FDA New Normal: Back to School with the A, B, CGMPs

The coronavirus (COVID-19) pandemic continues to impact the biopharmaceutical industry. In a recent guidance, Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency (the Guidance), FDA provides manufacturers a heads up on steps they should consider when resuming normal operations.

Key Takeaways

• FDA recognizes that manufacturers may have made changes to normal manufacturing operations to address COVID-19 challenges.
• Manufacturers are still responsible for ensuring that distributed drug and biologic products meet all necessary quality standards.
• As normal manufacturing activities resume, manufacturers should assess the impact of pandemic related deviations and changes, and institute any necessary steps to ensure the continued supply of quality drug products, based upon a written emergency plan.

When returning to normal operations, manufactures that deferred, or modified current Good Manufacturing Practice (cGMP) activities, should evaluate and institute any necessary measures to ensure continued product quality based upon a quality risk management approach. These activities may include:

• Proactive identification, evaluation, and investigation of changes and deviations from normal processes, systems, and materials both at the immediate manufacturer’s and suppliers’ facilities. Manufacturers should also assess any changes to utilities, equipment, logistics, and transportation processes. When conducting investigations, manufacturers should consider whether the scope of the investigation should be expanded based upon risk factors such as information loss due to decreased staffing or deviation response delays.
• Implementation of additional testing and monitoring to ensure that facilities and products continue to meet all necessary quality standards, including additional stability testing.
• Batch quarantine until critical quality attribute testing, deviation investigation, and change evaluations can confirm that drug products meet all applicable quality standards.
• Retrospective equipment performance evaluations if equipment changes were not prequalified. Consideration should also be given to whether alternative equipment servicing methods are appropriate if on-site servicing is not possible.
• Reassessment of cleaning procedures to the extent that the frequency or type of cleaning/disinfection processes or products changed.
• Review of any risk posed by product components. For instance, FDA recommends considering whether higher demand for certain materials may lead to quality or authenticity concerns, and whether there are observable material differences that may give reason to question the integrity of the source. Manufacturers should also consider alternative measures to ensure component quality, such as remote supplier audits, quality agreement revisions, and additional incoming material testing.
• Updates to investigation, deviation, nonconformance, and supplier qualification processes. Additionally, while not addressed by the Guidance, manufacturers should also consider additional or refresher training for employees who may have had prolonged facility absences.

If not already done, manufacturers should also implement an emergency plan for the resumption of manufacturing and cGMP activities. Such a plan should incorporate activities, such as those discussed above, prioritizing drugs at risk of shortage, activities related to restarting batch production, and activities that were deferred as a result of the pandemic. Such a plan should also provide for the review of changes by the manufacturer’s quality unit, documentation and justification of deviations, the potential for product recalls, and submission of Field Alert Reports, Biological Product Deviation Reports, and product shortage or discontinuation reports, as necessary. Manufacturers should finally revisit and update emergency and resumption plans, based on new and evolving information.

HOW WE CAN HELP

Morgan Lewis helps companies around the world interpret and assess cGMP requirements, prepare for FDA inspections, assist and defend inspections, and respond to inspectional observations. We provide legal and regulatory strategy and counsel on product submissions, product liability risks, and ongoing regulatory compliance. We can also assist companies to consider and prepare emergency or business contingency plans for regulatory functions.

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CONTACTS

If you have any questions or would like more information on the issues discussed in this LawFlash, please contact any of the following Morgan Lewis lawyers:

Washington, DC
Kathleen M. Sanzo
Jacqueline R. Berman