IPEC's New Safety Evaluation Procedure: A Q&A with IPEC Chairman Dave Schoneker

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 excipients.

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.

PharmTech: What can you tell us about the panel of experts involved in this review program?

Schoneker: IPEC has a new excipient evaluation procedure that we put together that allows a sponsor company to have an expert panel. The panel reviews the public and private information and develops an expert report. This expert report can be either given to a drug company in support of the use of a new excipient or a higher level of use of an existing excipient, which can be provided in the NDA or it can be incorporated into a company's drug master file (DMF). If the company felt the data, for whatever reason, was confidential and they couldn't supply it to their customer, then they could put it into a DMF with a reference to the customer who could then have FDA reference that data as part of its review. There are a couple of different mechanisms. This is a system we are working through now and starting to get usage on.

To make it even more beneficial, we are very fortunate to have the help of a key toxicologist, Dr. Robert Osterberg, who directed a group at FDA's CDER that reviewed the safety of new excipients or new excipient types at the agency. Fortunately, just as we were getting ready to roll this program out, Dr. Osterburg retired and went to work for a consulting company and we asked him to coordinate these panels.

There has been a material that has already gone through this system, and FDA said it would provide us with some feedback about the kind of report that was put together so that we would have an idea about the agency's expectations. We've done that and information about that project was provided at our IPEC conference (held in October).

Online references For more information regarding IPEC's safety evaluation process, visit the following resources:

http://ipecamericas.org/newsletters/Osterberg%20New%20Excipient%20Safety%20Eval%20Procedures.pdf

www.ipecamericas.org/public/whatsnew.html.