Janssen

FDA Clinical Inspection Summary: TMC435 (simepravir) submitted by Janssen

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 TMC435 (simepravir) submitted by Janssen. Four sites were inspected and site inspections ranged from four days to one week. One site received an FDA form 483.

Dr. Ferlizata was cited for:

  • Performing screening procedures on a subject who had not signed the IRB approved informed consent for the study. (FDA notes that the subject had signed consent for a sister study).

FDA Clinical Inspection Summary of Darzalex (daratumumab) by Janssen Biotech

FDA did not issue any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, here is the Clinical Inspection Summary of Darzalex (daratumumab), submitted by Janssen Biotech. Three sites plus the sponsor were selected for inspection of the Phase I and Phase 2 studies submitted as part of this BLA. Sites were selected for inspection due to high enrollment and significant contribution to efficacy. In addition, one site was selected due to prior FDA findings when the clinical investigator was at a different clinical site. Site inspection ranged from three to eight days, and the sponsor inspection lasted eight days. One site received a 483.

Dr. Lauder received a 483 for failing to follow the investigational plan, specifically:

  • Six out of twenty subjects did not receive the full dose of study drug at the initial infusion. FDA notes that these subjects had the infusions paused and restarted at half the infusion rate due to infusion reactions, and the site's decision to stop the infusion in order to observe subjects for safety reasons prior to the daily closing time of the infusion room. 
  • One subject received three concomitant medications to treat an adverse event (left eye swelling) that were not recorded on the case report form (CRF). 

FDA Clinical Inspection Summary for Yondelis®(trabectedin) submitted by Janssen

FDA did not issue any warning letters to Sponsors/Monitors/CROs, IRBs or Clinical Investigators this week. From the archives, the Clinical Inspection Summary for Yondelis (trabectedin)  shows that three of of eighty five participating clinical sites were selected for inspection, along with the sponsor of the pivotal study (Janssen). Site inspections ranged from four to eleven days, and the sponsor inspection was conducted over a ten day period. Two sites and the sponsor received 483s.

The sponsor, Janssen, received a 483 for:

  • Failure to follow the investigational plan, specifically:
    • For one of five sites reviewed by FDA, the Principal Investigator did not update the case report form (CRF) within ten days, as required by protocol.
    • Late entry of data resulted in adverse events not being reported within ten days
    • Late entry of data meant that adverse events were not included in the database by the time of the interim analysis
    • The FDA inspector reviewed the audit trail on the CRF to determine how late the data entries were
    • FDA notes that monitoring reports for this site consistently noted that the site was not up to date with data entry
    • Findings from this one site led FDA to question if this was a systemic issue, with the net result of a major amendment and extension to the NDA, delaying approval by three months.
  • Failure to ensure proper monitoring, specifically:
    • The electronic system used for monitoring reports does not use electronic and human readable audit trails to ensure they are trustworthy, reliable and generally equivalent to paper records.
    • The audit trail fails to capture all changes.
    • Changes to audit reports cannot be detected.

Dr. Schuetze received a 483 for failing to follow the investigational plan, specifically:

  • Four subjects were randomized prior to the investigator or subinvestigator reviewing all eligibility criteria, including laboratory reports.

Dr. Patel received a 483 for:

  • Failure to follow the investigational plan, specifically:
    • The reasons that two subjects were considered to be screen failiures were not recorded on the screening and enrollment log, and the investigator failed to list his name on the log for these two subjects. 
    • One screen fail subject did not have a case report form (CRF)
    • A pretreatment medication (dexamethasone) was not recorded for eight subjects in source records or on the CRF
    • Three subjects did not receive dexamethasone within the protocol-specified time frame. For one subject this happened four different times.
  • Failure to prepare and maintain adequate and accurate case histories, specifically:
    • One subject had adverse events of elevated cardiac enzymes, hypertension, shortness of breath, cough, and wheezing that were not captured on the adverse event form. (NOTE: The investigator provided language from the sponsor stating that diagnoses should be recorded as adverse events, not symptoms due to a common etiology. The investigator provided documentation that he believed all of these were symptoms of other, properly reported, adverse events.)
    • Another subject was missing an adverse event form for fatigue and headache.
    • Concomitant medications were not recorded for four subjects, including marijuana use.