An Industry Perspective on Compatibility Assessment of Closed System Drug-Transfer Devices for Biologics

Abstract

The Formulation Workstream of the BioPhorum Development Group (BPDG), an industry-wide consortium, has identified the increased use of closed system drug-transfer devices (CSTDs) with biologics, without an associated compatibility assessment, to be of significant concern. The use of CSTDs has increased significantly in recent years due to the recommendations by NIOSH and USP that they be used during preparation and administration of hazardous drugs. While CSTDs are valuable in the healthcare setting to reduce occupational exposure to hazardous compounds, these devices may present particular risks that must be adequately assessed prior to use to ensure their compatibility with specific types of drug products, such as biologic drugs, which may be sensitive. The responsibility of ensuring quality of biologic products through preparation and administration to the patient lies with the drug product sponsor. Due to the significant number of marketed CSTD systems, and the large variety of components offered for each system, a strategic, risk-based approach to assessing compatibility is recommended herein. In addition to traditional material compatibility, assessment of CSTD compatibility with biologics should consider additional parameters to address specific CSTD-related risks. The BPDG Formulation Workstream has proposed a systematic risk-based evaluation approach as well as a mitigation strategy for establishing suitability of CSTDs for use.

Stress Factors in Primary Packaging, Transportation and Handling of Protein Drug Products and Their Impact on Product Quality

“…Generally speaking, benchtop risk evaluation during device development involves the following four experimental categories: deviceability, leachables and lubricants, physical instabilities, and material-of-construction compatibility. 93 Given the fact that a combination product is both a drug and a device, any effects that the drug product may have on the drug delivery function of the device should also be evaluated. Just as importantly, any successful benchtop evaluations should be followed by an assessment of effect of the fill-finish process on the characteristics of the drug product as part of an overall risk mitigation strategy during biopharmaceutical device development.…”

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

“…A systematic risk-based approach for assessing compatibility and establishing suitability of CSTDs for use with biologic products has been proposed in recent literature. 8 Regulations Surrounding Hazardous Drugs, CSTD Use, and Medical Device Approvals…”

A Systematic Approach to Evaluating Closed System Drug-Transfer Devices During Drug Product Development

“…Detailed description and functionality of each component has been described elsewhere. [6][7] CSTDs have been available for use since 1997 but have become more prevalent in the last 2 − 3 years. [1][2][3] Most biologics, including those for oncology indications, are not routinely classified as occupationally hazardous.…”

“…oncology drugs irrespective of their NIOSH status. [7][8] This puts onus on pharmaceutical manufacturers to perform compatibility and dosing accuracy studies and provide dose preparation and administration instructions to healthcare staff. The years 2020 and 2021 saw a surge in CSTD-related publications that added tremendous value to our existing knowledge.…”

“…The years 2020 and 2021 saw a surge in CSTD-related publications that added tremendous value to our existing knowledge. [6][7][8][9][10][11] As of 2021, eleven CSTDs have been approved for use by the FDA 10 , all having similar mechanisms of action but having differences in their mechanical transfer technology, design, geometry, fluid contact material, and holdup volumes. 12,13,14,15,16 While this diversity may provide flexibility to the healthcare institutions, in-use testing of each product using multiple CSTDs is resource intensive for the biopharmaceutical manufacturer.…”