2023 White Paper on Recent Issues in Bioanalysis: EU IVDR 2017/746 Implementation/Impact, IVD/CDx/CLIA Approved Assays, High Dimensional Cytometry, Multiplexing Technologies, LBA Tissue Analysis, Vaccine Study Endpoints, Cell-Based Assays for Biomarkers, Cell Therapy and Vaccines ( - Recommendations on Development & Validation of Biomarkers, IVD, CDx, Cell-Based, Flow Cytometry, Ligand-Binding and Enzyme Assays; Advanced Critical Reagents Strategies).

The 17 Workshop on Recent Issues in Bioanalysis (17 WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Evaluating cone cut in rectangular collimation in intraoral radiography: application of ALADA and radiation stewardship.

Objective: Rectangular collimation is a popular method used in intraoral radiography to reduce patient exposure to ionizing radiation. One of the perceived drawbacks of rectangular collimation is the possibility of an increase in cone cut errors ultimately impacting the diagnostic value of the radiographs. Thus, the aim of this study was to explore the frequency of cone cut errors in radiographs taken using a rectangular collimator.

Comparative study of cranial measurements between sexes from Brazil and The Netherlands: A cone-beam computed tomography study.

The objective of this study was to better understand human variation by comparing cone-beam computed tomography-based cranial measurements between both sexes of individuals from two distinct populations: Brazilian and Dutch. Cone-beam computed tomography volumes of 311 patients between 20 and 60 years from Brazil and The Netherlands were selected. Two radiologists performed 16 linear measurements in the maxillary sinuses and mandibular canal.

[How to detect opacities in the orofacial soft tissue on a panoramic radiograph: heterotopic ossifications and foreign bodies].

Opacities in the orofacial soft tissue rather than the bone are frequently seen on panoramic radiographs. The differential diagnosis of these opacities is diverse and concerns frequently occurring disorders but also rare ones. Due to the diversity of diagnoses, the clinical interpretation of a soft tissue opacity is often difficult.

[How to detect opacities in the orofacial soft tissue on a panoramic radiograph? Idiopathic calcifications].

Opacities not in the bone but in the orofacial soft tissue, are frequently seen on panoramic radiographs. The differential diagnosis of these opacities is diverse and concerns frequently occurring disorders but also rare ones. Due to the diversity of diagnoses, the clinical interpretation of a soft tissue opacity is often difficult.

Galactosylsphingosine does not interfere with the quantitation of plasma glucosylsphingosine levels in Gaucher patients.

It has been shown that the plasma level of glucosylsphingosine (Lyso GL-1) is a useful biomarker for the diagnosis and monitoring of Gaucher disease. Potentially interfering with the quantitation of Lyso GL-1 is its isobaric structural isomer, galactosylsphingosine (psychosine). The contribution of psychosine is generally not accounted for in the determination of Lyso GL-1, due to the difficulty in separating these two isomers.

[How to detect opacities in the orofacial soft tissue on a panoramic radiograph? Dystrophic calcifications].

Opacities in the orofacial soft tissue rather than the bone are frequently seen on panoramic radiographs. The differential diagnosis of these opacities is diverse and comprises abnormalities both frequently seen and rare. On account of this diversity, the clinical interpretation of a soft tissue opacity is often difficult.

DIMITRA paediatric skull phantoms: development of age-specific paediatric models for dentomaxillofacial radiology research.

Objectives: This report aims to describe the development of age-specific phantoms for use in paediatric dentomaxillofacial radiology research. These phantoms are denoted DIMITRA paediatric skull phantoms as these have been primarily developed and validated for the DIMITRA European research project (Dentomaxillofacial paediatric imaging: an investigation towards low-dose radiation induced risks).

Methods: To create the DIMITRA paediatric phantoms, six human paediatric skulls with estimated ages ranging between 4 and 10 years- old were selected, protected with non-radiopaque tape and immersed in melted Mix-D soft tissue equivalent material, by means of a careful procedure (layer-by-layer).

