The withdrawal effectively re-instates the agency's fifteen-year-old Guideline on the Preparation of Investigational New Drug Products (Human and Animal), which required IND adherence to commercial-scale CGMP standards.

Under the Agency's direct final rule procedure, "the receipt of any significant adverse comment will result in the withdrawal of the direct final rule," according to the May 2 notice. Many of the comments submitted to FDA were, in fact, highly critical.

Some commentators, such as the Pharmaceutical Research and Manufactuers of America (PhRMA, Washington, DC, www.phrma.org) Vice-President Alice E. Till, Parenteral Drug Association (Bethesda, MD, www.pda.org) President Robert B. Myers, and Biotechnology Industry Organization (BIO, Washington, DC, www.bio.org) Managing Director Sara Radcliffe, expressed broad support while suggesting changes (some of them extensive) in the details. (Most comments are available on FDA's Web site, at http://www.fda.gov/ohrms/dockets/dockets/05n0285/05n0285.htm)

In her March 7 letter, Till said, "PhRMA strongly supports the development of this FDA guideline, as we believe there is currently a general consensus within Industry that there should be an incremental application of CGMP expectations throughout clinical development as a product approaches commercialization."

Others, like Peter Lurie and Sidney M. Wolfe of Public Citizen's Health Research Group (Washington, DC, www.citizen.org) and Barbara Immel of Immel Resources (Petaluma, CA, www.immel.com), voiced strong opposition, triggering the automatic withdrawal.

"We can see no reason," wrote Lurie and Wolfe, "why subjects in Phase I clinical trials should be any less deserving of FDA protection than those in later phases of development (or, subsequently, marketing). From the perspective of any patient injured by a GMP-violating drug in a Phase I study, it will be cold comfort that the FDA deemed following accepted standards too cumbersome. If some company or academic laboratory cannot follow GMPs, they should probably not be in the practice of preparing drugs for administration to humans."

Immel had similar concerns. "I am opposed to this rule," she wrote, "and believe that a guidance document, which is not legally binding, should not be used to replace an existing regulation that provides the minimum requirements for the safe manufacture of drugs or biologics for human beings. I believe that this rule may place patients in phase 1 in jeopardy."

1. US Food and Drug Administration, "Current Good Manufacturing Practice Regulation and Investigational New Drugs; Withdrawal,"" Federal Register 71 (84), 25747 (May 2, 2006, DOCID: fr02my06-6).
2. FDA, "Current Good Manufacturing Practice Regulation and Investigational New Drugs," Federal Register 71 (10), 2458-2462 (Jan. 17, 2006, DOCID:fr17ja06-4. Docket No. 2005N-0285).