ICH Q10 (here) states the following as it relates to outsourcing activities and purchasing materials (hereafter referred to as third party):
“The pharmaceutical quality system, including the management responsibilities described in this section, extends to the control and review of any outsourced activities and quality of purchased materials. The pharmaceutical company is ultimately responsible to ensure processes are in place to assure the control of outsourced activities and quality of purchased materials.”
Another FDA guidance, Contract Manufacturing Arrangements for Drugs: Quality Agreements Guidance for Industry (here) states the following when discussing third party activities:
“……. the owners’ quality units are ultimately responsible for ensuring that the products are manufactured in accordance with CGMP”
This ultimately means that the application owner (sponsor) who engages a third party takes ownership and has accountability for the veracity, cGMP compliance, and quality associated with the third-party activities. So, what does this mean from an owner’s perspective? Firstly, one needs to recognize the risk; a health agency investigator will not distinguish if a cGMP activity/deliverable was conducted directly by the firm or if it was conducted by an outsourced third-party provider in that with either scenario, the investigator expects the owner’s quality unit to “own” that activity and attest to its cGMP compliance. This naturally extends to investigations such that, if during an agency inspection, an investigation was selected that related a third-party activity, then the owners Quality Unit will be expected to defend it as if it was an investigation that generated internally – and let’s face it; this is what can keep the owner’s Quality Assurance head awake in the wee hours of the morning!
One of the critical tools that can mitigate this risk is the Quality Agreement where the expectations for the application owner and the third-party service provider as it relates to investigations should be clearly delineated. It is recommended that the owners’ internal investigation procedural requirements are referenced within the Quality Agreement, so it is clear what is expected as it relates to Root Cause Analysis, Trending, Impact Assessment, and CAPA between the owner and third party. In addition, the Quality Agreement should define the owner’s role as it relates to reviewing and approving the investigation, along with timing as it relates to notifications and the turnaround time for review and approval, along with addressing the owners’ comments/requests resulting from review. In addition, it must be assured that these are adhered to by the third party (via owners Quality Unit sign off on the investigation). Another system that can alleviate such risk that goes hand-in-hand with the Quality Agreement is the owner’s program for vendor/supplier qualification, which should include an assessment of the third-party investigation program where the owner’s Quality Unit must verify that it is GMP compliant and that is also aligns with the requirement of owner’s investigation program (and that this includes auditing of the procedures along with a review of representative completed investigations). The Quality Agreement should also include reference to third party oversight as it relates to monitoring performance via periodic audits.
If you have any questions relating to addressing investigations from a third party, Lachman Consultants can help you! Please contact Paul Mason at p.mason@lachmanconsultants.com for support with this critical undertaking.
