Rituximab (RTX) is a genetically engineered chimeric mouse anti-human monoclonal antibody (mAb)-targeting CD20 antigen. CD20 is a transmembrane protein that is thought to play a role in B-cell proliferation, activation and differentiation, and signal transduction [
1]. RTX is widely utilized in the treatment of several B cell-derived hematological malignancies [
2,
3]. In oncology, RTX is administered for the treatment of non-Hodgkin’s lymphoma, diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL). Additionally, RTX is indicated for the treatment of non-oncology indications such as autoimmune diseases [
4,
5]. RTX was the first CD20 mAb approved by the US Food and Drug Administration (FDA) for the treatment of relapsed or refractory, CD20-positive, B-cell, low-grade, or follicular non-Hodgkin’s lymphoma in 1997 [
6]. RTX mediates anti-tumor effects by a variety of mechanisms including induction of apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and direct induction of cellular apoptosis [
7,
8]. Extensive stability testing is required for biopharmaceuticals such as RTX by national health authorities to demonstrate that the product quality is not compromised by standard transport and storage conditions and that product specifications are met throughout the declared shelf-life [
9,
10]. Many stress factors are routinely encountered during the preparation, purification, shipping, or storage of protein products and especially mAbs. For RTX and further mAb-based therapeutics, several studies have evaluated various stability aspects, for example, in-use, out of fridge, or opened vial stability [
11‐
13].
Sandoz biosimilar of RTX (SDZ-RTX), marketed worldwide under the trade name Rixathon
® or Riximyo
®, is available as a concentrate solution for infusion as a single-dose vial containing either 100 mg or 500 mg of active pharmaceutical ingredient at a concentration of 10 mg/mL [
14]. As defined in the product’s Summary of Product Characteristics, SDZ-RTX should be stored in a refrigerator (2–8 °C) and kept in the original outer carton to protect from light exposure. However, based on the newly available stability data presented in this publication, some markets (e.g., the European Union [EU]) have already approved single-time temperature excursions outside 2–8 °C [
14].
In addition, none of the RTX manufacturers in the EU have claimed a permitted temperature excursion above 8 °C (MabThera
®, Ruxience
®, and Truxima
®) [
4,
15,
16]. On the contrary, for any short-term temperature excursion outside the intended storage conditions, it is recommended to discard SDZ-RTX unless the excursion is permitted according to the provided patient information leaflet (PIL). Of note, this is the case for the EU market alone at present. However, in other markets where out-of-fridge (OOF) excursion is not permitted according to the enclosed PIL, evaluation of short-term temperature excursion on the stability and quality of SDZ-RTX is required. The study, which is the basis for the defined OOF period in the PIL, was thus designed to evaluate the extended physicochemical and biological stability of Rixathon
®/Riximyo
® after exposure to OOF conditions.