RT Journal Article SR Electronic T1 Best Practices for Microbial Challenge In-Use Studies to Evaluate the Microbial Growth Potential of Parenteral Biological Products; Industry and Regulatory Considerations JF PDA Journal of Pharmaceutical Science and Technology JO PDA J Pharm Sci Technol FD Parenteral Drug Association (PDA) SP 475 OP 500 DO 10.5731/pdajpst.2022.012806 VO 78 IS 4 A1 Zamiri, Camellia A1 Leiske, Danielle L. A1 Hughes, Patricia A1 Kirwan, J. Paul A1 Der, Evelyn A1 Cox, Emily A1 Warburton, Rob A1 Goss, Monica A1 Weiser, Sarah A1 Perez-Brown, Janet A1 Gopalrathnam, Ganapathy A1 Liu, Jing A1 Mehta, Shyam B. A1 Shereefa, Shebeer A1 Specht, Sebastian A1 Aedo, Sandra J. A1 Goldbach, Pierre A1 Jia, Feng A1 Kuehnle, Barbara A1 Page, Scott A1 Voeten, Liesbeth A1 Yi, Li A1 Zhu, Chen YR 2024 UL http://journal.pda.org/content/78/4/475.abstract AB Microbial challenge in-use studies are performed to evaluate the potential for microbial proliferation in preservative-free single-dose biological products after first puncture and potential accidental contamination during dose preparation (e.g., reconstitution or dilution) and storage. These studies, in addition to physicochemical in-use stability assessments, are used as part of product registration to define in-use hold times in Prescribing Information and in the pharmacy manual in the case of clinical products. There are no formal guidance documents describing regulator expectations on how to conduct microbial challenge in-use studies and interpret microbial data to assign in-use storage hold times. In lieu of guidance, US Food and Drug Administration (FDA) regulators have authored publications and presentations describing regulator expectations. Insufficient or unavailable microbial challenge data can result in shortened in-use hold times, thus microbial challenge data enables flexibility for health care providers (HCPs) and patients while ensuring patient safety. A cross-industry/FDA in-use microbial working group was formed through the Innovation & Quality (IQ) Consortium to gain alignment among industry practice and regulator expectations. The working group assessed regulatory guidance, current industry practice via a blinded survey of IQ Consortium member companies, and scientific rationale to align on recommendations for experimental design, execution of microbial challenge in-use studies, and a decision tree for microbial data interpretation to assign in-use hold times. Besides the study execution and data interpretation, additional considerations are discussed including the use of platform data for clinical stage products, closed system transfer devices (CSTDs), transport of dose solutions, long infusion times, and the use of USP <797> by HCPs for preparing sterile drugs for administration. The recommendations provided in this article will help streamline biological product development, ensure consistency on assignment of in-use hold times in biological product labels across industry, and provide maximum allowable flexibility to HCPs and patients while ensuring patient safety.