Contract Laboratory Research Articles

Comparison of etonogestrel bioanalytical assay results in plasma and serum within and across laboratories

ObjectivesTo compare performance characteristics of etonogestrel bioanalytical assays across laboratories. Study designWe conducted a blinded, six laboratory study: five academic laboratories and one contracted commercial laboratory (reference). Etonogestrel was quantitated at each laboratory in both prepared serum and/or plasma samples of six known etonogestrel concentrations, and in 60 clinical samples from participants using etonogestrel-containing contraceptive methods. Per regulatory guidance, laboratory accuracy (percent bias) and precision (coefficient of variation; CV) were defined as ±15% of the nominal prepared concentration. We compared inter- and intra-laboratory agreement using a Kendall’s Tau-B and Passing-Bablok regression. ResultsFor prepared samples, six laboratories analyzed serum and three laboratories analyzed plasma. All etonogestrel results were within ±15% for accuracy across all concentrations at four labs, including the reference laboratory. All labs demonstrated high precision, with only one occurrence of CV >15%. We found a positive association between prepared plasma and serum etonogestrel results (Kendall’s Tau-B 0.80–0.88). For clinical samples, five laboratories analyzed serum and three laboratories analyzed plasma. Compared to the reference laboratory, inter-laboratory serum etonogestrel concentrations were positively correlated (Kendall’s Tau-B 0.76–0.95). Proportional bias was observed, meaning individual lab etonogestrel results were consistently higher (slope estimates 0.78–0.95) or lower (slope estimates 1.05–1.10) than the reference laboratory. In clinical samples, intra-laboratory results were well associated between plasma and serum (Kendall’s Tau-B 0.92–0.96). ConclusionsThere was good intra-laboratory agreement, irrespective of sample matrix; however, there was inter-laboratory variability in etonogestrel results. Differences between laboratory results should be considered when comparing etonogestrel pharmacokinetics across studies. ImplicationsEtonogestrel concentrations were highly precise within each laboratory and were comparable between serum and plasma. Results varied between laboratories (5–28% higher to 5–9% lower compared to the Organon commercial laboratory). To minimize variability, we recommend utilizing a single laboratory that conducts routine proficiency testing for etonogestrel analysis within a study.

Harmful and Potentially Harmful Constituents in E-Liquids and Aerosols from Electronic Nicotine Delivery Systems (ENDS).

In 2012, the U.S. Food & Drug Administration (FDA) published an established list of 93 harmful and potentially harmful constituents (HPHCs) targeting four tobacco product types (cigarettes, cigarette tobacco, roll-your-own tobacco, smokeless tobacco). In 2016, the FDA finalized the deeming rule to regulate electronic nicotine delivery systems (ENDS). However, knowledge gaps exist regarding whether certain HPHCs are present in ENDS e-liquids and aerosols. We identified and addressed these gaps by conducting literature searches and then experimentally quantifying HPHCs in the e-liquid and aerosol of 37 ENDS brands based on gaps in the literature. The literature searches identified 66 e-liquid HPHCs and 68 aerosol HPHCs that have limited to no information regarding the quantifiability of these constituents. A contracted ISO 17025 accredited laboratory performed the HPHC quantifications. The availability of validated analytical methods in the contracted laboratory determined the HPHCs included in the study scope (63/66 for e-liquids, 64/68 for aerosols). Combining the results from the quantifications and literature searches, 36 (39%) and 34 (37%) HPHCs were found quantifiable (≥limit of quantification [LOQ]) in ENDS e-liquids and aerosols, respectively, with 25 HPHCs being quantifiable in both matrices. Quantifiability results imply potential HPHC transfers between matrices, leaching from components, or formations from aerosol generation. The study results can inform the scientific basis for manufacturers and regulators regarding regulatory requirements for HPHC reporting. The HPHC quantities can also inform evaluations of the public health impact of ENDS and public communications regarding ENDS health risks.

Hepatitis A Virus Infection in Cynomolgus Monkeys Confounds the Safety Evaluation of a Drug Candidate.

