Special Report on Process- and Product-Related Impurities (A CMC Strategy Forum Special Focus Series): Extractables, Leachables, Particles, and Aggregates

The CMC Strategy Forums focus on relevant chemistry, manufacturing, and controls (CMC) issues throughout the life cycle of a therapeutic and thereby foster collaborative technical and regulatory interaction. Forum chairs share information with regulatory agencies to help them merge good scientific and regulatory practices. Outcomes of forum meetings are published in BioProcess International and on the CASSS website (www.casss.org). This process is meant to help ensure that biopharmaceutical products manufactured with advancing technologies in a regulated environment will continue to be safe and efficacious.

This special report series highlights a major subject area that has been covered over the first 10 years of the CMC Strategy Forum series: process- and product-related impurities. Appearing quarterly throughout 2016, these inserts reprint a number of original articles along with updated discussions of their subject matter. This final installment in our product- and process-related impurities series comes from an early discussion of extractables and leachables from containers, closures, and single-use technologies, which by 2008 were already showing great promise. The paper that resulted from that particular CMC Strategy Forum took two full years to develop and was published by BPI in February 2011 (1).

The general strategic approaches described herein have not changed. Analytical methods were already established for container–closure testing of leachables and extractables; their adaptation to analysis of single-use components and equipment continues. No single analytical method detects all extractables. Choosing among available technologies depends on the polarity and molecular weight of suspected contaminants. Liquid and gas chromatographic methods are commonly augmented with mass spectrometry and ultraviolet detection.

Finally, we include in the electronic version of this report an executive summary of a two-part report on aggregates and particles analysis published at the end of 2011 (2, 3). The meeting it describes took place in January of that year.

That CMC Strategy Forum focused on detection and characterization of protein aggregates. The meeting included real-life examples of using a historical database to gain product-specific knowledge necessary to conduct thorough risk assessments of aggregates’ effects on product quality, safety, and efficacy. Participants also discussed implementation of appropriate control strategies for lot release, stability, and comparability of protein aggregates. The meeting ended with a session covering the most recent experiments probing the role of protein aggregates in immunogenicity, with discussions of the best models to use and initial results.

Our thanks go out to Karen Bertani of CASSS (www.casss.org), an international separation science society, as well as the forum series program committee (below), for trusting BPI as their publishing partner in this endeavor. The CMC Strategy Forum series is ongoing, and more papers are on the way in the regular pages of BioProcessInternational. For information on upcoming meetings — in the United States, Europe, Japan, and Latin America — see the CASSS website at www.casss.org.

References1 Mire-Sluis A, et al. Extractables and Leachables: Challenges and Strategies in Biopharmaceutical Development. BioProcess Int. 9(2) 2011: 14–23.

2 Mire-Sluis A, et al. Analysis and Immunogenic Potential of Aggregates and Particles: A Practical Approach, Part 1. BioProcess Int. 9(10) 2011: 38–47.

3 Mire-Sluis A, et al. Analysis and Immunogenic Potential of Aggregates and Particles: A Practical Approach, Part 2. BioProcess Int. 9(11) 2011: 38–43.

Cheryl Scott is cofounder and senior technical editor of BioProcess International, [email protected]. At the time of first publication, Anthony Mire-Sluis was executive director of global product quality and quality sciences for Amgen Inc. MS-36-2-B, One Amgen Center Drive, Thousand Oaks, CA 91320-1799; 1-805-313-2415, fax 1-805-499-6843. Stacey Ma was director of early stage pharmaceutical development at Genentech, [email protected]. Ingrid Markovic, PhD, was an expert review scientist in the Division of Therapeutic Proteins at the US FDA’s Center for Drug Evaluation and Research; 1-301-827-1730, 1-301-480-3256; [email protected]. And Lorna McLeod was a contributing editor to BioProcess International. 

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