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Biologics Formulation Factors Affecting Metal Leachables from Stainless Steel

  • Research Article
  • Theme: Sterile Products: Advances and Challenges in Formulation, Manufacturing, Devices and Regulatory Aspects
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Abstract

An area of increasing concern and scientific scrutiny is the potential contamination of drug products by leachables entering the product during manufacturing and storage. These contaminants may either have a direct safety impact on the patients or act indirectly through the alteration of the physicochemical properties of the product. In the case of biotherapeutics, trace amounts of metal contaminants can arise from various sources, but mainly from contact with stainless steel (ss). The effect of the various factors, buffer species, solution fill volume per unit contact surface area, metal chelators, and pH, on metal leachables from contact with ss over time were investigated individually. Three major metal leachables, iron, chromium, and nickel, were monitored by inductively coupled plasma–mass spectrometry because they are the major components of 316L ss. Iron was primarily used to evaluate the effect of each factor since it is the most abundant. It was observed that each studied factor exhibited its own effect on metal leachables from contact with ss. The effect of buffer species and pH exhibited temperature dependence over the studied temperature range. The metal leachables decreased with the increased fill volume (mL) per unit contact ss surface area (cm2) but a plateau was achieved at approximately 3 mL/cm2. Metal chelators produced the strongest effect in facilitating metal leaching. In order to minimize the metal leachables and optimize biological product stability, each formulation factor must be evaluated for its impact, to balance its risk and benefit in achieving the target drug product shelf life.

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Acknowledgments

The 316L stainless steel coupons utilized in this study were supplied courtesy of Boehringer Ingelheim Pharma. We gratefully acknowledge Parag Kolhe (Biotherapeutic Pharmaceutical Science, Pfizer Inc.) for his help in calculating the probability factor using the JMP data analysis software and Bo Zhang (Biotherapeutic Pharmaceutical Science, Pfizer Inc.) for his help in analyzing the samples.

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Authors and Affiliations

  1. BioTherapeutics Pharmaceutical Sciences, Global Biologics, Pfizer Inc, St. Louis, Missouri, 63017, USA

    Shuxia Zhou & Satish K. Singh

  2. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047, USA

    Christian Schöneich

  3. Pfizer Inc, 700 Chesterfield Parkway West, AA3I, Chesterfield, Missouri, 63017, USA

    Shuxia Zhou

Authors
  1. Shuxia Zhou
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  2. Christian Schöneich
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  3. Satish K. Singh
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Correspondence to Shuxia Zhou.

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Guest Editors: Lavinia Lewis, Jim Agalloco, Bill Lambert, Russell Madsen, and Mark Staples

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Zhou, S., Schöneich, C. & Singh, S.K. Biologics Formulation Factors Affecting Metal Leachables from Stainless Steel. AAPS PharmSciTech 12, 411–421 (2011). https://doi.org/10.1208/s12249-011-9592-3

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  • DOI: https://doi.org/10.1208/s12249-011-9592-3

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