JULY 2024LIFE SCIENCES REVIEW8In My OPINIONI ntroductionAssessing the clinical in-use compatibility of biotherapeutics is a critical step toward developing a stable and safe drug product (DP). It is also a regulatory requirement to provide data to support the procedures for administering products during clinical testing in a clinical trial application submitted to a Health Authority to seek approval for clinical testing. In addition, commercial applications for products to be marketed must contain information to support the directions for handling and administration of the product. Data obtained from testing to support the administration of the product includes stability and compatibility studies spanning the clinical in-use time frame for the DP (comprising of the dose preparation, storage, and simulated administration). Data obtained from clinical in-use testing should demonstrate that the handling and administration procedures result in the delivery of DP that is safe, potent, and at the intended strength.Clinical in-use testing of biotherapeutic DPs for parenteral delivery faces numerous challenges that the drug developer must consider and address. In this article, we include the technical challenges associated with clinical in-use testing and potential strategies for biopharma companies to address these.Compatibility with infusion diluents and materialDP formulations are commonly optimized to ensure their stability, allowing for an appropriate shelf life. However, the DP is often diluted with a diluent prior to administration to patients. The compatibility of this diluent with the DP should be assessed, as incompatibility could result in drug quality and efficacy issues and raise potential patient safety concerns. Furthermore, the DP and the prepared product do come into contact with many new materials during dose preparation and administration, such as syringes, filters or filter-needles, closed system transfer devices (CSTDs), intravenous (IV) bags, in-line fil¬ters, administration lines, and catheters. Contact with these materials can have a critical impact on drug stability, quality, efficacy¬ and safety. A stringent assessment to ensure compatibility with the contact materials during dose preparation using a wide range of supportive analytical testing is recommended to identify potential incompatibilities. These studies should be conducted early in product development to prevent delays in the initiation of clinical testing. CONSIDERATIONS FOR CLINICAL IN-USE TESTING OF BIOTHERAPEUTICSBy Léa Sorret, Principal Scientist & Group Lead in Pharmaceutical Development, Lonza Drug Product ServicesLéa Sorret
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