In a 3-month toxicity study in cynomolgus monkeys at a European contract laboratory, animals were infected with HAV, initially resulting in hepatic injury being incorrectly attributed to the test compound. Elevated serum ALT/AST/GLDH (5- to 10-fold) were noted in individual animals from all groups including controls, with no apparent dose, exposure, or time-related relationship. Liver histopathology revealed minimal to slight inflammatory cell accumulation in periportal zones of most animals, and minimal to slight hepatocyte degeneration/necrosis in 10/42 animals from all groups. As these findings were more pronounced in 6 drug-treated animals, including 2/6 in the low dose group, the draft report concluded: "treatment-related hepatotoxicity at all dose levels precluded determination of a NOAEL." However, the unusual pattern of hepatotoxicity suggested a factor other than drug exposure might have caused the hepatic effects. Therefore, snap-frozen liver samples were tested for hepatitis viruses using a PCR method. Tests for hepatitis B, C, and E virus were negative; however, 20/42 samples were positive for hepatitis A virus (HAV). Infection was strongly associated with increased serum ALT/GLDH, and/or hepatocyte degeneration/necrosis. Re-evaluation of the study in light of these data concluded that the hepatic injury was not drug-related. A subsequent 6-month toxicology study in HAV-vaccinated cynomolgus monkeys confirmed the absence of hepatotoxicity. Identification of HAV infection supported progression of the drug candidate into later clinical trials. Although rarely investigated, subclinical HAV infection has occasionally been reported in laboratory primates, including those used for toxicology studies and it may be more prevalent than the literature indicates.

MAIT Cell Frequencies within PBSC Grafts Are Associated with Donor CMV Serostatus and Age: An Initial Analysis from the DKMS and NMDP Graft Composition Study

Introduction We have established an international collaboration between the DKMS (Germany) and the National Marrow Donor Program (NMDP; USA) to characterize more than 2000 donor peripheral blood stem cell (PBSC) grafts. We aim to correlate graft immunophenotype with patient outcomes and perform additional analyses on biobanked aliquots of selected samples to deepen our understanding of the relationships between features of the donor graft and key patient outcomes, such as graft-versus-host disease, relapse, and overall survival. Here, we present an interim analysis, focused on the CD8 T cell compartment, describing relationships between donor characteristics and graft composition. We have developed a novel computational clustering method to integrate cytometry data from both the US and German analytical laboratories. Methods 300 donor PBSC graft samples were collected, processed, freshly stained (34-color panel for immunophenotyping of lymphocytes and hematopoietic stem cells), and analyzed using an Aurora Cytek instrument at the NMDP contract laboratory (Roswell Park, Buffalo, NY). 53 additional samples were processed in the DKMS laboratory in Dresden, Germany (equivalent antibody panel and instrument). We have developed a novel analytical pipeline for integrating these data. First, we group samples by facility, and by month run for computational convenience, to form “batches” for initial clustering. We perform Leiden clustering, and subclustering, to generate a large number of clusters per batch. To integrate data from all batches, we then cluster all subcluster centroids from all batch-specific clusterings. This gives a global clustering for each stream ( e.g. the CD8+ T cells). Cluster frequencies per sample provide features for quantifying links between immunophenotype and donor metadata ( e.g., CMV serostatus, age, and sex). Our approach offers an important complement to traditional gating and allows full exploration of the data in an unbiased fashion. Results 353 donor products were included in the analysis. The median donor age was 28 years (range 18 - 60), 59% were female and 65% were CMV positive. Initial metaclustering demonstrated that the 53 DKMS samples and the 300 NMDP samples are each well represented in all clusters, and that site-driven batch effects, while present, are mild. We initially focused on the CD8 T cell compartment (UMAP in Fig 1A) and discovered several phenotypic differences when we compared CMV seronegative and seropositive donors. CD8 T cell clusters 10 and 11 (both TCRαβ+ CD45RA+ CCR7+ HLA-DR+ CD57+; cluster 10 CCR9+; cluster 11 CCR9-) were present at higher frequency in CMV+ donors (n = 116) compared with CMV- donors (n = 220; p <0.0001; Fig 1B). Conversely, clusters 9 and 12, enriched for mucosal-associated invariant T (MAIT) cells, were significantly reduced in CMV+ donors (p <0.001). Of note, CMV serostatus was not significantly associated with age (median age in the CMV+ group was 29.4 years; vs 28.4 years in CMV- donors). We also observed an association between cluster 8 (TCRαβ+ CD45RA+ CCR7+ HLA-DR+ CD38+; consistent with an activated phenotype) and age (p = 0.0009; Fig1B). There was a trend toward decreased MAIT frequencies with age (Cluster 9; p = 0.058). When we analyzed the MAIT cell frequency as defined by traditional flow cytometry gating (CD3+ CD8+ CD161+ Vα7.2+), we observed a statistically significant relationship between younger donor age and increased MAIT cell frequency (p = 0.0002), consistent with the trend seen in cluster 9. Sex at birth was not linked with immunophenotype in our analyses thus far. Conclusions In this initial analysis of our multi-center observational study of PBSC graft products, we demonstrate the development and application of new computational tools for large-cohort flow cytometric data analysis. CMV-positive serostatus and younger donor age are both associated with an increased frequency of MAIT cells in the graft. We also found differences in CD8 T cell activation status in association with age and CMV. In the future, we will assess the relationships between these populations and patient outcomes, as well as explore cluster frequencies in association with key patient outcomes including GVHD, relapse, and overall survival. Sample collection and analysis are ongoing at both US and German sites as an ongoing collaborative effort between the NMDP and the DKMS.

