Annales Pharmaceutiques Françaises (2013) 71, 376—389 Disponible en ligne sur www.sciencedirect.com ORIGINAL ARTICLE SFPO and ESOP recommendations for the practical stability of anticancer drugs: An update Mise à jour des recommendations de la SFPO et de l’ESOP pour la stabilité pratique des anticancéreux a,∗ b c d J. Vigneron , A. Astier , R. Trittler , J.D. Hecq , e f g h M. Daouphars , I. Larsson , B. Pourroy , F. Pinguet a Pharmacy, university hospital, rue du Morvan, 54511 Vandœuvre, France b UMR 7054, school of medicine, Henri-Mondor hospital, 94010 Créteil, France c University hospital, Freiburg, Germany d University hospital Mont Godinne, 5530 Yvoir, Belgium e Centre Henri-Becquerel, 76038 Rouen, France f Amgros, Copenhagen, Denmark g Pharmacy, university hospital, 13005 Marseille, France h Val d’Aurelle cancer center, 34298 Montpellier, France Received 20 May 2013; accepted 12 June 2013 Available online 28 August 2013 KEYWORDS Summary The recommandations for the practical stability of anticancer drugs published in Stability; 2010 by the French Society of Hospital Pharmacists (SFPO) and the European Society of Oncology Anticancer drugs; Pharmacists (ESOP) have been updated. Ten new molecules have been included (asparagi- Monoclonal nase, azacitidine, bevacizumab, clofarabine, eribuline mesylate, folinate sodium, levofolinate antibodies; calcium, nelarabine, rituximab, temsirolimus). Dose banding; © 2013 Elsevier Masson SAS. All rights reserved. Stabilis® ∗ Corresponding author. E-mail address: [email protected] (J. Vigneron). 0003-4509/$ — see front matter © 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.pharma.2013.06.002 SFPO and ESOP recommendations for the practical stability of anticancer drugs 377 MOTS CLÉS Résumé Les recommandations concernant la stabilité pratique des préparations Stabilité ; d’anticancéreux émanant de la Société franc¸aise de pharmacie oncologique (SFPO) et Anticancéreux ; de la Société européenne de pharmacie oncologique (ESOP) parue en 2010 ont été actual- Anticorps isées. Dix nouvelles molécules ont été ajoutées (asparaginase, azacitidine, bevacizumab, monoclonaux ; clofarabine, eribuline mesylate, folinate sodium, levofolinate calcium, nelarabine, rituximab, Dose banding ; temsirolimus) Stabilis® © 2013 Elsevier Masson SAS. Tous droits réservés. Introduction change in chemistry [i.e., peptide mapping] and biological activity [e.g. cytotoxicity on cells, bioassays). Other inter- These recommendations for storage conditions of anticancer esting studies which uses only one or two methods were not drugs are the result of the deliberations of the SFPO (French selected [3,4]. Society for Oncology Pharmacy) stability group. The first For some drugs, interesting results were not selected due edition of the data were published in 2008 by the Cen- to various reasons. The stability of bendamustine was stud- tre national hospitalier d’information sur le médicament, ied by Krämer et al. [5] with a 9 hours stability at room CNHIM — National Information Centre on Hospital Drugs. temperature and a 5 days in the refrigerator. The results The stability group comprised Arnaud P, Astier A, Bellanger of this study published in 1994 were based on the classi- A, Bonan B, Breilh D, Burnel S, Daouphars M, Ferrio AL, cal T90% of the initial concentration. However, today, the Havard L, Helvig A, Husson MC, Pinguet F, Poisson N, Sar- recommendations of the manufacturer [6] are based on the rut B, Vigneron J. These recommendations were adopted as T95% with a 3.5 hours stability at room temperature and the European standard by ESOP in 2010 and published in the 2 days in the refrigerator. These data were in accordance European Journal of Oncology Pharmacy [1]. with the T95% of Krämer et al. We decided to use the rec- A new group with members of SFPO and European hospital ommendation « Follow SPC) ». Moreover, this decision is in pharmacists has updated this work in 2012. This new group accordance with the European guideline for stability studies comprised Alain Astier, Mikaël Daouphars, Frédéric Pinguet, of anticancer drugs [7]. Bertrand Pourroy, Jean Vigneron for SFPO and Jean Daniel For vincristine, the extended stability in polyolefine bags Hecq from Belgium, Iben Larsson from Denmark and Rainer was also demonstrated in polypropylene syringes [8] but Trittler from Germany. the information has not been selected because of the rec- In this updated article, new drugs have been included ommendations of the World Health Organisation [9] who (asparaginase, azacitidine, bevacizumab, clofarabine, recommend to prepare the vinca-alcaloids only in infusion eribuline mesylate, folinate sodium, levofolinate calcium, bags to avoid inadvertent intrathecal injections. nelarabine, rituximab, temsirolimus). Some