CMC Strategy Forum Special Focus Series: Part 2 Product-Related Impurities, An Overview

by Cheryl Scott

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. 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 will reprint four original articles along with updated discussions of their subject matter. We continue this month with a general overview of product-related impurities (1) and continue in April with an overview of product-related impurities.

This month’s installment comes from an early CMC Strategy Forum, which took place on 19–20 July 2004 and was originally published a year later as a four-part article in BPI. The first day of that conference focused on process-related impurities, with an overview in the morning and a specific session on host-cell proteins (HCPs) in the afternoon. That overview (Part 1) was reprinted in its entirety as an insert to our February 2016 issue. Emily Shacter of ThinkFDA LLC (formerly of FDA-CDER), who was one of the authors of Part 2, provided commentary you can find online with our February 2016 issue.

Part 3 of “Defining Your Product Profile and Maintaining Control Over It” introduces product-related impurities, and Part 4 highlights concerns over aggregation (2). The former is reprinted in its entirety here along with an executive summary of the latter.

For the remainder of this year, whole reports will be featured on extractables and leachables (September 2016) and the immunogenic potential of aggregates and particles (November 2016). Again we will include commentary from authors or other industry experts to update these discussions.

Our thanks go out to Karen Bertani of CASSS, 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. For information on upcoming meetings — in the United States, Europe, Japan, and Latin America — see the CASSS website.

References1 Boerner R, Clouse K. Defining Your Product Profile and Maintaining Control Over It, Part 3: Product-Related Impurities. BioProcess Int. 3(9) 2005: 50–56.

2 Boerner R, Phillips J. Defining Your Product Profile and Maintaining Control Over It, Part 4: Tackling Aggregates. BioProcess Int. 3(10) 2005: 50–54.

Cheryl Scott is cofounder and senior technical editor of BioProcess International, [email protected].

Siddharth Advant (Kemwell Biopharma); Yves Aubin (Health Canada); John Bishop (FDA–CBER); Barry Cherney and Anthony Mire-Sluis (Amgen); JR Dobbins (Eli Lilly and Company); Julia Edwards (Biogen); Sarah Kennett (FDA– CDER); Joseph Kutza and Timothy Schofield (MedImmune–AstraZeneca); Kimberly May (Merck); Stefanie Pluschkell (Pfizer); Nadine Ritter (Global Biotech Experts); Reb Russell (Bristol-Myers Squibb); Oscar SalasSolano (Seattle Genetics); Dieter Schmalzing (Genentech– Roche); Zahra Shahrokh (STC Biologics and ZDev Consulting); Jeffrey Staecker (BioPhia Consulting); and Andrew Weiskopf (Biogen Idec)