The cited CGMP violations included:

• failure to establish certain laboratory controls;
• failure to routinely calibrate, inspect, or check automatic, mechanical, or electronic equipment;
• failure to ensure that all production and control records were reviewed and approved by the quality control unit to determine compliance;

The letter warned that the compressed oxygen cylinders manufactured by C&M are misbranded because the product's labels do not have the required statement "Rx Only" prominently placed so it would be likely to be read and understood by an individual during purchase and use.

REGULATORY

The US Food and Drug Administration (Rockville, MD, http://www.fda.gov/) issued a final guidance in June governing the safety evaluation of pharmaceutical excipients. The issuance of the guidance, however, has not created a regulatory pathway for evaluating pharmaceutical excipients independently of drug products.

The Guidance for Industry: Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients outlines the safety tests that should be performed on new excipients. According to Jay Goldring, PhD, a member of the Executive Board and the Regulatory Affairs Committee at the International Pharmaceutical Excipients Council (IPEC Americas, Arlington, VA, http://www.ipecamericas.org/ the guidance will be useful in some cases, but is really just a first step. "The regulatory framework [governing excipients] is the issue," he says.

Currently, there is no system for independently evaluating the safety of excipients, which are only evaluated by FDA in the context of a new drug application (NDA). "It's a catch-22," Goldring says. "No drug company wants to use a new excipient until it's been approved, but no drug company wants to submit a new excipient for approval within their drug application because it could jeopardize the approval of their entire application. So there's a regulatory hole here."

IPEC Americas has submitted a proposal to FDA to narrow that regulatory gap by forming an independent academic board to review safety data about new excipients. According to the proposal, FDA would take the board's conclusion into consideration when evaluating a new drug product that includes the excipient. "It would be a kind of preliminary approval," says Goldring. "FDA still would have final say, but it would allow the excipient manufacturer to go to drug companies and say, 'The panel has approved it, and about 90% of the time FDA takes the recommendations of the panel,' or something like that." Excipient safety still would have to be evaluated in each individual drug product, Goldring says, because excipients can interact differently with various active ingredients.

Goldring says the board could also help excipient companies determine exactly which safety tests are necessary for a given excipient, particularly when an older excipient has been modified. "For example, if you have an old excipient and just add a hydroxyl group or a new polymer, is there some abbreviated type of testing you could do? That is something that an independent evaluation panel also could determine," says Goldring.

IPEC hopes to have a formal meeting soon with FDA to discuss its proposal. The guidance lays the groundwork for the discussion, Goldring says, because it establishes the kind of testing needed to ensure excipient safety. "This is a stepwise process," he says. "The first step is done. Now we're moving on to the next step."

—Laura Bush

MANUFACTURING

Eli Lilly Scales Back Planned Virginia Insulin Plant

Eli Lilly and Co. (Indianapolis, IN, http://www.lilly.com/) has halved its planned insulin plant in Prince William County, Virginia, according to a recent Washington Post report that was confirmed by a Lilly spokesperson. The proposed plant is also two years behind schedule.

In a meeting with the Board of County Supervisors, the Post reported, company officials said they now intend to hire only half the approximately 700 workers originally planned and will reduce the planned 600,000-ft² complex to 300,000 ft². Construction is now expected to begin this winter, and the plant should be fully operational before 2009.