Part of this problem is due to a lack of communication between final dosage-form drug manufacturers and excipient manufacturers—it
is often the case that the excipient manufacturer and/or supplier do not know the use of a particular excipient. Industry
and regulators are trying to improve this dialogue through various transparency and information-sharing initiatives.
But the bottom line is that excipient manufacturers and suppliers do not want to have to upgrade their facilities or processes
to adhere to ICH Q7 for excipients used as atypical actives, especially when they have little business interest in selling
their excipient products for these purposes. The additional controls, documentation, and cost, in most cases, would not be
worth their return on investment. As a result, they may turn away from the pharmaceutical industry and this action could lead
to a shortage of supply of the atypical actives. This would be a huge problem, says Schoneker, because it could force many
drug manufacturers to have to reformulate their products or it could lead to the removal from the marketplace of many commonly
To address these growing concerns, IPEC has been working with PDA and other industry stakeholders to develop a guideline specifically
for atypical actives that would ultimately have FDA buy-in. Some potential solutions, says Schoneker, would involve having
regulatory flexibility related to GMP expectations for existing atypical actives that have been used for years without safety
problems. For atypical actives used in drug products, use of the IPEC–PQG excipient GMP guide, would be an appropriate GMP
to use. There may be situations where additional technical considerations or specifications are required depending on the
specific aspects of a particular material and its use. These details would need to be negotiated between the excipient manufacturer
and the final drug-product manufacturer based on the material's intended use, he explains. Additional technical considerations
and specifications, however, are not a higher level of GMP. The separation of the two definitions needs to be discussed among
industry and regulatory authorities.
"We need to have a resolution that is acceptable to excipient makers, users, and regulators that makes them feel comfortable
that appropriate controls are in place and that provides security to makers and users that they are not in a position of liability,"
IPEC's working group on atypical actives is in the process of working through this subject and will be presenting ideas and
discussions at various upcoming industry meetings. For more information, please contact IPEC–Americas at IPECAMER@aol.com
1. ICH, Q7 Good Manufacturing Practice for Active Pharmaceutical Ingredients (2000).
2. IPEC–PQG, GMP Guide for Pharmaceutical Excipients (2006).