degree. A new method for the center of rotation assessment by AQCP is introduced and the results of this proposed method as compared with the routine QC test and their differences are discussed in detail. We defined and measured a new parameter called Dynamic Mechanical Error (DME) for applying the gantry motion correction.

184-P: KEEP REAGENT RECEIPT AND QUALITY CONTROL UNDER CONTROL

Reagent receipt and quality control is very important in each laboratory, our aim was to implement an easy and efficient system that would document the receipt of each reagent and automatically trigger QC testing prior to use. The following steps were implemented: 1) One key technologist was identified to oversee the process. 2) An electronic Excel-based reagent tracking spreadsheet was developed. The information recorded on the tracking spreadsheet includes: reagent name, lot number, order date, receipt date, date of QC, technologist performing QC, date of QC review, date the reagent was put in-use, and, last date the reagent was in-use. The spreadsheet is simple to complete and a filtering option was added for easy searching. 3) A procedure was written and competency was documented. 4) QC testing to be completed within one week of reagent receipt was assigned by the key technologist to a specific workbench. 5) A simplified reagent QC guideline was developed. 6) QC data were reviewed for acceptability by the key technologist. 7) All QC data were then approved by the supervisor. 8) An audit of the tracking system was performed monthly. In January of 2013, after six months of implementing the system, we performed an audit of thirty random patient charts focusing on the completeness and documentation of reagent QC. The results of this audit revealed that all reagents used were documented and QC testing was complete. This represented a significant improvement over audit findings prior to the implementation of the tracking system. Streamlining reagent receiving and quality control testing is extremely important in every laboratory. Its successful implementation requires everyone’s participation. We have found that our restructured systematic process is not only easily monitored, but also 1)easily adhered to by all personnel, 2)saves time and facilitates inventory control, 3)avoids midnight reagent crises, and (best of all), 4)we are always ready for inspection.

Quality assurance and quality control in mammography: a review of available guidance worldwide

ObjectivesReview available guidance for quality assurance (QA) in mammography and discuss its contribution to harmonise practices worldwide.MethodsLiterature search was performed on different sources to identify guidance documents for QA in mammography available worldwide in international bodies, healthcare providers, professional/scientific associations. The guidance documents identified were reviewed and a selection was compared for type of guidance (clinical/technical), technology and proposed QA methodologies focusing on dose and image quality (IQ) performance assessment.ResultsFourteen protocols (targeted at conventional and digital mammography) were reviewed. All included recommendations for testing acquisition, processing and display systems associated with mammographic equipment. All guidance reviewed highlighted the importance of dose assessment and testing the Automatic Exposure Control (AEC) system. Recommended tests for assessment of IQ showed variations in the proposed methodologies. Recommended testing focused on assessment of low-contrast detection, spatial resolution and noise. QC of image display is recommended following the American Association of Physicists in Medicine guidelines.ConclusionsThe existing QA guidance for mammography is derived from key documents (American College of Radiology and European Union guidelines) and proposes similar tests despite the variations in detail and methodologies. Studies reported on QA data should provide detail on experimental technique to allow robust data comparison. Countries aiming to implement a mammography/QA program may select/prioritise the tests depending on available technology and resources.Main messages•An effective QA program should be practical to implement in a clinical setting.•QA should address the various stages of the imaging chain: acquisition, processing and display.•AEC system QC testing is simple to implement and provides information on equipment performance.

Evaluation of the Influence of Variation of Superpave HMA Mixtures Physical Properties on Pavement Performance

For numerous years, researchers have investigated hot-mix asphalt (HMA) plant production and the relationship between measured quality control/quality acceptance (QC/QA) parameters and field performance. After 12 years of service, this study presents a statistical evaluation of the relationship between HMA plant QC/QA data, roadway density, and field performance, as measured by international roughness index (IRI), rutting, and random cracking. Three Louisiana Superpave projects constructed in 1999 utilizing wearing and binder course mixtures were evaluated. Results indicated that, as Superpave Gyratory Compaction levels increased, roadway density variability increased. Generally, QC test results were less variable than QA test results and voids filled with asphalt (VFA) showed the highest variability between measured volumetric parameters. Statistical analysis indicated that the coarse aggregate portion (19.0 mm, 9.5 mm, and 4.75 mm sieves) and the 0.075 mm sieve had an effect on voids in the mineral aggregate (VMA), VFA, and air voids (V a). The percentage of asphalt cement significantly affected rutting and random cracking; the top size aggregate at or near the nominal maximum size aggregate, the 4.75 mm, and the 0.075 mm sieves had an effect on rutting, random cracking, and IRI for the HMA mixtures evaluated.

