Technical Decision Making with Higher Order Structure Data: Impact of a Formulation Change on the Higher Order Structure and Stability of a mAb. Issue 4 (30th September 2014)

• Record Type: Journal Article
• Authors: Gruia, Flaviu; Du, Jiali; Santacroce, Paul V.; Remmele, Richard L.; Bee, Jared S.
• Is Part Of: Journal of pharmaceutical sciences. Volume 104:Issue 4(2015:Apr.)
• Page Start: 1539
• Page End: 1542
• Publication Date: 2014-09-30
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24158
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Changes in formulation may be required during the development of protein therapeutics. Some of the changes may alter the protein higher order structure (HOS). In this note, we show how the change from a trehalose‐based formulation to an arginine‐based formulation concomitantly impacted the tertiary structure and the thermal stability of a mAb (mAb1). The secondary structure was not disrupted by the formulation change. The destabilization of the tertiary structure did not affect the long‐term stability or the bioactivity of mAb1. This indicates that loss of conformational stability was likely compensated by improvements in the colloidal stability of mAb1 in the arginine‐based formulation. The formulation‐induced changes in HOS were reversible as proven by measurements after dilution in a common buffer (phosphate‐buffered saline). For aggregation driven by assembly of aggregates (colloidally limited), small changes in conformational structure and stability as measured by HOS methods may not necessarily be predictive of long‐term stability. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1539–1542, 2014</p> </abstract>