Manufacturing Quality-Systems Guidance Spurs Improvement

The US Food and Drug Administration says the final version of "Quality Systems Approaches to Pharmaceutical Good Manufacturing Practice (cGMP) Regulations," issued September 29, will help manufacturers maintain consistent high quality while allowing them to make technological improvements more easily. The guidance finalizes the draft issued in September 2004.

The guidance describes a comprehensive quality systems model, and explains how each element of the model relates to the agency's current good manufacturing practices (cGMP) regulations (21 CFR Parts 210 and 211). The new guidance is designed to bridge the cGMP regulations, written in 1978, and the agency's current understanding of quality systems.

“The original regulations didn't express a lot about quality management,” says Joe Famulare, acting deputy director of the office of compliance. “So this [guidance] brings quality management and modern quality systems features in line with our regulations. It's an organized way, we hope, for industry to start thinking in a more holistic, quality systems approach.”

Changes to the Draft

Famulare says most of the modifications to the draft were just clarifications. In one significant change, however, the final guidance notes that “in very limited circumstances, a single individual can perform both production and quality functions.” That language first appeared in a draft guidance, "Approaches to Complying with cGMPs During Phase 1," issued in January 2006, along with a direct final rule that was later withdrawn.

“We wanted to strike a very good balance there,” says Famulare. “The GMPs emphasize a separate quality control unit. We wanted to be consistent with that, but also stress that quality is everyone's job.” He says the language also reflects reality in some very small organizations, in which a person may wear more than one hat.

“There are some instances where you may have one person performing both operations, and you have to take those circumstances into consideration and make adjustments,” he says. “But clearly the encouragement is to have more than one person.”

Aligned with the Quality Systems Inspection Model

The guidance is aligned with our six-system inspection model, implemented in 2001, in which the inspection evaluates the firm's ability to maintain a state of control,” says Famulare.

The model describes six systems-one each for quality, production, packaging and labeling, materials, laboratory controls, and facilities and equipment. In a full quality-systems inspection, the investigator checks four systems, always including the quality system. In an abbreviated inspection, just two systems are inspected, the quality system plus one other; this rotates from one visit to the next.

Issued before ICH Q10

In an unusual move, FDA issued this final guidance even while the International Conference on Harmonization is developing another guidance (Q10) on the same topic. Famulare, who is the FDA lead on the ICH working group, says industry didn't want to hold up this guidance, because it is perceived as “a good step forward in promoting modern quality systems.”

Once Q10 is completed, he explains, FDA will review it and either eliminate or change it, to defer to what was agreed on internationally. “Those areas where we compare modern quality systems and relate it to our existing GMPs may be useful to keep,” he says. “In many other facets, we may be able to defer to Q10.”

Promotes Continual Improvement

Famulare expects the quality systems guidance to help modernize pharmaceutical manufacturing. “We really hope that the implementation of modern quality systems will bring the pharmaceutical industry at a level on par with some other industries,” he says.