laboratory assessments

FDA Clinical Inspection Summary: Rhopressa (netarsudil) submitted by Aerie Pharmaceuticals, Inc.

FDA did not post any warning letters this week to Sponsors/Monitors/CROs, Clinical Investigators or IRBs. From the archives, here is the Clinical Inspection Summary for Rhopressa (netarsudil) submitted by Aerie Pharmaceuticals. Two sites were selected for inspection, based on enrollment and a large number of INDs listing the investigators (27 and 9) and no inspections or no inspections in the last twenty two years. Both sites received FDA Form 483s.

Dr. Cooke was cited for:

  • Failing to follow the investigational plan, specifically failing to repeat a test as directed by protocol for three patients
  • Assuming lab values were normal when a lab report was not available for one patient's visit

Dr. Logan was cited for:

  • Fourteen "transcription deficiencies" across eighteen patients' CRFs
  • Five instances of non-serious adverse events and concomitant medications not being captured in the CRF

FDA Clinical Inspection Summary:Mirvaso (brimonidine tartrate) submitted by Galderama research and development

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 Mirvaso (brimonidine tartrate) submitted by Galderama. Four sites were inspected. Inspections lasted from three days to over one month. Sites were inspected on the basis of enrollment and treatment response. One site received a FDA Form 483.

Dr. Jarratt was cited for:

  • Failing to conduct an investigation in accordance with the investigational plan, specifically:
    • Enrolling a subject without completing screening serum chemistry
    • A subinvestigator completed assessments of eighteen subjects prior to completing required training.
  • Failing to maintain adequate and accurate case histories, specifically
    • Site staff signed a reconsent document for one patient over a month after the patient signed the document.

At a different site, a study coordinator falsified one blood pressure reading. The investigator did not receive a 483 for this. FDA notes that the site had SOPs in place and the study coordinator was fired and the single data point did not contribute to efficacy and was not a safety concern. FDA notes that monitoring had promptly identified this issue and escalated it to the PI. 

 

FDA Clinical Inspection Summary: Mavyret (glecaprevir/pibrentasavir-ABT-493+ABT-530) submitted by Abbvie

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 Mavyret (glecaprevir/pibrentasavir-ABT-493+ABT-530), submitted by Abbvie. Seven sites were inspected. Inspections ranged from three to seven days. Two sites received FDA Form 483s.

Dr. Jazrawi was cited for:

  • Inadequate documentation to support one subject met inclusion criteria for two lab values

Dr. Zogg was cited for:

  • Lack of documentation to support kit numbers dispensed and returned. (NOTE: FDA notes that the investigator stated that this function was performed by the Interactive Response Technology provider contracted by the sponsor, but FDA still issued the 483 to the site. FDA further notes that the investigator submitted an acceptable corrective action plan.)

FDA Clinical Inspection Summary: Jentadueto (linagliptin and metformin) submitted by Boehringer Ingelheim

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 Jentadueto (linagliptin and metformin) submitted by Boehringer Ingelheim. Two sites were selected for inspection, based on geographic location (country providing 31% of enrolled patients) and randomization rate. Site inspections lasted four and fourteen days. One site received a FDA Form 483.

Dr. Srikanta was cited for:

  • Failing to adequately review lab reports, clinic  notes and patient diaries, specifically:
    • Patient diaries for two subjects were not signed off by site staff and review was not noted in clinic notes
    • One out of range lab report was not noted in clinic notes
    • Clinic notes did not correctly reflect the initiation of a concomitant medication
  • Failure to fully document the informed consent process in clinic notes. The FDA inspector specifically noted lack of documentation for Legally Authorized Representatives and illiterate subjects. 

FDA Clinical Inspection Summary: Austedo (deutertabenazaine) submitted by Teva

FDA did not post any warning letters to Sponsors/Monitors/CROs, Clinical Investigators or IRBs this week. From the archives, here is the Clinical Inspection Summary for Austedo (deutetrabenazine) submitted by Teva. Two of the thirty participating sites in the study were selected for inspection based on high enrollment and impact on decision making for approval. FDA notes that a statistical methodology was used for site selection. Site inspections ranged over four to eighteen days. One site received a FDA Form 483.

Dr. Claassen was cited for:

  • Two subjects were unable to provide a required blood sample at one visit and the site made arrangements for them to return another date to provide the sample. (Note: The FDA reviewer indicates that the inability to draw blood is understandable and that the action taken in response to the protocol deviation was acceptable.)
  • One subject's medical records indicated excessive alcohol consumption and an attempt to reduce alcohol intake to six beers a week, plus marijuana use on Fridays. FDA notes that this marijuana and alcohol use violate two of the eligibility criteria for the study.
  • Study records for one subject indicated no alcohol use at screening, but two months after screening this was changed to indicate alcohol use. Additionally, three months after screening the amount of alcohol used per week was changed from 1 beer per week to four beers per week with no explanation. 

Note: FDA meetings with the sponsor indicate a concern about alcohol's effect on the activity of the study drug. Study exclusion criteria addressed this.  

The other site that was inspected did not receive a FDA Form 483, but the inspection summary notes issues of prepopulation of some forms to "save time", write overs and inadequate source documentation for some visits.