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[Bonus Issue] Inside FDA's New Draft Guidance on Using "Alternative Tools" for Manufacturing Inspections
The guidance outlines methods previously used by the agency during the pandemic to examine drug manufacturing facilities, back when FDA inspections weren’t possible due to lockdowns
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On Wednesday, the FDA released a new draft guidance for assessing drug manufacturing facilities in upcoming applications. These guidelines highlight "alternative tools" that the FDA used during the pandemic when in-person inspections were halted due to lockdowns.
During the pandemic, the FDA's methods included:
Directly requesting records from the facilities.
Conducting remote regulatory assessments, which involved digital meetings and screen sharing.
Asking for inspection reports from reliable foreign regulatory bodies.
The draft guidelines also mention that the FDA might employ remote experts for pre-approval and pre-license inspections.
The Agency intends to reuse these methods for more adaptable inspections of manufacturing sites. However, they will only apply them selectively before or after a physical inspection. The decision to use these methods will depend on factors like the facility's inspection history, ongoing public health emergencies, and the feasibility of in-person inspections.
Given this flexible approach, the FDA anticipates that all facilities involved in manufacturing, packaging, and controlling drug substances and products should be prepared for inspection when they submit their applications.
We’ve broken down the new draft guidance below and provided some insights into how to prepare to accommodate these “alternative tools.”
Breaking down the new draft guidance: distilling the key takeaways
Introduction and purpose
The guidance aims to inform applicants about the FDA's intentions regarding using alternative tools to assess manufacturing facilities mentioned in marketing applications. FDA says it was influenced by the FDA's experiences during the COVID-19 pandemic, where alternative tools were employed due to inspection constraints.
Again, the FDA expanded the use of alternative tools during the COVID-19 pandemic when traditional inspections were not feasible, such as:
Requesting records: Directly from facilities under section 704(a)(4) of the FD&C Act.
Remote Interactive Evaluations (RIEs): This includes remote live-streaming video of operations, teleconferences, and screen sharing.
Collaboration with Foreign Regulatory Partners: Requesting existing inspection reports and other relevant information from trusted foreign regulatory partners through mutual recognition agreements and other agreements.
Risk-based use of alternative tools
The FDA's general practice is to conduct preapproval or prelicense inspections to ensure facilities adhere to current good manufacturing practice (CGMP) requirements.
The decision to use alternative tools is based on a risk-assessment approach.
Factors influencing this decision include:
The facility's drug inspection history.
The relevance of the proposed operations in the application to previous inspections.
The capability of alternative tools to adequately assess application-specific risks or facility operations.
The urgency of the product, such as addressing critical public health needs or drug shortages.
Considerations for using alternative tools
The FDA says it will decide on using alternative tools on a case-by-case basis, but facilities should be prepared for inspection upon application submission.
Regulators also noted it will not entertain requests from applicants or facilities to use alternative tools. The decision to use these tools will be based on various factors, including internal Agency practices.
Remote Regulatory Assessments: The FDA recognizes the potential benefits of virtual interactive technologies. They intend to supplement inspections with remote resources when necessary.
Collaboration with Foreign Regulatory Partners: The FDA may rely on inspections performed by capable foreign regulatory partners. They are also part of the International Coalition of Medicines Regulatory Authorities, piloting a collaborative hybrid inspection program.
Effects of using alternative tools
The use of alternative tools will aid the FDA in meeting user fee goal dates and making timely application decisions. If observations are identified through alternative tools, the FDA may present a written list of observations to the facility. Facilities should respond with corrective actions within 15 U.S. business days.
A few key takeaways
Embrace Digital Preparedness: Facilities should have the necessary technology and infrastructure to support remote regulatory assessments, including digital conferences and screen sharing. More on this below.
Maintain Comprehensive Records: Given the FDA's emphasis on requesting records directly from facilities, ensure that all documentation related to manufacturing processes, quality control, and other relevant areas are up-to-date and easily accessible.
