Site Audit with Corrective & Preventative Actions for Viral Vector Facility

EU Regulation: Building the Perfect Product

The Situation: Providing Regulatory Materials for the European Union

A new US viral vector FDA compliant facility was seeking assurance that their material for phase I/II clinical supply would also be suitable to produce material to satisfy European regulatory agencies compliance requirements. This would open the market to include the EU. Key requirements included identification and addressing of quality management and technical deficiencies.

GRA's Involvement: Expert CMC Audit

Multiple experienced GRA consultants, including a Qualified Person (QP) and a Senior CMC subject matter expert (SME) visited the site. An audit agenda was prepared that covered:

• Site: Area schematics, people flow, product/waste flows, HVAC, SMF, Quality Policy, and Gowning.
• Quality systems: QRM, contamination control, change control, deviations, document controls, recalls & complaints, staff training, and vendor management
• Receipt, Storage, Release: TSE/BSE policies & procedures, raw materials, stock management, storage areas monitoring
• Manufacturing: Master Batch Record controls, Input control, critical process parameters (CPPs), process monitoring systems, packaging & labelling control
• Equipment: HVAC validation, WFI sampling plans, data trending, autoclave validations, preventative maintenance systems, and pest control
• Validation: VMP, planned process review, process simulations, cleaning & sterilisation, computer, equipment and shipping validation.
• Quality Control (QC): Specifications, OOS & OOT, Product testing, QC result checking, result reporting, method validation, and product stability systems
• Quality Assurance: Stock status controls, QC batch review checks & release systems, and release documentation.

Value Added: Action Plan Developed to Meet EU Regulations

A mock audit was performed on the facility together with its good manufacturing processes (GMP) quality management system (QMS). This exercise highlighted a number of technical and QMS gaps and went further to offer solutions to all problems identified. This ensured that rather than being, what is often a guarded exercise, all of the site staff involved were entirely open. Thus, any identified deficiencies could be supported through to resolution by GRA, who brought industry expertise, regulatory knowledge and a deep understanding of what was trying to be achieved.. The deficiencies were prioritised, so that the facility’s leadership could address the most pressing issues in order of importance and impact. The ultimate resolution eliminated all deficiencies, such that the site could successfully release materials into the EU, meeting the regulatory standards.

Consultants: QP, CMC SME