Transduction of Human CD34+ Derived NSG Repopulating Cells with An Insulated SIN Lentiviral Vector for SCID-X1 From a Stable Producer Cell Line At Clinical Scale

Abstract 670▪▪This icon denotes a clinically relevant abstractWe have previously described the generation of a self-inactivating (SIN) lentiviral vector producer cell line that produces high titer supernatant for treatment of X-linked severe combined immunodeficiency (SCID-X1) (Throm R.E. et al Blood 2009). This system uses doxycycline withdrawal to induce production of a VSV-G pseudotyped SIN lentivector encoding a codon-optimized γc cDNA driven by an internal EF1α promoter and containing a 400 bp chicken HS4 insulator in the SIN LTR (CL20i4-EF1α-hγc-OPT). This vector was effective in correcting the SCID-X1 defect in mouse and human cells and does not cause enhancer mediated gene activation in a Jurkat based assay, immortalization in vitro, or oncogenesis in vivo (Zhou S. et al Blood 2010). Cells from our certified master cell bank were expanded and used to seed a 25 liter WAVE bioreactor. Supernatant was harvested daily for a total volume of 150 liters and purified with a Mustang Q XT cartridge anion exchange column followed by concentration and diafiltration against PBS using tangiential flow filtratration to a final volume of 500ml. This material demonstrated a final titer of 4.5 × 108 tu/ml on ED7R cells with a 29.6% tu yield and has successfully completed QC testing. Human CD34+ mobilized peripheral blood cells derived from healthy donors were transduced under GMP conditions in our Human Applications Laboratory in retronectin coated closed AFC Vuelife bags using 1.35 ×108 tu/ml of vector with 1 × 106 cells/ml for 24 hours following a 16 hour prestimulation in X-Vivo 10 media supplemented with 100 ng/ml of TPO,SCF, and Flt3-L with 4 ug/ml protamine sulfate. A transduction efficiency of 10–21% was observed in CFU derived from graft material treated with this vector preparation. Cell product from the bag transductions was transplanted into eight busulfan conditioned NOD/SCID/γc (NSG) mice at 1x 106 cells per mouse, of which all survived and were included in subsequent analysis. A mean of 14.5% human CD45+ engraftment (range 3.5–26.9%) compared to 9% for mock treated cell product (range 5.7–13.1%) was observed in bone marrow harvested after 12 weeks from treated mice, demonstrating no loss of viability or engraftment from vector treatment. A mean of 0.16 vector genomes/human genome (range 0.8–0.22) by real time quantitative PCR (RTQ-PCR) was observed in the human CD45+ cells sorted by FACS. A mean of 19% vector positive colonies by PCR (range 5–33%) with pooled colony genomic DNA showing a mean of 0.13 vector genomes/human genome (range 0.1–0.22) by RTQ-PCR was observed in CD45 sorted cells plated in methycellulose for CFU assay. Mean vector copy number as assessed by RTQ-PCR from lysates of known vector positive colonies was 2.89 vector copies per human genome (range 0.66–4.41). Vector treated human CD45+ sorted bone marrow clonal diversity was assayed using LAM-PCR with three different restriction enzymes per sample (Tsp509I, CviAII, CviQI). We sequenced the LAM-PCR products using a novel Illumina based deep sequencing assay. We chose to develop the Illumina platform rather than a 454 based platform to capitalize on the improved cost and increased number of sequence reads per run. Using this methodology, we identified 266,580 informative reads mapping to 1,437 unique vector insertion sites in 3 of the treated mice. Vector insertions into LMO2, MDS/EVI1, CCND2, BMI1, PRDM16, or HMG2A were not seen. Analysis of cells sorted for human CD19 or CD33 resulted in the identification of clones derived from both myeloid and lymphoid compartments providing molecular evidence of the transduction of human multipotent repopulating cells. The FDA has approved our IND application to use this vector product in two clinical trials for SCID-X1 which we plan to open for patient enrollment in the fall of 2011. Disclosures:No relevant conflicts of interest to declare.

