Quality Control Specifications Research Articles

Analysis of β-N-methylamino-L-alanine (BMAA) in spirulina-containing supplements by liquid chromatography-tandem mass spectrometry.

Over the last decade the amino acid beta-N-methylamino-L-alanine (BMAA) has come under intense scrutiny. International laboratory and epidemiological research continues to support the hypothesis that environmental exposure to BMAA (e.g., through dietary practices, water supply) can promote the risk of various neurodegenerative diseases. A wide variety of cyanobacteria spp. have previously been reported to produce BMAA, with production levels dependent upon species, strain and environmental conditions. Since spirulina (Arthrospira spp.) is a member of the cyanobacteria phylum frequently consumed via dietary supplements, the presence of BMAA in such products may have public health implications. In the current work, we have analyzed ten spirulina-containing samples for the presence of BMAA; six pure spirulina samples from two separate raw materials suppliers, and four commercially-available multi-ingredient products containing 1.45 g of spirulina per 8.5 g serving. Because of controversy surrounding the measurement of BMAA, we have used two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods: one based on reversed phase LC (RPLC) with derivatization and the other based on hydrophilic interaction LC (HILIC). Potential matrix effects were corrected for by internal standardization using a stable isotope labeled BMAA standard. BMAA was not detected at low limits of detection (80 ng/g dry weight) in any of these product samples. Although these results are reassuring, BMAA analyses should be conducted on a wider sample selection and, perhaps, as part of ongoing spirulina production quality control testing and specifications.

Key Construction Technology of Porous Concrete Permeable Base

Porous concrete also be called macropterous concrete or porous lean concrete.As a new base material,it is a lean concrete between cement stabilized macadam and ordinary concrete.Based on Luoyang beltway project,this paper describes the composition design of porous concrete,and discusses the combination of construction machinery,technological process,QCS(quality control specification) and test detection of porous concrete permeable base.Also we do research on many technological parameters such as mixing,paving,molding,maintenance in the construction of porous concrete permeable base.This provides a reference on construction technology and its application.

The Use of the Dynamic Cone Penetrometer for Quality Control of Compaction Operations

The use of a new quality control (QC) and quality assurance (QA) specification involving Dynamic Cone Penetrometer (DCP) testing in concert with conventional moisture and density testing is becoming more and more frequent in various parts of the world. The need for this additional testing is essential, as the regular in-situ density tests cannot alone ensure the compliance of the layers constructed with the compaction requirements. Recent analyses of the correlation between the DCP testing and the California Bearing Ratio CBR testing show that QC and QA DCP testing is adequate to verify compaction, stability and vertical uniformity in both cohesive and granular soils. Two examples of DCP usage in two Israeli earthwork projects, one of clayey soils and the other of silty-sand soils, indicate the benefits of this usage along with, though for the clayey example only, Falling Weight Deflectometer (FWD) testing.

Creating clinical target validation groups via quality assured transfer of robust clinical pharmacodynamic (PD) assays from the NCI: Clinical implementation of a PAR immunoassay in tumor biopsies.

e22080 Background: Early phase clinical trials of investigational agents benefit from laboratory assays that quantify intended mechanism of action on molecular target (1° PD effects), desired changes in mechanistic biomarkers (2° PD effects), and 3° PD effects on cell survival. Robust PD assay results are valuable for informing go/no‐go decisions about continued development of new agents and for identifying combinations of targeted agents that cover the multiple molecular defects underlying many malignancies. Methods: Readying PD assays for clinical use involves validating analytical performance, identifying and qualifying critical reagents, demonstrating fit‐for‐purpose for the clinical protocol, and finalizing companion SOPs specifying specimen handling and processing. Because clinical PD questions often demand assay performance that meets or even exceeds clinical diagnostic assay standards, but key assay reagents are usually R and D‐rather than GMP‐grade, stringent reagent Quality Control is critical for preventing assay failures due to lot-to-lot variability. Results: The poly(ADP-ribose) (PAR) Immunoassay was the first qualified assay developed by NCI for implementation in early phase clinical trials. Development of stringent production and internal Quality Control specifications for accepting/rejecting new lots of critical reagents and a defined Quality Assurance Plan allowed a network of users to achieve consistent results and quality using R&D-grade source materials. Conclusions: The NCI’s Division of Cancer Treatment and Diagnosis is developing a clinical PD assay portfolio capable of quantifying 1°, 2°, and 3° PD effects. Proven clinical assays are formally transferred from the NCI to requesting sites in academia and industry via laboratory‐based certification and training, centralized access to SOPs, assistance with assay transfer, and participation in the assay’s Quality Assurance Plan. Funded by NCI Contract No HHSN261200800001E.

