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
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.
New Excipient Guidance Doesn't Fill Regulatory Gap
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,
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."
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.