During product development, manufacturing processes undergo extensive testing and refinement, ultimately resulting in IQ, OQ, and PQ known as Process Validation. After the product is released to the market, occasional design and process changes, though usually small in scope, can accumulate. This calls the original process validation into question, as it may no longer be truly representative of the process or output product. Sometimes there are no changes to the product or process, but associated standards may change the requirements for safety (LTPD) or sample size (AQL). Other scenarios involve additional validation requirements due to clinical events encountered in the field.
In 2007, the FDA issued a Corporate Warning Letter to a major medical device manufacturer for failure to remediate their process validations to current industry standards (e.g., use of statistically meaningful sample sizes and validated test methods), under threat of escalating regulatory action. GCI was called in to assist, and conducted a gap analysis of existing legacy validation records against current industry standards. As we reviewed the inputs to the manufacturing processes, however, we recognized a concurrent challenge: the company had not updated its process, design or use FMEAs to the current risk management standard, so a risk-based approach to sample size selection, acceptance criteria, and other key determinations was impossible.
GCI’s team of engineers integrated with the client’s product and process experts to harmonize and update the FMEAs to be consistent with the revised risk management standard (BS EN ISO 14971:2012), proactively avoiding a potential audit finding by their Notified Body and the FDA. These updated documents were then referenced to develop a Master Validation Plan, and to generate defensible protocols for test method validation and process validation. GCI executed the process validations, while crunched data was compiled into validation reports and change requests were circulated for signatures through the client’s ERP system. These tasks were performed on-site by GCI’s “roll up your sleeves” level engineers, while occasional technical challenges were addressed through collaboration with GCI’s more seasoned engineers and the client’s subject matter experts. When a process was selected for verification rather than validation, or vice versa, the appropriate controls were implemented. Many opportunities to group and leverage similar processes were identified, further enhancing the efficiency of the project. Final deliverables included validated test methods, validated processes, ISO 14971:2012-compliant risk analyses, Master Validation Plans and Reports, and a robust suite of documents to fill the gaps in quality records that could stand up to the toughest audit.
Following this effort, FDA lifted the Corporate Warning Letter, and a subsequent QSIT inspection by FDA resulted in zero observations, enabling the client to continue to serve the needs of its customers and their patients safely and effectively.