Assuring control of process related impurities (PRIs) is a critical element of the control strategy for biopharmaceutical production. PRIs generally arise from cell substrates (e.g., host cell components), cell culture (e.g., media components) and purification (e.g., Triton X-100 used for viral inactivation) processes. PRIs can be divided into two categories: biological macromolecule impurities (such as host cell DNA, host cell protein, recombinant Protein A) and small molecule and synthetic macromolecule impurities (such as antifoams). This presentation will share the approaches taken at Medimmune for safety risk assessment of PRIs in the latter category.<br/><br/>The overall approach incorporates the several related ICH guidelines (e.g., M7, Q3C and Q3D) and addresses challenges that we face for their implementations for biopharmaceutical production processes. We will describe the stepwise process on risk identification, risk assessment and risk based testing as well as control strategies in the manufacturing process, including: Initial categorization of PRI compounds based on available safety/toxicity data from literature, Evaluation of potential risks based worst case assumption without taking process clearance into consideration to guide PRI sampling and testing plan, Factors that are taken for the risk calculation and basis for determination of the threshold value and safety limits, Incorporation of process understanding and platform knowledge to facilitate the application of an integrated risk assessment approach into the process and product risk control plan<br/><br/>Examples will be presented to illustrate a science based, integrated risk assessment strategy to support the development of safe biologic product.

Development of an integrated risk assessment strategy for process related impurities for biopharmaceutical production

253rd National Meeting (2017)

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