Guidelines for the practical stability studies of anticancer drugs: A European consensus conference

Bardin, Christophe; Astier, A.; Vulto, Arnold G.; Sewell, Graham; Vigneron, Jean; Trittler, Rainer; Daouphars, Mikaël; Paul, Murielle; Trojniak, Marta Paulina; Pinguet, Frédèric

doi:10.1016/j.pharma.2011.07.002

Cited by 138 publications

(103 citation statements)

References 32 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Stability of TRS with 100 ml saline has not been reported in the past. However, stability of TRS with concentration of 21 mg/ml stored for 24 hours at 2-8℃ was reported in the past based on evaluation of 60 mg and 160 mg of TSR diluted respectively in 3.0 ml and 7.2 ml of sterile water (Bardin et al, 2011). TRS is prepared only with sterile water and saline because of reported protein aggregation after dilution of TRS in 5% glucose solution.…”

Section: Discussionmentioning

confidence: 99%

Safety Assessment of Intravenous Administration of Trastuzumab in 100ml Saline for the Treatment of HER2-Positive Breast Cancer Patients

Abe¹,

Mori²,

Kawai³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: The infusion rate is considered to affect incidence and severity of infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml saline already being established. Materials and Methods: Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF), were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week cycle. Results: A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events were reported. Conclusions: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis as with the currently recommended dilution in 250 ml saline.

show abstract

Section: Discussionmentioning

confidence: 99%

Safety Assessment of Intravenous Administration of Trastuzumab in 100ml Saline for the Treatment of HER2-Positive Breast Cancer Patients

Abe¹,

Mori²,

Kawai³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…Astier then shared some results of stability analysis after thermal or mechanical stresses of therapeutic antibodies. In a preamble, he emphasized that analytical methods were chosen following the guidelines for the practical studies of anticancer drugs published by the French and European societies of oncology, 4 with the use of complementary methods to assess stability of biologics. The first study concerns the stability of diluted rituximab that was performed to address the feasibility of dose-banding to avoid product loss (residues in the vials or bags).…”

Section: Session 1: Administration Routesmentioning

confidence: 99%

MAbDelivery: Administration routes for antibody therapy Third LabEx MAbImprove industrial workshop, July 2, 2015 Tours, France

Bodier-Montagutelli

Respaud

Watier

et al. 2017

mAbs

View full text Add to dashboard Cite

The annual "LabEx MAbImprove Industrial Workshops" are primarily intended to provide a comprehensive view about topics of interest for the pharmaceutical industry to scientists involved in research on therapeutic antibodies. The third workshop in this series, held July 2, 2015 in Tours, was dedicated to the optimization of delivery, namely all processes leading monoclonal antibodies to reach their target site. The commonly used intravenous (IV) route, although advantageous in terms of pharmacokinetics and pharmacodynamics, presents some disadvantages in terms of patients' convenience, therapeutic target access or treatment cost. Such problems led pharmaceutical companies to consider more straightforward and patient-friendly administration routes, bringing the need for specific formulations adapted to the specific inherent physicochemical challenges. In this context, the workshop provided an overview of these advances and opened discussion on new administration routes and formulation development. In the first session, the opportunities and challenges of 3 main routes of administration (IV, subcutaneous (SC), and pulmonary) were discussed, integrating protein stability issues. The next session was dedicated to medical devices intended for SC and pulmonary administration. The last session focused on specific formulations for monoclonal antibodies, particularly to successfully protect antibodies upon aerosolization, to develop highly concentrated formulations for SC administration, and to use formulation as a mean to overcome the barriers to oral protein delivery. As in the previous editions, this workshop gathered people from the academic and industrial spheres and allowed rich debates and discussions.

show abstract

“…In-use stability studies for clinical trials, also referred to as compatibility, practical stability, or post-dilution studies, are critical studies conducted as a means to confirm maintenance of protein quality and quantity, thus ensuring that handling results in a diluted product that is both safe and efficacious. [12][13][14][15][16][17] Of particular importance to the clinic is confirmation that the subjects consistently receive the desired dose (i.e., no underdose or variable dose).…”

Section: Introductionmentioning

confidence: 99%

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

Morar-Mitrica

Puri

Sassi

et al. 2015

mAbs

View full text Add to dashboard Cite

The physical and chemical integrity of a biopharmaceutical must be maintained not only during long-term storage but also during administration. Specifically for the intravenous (i.v.) delivery of a protein drug, loss of stability can occur when the protein formulation is compounded with i.v. bag diluents, thus modifying the original composition of the drug product. Here we present the challenges associated with the delivery of a low-dose, highly potent monoclonal antibody (mAb) via the i.v. route. Through parallel in-use stability studies and conventional formulation development, a drug product was developed in which adsorptive losses and critical oxidative degradation pathways were effectively controlled. This development approach enabled the i.v. administration of clinical doses in the range of 0.1 to 0.5 mg total protein, while ensuring liquid drug product storage stability under refrigerated conditions.

show abstract

Guidelines for the practical stability studies of anticancer drugs: A European consensus conference

Cited by 138 publications

References 32 publications

Safety Assessment of Intravenous Administration of Trastuzumab in 100ml Saline for the Treatment of HER2-Positive Breast Cancer Patients

Safety Assessment of Intravenous Administration of Trastuzumab in 100ml Saline for the Treatment of HER2-Positive Breast Cancer Patients

MAbDelivery: Administration routes for antibody therapy Third LabEx MAbImprove industrial workshop, July 2, 2015 Tours, France

Development of a stable low-dose aglycosylated antibody formulation to minimize protein loss during intravenous administration

Contact Info

Product

Resources

About