FDA Withdraws Direct Final GMP Rule

Rockville, MD (April 4)-The US Food and Drug Administration withdrew a direct final rule that changed current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. The agency withdrew the rule because it received significant adverse comments from industry.

The direct final rule (72 FR 68064) was first published in the Federal Register on Dec. 4, 2007 and was designed as the first step in a plan to update CGMPs and harmonize CGMP requirements with those of international regulators.

FDA published an identical proposed rule (72 FR 68113) in the Federal Register on Dec. 4, 2007 as a companion to the direct final rule. The agency will consider industry’s comments when it modifies the proposed rule.

One of FDA’s revisions that drew objections was the requirement for one person to check critical manufacturing steps performed by automated equipment. The Biotechnology Industry Organization (BIO) commented that validated automated systems equipped with real-time alarms do not require human intervention and should not require human verification. “The proposed revision requiring operator verification of automatic mechanical and electronic equipment … may hinder the implementation of process analytical technology [PAT],” BIO said.

Schering-Plough (Kenilworth, NJ) commented that the modified water requirement was too vague. The rule required that facilities use water that is safe for human consumption, thus replacing the stipulation that water comply with Environmental Protection Agency (EPA) standards. Instead, Schering-Plough suggested that FDA require water to meet US National Primary Drinking Water Regulations or those of the European Union, Japan, or World Health Organization.

In addition, the withdrawn rule required manufacturers to validate aseptic processes. Russell Madsen, former acting president of the Parenteral Drug Association (Bethesda, MD), remarked that aseptic processing cannot be validated, but a state of control can be established. Madsen is president of The Williamsburg Group consulting firm and a member of Pharmaceutical Technology”s editorial advisory board.