Automated preparation of the dopamine D2/3 receptor agonist ligand [11C]-(+)-PHNO for human PET imaging studies

Carbon-11 labelled (+)-4-Propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([(11)C]-(+)-PHNO) is used as a high-affinity state, dopamine D(2/3) receptor ligand in clinical PET studies. To facilitate its use, robust, rapid, efficient and GMP compliant methods are required for the manufacturing and QC testing processes. Additionally, to allow for full quantification of the resulting signal in the CNS, a reliable method is required to establish the parent plasma concentration over the course of the scan. This paper provides high-quality methods to support clinical application of [(11)C]-(+)-PHNO.

Albumin and embryo culture: implications for quality control

Human serum albumin (HSA) is used in many areas of medicine including the IVF laboratory for embryo culture. Quality of albumin has been shown to vary when used in other areas of medicine. Most labs use HSA at 5 mg/mL and manufacturers perform QC testing at this concentration with the hybrid mouse embryo assay (MEA). It is unknown if variable HSA quality could cause sub-lethal damage to human embryos and thus affect IVF outcomes. Our objectives were to screen HSA from 3 manufacturers with an MEA optimized for protein testing and to identify potential causes of variation. An experimental laboratory study. In experiment 1, ten 1-cell mouse embryos from inbred mice were cultured with 5 or 15 mg/mL HSA from 3 manufacturers (A,B,C). Blastocyst rates (BR) were calculated at 96 hours of culture and the experiments were repeated in triplicate. In experiment 2, the samples were desalted (dsHSA) using spin columns with a molecular weight cut off of 7000 daltons. The MEA was then performed in triplicate with both original and desalted HSA at 15 mg/ml. Results were analyzed using ANOVA. At 5 mg/mL HSA, all samples had BR ≥70%. At 15 mg/mL BR for samples B and C were significantly reduced. Desalting did not affect sample B but significantly improved the BR of sample C (P<0.0001).Tabled 1Blastocyst Rates for HSA Culture.SampleExperiment 1 (BR%)Experiment 2 (BR%)HSA 5 mg/mLHSA 15 mg/mLHSA 15 mg/mLdsHSA 15 mg/mLA79 ± 1063 ± 6a70 ± 070 ± 10B77 ± 637 ± 6b43 ± 550 ± 10C76 ± 517 ± 6b20 ± 20c60 ± 10da,b: P<0.01; c,d: P<0.0001 Open table in a new tab a,b: P<0.01; c,d: P<0.0001 HSA has lot-to-lot variation but the cause is unknown. Some IVF laboratories use HSA at concentrations higher than the manufacturer tested 5 mg/mL, which may increase potential for adverse effects. In this study HSA quality from one manufacturer was improved after removing small molecular weight compounds, where another manufacturer's sample did not improve. Chemical characterization of these HSA samples is underway to determine the cause of toxicity.

SU‐E‐I‐86: Using Modulation Transfer Function as a Tool in a Digital Mammography QC Program