Comparative study between virus neutralisation testing and other serological methods detecting anti-SARS-CoV-2 antibodies in Europe, 2021

One consequence of the ongoing coronavirus disease pandemic was the rapid development of both in-house and commercial serological assays detecting anti-SARS-CoV-2 antibodies, in an effort to reliably detect acute and past SARS-CoV-2 infections. It is crucial to evaluate the quality of these serological tests and consequently the sero-epidemiological studies that are performed with the respective tests. Here, we describe the set-up and results of a comparative study, in which a laboratory contracted by the European Centre for Disease Prevention and Control offered a centralised service to EU/EEA Member and pre-accession Member States to test representative serum specimens with known serological results, with the gold standard technique (virus neutralisation tests) to determine the presence of neutralising antibodies. Laboratories from 12 European countries shared 719 serum specimens with the contractor laboratory. We found that in-house serological tests detecting neutralising antibodies showed the highest percent agreement, both positive and negative, with the virus neutralisation test results. Despite extensive differences in virus neutralisation protocols neutralisation titres showed a strong correlation. From the commercial assays, the best positive percent agreement was found for SARS-CoV-2 IgG (sCOVG) (Siemens - Atellica IM Analyzer). Despite lower positive percent agreement of LIAISON SARS-CoV-2 TrimericS IgG kit (Diasorin Inc.), the obtained results showed relatively good correlation with neutralisation titres. The set-up of this study allowed for high comparability between laboratories and enabled laboratories that do not have the capacity or capability to perform VNTs themselves. Given the variety of in-house protocols detecting SARS-CoV-2 specific neutralising antibodies, including the virus strain, it could be of interest to select reference isolates for SARS-CoV-2 diagnostic to be made available for interested EU Member States and pre-accession countries.

The future of pyrogenicity testing: Phasing out the rabbit pyrogen test. A meeting report

