2023 White Paper on Recent Issues in Bioanalysis: ISR for ADA Assays, the Rise of dPCR vs qPCR, International Reference Standards for Vaccine Assays, Anti-AAV TAb Post-Dose Assessment, NanoString Validation, ELISpot as Gold Standard (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Biotherapeutics Immunogenicity & Risk Assessment; ADA/NAb Assay/Reporting Harmonization).

The 17th Workshop on Recent Issues in Bioanalysis (17th WRIB) took place in Orlando, FL, USA on June 19-23, 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 17th 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. Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) are published in volume 16 of Bioanalysis, issues 8 and 9 (2024), respectively.

Natural history and management outcomes of segmental arterial mediolysis.

BACKGROUND: Segmental arterial mediolysis (SAM) is a poorly understood, nonatherosclerotic, noninflammatory disease resulting from arterial medial degeneration. Patients may present with aneurysm, dissection, stenosis, or bleeding from visceral or renal arteries. Treatment algorithms are poorly characterized. METHODS: A retrospective review of all patients diagnosed with SAM was performed at our institution. Patients were identified by established criteria that include clinical presentation in combination with radiographic and serologic findings. Demographics, presenting symptoms, diagnostic evaluation, management, and outcomes were reviewed. RESULTS: There were 117 patients diagnosed with SAM between 2000 and 2016; 67.5% (n = 79) were male. Mean age was 52.7 years (range, 23.4-90 years); 69.2% (n = 81) presented with acute abdominal pain, 22.2% (n = 26) with flank pain, and 19.7% (n = 23) with back pain; 15.4% (n = 18) had abdominal pain longer than 30 days; 13.7% (n = 16) had acute hypertension, and 5.1% (n = 6) were hypotensive; 10.3% (n = 12) were asymptomatic. There were 93 (79.5%) dissections and 61 (52.1%) aneurysms. Hemorrhage was seen in 10 (8.5%). The celiac axis was affected in 54.7% (n = 64), renal arteries in 49.6% (n = 5 8), superior mesenteric artery in 43.6% (n = 51), and inferior mesenteric artery in 2.6% (n = 3). After diagnosis of SAM, aspirin was prescribed in 60.7% (n = 71). Statins were prescribed in 29.9% (n = 35). Antihypertensive medications were prescribed in 65% (n = 76), including beta blockers in 42.7% (n = 50); 40.2% (n = 47) of patients were prescribed anticoagulation. Interventions were performed in 26 (22%) patients; 13 had endovascular intervention only, 9 open surgery only, and 4 open and endovascular interventions. Of the 17 patients undergoing endovascular intervention, 19 procedures were performed, most commonly embolization (78.9% [n = 15]), followed by stenting (10.5% [n = 2]). Of the 13 patients undergoing open surgery, 14 procedures were performed, including arterial bypass (50% [n = 7]) and splenectomy with aneurysm ligation (15.4% [n = 2]). Other surgery involved thrombectomy (21.4% [n = 3]) and angioplasty (14.3% [n = 2]). Only 11.5% (n = 3) experienced a perioperative complication, including one hematoma, one abscess, and one death secondary to ongoing hemorrhage. Follow-up imaging was performed in 96.6% (n = 112). Mean follow-up was 1258 days (range, 2-5017 days). Of these, 27.7% (n = 31) had regression, 43.8% (n = 49) stability, and 28.6% (n = 32) progression. Average time between initial diagnosis and progression was 666 days. CONCLUSIONS: SAM is an uncommon disease that may require intervention; it is therefore important that the vascular surgery community be aware of this disease. Follow-up imaging is required to monitor for disease progression.

Successful repair of a popliteal aneurysm with saphenous vein graft in a patient with Marfan syndrome.

Marfan syndrome is an autosomal dominant disorder caused by mutations in the fibrillin 1 gene (FBN1). This leads to defective elasticity of connective tissue in the arterial wall. Aortic aneurysms and dissections are the most common vascular anomalies; the incidence of peripheral artery aneurysms is not well understood. Treatment options for infrainguinal disease are limited as endovascular interventions are generally contraindicated. The best conduit for arterial reconstruction is also unknown because there is concern that saphenous vein may become aneurysmal. Currently, there are few case reports regarding outcomes of infrainguinal arterial reconstructions, and follow-up has been very short term. We report a rare case of successful repair of a popliteal aneurysm using a saphenous vein graft in a patient with Marfan syndrome.