A few years back, we sat down with former FDA Investigator and current consultant Chris Smith to discuss how FDA plans and conducts its PAIs — and how industry teams can effectively prepare for them.
Chris has over 35 years of experience, having held senior positions at FDA, large and small pharmaceutical companies, and contract research organizations.
This conversation was originally published as an episode of our companion podcast, The Life Science Rundown.
We also expanded this interview into a comprehensive written guide on our blog: Pre-Approval Inspection (PAI): An Expert Guide to Preparation.
Summary, Key Points, and Practical Takeaways
Preparation and Education: Smith emphasizes the critical importance of preparation for FDA inspections. He advises companies not to fear inspections, suggesting that fear often indicates underlying issues that need addressing. Instead, he recommends educating oneself on FDA inspection processes and expectations. This includes reviewing publicly available FDA databases to understand common findings. Smith stresses the importance of thorough staff training, ensuring employees can respond appropriately during inspections. He advocates for a proactive approach to compliance and quality management rather than reacting out of fear.
Understanding FDA's Role and Inspection Types: Smith clarifies that FDA investigators are akin to "policemen" — their primary role is to enforce regulations, not provide specific recommendations for fixes. He notes that inspectors may vary in experience and approach, with newer investigators sometimes being more stringent. Smith distinguishes between routine inspections and PAIs, explaining that PAIs are more focused on pending applications. He also mentions the trend towards specialized inspection teams, including microbiologists and engineers for specific areas.
Documentation and Investigations: Proper documentation is crucial. He emphasizes the importance of clear, thorough investigations written for an external audience. This means explaining terminology and processes that may not be familiar to outsiders. Investigations should demonstrate a clear understanding of the issue and appropriate corrective actions. Write these documents with the awareness that they may be reviewed by individuals unfamiliar with the company's specific processes.
Transparency and Cooperation: Throughout the inspection process, Smith advocates for transparency and cooperation with FDA investigators. He advises against trying to hide issues, instead recommending that companies demonstrate their understanding of problems and efforts to address them. Smith encourages working with the agency to make the inspection successful, including being open to reasonable accommodations in timing or personnel availability during inspections.
Adapting to Changes and Industry Challenges: Smith discusses the shift towards remote regulatory assessments during the pandemic, advising companies to prepare for increased transparency in sharing documents electronically. He also highlights challenges faced by smaller or family-owned businesses in keeping up with current regulations. For startup companies, particularly those led by clinicians, Smith notes a common lack of appreciation for the importance of manufacturing processes from a regulatory perspective.
Quality Management and Continuous Improvement: Smith emphasizes the need for qualified personnel in quality management roles. He stresses that from the FDA's perspective, manufacturing quality is equally important as clinical efficacy. Smith advocates for continuous improvement, encouraging companies to stay current with regulations and industry standards. This includes being aware of guidance documents from various regulatory bodies, including ICH, EMA, and Health Canada.
Communication and Cooperation: Effective communication with the FDA is key, according to Smith. He advises companies to communicate clearly if they need more time to respond to a 483 or warning letter. During inspections, Smith encourages companies not to hesitate in asking for reasonable accommodations. Overall, he promotes a cooperative approach, emphasizing that most experienced FDA inspectors are willing to work with companies to ensure a successful inspection process.
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Inside FDA Pre-Approval Inspections with Former Investigator, Chris Smith