An Impact assessment of Post-Approval Regulatory and Quality Compliance at a UK – Only Pharmaceutical Manufacturer

Purpose: To assess the regulatory compliance of operational processes at a British pharmaceutical manufacturing company (Company X). Provide remediation strategies for any compliance gaps identified to align operations with regulatory approvals. Ultimately, to assure Qualified Persons that finished pharmaceutical products released for sale are compliant with regulatory approvals and manufactured to current quality standards. Materials and methods: A gap analysis between regulatory-approved CTD sections and operational documentation is conducted for a single marketed product at Company X. Inclusion of CTD sections for review is determined according to those likely to contain Established Conditions (EC) as specified in the International Council for Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use Q12 guideline. A three-tiered review process is used to identify Established Conditions and describe compliance. Tier 3 (Student) identifies Established Conditions by comparing like-for-like (compliant), equivocal (further assessment required) and opposing (non-compliant) terminology in the CTD sections compared to operational documentation. Tier 2 (Subject Matter Experts (SMEs)) reviews and approves Tier 1 outputs. Equivocal terminology is assessed as either compliant or non-compliant. Non-compliant conditions are assessed as regulatory gaps if they deviate from the CTD or quality gaps if they are compliant with the CTD but deviate from Good Manufacturing Practices (GMP). A risk assessment is conducted using a risk priority numbering (RPN) tool and remediation proposals are made. Tier 1 (Governance) reviews and confirms Tier 2 compliance gap outputs and ratifies a final adjudication and remediation strategy. Results and discussion: Data outputs for this study could only be generated at Tier 3 and Tier 2 levels due to time constraints. A total of 62 compliance-related Established Conditions (EC) were identified with 37 representing compliance gaps. 49% (30 conditions) related to regulatory compliance gaps, 40% (25 conditions) were compliant and 11% (7 conditions) were quality compliance gaps. Six categories of regulatory compliance gaps were identified with the most commonly observed being the unavailability of regulatory-approved CTD sections for review. Three categories of quality compliance gaps were identified with the most commonly observed being the misalignment of operational and validating documentation. Conclusions: Company X is presently in a state of non-compliance. The unavailability of regulatory-approved documentation emerges as the most common compliance issue suggesting insufficiencies in regulatory document control may currently exist. A root cause analysis coupled with a corrective and preventative action plan may be beneficial to support sustained compliance. Further work is required to remediate identified compliance gaps to bring operations into regulatory compliance.