A Study on the Organizational Architecture and Standard System of the Data Sharing Network of Earth System Science in China

The aim of this paper is to discuss the organizational architecture and standard system for sharing research data at the national level. The Data Sharing Network of Earth System Science (DSNESS) is one of the nine pilot projects of the Scientific Data Sharing Project in China that has become a long-term operational research data-sharing platform in the National Science and Technology Infrastructure (NSTI) of China. First, a data sharing union mechanism was designed with the core principle being, “data come from research and will be reused in research”. Second, a data sharing organizational architecture was constructed that consists of three sections: data resource architecture, data management architecture, and data services architecture. A physical data sharing network was constructed that includes one general center and 15 distributed sub-centers based on the architecture. Third, a series of data sharing standards and specifications were designed and implemented in the DSNESS. The reference model of the DSNESS standard system includes three levels of standards: directive standards, general standards, and application standards. In total, 21 high level standards and specifications were developed and implemented in the DSNESS. Several core standards and specifications, such as the extensible metadata standard, data quality control specifications, and so on, were analyzed in detail. Finally, the data service effect was summarized in three aspects: dataset services, standard and specification services, and international cooperation services. This research shows that the organizational architecture and standard system is a very important soft environment for research data sharing. The practices of DSNESS will provide useful experiences for multi-disciplinary data sharing in Earth science and will help to eliminate the data gap between the rich and poor at the national level.

Track Substructure Assessment using Non-Destructive Load Tests. A Portuguese Case Study

Nowadays, there is an increased interest in developing performance based specifications for quality control during the construction, that can provide more realistic information about the life cycle behaviour of the track.In this research, Falling Weight Deflectometer (FWD) tests were undertaken during the construction of a 29km new railway line, at the top of the substructure and in different months. Based on FWD deflections, structural models of the track were established through back-calculation, and the variation of the moduli for different testing campaigns was evaluated. The main results obtained are presented and analysed in this paper.

Quantifying Cell-to-Cell Variations in Lithium Ion Batteries

Lithium ion batteries have conventionally been manufactured in small capacities but large volumes for consumer electronics applications. More recently, the industry has seen a surge in the individual cell capacities, as well as the number of cells used to build modules and packs. Reducing cell-to-cell and lot-to-lot variations has been identified as one of the major means to reduce the rejection rate when building the packs as well as to improve pack durability. The tight quality control measures have been passed on from the pack manufactures to the companies building the individual cells and in turn to the components. This paper identifies a quantitative procedure utilizing impedance spectroscopy, a commonly used tool, to determine the effects of material variability on the cell performance, to compare the relative importance of uncertainties in the component properties, and to suggest a rational procedure to set quality control specifications for the various components of a cell, that will reduce cell-to-cell variability, while preventing undue requirements on uniformity that often result in excessive cost of manufacturing but have a limited impact on the cells' performance.

Improvements to Standard Methodologies for the Analytical Determination of Metals in Stationary-Source Emissions Samples

ABSTRACT Deficiencies with the current European reference method for the analysis using inductively couple plasma–mass spectrometry of metals in samples from stationary emissions sources are presented based on experimental data obtained from real samples. The effect of these deficiencies on the quality and accuracy of data is highlighted with biases of up to 40% being observed in real samples. Suggestions to improve the performance of the standard method are presented. In particular, the beneficial effect of using a drift correction procedure to account for the decrease in instrument sensitivity observed during an analytical measurement series is demonstrated. It is shown that this corrective procedure results in substantial improvements to the accuracy of data produced. IMPLICATIONS This work highlights the deficiencies in the analytical and quality control specifications of documentary standard methods for the determination of metals in stationary-source emissions and the systematic biases in analysis that can occur as a result. There are implications of this work for policy-makers and enforcement officers with respect to the real possibility of mistakes being made when gauging compliance with legislative emissions limits when using current methods. The solutions presented to ensure accurate measurements will be of interest to documentary standards experts and legislators to consider when the relevant standards are next revised.