The rabbit pyrogen test (RPT) was the benchmark for pyrogenicity testing, but scientific advancements have provided innovative and humane methods, such as the in vitro monocyte-activation test (MAT). However, transitioning from the RPT to the MAT has been challenging. The European Directorate for the Quality of Medicines & HealthCare, the Council of Europe, and the European Partnership for Alternative Approaches to Animal Testing jointly hosted an international conference entitled "The future of pyrogenicity testing: phasing out the rabbit pyrogen test". The conference aimed to show how the European Pharmacopoeia intends to remove the RPT from its texts by 2026, facilitate the use of MAT, and identify gaps in the suppression of RPT. The events contributed to a better understanding of the barriers to RPT replacement and acceptance of in vitro alternatives. Participants comprised stakeholders from Asia, Europe, and North America, including vaccine developers, contract laboratories, and regulators. Participants shared their replacement strategies and experiences with MAT implementation. They emphasised the need for continued cooperation between stakeholders and stressed the importance of international harmonisation of regulatory requirements to help accelerate MAT acceptance outside Europe. Despite the challenges, the willingness to eliminate the unnecessary use of RPT was common across all participants.

Interlaboratory Comparison of 226Ra and 228Ra Activity Concentrations in Groundwater and Surface Water

226Ra and 228Ra are typically monitored for groundwater and surface water compliance at legacy U mining and milling sites. Groundwater monitoring results for combined Ra (226Ra + 228Ra) reported by the existing contract laboratory at a former U mine and mill Site (Converse County, WY, USA) have been highly variable and with increasing trends at the Site compliance and background wells since the method was changed in 2005. Sample reanalysis has indicated poor reproducibility and significant analytical error in 228Ra measurements. An interlaboratory comparison was conducted to evaluate the potential causes of the high variability and analytical error. Two different methods were used for 226Ra (M903.0 and M903.1) and 228Ra (M904.0 and Ra-05). 226Ra results were less variable compared to 228Ra, and 228Ra data from the existing laboratory were qualified as estimated with high bias due to detection of 228Ra in the field blank. Compliance with the 226Ra + 228Ra groundwater standard was either met or not met, depending on which laboratory conducted the analyses. Specific laboratory techniques, rather than the analytical method, are contributing to elevated 228Ra values being reported. It was recommended that samples whose 226Ra + 228Ra results exceed the Site standard in the future be reanalyzed by the existing laboratory with a sample split also being sent to an outside laboratory for confirmatory analysis.

PM 7/20 (3) Erwinia amylovora

PM 7/20 (3) <i>Erwinia amylovora</i>

PM 7/53 (2) Liriomyza spp.

PM 7/53 (2) <i>Liriomyza</i> spp.

An assessment of solvent residue contaminants related to cannabis-based products in the South African market

Organic solvents are used for manufacturing herbal medicines and can be detected as residues of such processing in the final products. It is important for the safety of consumers to control these solvent residues. South African cannabis-based product samples were analysed for solvent residue contaminants as classified by the United States Pharmacopeia (USP), chapter 467. The origin of these samples ranged anywhere from crude extract, product development samples, and market ready final products. Samples were submitted to a contract laboratory over a period of 2 years from 2019 to 2021. To date, no data of this kind exist in South Africa specifically relating to cannabis-based medicinal, recreational, or complementary products. A total of 279 samples were analysed in duplicate by full evaporation headspace gas-chromatography mass-spectrometry and the results are reported in an anonymised format. The results showed an alarming 37% sample solvent residue failure rate with respect to adherence to USP 467 specification. It is important to ensure regulation is enforced to control product quality. The South African public need to be educated about the risks associated with cannabis-based products.

A phase 2/3, participant-blind, observer-blind, randomised, controlled study to assess the safety and immunogenicity of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine) in adults in India

BackgroundThis phase 2/3 immunobridging study evaluated the safety and immunogenicity of the ChAdOx1 nCoV-19 Coronavirus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at the Serum Institute of India Pvt Ltd (SIIPL), following technology transfer from the AstraZeneca.MethodsThis participant-blind, observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). The study participants were enrolled from 14 hospitals across India between August 25 and October 31, 2020. Two doses of study products were given 4 weeks apart. The primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike IgG antibodies 28 days after the second dose (defined as lower limit of 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. The anti-spike IgG response was assessed using a multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Trial registration: CTRI/2020/08/027170.Findings1601 participants were enrolled: 401 to the immunogenicity/reactogenicity cohort and 1200 to the safety cohort. After two doses, seroconversion rates for anti-spike IgG antibodies were more than 98·0% in both the groups. SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·78–1·23). SAEs were reported in ≤ 2·0% participants across the three groups; none were causally related. A total of 34 SARS-CoV-2 infections were reported; of which 6 occurred more than 2 weeks after the second dose; none were severe.InterpretationSII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Pharmacovigilance should be maintained to detect any safety signals.FundingSIIPL funded the contract research organisation and laboratory costs, while the site costs were funded by the Indian Council of Medical Research. The study vaccines were supplied by SIIPL and AstraZeneca.

