FDA 483 - ImClone Systems, LLC - August 21, 2020

The FDA Form 483 details significant deficiencies in the firm's quality system, specifically regarding discrepancy investigations and laboratory controls.

The firm failed to thoroughly investigate unexplained discrepancies and batch failures. Incidents classified as "Observations" in their (b)(4) system (SOP# QAS-NC-0001) were closed without detailed investigation, root cause analysis, or corrective and preventive actions (CAPAs), despite serious GMP violations. Examples include TR# (b)(4), where a batch was discarded due to potential data (b)(4), and similar incidents (TR# (b)(4), (b)(4), (b)(4)) involving incorrect material usage, all improperly classified as Observations. The firm's rationale of "isolated occurrence" was contradicted by recurring issues.

Deviation investigations were also deficient. TR# (b)(4) involved an atypical result for Galcanezumab drug substance. The analyst retested using a different sample, invalidating the original result without initial investigation. A subsequent hypothesis study lacked scientific evidence for the root cause of the unexpected peak. TR# (b)(4) concerned Out of Specification (OOS) results for (b)(4) from cleaning monitoring. The identified root cause, cleaning with IPA, lacked scientific justification, and the investigation did not adequately explain the OOS results, which were significantly above specifications. The firm's study on IPA contamination was also incomplete. These (b)(4) are critical