Field Assessment and Specification Review for Roller-Integrated Compaction Monitoring Technologies

Roller-integrated compaction monitoring (RICM) technologies provide virtually 100-percent coverage of compacted areas with real-time display of the compaction measurement values. Although a few countries have developed quality control (QC) and quality assurance (QA) specifications, broader implementation of these technologies into earthwork construction operations still requires a thorough understanding of relationships between RICM values and traditional in situ point test measurements. The purpose of this paper is to provide: (a) an overview of two technologies, namely, compaction meter value (CMV) and machine drive power (MDP); (b) a comprehensive review of field assessment studies, (c) an overview of factors influencing statistical correlations, (d) modeling for visualization and characterization of spatial nonuniformity; and (e) a brief review of the current specifications.

Indian Drugs and Pharmaceutical Industry: The Impact of Intellectual Property Rights

The global pharmaceutical industry has shown high interest in India due to its sustained economic growth and health care reforms. In the last few years the Indian pharmaceutical industry has achieved significant momentum, making its presence felt in the global market, primarily through its focus on the global generics market. Better quality control and international packaging specifications are needed before India can compete with international norms in drug production.

Quality specification of Perillae Fructus

To improve the quality control specification of Perillae Fructus, the identification methods and assay were developed. Rosmarinic acid, luteolin and apigenin in the sample were identified by TLC. The content of rosmarinic acid was determined by HPLC. The linear calibration curve of rosmarinic acid was obtained in the ranges of 19.4-194.2 g x L(-1) (R2 = 0.9999). The arerage coveriy (n=9) for the assay was 99.8% (RSD 3.6%). The established methods are accuracy, sensitivity and reproducible, and can be used for the quality control of Perillae Fructus.

Subjectivity in defining quality specifications for quality control and test validation

Subjectivity in defining quality specifications for quality control and test validation

Purity, Potency and Safety: Quality Management Reports (QMR) as the Basis for An Effective Continuous Process Improvement System in An Academic Gene Therapy Program.

