In an era where quality assurance and risk management form the backbone of the pharmaceutical industry, understanding regulatory changes is essential for compliance and success. In a significant development on June 26, 2023, the FDA and the Center for Drug Evaluation and Research (CDER) updated their approach to prioritizing manufacturing site inspections, providing a new framework that emphasizes risk-based decision-making.
Unveiling the Site Selection Model (SSM)
Central to this revised approach is the Site Selection Model (SSM). This tool is used to allocate inspections based on quality risks, applicable to both domestic and foreign inspections. Unlike the traditional model, which emphasized inspection frequency, the SSM prioritizes known safety risks.
The SSM takes into account factors such as violations of Current Good Manufacturing Practices (CGMP) requirements, and targets sites listed in the CDER Catalog of Manufacturing Sites that produce pharmaceuticals, in-process materials, and Active Pharmaceutical Ingredients (APIs) for human use.
Decoding the Risk Factors
Risk assessment under the SSM is comprehensive and multifaceted, utilizing specific risk factors outlined in section 510(h)(4) of the Federal Food, Drug, and Cosmetic (FD&C) Act. From site type, time since the last surveillance inspection, FDA compliance history, foreign regulatory authority inspectional history, patient exposure, to hazard signals such as field alerts and inherent product risk, a diverse range of parameters are evaluated.
One of the notable features of the SSM is its ability to ensure equal inspection frequency for sites with similar risk scores, regardless of product type. It is instrumental in gauging the risk associated with each site and prioritizing inspections accordingly.
Integrating SSM into Routine Surveillance
The Office of Quality Surveillance (OQS) uses the SSM to generate the Site Surveillance Inspection List (SSIL), a priority roster for routine surveillance inspections. Quality control assessments are performed, and sites with a history of Official Action Indicated (OAI) or those on import alert are identified and removed from routine surveillance inspections. The reinspection of OAI sites is determined based on the enforcement action.
Furthermore, the SSM aids in the assignment and prioritization of newly registered sites for inspection. OQS collaborates with the Office of Regulatory Affairs (ORA) to confirm the eligibility of these sites for routine surveillance inspections. Removals from the program are dependent on a request for removal and subsequent OQS investigation.
The Path Forward
The SSM is not a static tool, and efforts are underway to refine it to align with evolving industry standards. The commitment of regulatory authorities to promote high-quality drug manufacturing practices for the benefit of manufacturers and patients is unwavering.
However, some ambiguity persists. Despite the FDA's shift towards a risk-based approach for some time, many companies still undergo FDA inspections based on the original frequency of every two to three years. Moreover, the specific criteria for assessing risk factors are not clearly delineated, leading to difficulties for facilities in understanding their likelihood of inspection.
To navigate this complex landscape, companies subject to CGMP surveillance inspections should consider revising their internal quality control scoring systems to align with the factors considered by the FDA's SSM. This proactive step would enable better prediction of conditions deemed high-risk by the FDA. The implementation of an improved internal scoring system could help direct resources more effectively towards higher-risk areas, ensuring inspection readiness and demonstrating a company's commitment to a risk-based approach to quality.
In conclusion, the adoption of the FDA's risk-based approach to inspection represents a paradigm shift in pharmaceutical site inspections. It underscores the importance of a proactive, risk-based approach to quality throughout the pharmaceutical industry and offers an opportunity for companies to align their practices with evolving regulatory standards.
About the Authors
Karla González-Bonilla, MS
Microbiologist with Master's in Molecular Biotechnology and extensive QA experience. Expertise in data integrity, change control, CAPA, lab control, equipment validation, deviation investigations, and SOPs. Harmonized standards to Annex-1 requirements. Strong background in DIRA, IQ/OQ/PQ, and QMS. Skilled in document management software.
Elizabeth Plaza, R. PH
Boasts over 35 years in the bio-pharmaceutical field, starting as a PD Scientist and later leading consulting ventures since 1993, focusing on compliance, project management, technology transfer and validation. Overseen 3000+ resources, completed 10000+ projects, including 1000+ in tech transfer & validation life cycle management. Currently leads a Third Party Consultant firm qualified as set forth in 21 CFR 211.34 to help establishments in meeting cGMP requirements. Co-authored PDA Technical Report #60 on Process Validation.