A quality-systems-based approach to drug manufacturing ensures compliance with cGMPs

By David M. Bliesner, Delphi Analytical Services

In January 2001, the U.S. Food and Drug Administration (FDA) issued the Compliance Program Guidance Manual (CPGM) 7356.002 titled “Drug Manufacturing Inspections (Pilot Program).” This manual provided guidance to FDA personnel for conducting inspections of pharmaceutical manufacturing sites in an efficient and structured fashion.1 The objective of this manual was to implement a quality systems-based approach to enforcing 21 CFR parts 210 and 211, the current Good Manufacturing Practice (cGMP) regulations.2 In February 2002, FDA formally adopted this guidance manual and in August of that same year announced the Pharmaceutical cGMPs for the 21st Century Initiative. This initiative explained the agency’s intent to integrate quality systems and risk management approaches into all its existing programs, the goal of which was to encourage industry to adopt more modern and innovative technologies. Subsequently, in September 2006, FDA issued guidance to the industry entitled “Quality Systems Approach to Pharmaceutical CGMP Regulations.”3 This guidance document built upon the principles delineated in CPGM 7356.002 and bridged the gap between cGMPs and the current industry understanding of quality systems.

The guidance describes in a straightforward manner a comprehensive quality systems model for manufacturing drugs, which, if properly implemented, ensures not only compliance with the cGMPs but ensures manufacturers provide high-quality drug product to patients and prescribers. The bottom line is that a quality systems-based approach to drug product manufacturing is just good business. As in CPGM 7356.002, the guidance document describes an inspectional model that divides the operations of pharmaceutical manufacturing into six systems. These include the quality system, the packaging and labeling system, the production system, the facilities and equipment system, the materials system, and the laboratory control system. The diagram shows the relationship among these six systems. Note that the quality system provides the basis for the other five manufacturing systems that are linked and function within it.

Of these five “inner” systems, the laboratory control system remains perhaps one of the most difficult to understand and master and leads to numerous quality failures. A cursory review of warning letters listed on the FDA web site (http://www.fda.gov/foi/warning.htm) shows that the laboratory is rarely not part of the regulatory action.

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