Challenges of Using Closed System Transfer Devices With Biological Drug Products: An Industry Perspective

Abstract

Impact to deliverable dose, holdup volumes of various CSTDs, and stopper coring were also reported that has significant impact to patient safety. Given the fact that USP chapter <800> will be implemented in December 2019, feedback from health authorities regarding the use of CSTDs for biological drug products is needed to provide an appropriate risk/benefit balance to ensure patient safety and quality of the biologic drug product while also protecting the health care worker and the environment. The purpose of this commentary is to provide an industry perspective on the challenges during the use of CSTDs for biologic drug products and is intended to raise caution and awareness on the benefits and shortcomings of these devices.

An Industry Perspective on the Challenges of Using Closed System Transfer Devices with Biologics and Communication Guidance to Healthcare Professionals

“…11 This will be an important challenge to overcome as studies have shown the use of certain CSTDs with biologics can lead to elevated insoluble particle counts and an increase in soluble aggregates, mainly due to lubricants in CSTDs. 2,12 Technical and clinical site-related challenges that may be encountered with CSTD use with biologics can be categorized as productspecific and product-agnostic and are described in the following subsections. Device-related challenges are described in the Drug Vial Optimization subsection.…”

“…Additionally, despite some similarities in material of construction, some devices exhibit incompatibilities, either consistently or inconsistently across drug products. 2,12 Some of the features of a CSTD that drive towards a good user experience may inevitably cause incompatibility with biologic drug products. For example, maintaining constant pressure equilibration between the drug vial and the CSTD helps with easy withdrawal of drug but may increase foaming, resulting in drug aggregation due to interfacial stress.…”

“…The geometry of a CSTD's construction dictates the holdup volume, which varies among different brands, and can be as high as 1.0 mL. 2,13 This is especially impactful for certain biological products in oncology, which may have low-volume vial presentations. Thus, there may be a risk of underdosing or incorrectly dosing these drugs if healthcare workers do not account for the holdup volumes during dose preparation and administration.…”

“…Studies have shown the use of certain CSTD vial adaptors can result in coring of rubber stoppers, where the spike introduces slivers of rubber into the drug product as it passes through the closure. 2,15 As the use of CSTDs has increased, so have the reports of stopper coring at clinical sites. These reports vary across multiple CSTDs and increases the risk of vial wastage, as a new drug product vial needs to be prepared if visible particulates are observed.…”

“…1 CSTDs are used primarily for intravenous infusion therapies, although usage of these devices is reported for dose preparation of subcutaneous and intravitreal administration routes as well. 2 In 2012 the Food and Drug Administration (FDA) created a device product code (ONB) specifically for CSTDs. This code defines a Closed Antineoplastic and Hazardous Drug Reconstitution and Transfer system as, "a product used to reconstitute and transfer antineoplastic and other hazardous drugs in healthcare setting indicated to reduce exposure of healthcare personnel to chemotherapy agents in healthcare setting".…”