Collaborate with International Partners: If you have facilities outside the U.S. or collaborate with foreign manufacturers, be aware of the FDA's interest in inspection reports from trusted foreign regulatory agencies. Ensure that any such reports are available and meet FDA standards.
Stay Inspection-Ready: Regardless of the flexibility offered by the new guidance, the FDA expects all manufacturing, packaging, and control sites to be ready for inspection upon application submission. Regular internal audits and mock inspections can help maintain readiness. Talk to us to access the industry’s best auditors.
Understand the Criteria: Familiarize yourself with the factors the FDA will consider when deciding on the type of inspection, such as the facility's drug inspection history and the feasibility of an in-person inspection.
Engage Remote Experts: If you have subject matter experts who are not on-site, ensure they are available and trained to participate in remote inspections, as the FDA may use remote experts for pre-approval inspections.
How to prepare your facility for alternative inspection tools
Given that the FDA is adapting its inspection methods to include these alternative tools, it’s prompted many in the industry to rethink their preparation strategies for FDA inspections. As remote evaluations become more commonplace, it's crucial for facilities to be well-prepared for this new mode of inspection.
Here's a quick starter guide on how to get your facility ready:
1. Optimize your IT infrastructure
Bandwidth & Connectivity: Ensure that your facility has adequate bandwidth, especially if you plan to do virtual walkthroughs are part of your auditing program. This ensures smooth streaming and minimizes disruptions.
IT Security: Engage IT teams early in the planning process. They can identify potential firewall, software, and security issues hindering the remote inspection/auditing process.
FDA-Approved Platforms: The FDA has specified in pandemic-era guidances that it will use platforms like Microsoft Teams, Zoom for Government, and Adobe Connect. Ensure your IT environment is compatible with these tools.
2. Invest in quality audio-visual equipment
Camera & Audio Quality: The FDA has in the past emphasized the importance of clear visuals and audio, especially for detailed evaluations like aseptic practices or equipment setup. Invest in high-quality cameras and microphones.
Real-time Communication: Ensure that your A/V equipment supports seamless communication.
Test Runs: Conduct dry runs to test the equipment in various parts of your facility. This helps in identifying potential dead zones or areas with poor connectivity.
3. Streamline document accessibility
Electronic Format: The FDA prefers documents in electronic format or accessible via screen sharing. Ensure that all necessary documents are digitized and easily shareable.
Encryption and Security: While security is paramount, the FDA must be able to access encrypted and password-protected files. Have a process in place to provide access securely.
Quick Retrieval: Documents should be organized in a manner that allows for quick retrieval without the need for additional processing. Consider using cloud storage or a dedicated server for easy access.
4. Revamp your inspection preparation materials
Virtual Document Organizer: Traditional inspection binders or organizers should be translated into a virtual format. Ensure that every document is cross-referenced and easily accessible.
Clear Labeling: Clearly label all assets and documents to ensure smooth navigation during the inspection.
5. Conduct mock audits
Purpose of Mock Audits: These are essential for simulating an actual FDA inspection. They help identify potential issues that can be addressed before the inspection.
Internal vs. External Audits: While internal teams can conduct these audits, an external team, especially those with former FDA employees, can provide invaluable insights.
Benefits of Mock Audits: They help in evaluating various facets of your operations, from management oversight to compliance with regulatory standards.
As the FDA continues to adapt to the changing landscape, it's imperative for facilities to be proactive in their preparation. Remote evaluations, while challenging, also offer an opportunity for facilities to showcase their commitment to quality and compliance in innovative ways.
By following the above guidelines and continuously seeking to improve, facilities can ensure they are well-prepared for any remote or in-person inspection.
We routinely help manufacturers in the FDA-regulated life science industries conduct mock GMP, GCP, and GLP audits in a number of specific applications, both on-site and remotely. Learn more about our auditing services and connect with us to schedule a mock audit.
Want to dive deeper into planning and hosting remote audits? Grab our free guide, packed with expert advice and a series of steps quality and compliance teams can take to fully prepare.
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