There are several factors that may be considered major hurdles in the innovation toward developing "new" excipients for pharmaceutical
applications. One major obstacle is the traditional reluctance of a company to be the first to try a material that may not
be well-known and that may slow down the review by the US Food and Drug Administration or risk FDA approval.
Currently, there is no regulatory framework in the United States for the approval of new excipients. These materials are approved
only as a part of a new drug application (NDA) or abbreviated new drug application (ANDA). However, international regulatory
bodies, independent organizations such as the International Pharmaceutical Excipients Council (IPEC), and drug companies have
recognized the need for such a framework. IPEC is taking steps toward providing a safety assessment guidance to help in the
review of excipients for pharmaceutical use. IPEC-America's Chairman and Pharmaceutical Technology Editorial Advisory Board
member David R. Schoneker recently discusses the organization's "New Excipient Safety Evaluation Procedure" with Pharmaceutical Technology.
PharmTech: How did thoughts about constructing a safety evaluation process for excipients orginate?
Schoneker: If we think about what goes on in the food industry, we have a process called self-affirmed GRAS [generally regarded
as safe]. If a company has a new food additive and it doesn't want to go through a full FDA petition, it can have a panel
of expert toxicologists review the safety data for the intended use and exposure level. The panel of experts provides an opinion
that it believes the additive is safe for that level of use and for that intended use, and the additive becomes a self-affirmed
GRAS. Once it has gone through that process, a company can take the product to market without the need to have FDA review
it. There is no requirement that they even have to look at it or know about it; as long as the company has gone through this
self-affirmed GRAS process, it has the right to bring the product to market.
Of course, at any point in the future and if FDA has some concerns about the material, it can review the data, but if the
company has done its homework, it shouldn't have a problem. There are many materials that have never gone through a food-additive
petition but are currently being used through the self-affirmed GRAS process. So we looked at this process in the food industry,
in which there is an expert independent panel that reviews the data, and we thought about how we can use this model for pharmaceutical
PharmTech: To what extent has IPEC worked with FDA to establish this program?
Schoneker: We had to keep in mind that FDA will always do the review, no other body is going to be able to "approve" the excipient.
That said, we wanted to address the companies' conservative nature and fear of triggering concerns from FDA. How can we minimize
this level of concern or the level of fear that someone will ask questions they didn't anticipate? IPEC tried to build a program
to get at that piece. It worked closely with FDA so that the agency knows what we're doing and can support it.
As we talked with FDA, it became evident that because these excipients are used in drugs that have many different potential
issues based on the particular formulation and therapeutic use, that FDA was never going to accept the idea of something like
a self-affirmed GRAS; that just wasn't going to happen. However, FDA did give us the indication that if a company went through
a expert review process like that of the food industry, for example, if it had an expert report that summarized the experts'
opinions and review of the data in which the outcome was favorable for a specific application, then this process could help
minimize concerns during an application review. Of course, there is no guarantee, and it doesn't mean that someone at the
agency will not have a different question, but it certainly minimizes the likelihood of there being any real concerns that
would come out of this that would cause any problems.