Purpose: To evaluate the efficacy of MTF measurement on digital mammography systems in the Ontario Breast Screening Program (OBSP). Methods: An MTF tool, composed of a copper square on a flexible printed circuit film is supported on top of a 40 mm PMMA slab and imaged with an x‐ray technique appropriate for this thickness. In‐house software, QuickQC, is used to review the image, define regions of interest (ROIs) over each copper edge and calculate the presampled MTF from the line spread function (LSF), by differentiating the edge spread functions (ESF). The noise in the LSF is zero at zero frequency, making the normalization of MTF(0) possible. Since implementing this test in the OBSP 5 years ago, over 180 digital mammography systems have been surveyed semi‐annually (∼ 800 reports). The physicist collects and analyzes the MTF images for all targets and focal spot sizes. MTF results for each digital mammography vendor were summarized to develop pass‐fail criteria. Results: Using appropriate x‐ray techniques, the MTF obtained in this way is similar to values published elsewhere. The noise in the MTF linearly increases to the cutoff spatial frequency, but doesnˈt seriously impair the ability to evaluate compliance. The effects of phosphor glare and extra focal radiation are evident in the low frequency region. Focal spot deterioration is observed as a decrease in MTF compared to the performance for other units of the same model. Underexposure of the phantom causes excessive noise in the MTF. The frequency at which the MTF drops to 50% is typically between 2.5 to 3.5 mm−1 for phosphor based systems with both 50 and 100 um pitch, and 4.0 to 5.0 mm−1 for Se systems with 74–85 um dels. Conclusions: This objective QC test is effective in identifying MTF degradation in a range of different digital mammography systems in the field.

Functional FCGR2B gene variants influence intravenous immunoglobulin response in patients with Kawasaki disease

In Kawasaki Disease patients, the authors show associations between high-dose intravenous immunoglobulin (IVIG) response and a polymorphism in the FCγRIIB. This provides basis for defining the IVIG regulatory mechanisms and pharmacogenomic approach to IVIG therapy.

Abstract LB-178: Analysis of restored FFPE samples on Infinium methylation arrays

Abstract Millions of Formalin Fixed Paraffin Embedded (FFPE) cancer tissue samples currently present in the US and worldwide provide an enormous, invaluable repository to the discovery of biomarkers in cancer research, drug development, diagnosis and treatment of diseases. However, the processes of fixation and storage of FFPE samples leads to degradation and base modification with chemical residues. This degraded FFPE DNA is inefficiently amplified by the Infinium® whole genome amplification (WGA) step leading to poor performance in genome wide methylation analysis. In this study, purified FFPE DNA or crude lysates (200–500 ng input) were bisulfite converted and restored through Illumina's Infinium HD DNA Restoration kit consisting of a combination of treatment with a DNA polymerase, a repair enzyme, and a ligase. Results of methylation analysis on high density HumanMethylation450 BeadChip®, featuring over 450,000 assays indicated that even highly degraded samples which show initial call rates (genes detected p =0.01) of 50–70% can be successfully restored to a state that achieved call rates of greater than 90%. Direct comparison of frozen and FFPE samples from the same tumors showed an R2 correlation of beta values of greater than 95.0% between fresh frozen (FF) and FFPE samples. We also developed a method to assess FFPE sample quality based on a 90 bp qPCR assay (Infinium HD FFPE QC kit). In this assay FFPE samples exhibiting a Ct (Cq) difference of less than six relative to an intact standard are considered to pass the QC test and generally perform well in the assay. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-178. doi:10.1158/1538-7445.AM2011-LB-178

Quality Requirements for Critical Assay Reagents Used in Bioanalysis of Therapeutic Proteins: What Bioanalysts Should Know About Their Reagents

Ligand-binding assays are the standard technology used for bioanalysis of therapeutic proteins, for example, for drug quantification (pharmacokinetics assays) and immunogenicity testing (antidrug antibody assays). Besides the selection of the most suitable technology platform (e.g., ELISA, electrochemiluminescence assays and surface plasmon resonance assays) and assay procedure, a pivotal prerequisite for good assay performance on any technology platform is the design, production and characterization of high quality reagents. To enable bioanalytical project support over the complete product life cycle, an appropriate long-term reagent supply is needed. This perspective describes our opinion on the requirements for generation and QC of critical reagents used in ligand-binding assays for drug quantification and antidrug antibody detection to enable high-quality assays and long-term supply, including reagent batch switches. The critical parameters during reagent design, production and long-term supply, along with the appropriate analytical methods for QC testing and appropriate certification, are discussed.

SU-GG-I-47: How Stable are the Qualities of Medical-Grade LCD Monitors? Is the TG18 QC Test Pattern Sensitive Enough to Detect Any Quality Degradation?

