San Juan, PR (Apr. 25)—Regulatory and quality issues were prominent discussion topics at this year’s ExcipientFest conference and exhibition. Many excipient manufacturers who attended the show said that cooperating with agencies such as the US Food and Drug Administration (Rockville, MD, www.fda.gov) and the United States Pharmacopeia (USP, Rockville, MD, www.usp.org) was a priority for them. Questions about excipient quality, particularly regarding Asian sources, also were on many manufacturers’ minds.
These concerns were reflected in the lectures given during the show. During her talk entitled “The Changing Paradigm of Excipient Qualification,” Alexa Smith, global regulatory service manager at Colorcon (West Point, PA, www.colorcon.com) observed that excipients are receiving greater regulatory scrutiny than they previously have. She predicted that FDA’s quality by design (QbD) and process analytical technology (PAT) initiatives would spur companies to gain a better understanding of their manufacturing processes and the effect that excipients have on those processes. Under PAT, FDA will allow a manufacturer that demonstrates adequate knowledge of its excipient–process relationships to adjust its processes to maintain consistent output without filing a change notification with the agency.
Smith noted that the European Pharmacopoeia had begun adding nonmandatory functionality-related characteristics (FRCs) to excipient monographs based on tests experts think might be useful for a given material. PAT, however, may require entirely different tests. Smith said that adding FRCs to monographs places a significant burden on manufacturers, even if the FRCs are nonmandatory. The three member groups of the International Pharmaceutical Excipients Council (IPEC, www.ipec.org) requested that pharmacopeias address FRCs using a General Chapter approach, rather than in monographs. USP began developing a General Chapter on performance testing that could address IPEC’s concerns.
Brian Carlin, global research and development director for FMC BioPolymers USA (Philadelphia, PA, www.fmc.com), examined the relationship between regulation and excipient quality in his presentation entitled “Does Characterization of Excipient Physical and Chemical Properties Build Quality into the Drug Product?” He noted that the excipient industry began using PAT principles and continuous production long before the FDA initiative was introduced.
Carlin said that excipient characterization could build quality into drug products under certain conditions. For example, pharmaceutical companies must tell excipient suppliers which functionalities they desire. In addition, Carlin advised that companies must take into account excipient producers’ process capability. Companies also must understand that raw-material variability can lead to finished-product lots that are out of specification, despite the suppliers’ process control, if the supplier is unaware of what needs to be controlled.
Thomas Mallon, business manager for North America at Degussa (Piscataway, NJ, www.degussa.com) told Pharmaceutical Technology that excipient manufacturers are concerned about the quality of excipients provided by suppliers in China, India, and other developing countries. He said that the harmonization of quality specifications would help industry and regulators provide safe drugs to patients around the world. The initiatives undertaken by IPEC and USP, which Smith described, could provide models for future harmonization efforts.