FDA 483 - Stanislaw R Burzynski, MD - March 15, 2013

The FDA Form 483 details multiple violations during an inspection of a facility conducting clinical trials BT-09, BT-10, BT-21, and BT-22. The facility failed to conduct investigations according to the signed statement of investigator and investigational plan, specifically regarding the primary outcome (therapeutic response) for 67% of reviewed subjects (18 of 27).

Inclusion/exclusion criteria were not consistently met, as exemplified by subjects in BT-09, BT-22, and BT-10. For Protocol BT-22, Subject 01234 was enrolled and dosed without prior arrangements for local physician involvement, despite the private physician's refusal. Study treatment discontinuation requirements were not followed, with ANP treatment continuing despite serum sodium levels exceeding 147 mmol/L, and patients not being removed for repeated Grade 3/4 or any Grade 4 toxicity.

Not all Adverse Events (AEs) were reported to the sponsor as required, and AEs were not adequately and accurately captured for Study BT-09. The facility failed to protect subject rights, safety, and welfare, with 48 subjects experiencing 102 investigational drug overdoses between 2005 and 2013.

Inadequate case histories were maintained; original MRI tumor measurement worksheets were destroyed and unavailable. Original case report forms (CRFs) for studies BT-0