Background: Medical‐grade LCD monitors have been used in PACS for nearly a decade and they have been touted as much more stable than their CRT predecessor thus might have lead some PACS users to become complacent in their monitor QC efforts. In this study, we wanted to determine the effect of extensive, long‐term clinical use upon these monitors in a large‐scale picture archiving and communications system (PACS). Additionally, we evaluated the sensitivity of sharp edged low‐contrast objects (as often contained in the AAPM TG18 test patterns) in the detection of contrast resolution degradation in monitors. Materials and Methods: A group of medical‐grade monitors were selected for this study based on their durations of operational use. The contrast‐detail (C‐D) characteristics of these monitors were measured with both a disc‐like object with sharp edges and a nodular object with fuzzy boundaries against uniform backgrounds at various luminance levels. The monitors were sorted into three groups according to their length of use, which ranged from 20 hours to ∼35,000 hours, and their C‐D curves were compared. Results: There was a trend of gradual degradation in the monitors' contrast sensitivity although the changes were not statistically significant at all object sizes and luminance levels. Contrast thresholds measured with nodular objects were higher (thus more difficult to detect) than those measured with disc‐like objects and should probably be used in the quality assessment of monitors. Conclusion: Extensive clinical use over time may cause gradual but not statistically significant changes in image quality of monitors. Sensitive measures may be needed to detect subtle deterioration in monitors used for primary diagnostic purposes.

Stability-Indicating High-Performance Thin-Layer Chromatographic Method for Quantitative Determination of Omeprazole in Capsule Dosage Form

A novel HPTLC method has been developed and validated for quantitative determination of omeprazole (OPZ) in capsule dosage form. The method was validated according to the International Conference on Harmonization guidelines for accuracy, precision, linearity, specificity, and robustness. HPTLC aluminum sheets precoated with silica gel 60F24 were used as the stationary phase and chloroform-methanol (9 + 1) as the mobile phase. The mobile phase was found to give compact bands for OPZ (Rf value of 0.39 +/- 0.12) in densitometric analysis in the absorbance mode at 302 nm. The linear regression analysis data for the calibration plots showed good linearity (r2 = 0.997) with respect to peak area in the concentration range 50-3000 ng/band. The mean values of the slope and intercept were 9.896 +/- 0.0753 and 1870.761 +/- 16.866, respectively. The method was also applied for stability testing of OPZ in different stress conditions and found to be accurate, linear, precise, robust, specific, and stability indicating. The method proposed can be used for QC and stability testing of different dosage forms such as tablets and capsules, as well as for bulk drug analysis of OPZ.

Trial of a proposed protocol for constancy control of digital mammography systems

Evaluate the utility of tests in a proposed protocol for constancy control of digital mammography systems. The protocol contained tests for image acquisition, mechanical function and safety, monitors and printers, and viewing conditions. Nine sites with digital systems from four equipment manufacturers were recruited. Dedicated PMMA test objects and Excel spreadsheets were developed. Quantitative measurements were done on processed images for systems where these images were the ones most readily available. For daily assessment of the automatic exposure control system, a homogeneous PMMA phantom was exposed under clinical conditions. The mAs and signal to noise ratio (SNR) were recorded, the deviation from a target value calculated, and the resulting image inspected for artifacts. For thickness tracking, the signal difference to noise ratio obtained for three thicknesses was calculated. Detector uniformity was assessed through comparison of SNR values for regions of interest in the center and corners of an image of a homogeneous test object. Mechanical function and safety control included a compression test, a checklist for mechanical aspects, and control of field alignment. Monitor performance was evaluated by visual inspection of the AAPM TG 18 QC test image [E. Samei et al., "Assessment of display performance for medical imaging systems," Task Group 18 (Madison, WI, April 2005)]. For quantitative parameters, target values and tolerance limits were established. Test results exceeding the limits were registered. Most systems exhibited stable mAs values, indicating that the tolerance limit of +/- 10% was readily achievable. The SNR also showed little variation, indicating that the tolerance limit of +/- 20% was too wide. At one site, a defective grid caused artifacts that were visible in the test images. The monitor controls proved more difficult to implement due to both difficulties importing and displaying the test image, and the radiographic technologists not getting necessary access to the reading stations. The proposed tests could easily be performed by trained radiographic technologists and within a time frame comparable to similar programs for analog systems. Tests with quantitative measures were more readily performed than procedures that required a subjective evaluation. Several of the proposed tests revealed equipment performance that required intervention, and which would otherwise have gone unnoticed. They therefore defend a place in a vendor-independent constancy control protocol.