Abstract 1417Poster Board I-440Gene-modified cellular products (GMCP) hold great promise for the management of numerous disease indications but are considered high-risk biological agents and are derived through extremely complex design and manufacturing processes. Thus, a robust Quality Management System (QMS) is essential for safe production of GMCP for clinical investigation. Development of a QMS that ensures compliance with current Good Manufacturing Practices (cGMP) and current Good Tissue Practices (cGTP) is particularly challenging in an academic setting where basic researchers, clinical investigators, regulatory, administrative, facilities and manufacturing personnel are all involved in the realization of a single GMCP. Following an ISO9001-based gap analysis of the Cellular Therapeutics program at the City of Hope, we implemented Quality Management Reports (QMR) as a tool for capturing data related to GMCP manufacturing. The QMR system was used to document and facilitate corrective and preventative actions (CAPA) as required following protocol deviation and/or Out of Specification (OOS) analyses. QMR data is captured in real-time and includes a detailed description of the event, impact analysis, root cause investigation, action plan and effectiveness analysis for resulting interventions. QMRs are documented using the Labware® (Wilmington, DE) Laboratory Information Management System (LIMS) that is available in real-time to authorized participants in GMCP production. A key aspect in the development of this on-line system was creation of links between the QMRs, OOS and CAPA documentation and investigation. The investigation database contains a series of templates: CAPA, SOP deviations, OOS and QMR that are designed to fully capture any events that impact or have the potential to impact quality, safety or efficient realization of a GMCP. The QMR process was applied to 2 manufacturing campaigns: a lentiviral vector-transfected CD34 GMCP for autologous transplantation in patients with AIDS lymphoma and a Master Cell Bank that was created for the treatment of patients with recurrent Glioblastoma Multiforme based upon an oligoclonal allogeneic T-cell product that contained both a chimeric antigen T-cell receptor and a zinc finger disrupted glucocorticoid receptor genomic sequence. Between May 2008-June 2009, 22 QMRs were generated related to product/reagent transfer, reagent quality/storage, equipment malfunction/OOS, product/environmental sterility, biological reagent OOS and Quality Control specifications for product release. Seventeen of 22 QMRs were resolved and closed. The average time to closing a QMR was 82 days (range 4-198 days). QMR findings lead to a revision of the program organizational chart, lead to the development and implementation of a new standard operating procedure (SOP) for Root Cause Analysis (RCA) investigations, development of new forms (GMP Equipment Approval Forms, a Quality Systems Project Proposal Form and Quality Assurance Customer Satisfactions Survey Forms), revisions to the SOP for CAPA and retraining of manufacturing staff as part of the resultant CAPA investigations to prevent repeat occurrences. Based upon QMR findings, 2 multidisciplinary RCAs were performed and resulted in revisions to documentation for CD34-cell selection and a major revision to the use of RODI water and manufacturing flow during GMCP production campaigns. Only 1 of 22 QMR-captured events has recurred (failure of an equipment monitoring system) and no events have re-occurred that might have had an impact upon product quality or safety. User satisfaction surveys performed by QA following the completion of a multidisciplinary RCA investigation indicate that the QMR process was viewed as fair, unbiased and transparent by a majority of the users (86% were either “Extremely Satisfied” or “Satisfied” with the experience). The QMR process is a powerful tool for the safe realization of GMCP and allows for real-time capture and multidisciplinary communication of complex events, including OOS that either individually or in aggregate may impact the purity, potency or safety of manufactured GMCP. These are often events that would not be routinely captured either as part of a batch record or merit CAPA. Because effectiveness analysis is included as part of the QMR process, it provides a key mechanism for continuous process improvement. Disclosures:Alvarnas: Novartis: Speakers Bureau.

Impurities in Herbal Substances, Herbal Preparations and Herbal Medicinal Products, IV. Heavy (Toxic) Metals

The main source of available forms of heavy metals (toxic metals) for the plant kingdom is anthropogenic, resulting from diverse activities such as metallurgic processing of ore, cement plants, uncontrolled discharge of sewage sludge, burning of fossil fuels and waste incineration plants, and leaded petrol. Agricultural chemicals (e.g. phosphate fertilizers containing cadmium) may also contribute to the contamination of cultivated plants. The main threats to human health from toxic metals are associated with exposure to lead, cadmium, mercury (organic forms, especially methylmercury) and arsenic (mineral form only), which have no known vital or beneficial effect on living organisms. As their toxicity often takes years to manifest and may go unsuspected, their toxicological risk is defined on the basis of the so-called Provisional Tolerable Weekly Intake (PTWI) values. Beside anthropogenic causes, the main factors that may lead to high levels of toxic metals in medicinal plants are their availability in the soil with soil pH as the most important parameter for uptake by the plant. Indeed, genetic features of certain plant species show a tendency to accumulate certain trace elements, especially cadmium (“cadmium collector”). A very recent revision draft of the monograph “Herbal drugs” (Ph. Eur., 1433) includes acceptance criteria for lead, cadmium and mercury. This proposal is discussed in detail, based on literature data dealing with terrestrial plants and seaweed. Additionally, the need for inclusion of tests for inorganic impurities in quality control specification is examined, based on a risk assessment. As the daily intake of food supplements is very similar to the one of herbal remedies, it would be advisable to take into account the same acceptance criteria. The specific situation has also been considered of exotic herbal remedies, particularly those of Asian origin, which have been repeatedly reported to contain toxic levels of heavy metals and/or arsenic resulting in heavy metal poisoning.

Evaluation of Dynamic Cone Penetration Quality for Cohesive Soil Embankment Construction

A pilot project at US-34 in Iowa recently required the use of a new quality control (QC) and quality assurance (QA) specification involving dynamic cone penetration (DCP) testing in concert with conventional moisture and density testing. The contractor's QC test results were verified with occasional QA testing by Iowa State University and the Iowa Department of Transportation. Cone penetration testing and laboratory unconfined compressive strength testing were conducted on samples obtained on natural fill material before excavation and afterwards on the compacted fill to evaluate the performance properties of the final product. The research findings documented in this paper focus on (a) statistical comparisons between contractor QC and independent QA test data, (b) statistical analysis of the contractor QC data, and (c) evaluation of the performance of a completed embankment. The study findings show that the DCP can be used for QC and QA testing for cohesive soils to evaluate stability and vertical uniformity.

