End-to-End Approach to Surfactant Selection, Risk Mitigation, and Control Strategies for Protein-Based Therapeutics.

A survey performed by the AAPS Drug Product Handling community revealed a general, mostly consensus, approach to the strategy for the selection of surfactant type and level for biopharmaceutical products. Discussing and building on the survey results, this article describes the common approach for surfactant selection and control strategy for protein-based therapeutics and focuses on key studies, common issues, mitigations, and rationale. Where relevant, each section is prefaced by survey responses from the 22 anonymized respondents. The article format consists of an overview of surfactant stabilization, followed by a strategy for the selection of surfactant level, and then discussions regarding risk identification, mitigation, and control strategy. Since surfactants that are commonly used in biologic formulations are known to undergo various forms of degradation, an effective control strategy for the chosen surfactant focuses on understanding and controlling the design space of the surfactant material attributes to ensure that the desired material quality is used consistently in DS/DP manufacturing. The material attributes of a surfactant added in the final DP formulation can influence DP performance (e.g., protein stability). Mitigation strategies are described that encompass risks from host cell proteins (HCP), DS/DP manufacturing processes, long-term storage, as well as during in-use conditions.

How to Qualify Container Closure Systems for Intended Use, Part 2: Choosing the Right Components for Container Closure Systems.

The U.S. Food and Drug Administration regulates outsourcing facilities with the same stringency they apply towards drug manufacturers. This means that outsourcing facilities, who must navigate the changing regulatory landscape to achieve and maintain 503B status, must now focus on qualifying container closure systems for their intended use. This article, the second in a two-part series, examines component selection and methods for demonstrating that the container closure system will protect and maintain the quality of the compounded drug and ensure that the compounded drug can be safely administered to a patient.

Acute alcohol intoxication in a child following ingestion of an ethyl-alcohol-based hand sanitizer.

While uncommon, ingestion of ethanol-based hand sanitizers by children may be associated with significant intoxication. We report the case of a 7-year-old with acute alcohol intoxication following hand sanitizer ingestion. Alcohol elimination in this patient followed zero-order kinetics with a clearance rate of 22.5 mg/kg/h, consistent with the limited pharmacokinetic information available for children who experience alcohol intoxication from more traditional sources.