Long-term physico-chemical stability of diluted trastuzumab

Paul, Muriel; Vieillard, Victoire; Lemos, Ricardo Da Silva; Escalup, Laurence; Astier, A.

doi:10.1016/j.ijpharm.2013.02.039

Cited by 34 publications

(19 citation statements)

References 15 publications

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“…Moreover, diluted antibody is also stable at 22 C for 6 months, arguing for the possibility to administer it safely in case of temperature excursion. Similar conclusions could be drawn from stability studies of diluted trastuzumab 6 and of diluted ipilimumab, which is a very expensive treatment. 7 The last study presented was a stability analysis of the mechanical stresses on antibodies transported via pneumatic conveying systems.…”

Section: Session 1: Administration Routessupporting

confidence: 70%

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

Bodier-Montagutelli

Respaud

Watier

et al. 2017

mAbs

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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.

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Section: Session 1: Administration Routessupporting

confidence: 70%

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

show abstract

“…To date, the data reported herein may represent the most extensive stability testing of a trastuzumab conjugate, albeit modified with the TCMC chelate. Previously, a stability study conducted with trastuzumab diluted at 0.8 and 2.4 mg/mL that indicated the mAb was stable for up to 6 months at either 4 °C or room temperature [ 15 ]. In this particular study, CEX-HPLC and SE-HPLC methodologies were employed to detect alterations in trastuzumab.…”

Section: Discussionmentioning

confidence: 99%

“…Papers attesting to the stability of mAbs that have been diluted as they would for a patient dosage and stored for 14 days in a PVC bag are easily found. [ 15 , 16 , 17 , 18 ] Invariably, many of these reports and notes only measure one variable to report on the stability of the specific mAb and that measurement tends to be a physical property, i.e ., protein concentration, which is limited to the detection of the presence of the mAb and not its biological functionality. The possibility of loss of bioactivity, formation of aggregates or degradants apparently seems to not be an important consideration for many investigators and has therefore not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

Bench to Bedside: Stability Studies of GMP Produced Trastuzumab-TCMC in Support of a Clinical Trial

2015

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The first-in-human phase 1 clinical radioimmunotherapy (RIT) trial with 212Pb-1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamoylmethyl)-cyclododecane-trastuzumab (212Pb-TCMC-trastuzumab) was completed in October 2014 as a joint effort at the University of Alabama (UAB) and the University of California San Diego Moores Cancer Center. The preliminary reports indicate that after five dose-levels of intraperitoneally administered 212Pb-TCMC-trastuzumab, patients with carcinomatosis experienced minimal agent-related toxicity. This report presents the data accumulated to date on the stability of the clinical grade, produced according to current good manufacturing practices (cGMP), TCMC-trastuzumab conducted in support of that clinical trial. Of the eleven tests performed with the cGMP TCMC-trastuzumab all but one remained within specifications throughout the 5 year testing period. The protein concentration varied by 0.01 mg/mL at 48 months. Two other assays, ion-exchange high performance liquid chromatography (IEX-HPLC) and a competitive radioimmunoassay (RIA) indicated that the cGMP TCMC-trastuzumab integrity may be changing, although the change thus far is within specifications. Subsequent stability testing will confirm if a trend has truly developed. The cGMP TCMC-trastuzumab was also evaluated for tolerance to higher temperatures and the potential of storage at −80 °C. The immunoconjugate proved stable when subjected to the lower temperatures and to multiple freeze-thaw cycles. The size exclusion (SE) HPLC analysis of the 203Pb-TCMC-trastuzumab was the only indicator that cGMP TCMC-trastuzumab may be sensitive to storage at 37 °C for 3 months.

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“…Preparing in a pharmacy a ready-to-use form could provide a solution to reduce mistakes (Berthouzoz et al, 2012) and guarantee the chemical stability and the microbiological quality (Hecq, 2011;Shah et al, 2011). In that way, stability studies are needed and have been published for various formulations (Abdulla et al, 2015;Bazin et al, 2015;Feutry et al, 2015;Jain et al, 2014;Paul et al, 2013;Walker et al, 2014;Zhang and Trissel, 2005). Moreover, in order to reduce costs, it could be interesting to use the same reconstituted vial during several days or to prepare treatment for a week.…”

Section: Introductionmentioning

confidence: 99%

Stability of micafungin sodium solutions at different concentrations in glass bottles and syringes

Briot

Vrignaud

Lagarce

2015

International Journal of Pharmaceutics

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Long-term physico-chemical stability of diluted trastuzumab

Cited by 34 publications

References 15 publications

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

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

Bench to Bedside: Stability Studies of GMP Produced Trastuzumab-TCMC in Support of a Clinical Trial

Stability of micafungin sodium solutions at different concentrations in glass bottles and syringes

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