How Will Changes to EU GMP Guidelines Chapter 7 Impact Your Outsourcing Activities?
Our previous blog commented on the changes to Chapter 1, Chapter 7 and Annex 2 of EudraLex Volume 4, but changes to Chapter 7 warrant a deeper review to assess the impact those changes are expected to have on future outsourcing activities. Many of the changes are pure common sense, and companies with sophisticated outsourcing practices adopted them a long time ago. However, there had been sufficient variation among Sponsors and CMOs in the application of outsourcing practices that EMA felt compelled to formalize and clarify its expectations. Beginning in January 2013, Chapter 7 will require the Sponsor to control and review any outsourced activities under its Pharma Quality System. Virtual companies, and those new to outsourcing, are often deficient in clearly defining their procedures for managing outsourced activities in their Quality Management, which can lead to inconsistent oversight of the CMO. Chapter 7 will also require the Sponsor to audit the CMO to assess its cGMP competency. Even if the Sponsor is not physically performing the activities, it is ultimately accountable for the compliance and quality of the services being performed, and this responsibility cannot be delegated to the CMO. Furthermore, performance monitoring is not a static activity, and the Sponsor should monitor and document the quality of the CMO’s performance and identify and implement any needed improvements. Surprisingly, this had not been an explicit requirement in the previous version of Chapter 7, and now after several high profile cGMP deficiency findings from regulatory authorities, EMA is codifying this logical practice.
Two of the more impactful changes require the CMO to obtain pre-approval for any subcontracting and allow the Sponsor to audit the CMO’s subcontractors. As supply chains become more global and complex, it is imperative that the Sponsor have greater visibility into and understanding of the secondary and tertiary suppliers. Some CMOs may struggle to comply with these provisions as they may perceive them as intrusive to their operations, but the intent is to ensure that critical activities are not being performed by unqualified parties and it should provide another layer of supply chain oversight.
Other significant changes require clear definitions of the decision making authority, approval rights and batch failure remedies. Again, all very common sense expectations, but some CMOs’ contractual procedures were still deficient in these provisions resulting in poorly defined terms and lack of clear accountability. Lastly, Chapter 7 will now require all records related to the outsourced activities be kept by, or be available to, the Sponsor. Some CMOs still make certain documentation available only “on-site”, which requires the Sponsor to physically travel to the CMO to view them. In the era of cloud computing, secure portals and outrageous travel costs, surely CMOs can make all records securely available electronically.
The fact that the final version of Chapter 7 closely resembled the draft version issued in 2010 is a testament to a well-thought-out guidance, as well as simply applying common sense when drafting the revision. The changes will create consistent approaches to outsourcing practices, improved compliance and greater control of and visibility into the outsourced activities. For those Sponsors and CMOs with sophisticated outsourcing systems, this revised guidance should have little or no impact on their future outsourcing activities. For those companies who thought they could get by with minimally defined Quality Systems, ambiguous procedures and contracts, and arms-length CMO oversight, it will be ‘a long row to hoe’ to comply with the new expectations of Chapter 7.