PM 7/ 30 (3) Beet necrotic yellow vein virus

Specific scopeThis Standard describes a Diagnostic Protocol for beet necrotic yellow vein virus.This Standard should be used in conjunction with PM 7/76 Use of EPPO Diagnostic Protocols1.Specific approval and amendmentThis Standard was originally developed under the EU DIAGPRO Project (SMT 4‐CT98‐2252) by partnership of contractor laboratories and interlaboratory comparison in European countries. Approved as an EPPO Standard in 2003–09. First revision approved in 2006–09. Second revision approved in 2021–08.Authors and contributors are given in the Acknowledgements section.

An assessment of the potency related to Cannabis-based products in the South African market

It was the aim of this study to analyse a portion of the South African cannabis-based products market and provide a detailed overview of their THC and CBD profiles. To date, no data of this kind exists in South Africa. Samples were submitted to a contract laboratory. A total of 840 samples were analysed in duplicate (1680 datapoints in total) and reported in an anonymous format. Samples were categorised into 7 different types: Edible, Extract, Infusion, Liquid, Other, Plant material, and Solid. Each category was divided into the following weight by percentage concentration levels:<0.1 wt.-%, 0.1 wt.-% to 1 wt.-% and finally>1 wt.-%. Both HPLC-UV, as well as, GC-MS was employed for analysis with the datasets combined. The results indicated that high amounts of THC are present in most of the cannabis-based products in South Africa. This is of concern due to the health implications of these products, and the current South African legislation related to CBD and THC. Medicines and controlled substance regulators as well as the South African public will be informed about the current state of cannabis-based products in South Africa.

In vitro estrogenic activity of cereal‐based products: Reliability and relevance considerations

AbstractBackground and objectivesThe presence of endocrine disruptors in food is creating concern, and consequently, efficient methods for their identification are needed. In vitro bioassays have been developed to study endocrine properties of pure chemicals as well as mixtures. Because of their relative ease of execution and low cost, application of such techniques to whole foods is tempting. This raises a number of technical challenges. To address them, a study was commissioned in a contract laboratory offering in vitro estrogenicity testing of food products.FindingsFour different commercial and regulatory compliant cereal products were sent in blinded triplicates. Some samples were reported to be active by the laboratory. However, the results were not reproducible and very close to the 0% measurable activity. Furthermore, a statistical analysis of the raw data indicated an absence of activity. This was surprising since these products were expected to naturally contain estrogenic compounds such as the phytoestrogens lignans and flavones. However, phytoestrogens in cereals are known to occur mainly in bound, inactive, forms, suggesting that the sample preparation used in the present study was not suitable to release active estrogenic substances. This hypothesis was supported by preliminary data using a high‐resolution mass spectrometry method which did not detect any significant levels of phytoestrogens in the tested cereal extracts.ConclusionsUsing a yeast‐based method, no estrogenic activity was found in breakfast cereals. However, benchmarking the bioassay data against quality criteria raised the question of the qualification of the sample preparation and bioassay used to adequately address estrogenic activity of whole foods.Significance and noveltyThe quality requirements for testing whole food samples were formally addressed. The application of validated and harmonized methods for both sample preparation and bioassay testing is strongly advocated.

Validation of the SafTest Percent Fat for the Measurement of the Fat Content of Meat Meals, Fish Meal, and Potato Chips, Crackers, and Other and Grain-Based Snack Products: AOAC Performance Tested MethodSM #082004.

