Satish K. Singh,1 Nitin Rathore,2 Arnold McAuley,2 Anurag S. Rathore,3
1 Pfizer Inc.
2 Amgen Inc.
3 Biotech CMC Issues.
PUBLICATION: BioPharm International. 22(6): (2009)
ABSTRACT: Maintaining product stability during the various drug product process unit operations is paramount to our ability to supply safe and efficacious biotech products to patients. New technologies are helping us ensure that we meet these challenges successfully and are able to embrace the Quality by Design paradigm. This article presents best practices to meet three of the significant technical challenges experienced in drug product manufacturing, namely, maintaining product stability during frozen storage, performing visual inspection of drug product vials, and controlling protein particulates.
CHI-TING HUANG,1 DEEPAK SHARMA,2 PETER OMA,2 RAJESH KRISHNAMURTHY3
1Acceleron Pharma, 149 Sidney Street, Cambridge, Massachusetts 02139
2ProteinSimple Technologies, Inc., 115 Terence Matthews Crescent, Ottawa, Ontario, Canada K2M 2B2
3ImmunoGen, Inc., 830 Winter Street, Waltham, Massachusetts 02451
PUBLICATION: Journal of Pharmaceutical Sciences. 98(9): 3058-3071. (2010)
DOI: 10.1002/jps.21575
ABSTRACT: The U.S. and European Pharmacopeias require subvisible (≥10 and ≥25 µm) and visible particulate testing of therapeutics to ensure their safety and suitability for clinical use. The objective of this article is to compare the sizing and counting accuracies of light obscuration, which is the standard technique used to measure subvisible particulate matter, and Micro-Flow Imaging (MFITM), a new imaging-based technology. An immunoconjugate was selected as the model protein for this study since it could be induced to form particulate matter in PBS. Light obscuration was performed as described in USP chapter <788> while MFI measurements were conducted per the manufacturer’s procedures. The two techniques yielded similar results when polystyrene standards were analyzed. However, the MFI measurements indicated the presence of significantly more particles in the protein-containing solution compared to the light obscuration measurements. The presence of nonspherical protein particles as well as particles that possess a refractive index similar to the solvent that they are in appear to be detected by MFI, but not by light obscuration, leading to the difference in the results. Imaging-based technologies could aid in developing formulations and processes that would minimize the formation of protein particulates. ©2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3058–3071, 2009
Keywords: analytical chemistry; proteins; excipients; protein formulation; image analysis; imaging methods; injectables; light-scattering; particle size; protein aggregation
LINK TO ARTICLE: http://onlinelibrary.wiley.com/doi/10.1002/jps.21575/abstract
