FDA did not issue any warning letters to Clinical Sponsors/Monitors/CROs, IRBs or Investigators this week. From the archives, here is the clinical inspection summary for Kanuma (sebelipase alfa) submitted by Alexion. This therapy was acquired from Synageva. Two pivotal studies were submitted to FDA, from which four sites, three CROs and the sponsor were selected for inspection. Site inspections were based on high enrollment and participation in more than one study. The CROs were selected due to the importance of MRI readings and liver histopathology analysis to the efficacy analysis. The sponsor was selected because this Biologics Licensing Application was for a new molecular entity. Site inspections ranged over four to eight days, and the sponsor inspection took place over six days. No Form FDA-483s were issued to clinical sites.
Synegeva received a 483 for failure to ensure that an investigation was conducted in accordance with the general investigational plan and protocols as specified in the IND, specifically:
- Failing to ensure that serious adverse events at one site were reported to the sponsor within 24 hours, as required by protocol.
Sponsors are permitted to redact a great deal of information in publicly available inspections for CROs. However, it may be useful to note the specific areas covered in the inspections for the CROs on these two trials:
- Quality Assurance
- Quality Control
- Subject Masking
- Process Flows
- Organizational Responsibilities
- Operating procedures for imaging and pathology
- Training of staff
- System validation
- Correspondence between the CRO, Sponsor, Clinical Sites and sub-contractors
- Validation of subject data points
- Protocol deviations
- Data storage
- Work Orders
- Service Agreements
It is also notable that FDA made inquiries to the sponsor regarding blinding of the trial, apparently in the same time frame as the inspection of the CROs. The sponsor submitted an erratum to the Clinical Study Report further clarifying the blinding issue.