iloprost (CiVi 030 / CIVI030 / Civi 030)

Setting expectations for current and future directions of native mass spectrometry in the biopharmaceutical industry.

Hecht Elizabeth E, Martin Esther E, Liko Idlir I, Mahan Andrew A et al.

While native mass spectrometry (native-MS) has been widely explored in academic laboratories, its practical role within biopharmaceutical research remains less clearly defined. In this perspective, we present an industry-driven view of how native-MS is currently applied, where it offers unique advantages over established analytical technologies, and where alternative methods remain more practical for routine characterization. Within biopharma workflows, characterization strategies traditionally rely on orthogonal techniques such as size-exclusion chromatography (SEC), ion-exchange chromatography (IEX), electrophoresis, light scattering, calorimetry, and denaturing liquid chromatography (LC) MS. Native-MS complements these methods by enabling direct assessment of intact molecular assemblies, including monoclonal antibodies (mAbs), multispecific antibodies, antibody-drug conjugates (ADCs), glycoproteins, and protein complexes. Applications include evaluation of higher-order assembly, ligand or cofactor binding, stoichiometry of target complexes, and heterogeneity that may be obscured under denaturing conditions. However, challenges related to throughput, sensitivity, automation, and accessibility have limited widespread adoption in industrial laboratories. Emerging developments, including chromatographic hyphenation, online buffer exchange (OBE), improved automation, and charge-detection MS (CDMS), are beginning to address these constraints. We argue that the future impact of native-MS in biopharma will depend on integrating these technological advances with platformed analytical workflows and software capable of supporting high-throughput characterization across therapeutic pipelines. We hope that the ideas raised in this article spur debate on when, how, and if native-MS would or should see increased adoption.

Regulatory science for AI-based software as a medical device in computational pathology and biomarker-driven drug development.

Liebes-Peer Yael Y, Czeisler Shlomo S, Broderick Rachel R, Vecsler Manuela M et al.

Artificial intelligence (AI)-enabled software is increasingly integrated into digital and computational pathology, driving new regulatory and quality management requirements that extend beyond traditional laboratory practice and classical medical-device oversight. Practical, experience-based guidance on balancing development agility with global regulatory readiness remains limited for biomarker developers and translational pathologists navigating the convergence of AI governance, cybersecurity, and regulated clinical deployment. We reviewed our multi-year regulatory, quality, information security management program, and software lifecycle artifacts associated with AI-based diagnostic software development across multiple jurisdictions. Documentation, change control processes, and internal coordination mechanisms were analyzed to identify structural patterns supporting parallel progress in regulatory submissions, product releases, and assurance infrastructure. Our assessment consistently showed four transferable operational determinants to maintain iterative development while preserving regulatory readiness across jurisdictions: (1) Regulatory submissions and approvals (e.g., IVDR, FDA clearance); (2) product releases and lifecycle control; (3) quality and assurance infrastructure, including quality management system (QMS) certifications (e.g., ISO 13485, MDSAP); and (4) cybersecurity and information security certifications (e.g., ISO 27001, HITRUST, and C5). Together, these determinants enabled coordination of regulatory, release, and quality milestones in parallel, reducing friction at later submission stages and supporting synchronized readiness across jurisdictions. This technical note presents a transferable framework for managing AI-based pathology software development in regulated environments. High-quality deployment requires more than model performance alone; it depends on technical, regulatory, and operational maturity across many dimensions, including change control, documentation, security-aligned quality systems, post-market surveillance, technical support, and workflow integration. The presented framework is directly relevant to computational scientists, pathologists, and laboratory/medical directors tasked with evaluating AI systems by supporting informed evaluation and adoption decisions, including procurement considerations, in clinical and biopharma settings.

A Protocolized Intravenous Epoprostenol Pathway for Frostbite: A Canadian Burn Centre Quality Improvement and Implementation Report.

Natanson Rimona R, Adibfar Alex A, Au Anita A, Tillman Bourke B et al.

Severe frostbite is a dynamic microvascular injury that can progress to delayed tissue loss despite appropriate initial care. Contemporary management emphasizes rapid rewarming, antithromboxane therapy, clinical grading, selective thrombolysis, and prostacyclin-based treatment. Iloprost is the prostacyclin analogue most often described, but access may be delayed in some Canadian settings. We developed and implemented a monitored intravenous epoprostenol pathway for Cauchy grade 2 to 4 frostbite and retrospectively evaluated 23 patients treated between December 2017 and November 2025. The pathway incorporated rapid rewarming, grading, topical and systemic antithromboxane therapy, eligibility criteria, dose titration, physiologic monitoring, dose modification, multidisciplinary care, and follow-up. Overall, 153 of 216 affected digits were preserved. Preservation varied by severity: 62 of 65 grade 2 digits, 74 of 100 grade 3 digits, and 7 of 41 grade 4 digits were preserved. Twelve patients avoided amputation altogether. Mean treatment duration was 3.8 days, and most patients reached 8 ng/kg/min at least once. Documented adverse effects or dose-limiting symptoms occurred in nine patients and were managed with dose reduction or temporary interruption. Available records did not identify thrombolytic therapy, permanent discontinuation for adverse reaction or grade 2 reassessment, or serious drug-attributed adverse events. Protocol-guided intravenous epoprostenol was feasible and generally well tolerated. Findings should be interpreted as descriptive and hypothesis-generating rather than evidence of treatment efficacy.

Comment on 'effects of locally applied water-filtered infrared a irradiation adjunctive to iloprost and carbon dioxide hand baths in patients with systemic sclerosis and severe Raynaud's phenomenon - a randomized controlled trial'.

Singh Ritu Raj RR, Sharma Sunita S, Khatun Aiyesha A