FDA’s Center for Drug Evaluation and Research (CDER) is stressing that communication problems between the CMC and clinical groups working in Phase I can result in important risks not being identified and can impede IND/Phase I progress.
Discussing CMC issues that can cause problems during the IND development and marketing application submission phases, CDER Biology Team Leader Chana Fuchs noted at the AAPS National Biotech Conference in San Francisco in mid-May that “speed bumps“ causing delays in Phase I are divided into two general categories: ● not identifying a significant and unreasonable risk, and ● submitting insufficient information to FDA to assess the risk to the subjects.
Significant and unreasonable risks include unacceptable specifications, product contamination, mislabeled product and the use of penicillin either in the medium or in the facility. While not common, the penicillin issue is still seen on occasion. “Sometimes for early phase products the less-experienced sponsors would not necessarily realize that this is so critical,” Fuchs commented.
The CDER official noted that “unreasonable risks not identified” can arise due to communication problems between the CMC and clinical groups working together in Phase I.
Unacceptable specification — for example, endotoxin limits that would result in the use of a product over a safety limit — should not appear in a Phase I application. “The communication between your clinical and CMC groups needs to be rather tight to assure we do not have these conflicts,” she noted.
[Fuchs’ continued discussion of the importance of communication between CMC and clinical groups and the issues that can arise is provided for subscribers here. See the companion story in IPQ’s “In the News” for FDA advice on facilitating Phase III and BLA submissions.]