Automated Robotic Titration System, Tix0 pages

www.abcontrols.com Tel: 949-341-0977
Authors:
Philippe Lam, Sr. Engineer. Genentech, Inc., Pharmaceutical Process R&D, 1 DNA Way, South
San Francisco, CA 94080
Mike Nariman, AB Control, Inc., Irvine, CA, www.abcontrols.com.
Abstract
Genentech had a requirement for unattended robotic titration. The existing system was not robust and
the manual method was too time-consuming. Per Genentech’s request AB Controls
developed a fully automated robotic system for conducting Karl Fischer moisture assay. AB
Controls customized their “Focus” software to handle all automation and robotic tasks. The
choice of measurement instruments were made by Dr. Philippe Lam, and AB Controls integrated
them all on a robust and versatile platform that occupied 1/4th of the space of the previous unit. The
design of the platform and robotic tooling was done such that multiple functions could be
performed by the same end of arm tooling. This machine is validated for use in Genentech’s
manufacturing operation and has provides significant time and labor savings over the manual assay
method. While some sample preparation is required from the analyst, the system fulfills moisture
assay needs for all our lyophilized products.
Introduction
Karl Fischer titration is one of the few assay techniques recognized by the FDA for the
determination of residual moisture in lyophilized pharmaceutical product. Because the iodinewater
reaction is very specific and quantitative, this technique offers high accuracy and
precision.
However, conventional Karl Fischer titration is not considered a “high throughput” assay and
requires significant manual intervention from the analyst. This presents a challenge when large
number of samples need to be analyzed in a very short time. Furthermore, most lyophilized
products are hydroscopic and must be processed promptly after removal from the primary
container. The few off-the-shelf automated systems offered by Karl Fischer titrator vendors were not
suitable for our needs.
The following communication summarizes our approach at developing a reliable system
intended at performing unattended Karl Fischer titration on numerous samples. We present our
rationale for selecting instrumentation and discuss sample preparation strategies, both of which
impact the overall design of the automated system.