FDA 483 - Valerie K Arnold MD - December 08, 2004

An FDA inspection was conducted at Valerie Arnold, MD, in Memphis, TN, from November 29 to December 8, 2004. This pre-approval clinical investigator data validation inspection, conducted under compliance program 7348.811, focused on a Phase III study (SLI381-314) of ADDERALL XR sponsored by Shire Pharmaceutical Development Inc. The regulatory framework for the observations cited was 21 CFR 312.62(b), pertaining to the obligation to prepare and maintain adequate and accurate case histories.

The main issues identified in the FDA-483 included several discrepancies between the clinical investigator's source documents and the case report forms. Specifically, changes made in source files regarding Clinical Global Impressions – Improvement (CGI-I) for three patients (03-005, 03-012, 03-014) were not accurately transferred to the case report forms. Additionally, one patient's (03-007) diagnostic interview booklet was found to be incomplete, lacking documentation for all screened disorders. Another observation noted that a blood pressure correction on a case report form (patient 03-002) was initiated but the correct reading was not recorded on the form itself, though it existed in source documentation. The inspection also highlighted inconsistencies in reporting significant weight loss as adverse events. In response to these inspectional observations, the firm's management committed to providing a written response to the FDA.