Validation study of a new method for sexual prediction based on CBCT analysis of maxillary sinus and mandibular canal.

Objective: The aim of this study was to evaluate the accuracy of two craniometric methods for sexual prediction (SP) using cone-beam computed tomography (CBCT) in the Dutch population and to construct a formula for each method and then the two combined.

Design: One-hundred sixty CBCT images were selected from a Dutch database (80 males and 80 females). The images were analyzed by two examiners taking seven measurements in the maxillary sinus (MS) region (first method) and nine in the mandibular canal (MC) region (second method).

Predictive Value of Panoramic Radiography for Injury of Inferior Alveolar Nerve After Mandibular Third Molar Surgery.

Purpose: The purpose of the present systematic review was to assess the added value of panoramic radiography in predicting postoperative injury of the inferior alveolar nerve (IAN) in the decision-making before mandibular third molar (MM3) surgery.

Materials And Methods: MEDLINE and EMBASE were searched electronically to identify the diagnostic accuracy of studies that had assessed the predictive value of 7 panoramic radiographic signs, including root-related signs (darkening of the root, deflection of the root, narrowing of the root, and dark and bifid apex of the root) and canal-related signs (interruption of the white line of the canal, diversion of the canal, and narrowing of the canal) for IAN injury after MM3 surgery.

Results: A total of 8 studies qualified for the meta-analysis.

A DBS method for quantitation of the new oral trypanocidal drug fexinidazole and its active metabolites.

Aim: Fexinidazole (FEX) is a nitroimidazole being developed as a new trypanocide treatment for human African trypanosomiasis/sleeping sickness. Its main metabolites, fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2), show the same in vitro pharmacological activity as FEX.

Methods & Results: An LC-MS/MS assay was developed for quantitation of FEX in DBS, collected via finger-prick from healthy subjects.

Dried Blood Spot Methodology in Combination With Liquid Chromatography/Tandem Mass Spectrometry Facilitates the Monitoring of Teriflunomide.

Background: Teriflunomide, a once-daily oral immunomodulator approved for treatment of relapsing-remitting multiple sclerosis, is eliminated slowly from plasma. If necessary to rapidly lower plasma concentrations of teriflunomide, an accelerated elimination procedure using cholestyramine or activated charcoal may be used. The current bioanalytical assay for determination of plasma teriflunomide concentration requires laboratory facilities for blood centrifugation and plasma storage.

The value of thyroid shielding in intraoral radiography.

Objectives: To evaluate the utility of the application of a thyroid shield in intraoral radiography when using rectangular collimation.

Methods: Experimental data were obtained by measuring the absorbed dose at the position of the thyroid gland in a RANDO(®) (The Phantom Laboratory, Salem, NY) male phantom with a dosemeter. Four protocols were tested: round collimation and rectangular collimation, both with and without thyroid shield.

Reducing an already low dental diagnostic X-ray dose: does it make sense? Comparison of three cost-utility analysis methods used to assess two dental dose-reduction measures.

Objectives: To find a method that is suitable for providing an objective assessment of the cost effectiveness of a dose-reducing measure used for diagnostic dental X-ray exposures.

Methods: Three cost-utility analysis (CUA) methods were evaluated by comparing their assessments of two dose-reduction measures, a rectangular collimator and the combination of two devices that reduce the radiation dose received during orthodontic lateral cephalography. The following CUA methods were used: (1) the alpha value (AV), a monetary valuation of dose reduction used in the nuclear industry; (2) the value of a statistical life for valuation of the reduction in stochastic adverse effects; and (3) the time-for-time method, based on the postulate that risk reduction is effective when the number of years of life gained is more than the years that an average worker must work to earn the costs of the risk-reducing measure.

A phase I open-label study investigating the disposition of [14C]-cabazitaxel in patients with advanced solid tumors.

