iloprost (CiVi 030 / CIVI030 / Civi 030)

Continuous intravenous infusion of vancomycin in preterm neonates: case series from a neonatal intensive care unit.

Tang Kai Lun KL, Chew Khai Shing KS, Leong Jen Jen JJ, Lim Catherine Tze Yinn CTY et al.

There is no standard dosing guideline available for continuous intravenous infusion (cIVI) vancomycin in the neonatal population. Vancomycin administered as cIVI is the current practice in our neonatal intensive care unit. Data from this case series provided preliminary information on dosing range of cIVI vancomycin, serum vancomycin concentration (SVC), microbiological clearance, and incidence of vancomycin-related nephrotoxicity in neonates. Clinical and laboratory data of this retrospective case series were extracted from patient's medical record and therapeutic drug monitoring database. Of the total 36 steady-state SVCs from 15 records analysed, 64% (n = 23) were within a therapeutic range of 15-25 mg/l. Initial SVCs were generally taken within 20-24 h, however, only 20% (n = 3) were within therapeutic range. Loading dose given ranged between 10 and 15 mg/kg, and the mean maintenance dose was 26 ± 6.58 mg/kg/day. Most of the cases (86.7%, n = 13) were targeted treatment for infections which involved Bacillus spp, Coagulase-negative Staphylococcus (CoNS), and methicillin-resistant Staphylococcus aureus (MRSA). Microbiological clearance was achieved in all targeted cases, and no cases of vancomycin-induced acute kidney injury were reported. This indicates vancomycin continuous infusion dosing regime in neonates seems practicable and was not associated with any incidence of nephrotoxicity. NMRR ID: NMRR-17-3502-37577 (IIR).

Single-use technologies and sustainability by design in biopharma production.

Ottinger Melanie M, Wenk Irina I, Brühlmann Béla B, Junne Stefan S

Sustainability has become a central challenge for the biopharmaceutical industry, which is characterized by resource-intensive manufacturing processes, complex supply chains, and increasing regulatory expectations for environmental transparency. This review examines the role of single-use technologies (SUTs) and sustainability by design (SbD) approaches in improving the environmental performance of modern biomanufacturing systems. While SUTs offer operational advantages such as increased flexibility, faster facility turnaround, and reduced water and energy consumption compared with stainless steel systems, their widespread adoption also raises concerns regarding plastic waste generation and end-of-life management. Survey results from industry stakeholders further indicate increasing awareness of sustainability challenges, but also reveal gaps in knowledge, governance structures, and practical implementation across the value chain. The paper aims to summarize recent developments in environmental assessment, process engineering, and digital bioprocessing to evaluate pathways toward more sustainable production and, at the same time, to identify knowledge gaps that remain. Emphasis is placed on the integration of life cycle assessment (LCA) and quantitative sustainability metrics into early process development, enabling more informed technology selection and design decisions now and in the future. In addition, emerging technological strategies are discussed, including process intensification, continuous and hybrid manufacturing configurations, and advanced process analytical technologies (PATs) that support real-time monitoring and resource-efficient operation. Overall, the findings highlight that an integrated systems perspective is required that combines technological innovation, standardized environmental metrics, and collaborative industry frameworks. Embedding SbD principles early in product and process development can significantly reduce environmental impacts while maintaining regulatory compliance and economic feasibility.

Risovalisib for PIK3CA-mutated recurrent or persistent ovarian clear cell carcinoma: a single-arm, multicentre, phase 2 trial.

Li Jiajia J, Yonemori Kan K, Niimi Kaoru K, Nakagawa Satoshi S et al.

Ovarian clear cell carcinoma is a rare but aggressive and biologically distinct subtype of ovarian cancer, in which PIK3CA mutations are common. Advanced ovarian clear cell carcinoma is very difficult to treat, and after failure of platinum-based chemotherapy, therapeutic options are limited. We aimed to evaluate the anti-tumour activity and safety of the PI3Kα inhibitor, risovalisib, for treatment of patients with recurrent or persistent PIK3CA-mutated ovarian clear cell carcinoma. We conducted a single-arm, phase 2 trial of the PI3Kα inhibitor, risovalisib, in 27 centres in China and 12 centres in Japan. Eligible participants were adult patients (aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0 or 1) with recurrent or persistent PIK3CA-mutated ovarian clear cell carcinoma and one to three lines of previous systemic anti-tumour treatment. Risovalisib was given orally at 40 mg daily in 21-day cycles until disease progression, unacceptable toxicity, or other protocol-defined reasons for discontinuation. The primary endpoint was objective response rate assessed by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumours (version 1.1), among all treated patients with a confirmed PIK3CA hotspot mutation and baseline tumour assessments with measurable lesions per BIRC (efficacy analysis set). The primary endpoint was considered met if the lower 95% CI was greater than 8%. Safety analyses were performed in all patients who received at least one dose of risovalisib (safety analysis set). The trial is registered with ClinicalTrials.gov (NCT05043922) and is ongoing but no longer recruiting patients. Between Oct 6, 2021, and Jan 31, 2024, 93 patients were enrolled and received risovalisib. The median age was 49 years (IQR 43-58), all patients were female, 52 (56%) were from Japan, 41 (44%) were from China, and 63 (68%) had two or more previous lines of therapy. The median duration of follow-up was 14·5 months (IQR 8·6-18·3). The objective response rate was 29 (35% [95% CI 25-46]) of 84 patients in the efficacy analysis set. The most commonly reported grade 3 or worse treatment-related adverse events in 93 patients were rash (30 [32%]), hyperglycaemia (28 [30%]), and decreased weight (7 [8%]). Treatment-related serious adverse events occurred in 36 (39%) patients, the most common being rash (eight [9%]), pneumonitis (six [6%]), and decreased appetite (four [4%]). There were no treatment-related deaths. These results support risovalisib as a potential novel treatment option for PIK3CA-mutated ovarian clear cell carcinoma, a rare yet lethal cancer in dire need of additional treatment options. Combination strategies including risovalisib could also be explored to further increase efficacy observed in this study. Haihe Biopharma.

Decision quality in biopharma portfolio renewal.

Loche Alberto A, Agrawal Gaurav G, Ascher Jan J