Formulation: An industry perspective on compatibility assessment of closed system drug-transfer devices for biologics

The use of closed system drug-transfer devices (CSTDs) has increased significantly in recent years due to the United States Pharmacopeia and the National Institute for Occupational Safety and Health recommending that they be used during the preparation and administration of hazardous drugs. However, while they help reduce occupational exposure to harmful compounds, CSTDs have risks that must be properly assessed before use to ensure they are compatible with specific types of drug products, such as biologics.

BioPhorum’s Formulation Workstream has identified that using CSTDs with biologics is a significant concern, given the wide variety of marketed CSTDs with different materials of construction and functional attributes that may impact product stability and quality. With the growing number of biologics products on the market and in development, and the increasing potential for CSTD use in dose preparation and/or administration of these products, there is a need to ensure that compatibility with CSTDs is evaluated in an efficient way that focuses on the risks involved.

For these reasons, the team has written An Industry Perspective on Compatibility Assessment of Closed System Drug-Transfer Devices for Biologics, which proposes a systematic risk-based evaluation approach for establishing the suitability of CSTDs before use.

Risks and mitigation strategies

Published in the Journal of Pharmaceutical Sciences, the paper summarizes the potential risks of CSTDs, their impact on product critical quality attributes and patients’ safety, and the proposed mitigation strategies to address each risk.

Example risks include a biopharmaceutical exposed to an incompatible contact surface (or excessive foaming during product withdrawal or transfer) that becomes physically unstable. This may result in the formation of undesired protein aggregates and/or visible particles in the dosing solution that may present safety concerns.

A detailed decision tree is included to guide CSTD compatibility risk assessments for hazardous biologic drug products to enable recommendations for using CSTDs with these products.

Risks are grouped into four categories: ‘deviceability’, leachables and lubricants, physical instabilities and material-of-construction compatibility. To minimize the effort required for the risk assessment, the decision tree is organized for assessments that could be paper-based instead of needing actual experiments.

Using the proposed approach will help overcome the practical limitations of testing the significant number of CSTDs available, and the large variety of components offered for each system, with every drug product. Increasing CSTD use brings greater responsibility for device vendors and biopharmaceutical manufacturers, not only to maintain the safety of healthcare workers but also the safety of patients by ensuring that devices do not compromise the quality of the drug product to be administered. Using BioPhorum’s risk-based approach for evaluating CSTDs will allow drug makers to address some of the potential challenges of using their products with CSTDs while also optimizing their resources.