Introducing Quality Control in the Chemistry Teaching Laboratory Using Control Charts

In subsequent years the QC chart archive will grow allowing for the optimization of the limits set at the start of each year. Limits set must not be too strict or too lenient but rather should allow for a reasonable compromise between allowing progress with laboratory teaching, yet providing regular incidences where trouble shooting is required. The detection and rectification of errors must be possible with reasonable extra care, within the time constraints of a laboratory teaching session and respecting student ability. Because of high incidences of calculation errors where results were calculated manually, we have opted for computer-assisted calculations (templates) allowing the focus to be on laboratory error in future. In the first year we were surprised to find that virtually all QC data points were outside the control limits for the simpler UV-vis experiment for master's and undergraduate students. We believe that feedback and student discussion prior to the start of the second year contributed to improved quality of results and better compliance for undergraduate students although most data points were still outside the staff-generated limits. Total compliance was achieved in the second year based on limits calculated using the first-year student data. For subsequent years we shall continue to use and fine tune student-generated limits for this experiment. For the HPLC experiment in the first year, total compliance for k and a 20% failure rate for N was achieved by master's students. The undergraduate class had a 30% failure rate for N and a 35% failure rate for k. These dramatically higher failure rates perhaps reflects the less experience of the undergraduate students. A marked improvement in quality of results was again observed for the second year. Undergraduates achieved total compliance with staff-generated limits of k and improved compliance in the QC test for N, with about 7% results outside the control limits of N, requiring troubleshooting and repeat analysis. For the HPLC experiment we intend to continue using staff-generated QC chart limits. Unlike for the UV-vis experiment, the wider student data-based limits are perhaps too lenient, not providing enough incidences where student action is required. We have found that the quality of results does not necessarily follow the perceived simplicity of an experiment. Each experiment is clearly unique and the process of establishing an appropriate mean and limits varies. The goal is the same in all cases, where adequate progress learning laboratory skills must be balanced with the provision of enough realistic troubleshooting scenarios (occasional quality failures). With time and a growing archive of QC data, the instructor can get a better feel for the level of performance that can be reasonably expected from students. An additional step in the future may be that a student or a small group of students could take charge of a particular QC chart, collecting data from other groups over consecutive weeks. By communicating with teachers and colleagues, they could help manage the quality and troubleshooting for their experiment, thereby taking responsibility and developing a greater sense of involvement with the laboratory function. Interestingly the QC components in the experiments, besides motivating the individual, were found to nurture a healthy element of competition between students helping to achieve better quality results. Students were shown the real-world fact that improving quality control is a dynamic never-ending yet essential task. Both the QC tolerances and achieved quality continually vary with changing technology, market expectations, and caliber of laboratory personnel. © Division of Chemical Education.

Assessing the Impact of the Frequency of Quality Control Testing on the Quality of Reported Patient Results

The traditional measure used to evaluate QC performance is the probability of rejecting an analytical run that contains a critical out-of-control error condition. The probability of rejecting an analytical run, however, is not affected by changes in QC-testing frequency. A different performance measure is necessary to assess the impact of the frequency of QC testing. I used a statistical model to define in-control and out-of-control processes, laboratory testing modes, and quality control strategies. The expected increase in the number of unacceptable patient results reported during the presence of an undetected out-of-control error condition is a performance measure that is affected by changes in QC-testing frequency. I derived this measure for different out-of-control error conditions and laboratory testing modes and showed that a worst-case expected increase in the number of unacceptable patient results reported can be estimated. The laboratory thus has the ability to design QC strategies that limit the expected number of unacceptable patient results reported. To assess the impact of the frequency of QC testing on QC performance, it is necessary to move beyond thinking in terms of the probability of accepting or rejecting analytical runs. A performance measure based on the expected increase in the number of unacceptable patient results reported has the dual advantage of objectively assessing the impact of changes in QC-testing frequency and putting focus on the quality of reported patient results rather than the quality of laboratory batches.

