(594d) Residence Time Distribution and Material Traceability for Continuous Drug Substance Processes
AIChE Annual Meeting
2017
2017 Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Continuous Processing Technologies Applied in Drug Substance Manufacturing
Wednesday, November 1, 2017 - 4:21pm to 4:43pm
Authors: Christopher Polster1, Venkata Ramana Reddy3, Carla Luciani1, Stephen Jeffery2, Martin Johnson1, Kevin Chinn4, Hod Finkelstein4
1 Eli Lilly & Co., Indianapolis, IN-46221, USA
2 Eli Lilly S.A. Irish Branch, Dunderrow, Kinsale, Co. Cork, Ireland, P17 NY71
3 Lilly Capability Center India, Bangalore, India
4Trutag Technologies, Inc., 2045 Lauwiliwili St, Unit 301, Kapolei, HI 96744
Abstract
The concept of residence time distribution (RTD) to analyze chemical reactor performances appeared earlier 1930’s.[1] Danckwerts materialized the field by defining the most common RTDs.[2] Currently, the use of RTDs to understand mixing characteristics of the units/trains as well as material traceability and batch definition is an established approach.
With the rapidly growing adoption of continuous manufacturing processes in the pharmaceutical industry, the understanding of RTD through modeling and characterization is imperative to support both R&D activities and long term commercial manufacturing of both drug substance and drug product.[3],[4],[5]
In this work, some of the techniques used to measure RTD are described. Also, libraries were developed to provide a tool for R&D and manufacturing scientists to develop and simulate plant flowsheets that can be used for material traceability, determining diversion boundaries, and guide decision trees for diversion scenarios. Specific case studies will be shared.
[1] MacMillin, R.B., Weber, M. The Theory of Short-Circuiting in Continuous-Flow Mixing Vessels in Series and the Kinetics of Chemical Reactions in such Systems. Transactions of American Institute of Chemical Engineers 1935, 31, 409-458.
[2] Danckwerts, P.V. Continuous Flow Systems. Distribution of Residence Times. Chem Eng. Sci. 1953, 2, 1-13.
[3] Manley, L. Manufacturing Platform’s Residence Time Distribution Using Major and Minor Unit Formula Excipient Step Changes and Soft Sensors. 2016 AIChE Annual Meeting (342c).
[4] Garcia-Muñoz, S., Luciani, C., Shi, Z., Roth, W., Butterbaugh, A. Hanson, J., Manley, L., Barnes, L., Leavesley, I., Almaya, A. Model-Aided Development of a Continuous Drug Product Manufacturing Process.
[5] Engisch, W., Muzzio, F. Using Residence Time Distribution (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing. J. Pharm Innovation 2016, 11, 64-81.