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

Closed system transfer devices (CSTDs) have been used with hazardous drugs for several decades. The goal of this whitepaper is to increase awareness among healthcare professionals, device manufacturers, regulators, and pharmaceutical/biotech companies on the potential issues around the use of CSTDs with biologic drug products to allow their informed use in clinics. Specifically, we discuss the key topics related to the use of CSTDs with biologics products, including components and materials of construction, a breakdown of regulatory, technical, clinical site-related risks and challenges associated with the use of CSTDs with biological products, gathered from stakeholder discussion at the IQ CSTD workshop, and considerations on current testing requirements and communication strategies to drive further dialog on the appropriate use of CSTDs. Given the technical challenges of using CSTDs with biologics, coupled with the current regulations surrounding CSTD approval and proper use, as well as a need for alignment and standardization to enable a consistent strategy for compatibility testing and communication of incompatibilities, it is recommended that global health authorities and other stakeholders seek to understand these issues, in order to alleviate these problems and keep healthcare workers and patients safe from harm.

Determination of Holdup Volume and Transient Contact Compatibility of Closed System Transfer Devices for a Reconstituted Lyophilized Drug Product.

Closed system transfer devices (CSTD) are broadly used in healthcare settings as an adjunct engineering control to limit personnel exposure to hazardous drugs (HD). Mechanistic and material differences between CSTD and traditional in-use devices warrant assessment of their impact to product quality and deliverable dose. A lyophilized antibody-drug conjugate (ADC) product was assessed for holdup volume and material compatibility with 14 diverse CSTD sets in a simulated dose compounding scheme. Transient exposure to CSTD showed no negative impact to product quality attributes; however, 6 CSTD sets showed a substantial increase in subvisible particles with a morphology consistent with silicone oil. CSTD led to variable but consistently reduced recovery of dose from the product. In addition, devices with high holdup volumes resulted in dilution of reconstituted drug product and protein concentrations below the target. Given the complexities and potential implications for efficacy and patient safety, this study illustrates the need for proactive assessment and risk mitigation, as well as increased awareness from clinicians, pharmaceutical manufacturers, device developers, and relevant regulatory authorities.