Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

作     者：Natalia Navas Jesús Hermosilla Anabel Torrente-Lopez Jose Hernandez-Jim
enez Jose Cabeza Raquel Perez-Roblesa Antonio Salmeron-García Natalia Navas;Jesús Hermosilla;Anabel Torrente-L(o)pez;Jos(e) Hern(a)ndez-Jim(e)nez;Jose Cabeza;Raquel P(e)rez-Robles;Antonio Salmer(o)n-García

作者机构：Department of Analytical ChemistryScience Faculty/Biomedical Research Institute ibs.GranadaUniversity of GranadaGranadaE-18071Spain UGC Farmacia HospitalariaBiomedical Research Institute ibs.Granada.Hospital Universitario San Cecilio de GranadaGranadaE-18012Spain 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2020年第10卷第6期

页      面：532-545页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 10[医学] 0702[理学-物理学] 

基　　金：Project FIS PI-17/00547(Instituto CarlosⅢ,Ministerio de Economía y Competitividad,Spain),which means that it was also partially supported by European Regional Development Funds(ERDF) the University of Granada(Spain)for the support。 

主　　题：COVID-19 Tocilizumab Critical quality attributes IV and SC medicines 

摘      要：COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.