The Official American Oil Chemists Society (AOCS) Standard Procedure Aa 4-38, AOCS Standard Procedure Am 5-04, ISO 11085:2015, and similar methods are based on extraction of fats from food products using organic solvents. These methods require large volumes of organic solvents and up to 18-hour extractions. The SafTest Percent Fat measures fat content as "total triglycerides" in solubilized snack products and meals using micro-analytical and membrane separation principles. The study objective is to validate the SafTest Percent Fat in an internal study and an independent laboratory study. Comparability to AOCS Standard Procedure Aa 4-38 or AOCS Standard Procedure Am 5-04, LOQ, selectivity, robustness, stability, and consistency were determined. Mean recoveries from replicate analyses of SafTest control samples at three concentrations yielded 101 to 103%. The relative standard deviations of repeatability (RSDr) were below 5%. Studies of meat meals and snacks analyzed using the SafTest Percent Fat demonstrated RSDr of 2.3 to 5.6% compared to 2.6 to 4.9% for AOCS Aa 4-38. The method demonstrated average recoveries ranging from 88.8 to 116.2% compared to the AOCS methods results performed in two contract laboratory studies and an independent laboratory validation. The SafTest Percent Fat test can determine fat content in meals and snack matrices with accuracy and precision comparable to results from AOCS Aa 4-38 and AOCS Am 5-04. The SafTest Percent Fat test uses small reagent volumes, instrumental analysis, easy-to-use standardized procedures, and rapid analysis times for fat content determination.

Genetic testing costs and compliance with clinical best practices.

We sought to determine the costs of genetic testing and compliance with published guidelines and clinical best practices at our institution. A cost analysis was performed comparing the costs of ordered tests to the cost of the recommended testing. This was an approved quality improvement project at a tertiary teaching hospital in California. We identified charts associated with the genetic testing billing codes for common genetic tests through our contracted laboratory (cystic fibrosis genotyping, Breast cancer susceptibility gene (BRCA 1&2), Methylenetetrahydrofolate reductase (MTHFR), factor V Leiden (FVL), prothrombin gene pathogenic variant, alpha-thalassemia, hemochromatosis, and cell-free fetal DNA). Charts were reviewed retrospectively by a licensed, certified genetic counselor to assess the compliance with published clinical practice guidelines identified on GeneReviews and the American College of Obstetricians and Gynecologists (ACOG). Tests were classified as: appropriate, misordered/not indicated, misordered/false reassurance, and misordered/inadequate. We performed a cost analysis for the recommended test changes. We reviewed 114 charts over a three-month period. Forty-four (38.6%) of the tests were misordered based on published clinical practice guidelines: 24 (21%) were misordered/not indicated, 8 (7%) were misordered/false reassurance, and 12 (10.5%) were misordered/inadequate. Costs of ordered testing ($75,177) were compared to recommended testing after review ($54,265), with a total cost savings of $20,912. In clinical practice, over one-third of genetic tests reviewed were misordered. As these tests are a small fraction of all genetic tests at our institution, future studies should broaden the scope of testing evaluated to understand the magnitude of this problem and potential cost savings. Genetic counselor review and involvement in genetic test ordering can decrease inappropriate healthcare expenditures and improve patient care.

Applying adaptive management and lessons learned from national assessments to address logistical challenges in the National Wetland Condition Assessment

The National Wetland Condition Assessment (NWCA) is one of a series of probability-based National Aquatic Resource Surveys (NARS) conducted by the U.S. Environmental Protection Agency (USEPA) to provide a comprehensive assessment of the condition of the Nation’s waters. Randomized design and standardized training and protocols allow USEPA to analyze data that are nationally consistent and regionally relevant. Each NARS assessment was preceded by careful consideration of key logistical elements that included pre-survey planning, training, sampling logistics, and laboratory analysis. Numerous state, tribal, and contractor crews were supported across the country for each assessment; sampling and sample analyses were tracked from initiation; laboratory analyses were completed at USEPA, state, regional, and contract laboratories; and the data analyses and reporting were completed by USEPA-led workgroups, states, and contractors. The complexity and difficulty of each step offered unique challenges and provided lessons learned for each of the NARS assessments. Major logistical elements for implementing large scale assessments that are constrained by sampling period and number and duration of visits are covered in this paper. These elements include sample transport, equipment and supplies, sampling and sample tracking, information management regional technical expertise, and a sound field training program. This paper describes how lessons from previous assessments were applied to the NWCA and how new challenges faced in the NWCA were addressed and carried forward into future surveys.

