FDA did not post any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the clinical inspection summary for Orbactiv (oritavancin) submitted by the Medicines Company. Five sites plus the sponsor were selected for inspection of the two pivotal trials submitted. Site inspections ranged over one to three weeks and the Sponsor inspection took place over one week. Four sites received FDA form 483s.
Dr. Kabler was cited for:
- Failing to ensure proper storage of study drug due to multiple temperature excursions of the refrigerator where drug was stored.
- Failing to report two adverse events noted in source documents in the electronic Case Report Form (CRF).
- The CRF indicated that due to a fever one subject could not be considered a clinical success but the source document had not been updated to reflect this.
Dr. Porwal was cited for:
- Failing to report thirty protocol deviations in the clinical database. FDA notes that Dr. Porwal's response stated that the study coordinator had identified these items prior to the closeout visit at which point the database was locked and the deviations could not be entered.
Dr. Keech was cited for failing to comply with the protocol, specifically:
- Enrolling a subject with ineligible lab values.
- Failing to perform a protocol required blood test for HbA1C at the baseline visit for a subject with high glucose values.
- Failure to report a mild adverse event at the injection site for one subject.
- Three out of range lab values were not reported as adverse events. FDA notes that the protocol was ambiguous with regards to report laboratory abnormalities as adverse events, and notes that assessment of laboratory results would take place by the FDA safety reviewer.
Dr. Manos was cited for:
- Failing to perform protocol required lab tests on five separate occasions. FDA notes that this was due to a study coordinator revising the source document worksheets.
FDA did not issue a 483 to the sponsor, but notes that two items were noted during the inspection. One site had been discontinued from the study and reported to the FDA for enrolling one subject with inconclusive pregnancy results who was later found to be pregnant and another who had exclusionary liver function tests. The site had also failed to submit lab tests to the central lab for three subjects and performed the tests locally only.