The letter takes issues with Vertical’s protocols to monitor, receive, evaluate and report postmarketing adverse drug events and raises concerns about the drug company’s failure to submit adverse events reports for one of its NDAs.
The FDA issued a warning letter to Vertical Pharmaceuticals after inspectors uncovered serious deficiencies in Postmarketing Adverse Drug Experience (PADE) reporting requirements, which it states raise questions about Vertical’s ability to properly monitor the safety of its products.
Inspectors found the drugmaker had no protocols in place outlining how it and its pharmacovigilance vendor comply with PADE regulations and how incoming adverse drug experiences (ADEs) are assessed for seriousness and expectedness. They found Vertical’s existing procedures were outdated, as they placed responsibility for adverse event evaluation on a defunct service provider and referenced obsolete MedWatch forms. The existing procedures also lacked measures to assess product complaints for adverse drug experiences and failed to outline practices for the exchange and evaluation of safety information with business partners. Inspectors found that Vertical had failed to submit 15-day Alert reports for its Divigel NDA-022038 until the time of the inspection; one report was 913 days late.
Inspectors provided Vertical with a Form 483 outlining the issues, but the FDA determined Vertical’s response was insufficient. Though the company provided a standard operating procedure stating the pharmacovigilance provider will be responsible for receiving and reviewing ADEs and preparing 15-day Alert reports, the FDA said it failed to provide a corrective action plan to prevent similar violations in the future. The new procedure failed to address how Vertical will investigate ADEs for reportability and failed to designate responsibility for who makes the final determinations of seriousness and expectedness. Vertical had also failed to ascertain whether it possessed other case safety reports that haven’t been gauged for seriousness and expectedness and reported to the regulatory authority.
In addition, inspectors found the company failed to submit to the FDA three Periodic Adverse Drug Experience Reports (PADERs) for Divigel, as well as at least 25 non-15-day Alert reports. Though the missing PADERs were submitted in response to the Form 483, the SOPs provided failed to outline measures to make sure all PADERs are completed and submitted on time.