Excipient approval mechanics

In the absence of existing human exposure data or other review of the excipient, FDA recommends in its guidance on Pharmaceutical Excipients (2) that the excipient be evaluated using a battery of standard nonclinical tests (7). Which tests are appropriate depends upon the likely patient exposure given the intended use of the drug if approved. Table 1 provides a summary of the necessary tests. This test paradigm will likely be considered as setting the standard for data requirements for any new excipients, whether or not approved by the FDA in an NDA or ANDA, or reviewed by some future alternative review/approval mechanism. 

There is no process or mechanism currently in place within the FDA to independently evaluate the safety of pharmaceutical excipients. Instead, for drugs subject to FDA premarket approval, excipients are only approved as components of new drugs. 

CDs are not standard inactive ingredients, and their uncertain regulatory status causes hesitancy in their use in formulations. A common perception exists that an approval process is in place for the evaluation of new excipients, such as the CDs. In fact, there is no mechanism for submission and review of data on a new excipient that would lead to approval of that excipient. In the United States, the FDA reviews a new excipient only in relationship to the review of a drug formulation. Only the final drug product is approved by the FDA. By this method the excipient... 

Cyclodextrins have been used for enhancing the solubility of poorly water-soluble small molecules (Shimpi et ah, 2005). The mechanism of solubilization is formation of reversible complexes between the hydrophobic moiety of the drug molecule and the hydrophilic cyclodextrin that is highly water soluble. A similar observation has been made with some proteins and peptides (Brewster et ah, 1991 Johnson et ah, 1994 Flores et ah, 2001). Sulfated cyclodextrins and 2-hydroxypropyl-beta-cyclodextrins are approved excipients for parenteral administration, however, use of these compounds should take into consideration the cost involved. 

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