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.

Overcoming Challenges of Implementing Closed System Transfer Device Clinical In-Use Compatibility Testing for Drug Development of Antibody Drug Conjugates.

Closed system transfer devices (CSTD) are a supplemental engineering control designed to reduce occupational exposure of hazardous drugs and are currently implemented in accordance with evolving regulations. Owing to the novelty and complexity of these devices and their importance in clinical in-use testing, here we evaluated FDA-approved CSTD, assessing product quality through stability indicating assays to determine any drug product incompatibilities. Six devices were used in a simulated compounding and administration of a late-phase IgG1 antibody-drug conjugate (ADC) and the resulting samples were analyzed for visible and subvisible particle counts by light obscuration and micro-flow imaging, physical stability by size exclusion chromatography, and biological activities by relative potency. Potential challenges included improper fit of CSTD components, loss of product to void volume, and material incompatibility. Results showed compatibility of the ADC with the 6 CSTD evaluated. One CSTD introduced subvisible particles into the ADC during compounding that were identified through morphological assessment as silicone oil. This study highlights the importance of clinical in use testing with new devices and proposes strategies to mitigate the risk of drug product incompatibility with CSTD.