Pharma Fundamentals: An Introduction to Hold Times in Biopharmaceuticals

In this Pharma Fundamentals episode, Robert Dream, managing director of HDR Company and a PharmTech Editorial Advisory Board member, explains hold times in biopharmaceutical manufacturing. A hold time is the maximum validated period an intermediate or product can sit between processing steps without harming quality, safety, purity, potency, or stability. Pauses occur for reasons like equipment availability, quality control testing, scheduling, cleaning, or transport, and materials must remain under controlled conditions (refrigeration, freezing, controlled room temperature, nitrogen blanketing, light protection) throughout.

Dream distinguishes drug substance (the API—monoclonal antibodies, recombinant proteins) from drug product (the final formulated medicine), noting hold times apply at multiple points and that total cumulative hold time across the whole process matters, not just individual step-to-step holds. Hold times are established through validation studies testing material at set time points (e.g., 0, 12, 24, 72, 96 hours) until failure defines the ceiling; manufacturers then apply a safety margin below that maximum. Monitored parameters include temperature, sterility, bioburden, pH, protein concentration, appearance, potency, and purity.

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