WE-C-AUD A-04: Beyond FMEA: Summary and Future Developments

Failure Modes and Effects Analysis (FMEA) is a useful tool for deepening understanding of the radiation therapy (RT) delivery process flow and for identifying specific process steps that are likely to result in patient harm in the event of errors. Developing an RT process tree can in itself can lead to improved efficiency and safety. FMEA encourages the treatment delivery team to view RT delivery holistically, as it requires the team not only to catalogue possible errors at each process tree step, but to assess their frequency, clinical impact, and potential for propagation without detection into downstream processes. Thus, an FMEA helps focus physics attention on relatively low probability process errors with potential for inflicting catastrophic harm on patients. The AAPM FMEA IMRT analysis raises many questions and issues: 1. How much benefit can a clinic derive from a model FMEA developed for a generic process tree compared to taking their own treatment delivery team through FMEA of their specific process? 2. FMEA gives limited insight into causes of errors; correlation or propagation of errors into other steps; or how to modify a process in order to mitigate errors. 3. FMEA ranks possible errors in order of risk (RPN) to the patient under the artificial assumption that no QA is being performed. The impact of QA tests chosen to address a high RPN error mechanism on remaining risk rankings is not accounted for. A number of other risk assessment strategies for improving QA cost-effectiveness and robustness should be investigated. (a) Formal engineering tools such as fault-tree analysis, probabilistic risk assessment, and human error classification schemes all start with observed treatment delivery errors or near misses. Such techniques seek uncover the detailed mechanism of the event, its causal relationships to other events, and seek to assign root causes. (b) Sensitivity of the process outcome (e.g., dose delivery accuracy) to system parameters (e.g., MLC leaf-gap calibration) monitored by QC tests. Such analyses may provide a rational basis for assigning tolerances and action levels to device QC test outcomes. (c) Statistical process control techniques for identifying optimal QC test frequencies and action levels. (d) Multidisciplinary forums for developing QA guidance that bring together representatives of all constituencies impacted by RT QA and delivery errors, including radiation oncologists, vendors, and therapists as well as physicists. Educational Objectives: 1. To understand the potential clinical applications and value of FMEA in designing safe and robust RT processes. 2. To appreciate the limitations of FMEA especially an analysis developed by a consensus panel using a generic process tree. 3. To assess audience feedback on possible future directions of the TG-100 work. 4. To review the potential costs and benefits of additional industrial engineering QM tools for more detailed and specific followup analysis of FMEA findings.

Design an Adaptive Quality Control Phantom to Optimize Integral and Differential Uniformity, Collimator Hole Angulation and Center of Rotation of SPECT

The main objective of this research is to introduce a newly developed device called “Adaptive Quality Control Phantom” (AQCP) designed to perform the QC tests. This paper describes complete details of the AQCP structure and its potential as a QC phantom. AQCP is the computer-controlled phantom which positions and moves a radioactive source in the Field of View (FOV) of an imaging nuclear medicine device on a definite path to produce any spatial distribution of gamma rays to simulate QC phantoms. Different tests that include systematic uniformity, collimator hole angulation and center of rotation were conducted by this device and the results, findings and differences of these tests were compared with the QC classic method tests. The performance of systematic uniformity test show a considerable reduction in the technologist dose compared to the IAEA-TECDOC-602 method. On the other hand the average error difference between two methods for evaluating uniformity parameters of uniform images is less than 0.07%. The collimator hole angulation for three collimators was measured by using a point source and computer-controlled cylindrical positioning, the results of which show that the measurement accuracy for absolute angulation errors is better than 0.047 (degrees) or ±0.024° . The Root Mean Square (RMS) of CHA for LEHR, LEHS and LEUHR collimators was measured to be 0.290° , 0.292° and 0.208° respectively. A method for center of rotation assessment is introduced by AQCP and the results of this proposed method as compared with the routine QC test and their differences are discussed in detail. Based on the discussion made in this paper regarding AQCP, the authors believe that this device is able to simulate QC phantoms. Keywords: Nuclear medicine, Adaptive quality control phantom, Systematic uniformity, Collimator hole angulation, Center of rotation