Quality System Adjustments Needed for Continuous Manufacturing

The quality system adjustments needed to accommodate continuous manufacturing are getting attention at regulator/industry forums where the dialogue on how to drive forward the new processing technologies is underway.

Key GMP-related issues that need attention in continuous processes include:  ● process validation, complicated by complex systems that must be demonstrated as stable over time and able to compensate for upsets rapidly ● sample plans that must take into account sample locations that are representative of the material in a dynamic process stream ● cleaning to ensure residue buildup does not cause quality issues, and ● the use of diverters that catch out-of-specification product and isolate it from the product stream.

The opportunities and challenges that continuous manufacturing processes present were explored by CDER Compliance Officer Francis Godwin at ISPE’s annual Tampa meeting held in late February.

Godwin’s discussion at ISPE complemented a presentation on regulatory perspectives on continuous manufacturing (CM) by Office of New Drug Quality Assessment (ONDQA) Science and Policy Deputy Director Christine Moore at a session of the American Association of Pharmaceutical Scientists (AAPS) annual meeting in New Orleans in November (see IPQ “In the News” March 5 companion story).

Both having strong engineering and operations experience in industry, the two CDER officials are making a substantial contribution to the industry/regulator dialogue on how to drive forward the new pharmaceutical manufacturing and control approaches.  Godwin’s GMP perspective on CM design and implementation at the ISPE session complemented Moore’s exploration of the CMC and development implications of continuous processes at AAPS.

Emphasizing that “FDA does support continuous manufacturing,” Godwin noted at the ISPE meeting that it provides “both technical challenges as well as potential benefits.”  [Editor’s Note:  The May 2010 IPQ Report includes a discussion of continuous manufacturing as part of the issue’s in-depth analysis of the impact the new quality-by-design paradigm is having on the initiatives and dialogue around reshaping the CMC review process.]

The compliance official presented a comprehensive anatomy of the practical and regulatory considerations for continuous manufacturing processes, including insights on:  ● why CM interest is increasing ● definitions and terminology ● advantages and disadvantages ● batch vs. continuous processes ● the role of process analytical technology (PAT) ● process validation ● in-process controls, and ● defining a lot or batch.

[Godwin’s analysis is provided for subscribers here.  Nonsubscribers can purchase the story for $195 by contacting Karen Bertani (Jonathan@ipq.org).  For IPQ subscription information, click here.]