Preparation of genetically engineered A/H5N1 and A/H7N1 pandemic vaccine viruses by reverse genetics in a mixture of Vero and chicken embryo cells.

Background In case of influenza pandemic, a robust, easy and clean technique to prepare reassortants would be necessary. Objectives Using reverse genetics, we prepared two vaccine reassortants (A/H5N1 × PR8 and A/H7N1 × PR8) exhibiting the envelope glycoproteins from non‐pathogenic avian viruses, A/Turkey/Wisconsin/68 (A/H5N9) and A/Rhea/New Caledonia/39482/93 (A/H7N1) and the internal proteins of the attenuated human virus A/Puerto Rico/8/34 (H1N1). Methods The transfection was accomplished using a mixture of Vero and chicken embryo cells both of which are currently being used for vaccine manufacturing. Results This process was reproducible, resulting in consistent recovery of influenza viruses in 6 days. Because it is mainly the A/H5N1 strain that has recently crossed the human barrier, it is the A/PR8 × A/H5N1 reassortant (RG5) that was further amplified, either in embryonated hen eggs or Vero cells, to produce vaccine pre‐master seed stocks that met quality control specifications. Safety testing in chickens and ferrets was performed to assess the non‐virulence of the reassortant, and finally analysis using chicken and ferret sera immunized with the RG5 virus showed that the vaccine candidate elicited an antibody response cross‐reactive with the Hong Kong 1997 and 2003 H5N1 strains but not the Vietnam/2004 viruses. Conclusions The seeds obtained could be used as part of a pandemic vaccine strain ‘library’ available in case of propagation in humans of a new highly pathogenic avian strain.

Evaluation of the most effective measures of infectivity of a precocious line of Eimeria acervulina in poultry

Coccidiosis is an economically important parasitic disease of chickens that, in Australia, is caused by seven species of the genus Eimeria.1 The disease has traditionally been controlled by prophylactic drugs, but vaccination with attenuated lines of the parasites2–4 is rapidly gaining acceptance world wide. Live Eimeria vaccines are produced in batches which are not frozen and have a limited shelf life. The per cent infectivity of vaccine seed stocks and the vaccines produced from them must therefore be accurately monitored using standardised dose dependant assays to ensure that shelf life, quality control and vaccine release specifications are met. Infectivity for the chicken host cannot readily be determined by microscopic observation of oocysts or sporocyst hatching.5 Dose dependent parameters such as body weight gain, feed conversion ratio, visual lesion scores, mortality, oocysts production, clinical symptoms and microscopic lesion counts could be used as measures of infectivity.6–11 These parameters show significant dose dependant effects with field strains, but lines of vaccine parasites that have been selected for precocious development with associated reduced virulence and reproductive capability may not have the same effect.3,4 The aim of this trial was to determine which parameters provide the most effective measures of infective dose in birds inoculated with a precocious vaccine strain.

Development of Pavement Smoothness Index Relationship

Abstract In its pursuit for providing smooth pavements, the Directorate General of Highways in Taiwan is developing and implementing ride quality specification as part of the construction assurance program. The straightedge and the profiler were used to measure pavement smoothness on 561 test sections. Probability distribution analysis showed that measurements of pavement smoothness of both devices follow the normal distribution. Smoothness specifications for construction quality control were developed for straightedge and profiler, respectively. The full-pay range is 1.36 to 2.45 mm and 2.16 to 3.65 m/km for straightedge and profiler, respectively. The smoothness relationship between straightedge and profiler was developed.

