The lack of communication between sponsors and contract manufacturing organizations (CMOs) – particularly those located abroad – can make the FDA inspection process a difficult one and can jeopardize the compliance position of the CMO involved as well as the approval of the sponsor’s application, agency investigators are warning.
The difficulties that occur during inspections where knowledge has not been adequately transferred and the sponsor is not sufficiently forthcoming with the CMO were highlighted in a case study presented by FDA Cincinnati District Field Investigator and Drug Pre-Approval Manager Kathleen Culver at a Global Outsourcing Conference co-sponsored by Xavier University and FDA in Cincinnati in October.
“When the sponsor’s attitude is, ‘we are the sponsor, we own the drug, and you just do what we tell you to do and do not question our decisions,’” she commented, “that is not a business plan – not for the consumer.”
In her presentation, Culver highlighted the significance of a relatively new FDA inspection tool – the knowledge transfer memo (KTM) – and explained how it is used by field investigators during preapproval inspections (PAIs) to answer questions that reviewers and compliance officials may have about pending applications.
She also focused on how the integrity of the ingredient supply chain is integral to the inspection and application approval processes.
Culver’s comments at the Xavier/FDA conference reflect the increasing emphasis that FDA’s compliance and field offices have been placing on contractor/sponsor relationships from the podium and in inspections and follow up warning letters (IPQ “The News in Depth” June 18, October 6, October 16, and October 28, 2010).
While gaps in these relationships have been compliance red flags, a clear communication pathway with contract partners for escalating issues during and after development by contrast has been key to the success of virtual companies in building state-of-the-art, quality-by-design (QbD) applications and passing preapproval inspection reviews (IPQ “The News in Depth” June 21, 2012).
Paralleling the heightened attention that the area is getting from FDA, the EU has been revising Chapter 7 of its GMP guide on contracting and outsourcing to expand its scope of coverage and incorporate quality system and risk management principles (IPQ “The News in Depth” November 22, 2010).