Effects of Surfaces and Leachables on the Stability of Biopharmaceuticals

• Published in: Journal of pharmaceutical sciences Vol. 100; no. 10; pp. 4158 - 4170
• Main Authors: Bee, Jared S., Randolph, Theodore W., Carpenter, John F., Bishop, Steven M., Dimitrova, Mariana N.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.10.2011; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: adsorption; agitation; air-water interface; Biological and medical sciences; biopharmaceuticals characterization; Biopharmaceutics - methods; Chemistry, Pharmaceutical; Drug Contamination; Drug Delivery Systems - instrumentation; Drug Packaging; Drug Stability; Equipment Design; formulation; General pharmacology; leachables; Medical sciences; particles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Protein Aggregates; protein aggregation; Protein Stability; Proteins - chemistry; stability; surface; Surface Properties; Surface-Active Agents - chemistry; Technology, Pharmaceutical - methods; Water - chemistry; agitation; adsorption; surface; protein aggregation; air–water interface; formulation; biopharmaceuticals characterization; particles; stability; leachables; Drug; Agitation; Stability; Pharmaceutical technology; air-water interface; Air water interface; Biopharmaceuticals; Protein; Aggregation; Characterization; Particle; Adsorption; Formulation; Physicochemical properties
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1002/jps.22597

Therapeutic proteins are exposed to various potential contact surfaces, particles, and leachables during manufacturing, shipping, storage, and delivery. In this review, we present published examples of interfacial- or leachable-induced aggregation or particle formation, and discuss the mitigation strategies that were successfully utilized. Adsorption to interfaces or interactions with leachables and/or particles in some cases has been reported to cause protein aggregationor particle formation. Identification of the cause(s) of particle formation involving minute amounts of protein over extended periods of time can be challenging. Various formulation strategies such as addition of a nonionic surfactant (e.g., polysorbate) have been demonstrated to effectively mitigate adsorption-induced protein aggregation. However, not all stability problems associated with interfaces or leachables are best resolved by formulation optimization. Detectable leachables do not necessarily have any adverse impact on the protein but control of the leachable source is preferred when there is a concern. In other cases, preventing protein aggregation and particle formation may require manufacturing process and/or equipment changes, use ofcompatible materials at contact interfaces, and so on. This review summarizes approaches that have been used to minimize protein aggregation and particle formation during manufacturing and fill–finish operations, product storage and transportation, anddelivery of protein therapeutics. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4158–4170, 2011