Prevention of Refinery Plugging by Residual Oil Gellant Chemicals in Crude-Optimization of Phosphonate Ester Oil Gellants

Abstract Previous research(1, 2) described refinery plugging caused by volatile phosphorus components originating from phosphate ester oil gellants. Also documented were two successful field trials of new phosphonate ester oil gellants used to address this problem. In this paper, results of additional field testing are presented as a final step to broad field application. The objectives of this additional work were to optimize cost and performance, investigate any remaining questions, and establish quality control specifications based on both performance testing and NMR compositional analysis. The synthesis methodology of this new molecule has been refined as a means to reducing final production costs. One objective of the additional field testing was to ensure both operational performance and the ability to control volatile phosphorus while continuing to meet the standards of the first two field trials. Several questions also needed further investigation. One issue was the ability of phosphonate esters to control volatile phosphorus at higher temperatures. Distillations used to evaluate volatile phosphorus to date have had a 250 °C end point. This temperature was chosen because it represents the approximate temperature experienced at the distillation tower trays where plugging has been observed from components condensing from the gas phase. However, the actual peak temperature in the tower bottom is closer to 350 °C. This higher temperature is the actual temperature at which decomposition or volatilization will occur. Therefore, to more fully understand our ability to control volatile phosphorus, distillations were conducted with a 350 °C end point. Volatile and total phosphorus to both 250 °C and 350 °C end points are reported. Another continuing area of concern has been organic halide formation under distillation tower conditions. Although no organic halides were detected in either of the two initial field trials, further testing was conducted during the additional field trials reported in this paper. Finally, quality control methods have been established based on both performance testing and compositional analysis determined using NMR. Overall conclusions are drawn in preparation for broad field implementation regarding:Ability to control volatile and total phosphorus;Ability to prevent organic halide formation;Cost and availability;Rheology and CO2 compatibility;Temperature stability;Field handling and typical concentration ranges; and,Quality control specifications based on performance testing and NMR analysis. Theory Free-radical addition of dimethyl phosphite to an alpha olefin can result in a mixture of isomers. The desired 1 ° product arises from addition to the terminal carbon of the double bond, but some addition of the double bond results in formation of the 2 ° isomer (Figure 1). Depending on the reaction conditions, this byproduct can account for as much as 20% of the product. Both of these isomers are carried through the subsequent dealkylation reaction, again resulting in a mixture of isomers (Figure 2). To obtain a successful product, two characteristics are required: low volatility to prevent distillation tower fouling and the ability to form a good gel. Gelation results from metal complexation with the phosphonate monoester.

The effects of poultry meal source and ash level on nursery pig performance.

Weanling pigs (total of 560) were used in two experiments to determine the effects of poultry meal in nursery diets on pig performance. In Exp. 1,210 barrows and gilts (initially 7.4 kg and 21 +/- 2 d of age) were fed one of five diets, which included a control diet with no specialty protein products or (as-fed basis) the control with 2.5 or 5.0% fish meal, or 2.9 or 5.9% poultry meal (11.8% ash). Poultry meal replaced fish meal on an equal lysine basis. Overall (d 0 to 28), pigs fed diets containing fish meal had greater (P < 0.01) ADG than pigs fed poultry meal. Increasing fish meal tended to have increased (quadratic, P < 0.07) ADG, with the greatest improvement observed in pigs fed the diet containing 2.5% fish meal. Pigs fed diets containing fish meal had improved (P < 0.01) G:F compared with pigs fed diets containing poultry meal. In Exp. 2, a total of 350 barrows and gilts (initially 8.9 kg and 22 +/- 2 d of age) were fed one of seven experimental diets, which included a control diet with no specialty protein products, or the control with 2.5 or 5.0% fish meal, 2.9 or 5.8% low-ash (10.9%) poultry meal, and 3.1 or 6.2% high-ash (13.5%) poultry meal. Poultry meal replaced fish meal on an equal lysine basis. Overall (d 0 to 15), there were no differences in ADG and ADFI (P = 0.14); however, pigs fed diets containing fish meal or poultry meal had improved (linear, P < 0.01) G:F compared with pigs fed the control diet. Pigs fed diets containing low-ash poultry meal had greater (P < 0.01) G:F compared with pigs fed diets containing high-ash poultry meal. Based on these data, quality control specifications, such as ash content, need to be considered when using poultry meal as an animal protein replacement in diets for nursery pigs.