drugs received Below, we present the new informations and their inter- new informations (cisplatine, docetaxel, fludarabine, oxali- ests in the daily practice. We have separated the long-term platine, vincristine). Three drugs no longer available on the and the short-term stability studies. ‘‘Long-term’’ has been market have been removed from the table: chlormethine, arbitrarily defined as a stability of at least 2 weeks. mitoguazone and pirarubicine. The updated recommendations are presented in Table 1. Long-term stability studies Selection criteria for the articles These studies can be divided into five categories. New informations were selected by using the Stabilis database. For each monograph, the new publications until 2008 have been revised according to a checklist to select The stability of monoclonal antibodies inclusion criteria for the physical and chemical stability. The articles were selected if they brought new informations for The three studies presented here are the first fully validated the daily practice (for example, extended stability for the stability studies according to the ICH guideline Q5C. Several preparation in advance). We decided to include the infor- complementary methods have been used to evaluate the sta- mations presented in posters if the stability study was in bility of rituximab. Various protein characterization methods accordance to our criteria and submitted to publication. were used to determine changes in physicochemical proper- The stability data of simple solutions (one drug in one con- ties of rituximab, including size-exclusion chromatography, tainer) have been selected. The stability of mixtures or of dynamic light scattering, turbidimetry, cation-exchange non-injectable drugs were not in the field of this work. chromatography, second-derivative ultraviolet and infrared Stability studies of monoclonal antibodies carried out spectroscopy, and peptide mapping. Cell culture was used in accordance with the recommendations of ICH Guide- to assess biological stability. lines Q5C [2] were selected. These stability studies use The authors have demonstrated a 6 months stability for at least three complementary methods (study of aggre- the infusions at 1 mg/mL in 0.9% sodium chloride in poly- ® gation [e.g. size exclusion chromatography, turbidimetry], olefine container (Freeflex ) [71]. This long-term stability 378 Table 1 SFPO and ESOP recommendations for the practical stability of anticancer drugs. Recommandations SFPO et ESOP pour la stabilité pratique des anticancéreux. Product Container Vehicle Concentration Recommendations for References storage conditions Alemtuzumab Follow SPC Amifostine Follow SPC ◦ 3 Asparaginase Polypropylene NaCl 0.9% 80 UI/mL 7 days at 2—8 C ◦ ◦ Azacitidine Polypropylene WFI (4 C) 25 mg/mL 23 days at −20 C [10—12] ◦ syringes 5 days at 2—8 C Bendamustine Follow SPC ◦ 1 Bevacizumab Polypropylene NaCl 0.9% 2 to 16 mg/mL 90 days at 4 or 25 C Bleomycin Follow SPC ◦ Bortezomib Glass - NaCl 0.9% Reconstituted: 1 mg/mL 35 days at 2—8 C [13,14] polypropylene syringes ◦ Glass NaCl 0.9% Reconstituted: 2.5 mg/mL 30 days at 2—8 C [15] ◦ Busulfan 2-piece Non-diluted solution: 28 days at 2—8 C or at [16] Never freeze busulfan syringes 6 mg/mL room temperature ◦ ◦ Incompatible with polycarbonate Polypropylene NaCl 0.9% Diluted in administration 19 hours at 2 C—8 C [17] (dimethylacetamide) vehicle: 0.5 mg/mL Protected from light ◦ Glass NaCl 0.9% Diluted in administration 48 hours at 2—8 C vehicle: 0.5 mg/mL ◦ ◦ Polypropylene NaCl 0.9% Diluted in administration 36 hours at 13 C—15 C or glass vehicle: 0.5 mg/mL Protected from light Caelyx Follow SPC ◦ Carboplatin PVC - Dextrose 5% Diluted in administration 84 days at 4 C or 84 days [18—20] ◦ polyethylene vehicle: 0.70—2.15 mg/mL of which 83 days at 4 C and 1 day at room temperature Protected from light Polyethylene - Dextrose 5% Diluted in administration 30 days at room polypropylene vehicle: 3.2 mg/mL temperature J. protected from light Vigneron ◦ Carmustine Glass - Dextrose 5% Diluted in administration 48 hours at 4 C, 2.5 hours [21,22] Never use PVC polyethylene vehicle: 0.2 mg/mL in polyethylene at room Should be protected from light temperature et Protected from light al. SFPO and Table 1 (Continued) ESOP Product Container Vehicle Concentration Recommendations for References storage conditions recommendations ◦ Polyethylene Dextrose 5% Diluted in administration 4 hours at 25 C in the light ◦ vehicle: 0.1—0.5 mg/mL and 48 hours at 4 C ◦ Polyethylene Dextrose 5% Diluted in administration 4 hours at 25 C and ◦ vehicle: 1 mg/mL 24 hours at 4 C Cisplatin Ethyl vinyl NaCl 0.9% Diluted in administration 28 days at room [23—25] for acetate - vehicle: 0.5—0.9 mg/mL temperature polyethylene - 0.1—0.4