FDA did not post any warning letters this week to Sponsors/Monitors/CROs, IRBs or Clinical Investigators. From the archives, here is the Clinical Inspection Summary for Natpara, submitted by NPS Pharmaceuticals. Three sites, plus the sponsor and CRO were inspected for the submission. Site inspections over from one to three weeks, the sponsor inspection was conducted over two months, and the length of time (as well as the identity) of the CRO is redacted in the publicly available documents. One site inspection was classified as "Official Action Indicated" (OAI); another site, the sponsor and the CRO received an inspection classification of "Voluntary Action Indicated" (VAI).
Dr. Bilezikian received a FDA Form 483 for the following:
- The study coordinator forged the Principal Investigator(PI)'s signature on the FDA Form s 1572.
- The study coordinator forded the PI's signature on two Serious Adverse Event (SAE) reports.
- The study coordinator forged 127 prescriptions (including for investigational product) related to the study.
- The FDA inspector questioned the timing of the PI's signature on inclusion/exclusion criteria on source documents, as the signature was dated on Thanksgiving day, which was a holiday and the PI's appointment book did not contain any patient appointments on that day.
- The study coordinator forged the PI's signature on the Investigator's Agreements.
- FDA concluded that data from this site were unreliable.
Dr. Watts was cited for:
- Failure to prepare and maintain adequate and accurate case histories, specifically in that one subject did not have four inclusion criteria documented in source documents.
- FDA notes that the PI did not sign the paper source document, and signed 1-2 months late for other subjects.
- FDA notes that the Electronic Data Capture System (EDC) did not capture two of the inclusion/exclusion criteria identified in a protocol amendment.
- Three adverse events were marked as "moderate" in the paper source documents, but recorded as "mild" in the EDC.
The Sponsor, NPS, was cited for:
- Failing to bring a noncompliant investigator promptly into compliance
- Failure to ensure proper monitoring
- FDA notes that the CRO monitor was aware of signature irregularities in 2011 at Dr. Bilizekian's site, but a follow up meeting with the PI and monitor was held where the PI attested to the signatures in question. Due to the monitoring reports from 2011 and 2012, FDA disputes the sponsor's assertion that the irregularities were only discovered in 2014.
The undisclosed CRO was cited for:
- Failing to ensure proper monitoring of a study and failing to ensure that an investigation was conducted in accordance with the investigational plan.
- FDA notes that the undisclosed CRO had purchased the original CRO responsible for the study and all but one person who had worked on the original study had left the company.