Perspectives on gender parity in bioanalysis: an interview with Shane Needham.

Dr Shane Needham received his BS degree in chemistry from Washington State University and his PhD in chemistry from the University of Rhode Island. Dr Needham is Co-Founder and Chief Scientific Officer of Alturas Analytics, Inc. Dr Needham manages all scientific aspects of the HPLC/MS/MS bioanalytical contract laboratory at Alturas Analytics, Inc. Currently, Dr Needham's work is focused on the development and validation of assays for the determination of therapeutic agents and biomarkers from biological matrices. His laboratory leads in the area of dried blood spot analysis, microflow HPLC-MS/MS and LC-MS/MS oflarge molecules (Antibody Drug Conjugates, Biomarkers, New Biological Entities etc.) to support Drug Metabolism and Pharmacokineticsresearch.

Enterovirus Echo 11 Infections in Neonates, Taiwan, 2018

Taiwan Centers for Disease Control detected that enteric cytopathic human orphan virus 11, Echo 11 was prevalent in the community through contract laboratory surveillance in May, 2018. Neonatal cases of Echo 11 infections with severe complications and Echo 11 clusters in neonatal care units of hospitals or nursing homes were also confirmed successively. As of September 14, 2018, a total of 181 Echo 11 cases were detected, showing a significant increase compared with the numbers in 2016 and 2017. Among these 181 cases, 35 were neonates (19.3%); 8 of which were with severe complications. The proportion of neonatal Echo 11 infection with severe complications (22.9%) was higher than other age groups, and the number of cases with severe complications and deaths was also higher than those in previous years, indicating that neonatal Echo 11 infection was associated with a higher risk of severe complications. Echovirus used to cause severe complications or death in newborns. Because the virus can be transmitted through the placenta, birth canal or asymptotic care unit personnel, it is hard to prevent. We recommended strengthening the neonatal and maternal enterovirus infection prevention and protection measures to reduce cases with severe complications and deaths, and strengthening implementation of infection control measures in maternal and neonatal care units to avoid clusters.

PM 7/29 (3) Tilletia indica

Specific scopeThis Standard describes a diagnostic protocol for Tilletia indica. It should be used in conjunction with PM 7/76 Use of EPPO diagnostic protocols.Specific approval and amendmentThis Standard was originally developed under the EU DIAGPRO Project (SMT 4‐CT98‐2252) by a partnership of contractor laboratories and interlaboratory comparison in European countries.First approved as an EPPO Standard in 2003–09.First revision approved in 2007–09.Second revision approved on 2017–11.Although this EPPO Diagnostic Standard differs in terms of format it is in general consistent with the content of the IPPC Standard adopted in 2014 on Tilletia indica (Annex 4 to ) with the following exceptions. (1) In the EPPO region, as the pest is not present, a higher confidence in the results is required, a sieve wash test should be carried out (optional in the IPPC protocol). (2) When fewer than 10 teliospores are found the options should allow testing the (&lt;10) teliospores with conventional or real‐time PCR (this was not an option in the IPPC protocol flow chart, although it was stated that direct real‐time PCR could be used on individual teliospores in the text). (3) The method for extracting teliospores from untreated seed or grain by size‐selective sieving is slightly different based on the experience in the region (European Union test performance study). The EPPO Diagnostic Standard also includes a test for a direct real‐time PCR for use on pellets (developed in 2016). Some additional information on methods for morphological identification, from the former version of the EPPO Standard, which are not in the IPPC protocol are included in this protocol in Appendix 3 as they were considered useful by the members of the Panel on Diagnostics in Mycology.