Cabazitaxel is a semisynthetic taxane approved for the treatment of patients with hormone-refractory metastatic prostate cancer (now known as metastatic castration-resistant prostate cancer) treated previously with a docetaxel-containing treatment regimen. The human plasma pharmacokinetics of cabazitaxel have been described previously, but detailed analyses of the metabolism and excretion pathways of cabazitaxel have not yet been published. Metabolite profiling, quantification, and identification as well as excretion analyses were carried out on samples from patients with advanced solid tumors who received an intravenous infusion of 25 mg/m [C]-cabazitaxel (50 μCi, 1.

Effect of head position on cephalometric evaluation of the soft-tissue facial profile.

Objectives: During a cone beam CT scan, the patient is in an upright or supine position. This position depends on the brand and type of the scanner. The aims of this study are: (1) to investigate if the head position has an effect on cephalometric evaluation of the soft-tissue facial profile, comparing the recordings in natural head position (NHP) and supine head position (SHP) and (2) to investigate if age, gender and body mass index (BMI) are contributing factors to the effect of the head position.

Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis.

Aim: To assess the bioequipotency of equimolar doses of idraparinux (2.5 mg) and idrabiotaparinux (3.0 mg).

Dose reduction of cone beam CT scanning for the entire oral and maxillofacial regions with thyroid collars.

Objective: The aim of this study was to evaluate the influence of thyroid collars on radiation dose during cone beam CT (CBCT) scanning.

Methods: Average tissue-absorbed dose for a NewTom 9000 CBCT scanner (Quantitative Radiology, Verona, Italy) was measured using thermoluminescent dosemeter chips in a phantom. The scans were carried out with and without thyroid collars.

A mechanism-based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects.

Aim: Aflibercept (VEGF-Trap), a novel anti-angiogenic agent that binds to VEGF, has been investigated for the treatment of cancer. The aim of this study was to develop a mechanism-based pharmacokinetic (PK) model for aflibercept to characterize its binding to VEGF and its PK properties in healthy subjects.

Methods: Data from two phase I clinical studies with aflibercept administered as a single intravenous infusion were included in the analysis.

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

Background: Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity.

Objective: This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland.

Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified release products: workshop summary report.

Modified release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current industry practices and regulatory expectations for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products.

Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified-release products: workshop summary report.

Modified-release products are complex dosage forms designed to release drug in a controlled manner to achieve desired efficacy and safety. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This workshop provided an opportunity for pharmaceutical scientists from academia, industry and regulatory agencies to discuss current regulatory expectations and industry practices for demonstrating pharmaceutical equivalence and bioequivalence of MR products, further facilitating the establishment of regulatory standards for ensuring therapeutic equivalence of these products.

Comparing the performance of storage phosphor plate and Insight film images for the detection of proximal caries depth.

Objectives: To compare proximal caries depth between conventional film images, unenhanced and enhanced storage phosphor plate images.

Method: Bitewing radiographs were taken on 100 patients presenting for Conservative and Periodontal treatment. Only one bitewing was taken on a patient either the right or left hand side of the patient A DenOptics storage phosphor plate and size 3 Kodak Insight film were simultaneously placed into a Rinn bitewing holder.

Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion.

Background: Idraparinux is an inhibitor of activated factor X (FXa) with a long half-life allowing once-weekly dosing. Idrabiotaparinux is a biotinylated version of idraparinux; its activity can be reversed with avidin.

Objective: To investigate the tolerability, safety and pharmacodynamics of avidin in healthy subjects and patients with deep vein thrombosis (DVT) receiving idrabiotaparinux.

The pharmacokinetics of idraparinux, a long-acting indirect factor Xa inhibitor: population pharmacokinetic analysis from Phase III clinical trials.

Background: Idraparinux, a long-acting synthetic pentasaccharide, is a specific antithrombin-dependent inhibitor of activated factor X that has been investigated in the treatment and prevention of thromboembolic events.

Objectives: To characterize the population pharmacokinetic profile of idraparinux in patients enrolled in van Gogh and Amadeus Phase III clinical trials.

Patients And Methods: Idraparinux was administered once-weekly subcutaneously at a dose of 2.