Conclusions
AVI of injectable drug products offers several advantages over manual inspection, including process consistency, speed, and
potential cost effectiveness. This study investigated the role of machine settings, formulation properties, and fill configuration
on the performance of an AVI. Higher spin speed and brake settings were shown to improve detection rates of the AVI system.
Product properties such as viscosity, density, and surface tension affect the manner and duration of particle suspension in
solution and thereby affect process performance. Other inherent solution properties such propensity to form air-bubbles and/or
protein particles can also cause potential interference with the inspection system resulting in false rejections. Low fill
volumes are also challenging because of the smaller inspection window. It is suggested that any equipment qualification or
process characterization work should evaluate the system performance over a wide range of these process parameters and solution
properties to arrive at a robust and consistent visual inspection process. DOEs can be conducted to study these parameters
and any potential interactions. Formulation properties and fill configurations can be bracketed to minimize the number of
experiments.
Acknowledgments
The authors wish to thank Aarti Gidh, Deborah Shnek, Erwin Freund, and Ed Walls in process development at Amgen for useful
discussions and suggestions for this paper. We also thank Jeff Stephens, Ari Levy, and Damien Villanueva in clinical manufacturing
at Amgen for providing valuable experimental support toward the execution of these studies.
Nitin Rathore*, is a senior scientist, Cylia Chen is a senior associate scientist, Oscar Gonzalez is a senior engineer, and Wenchang Ji is principal scientist, all in drug product and device development at Amgen, Thousand Oaks, CA, nrathore@amgen.com
, tel. 805.313.6393.
*To whom all correspondence should be addressed.
References
1. N. Rathore and R. Rajan, Biotechnol. Prog.,
24 (3), 504–514 (2008).
2. T.A. Barber, Control of Particulate Matter Contamination in Healthcare Manufacturing (CRC Press, 1999).
3. C. Jones, presentation before the PDA Visual Inspection Forum (Bethesda, MD, 2007).
4. J.Z. Knapp and L.R. Abramson, Jrnl. of Parenteral Sci. and Technol.,
44 (2), 74–107 (1990).
5. J.Z. Knapp, PDA Jrnl. of Pharma. Sci. and Technol.,
75 (2), 131–147 (2007).
|
