New Excipient Guidance Doesn?t Fill Regulatory Gap

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New Excipient Guidance Doesn?t Fill Regulatory Gap

The US Food and Drug Administration (Rockville, MD) issued a final guidance this month 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,, 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 must still 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 what kind of testing is 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.”

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