A new temporary guidance for drug and biologics manufacturers from the U.S. Food and Drug Administration (FDA) details recommendations for returning to normal production operations during the public health emergency of the COVID-19 pandemic. The FDA announced in a statement, “This guidance provides recommendations to help manufacturers prioritize products as they resume normal operations and as they remediate current good manufacturing practice (CGMP) activities that were necessarily delayed, reduced, or otherwise modified during the public health emergency in order to maintain production and the drug supply.”05
Temporary Guidance
FDA acknowledges that during the public health emergency, drug and biologics manufacturers have faced unusual challenges, including employee illness and absenteeism, travel restrictions, site closures, and other potential supply chain disruptions. Measures to prevent COVID-19 transmission have also been implemented across companies and have further impacted normal manufacturing operations and CGMP activities. In order to maintain production of the drug supply, drug and biological product manufacturers necessarily delayed, reduced, or modified CGMP activities due to pandemic-related exigent circumstances.
This guidance provides detailed considerations for resuming normal operations where such CGMP activities have been impacted by the public health emergency. In the guidance, FDA also pays particular attention to advise on steps that manufacturers should undertake to mitigate the risk that pandemic-related disruptions in manufacturing and quality-assurance activities could lead to shortages of critical products. While CGMP requirements remain in effect during the COVID-19 public health emergency, and this guidance is not intended to signal specific FDA enforcement priorities, drug and biologics manufacturers whose operations have been disrupted are encouraged to follow an established plan, part of which should address a transition back to normal CGMP operations that will be maintained for an extended period of time.
First, FDA writes drug and biologic manufacturers should assess the impact of the public health emergency on their CGMP activities and identify remediation to ensure drug quality as they work to return to normal manufacturing operations. This could include modification to an activity, or a new activity, or a more comprehensive program that mitigates the risk of a product-quality issue. FDA identified examples of areas where remediation may be needed and set forth specific examples of the need and type of remediation in response.
For example, if investigations into non-critical product or process discrepancies and deviations that occurred before or during the COVID-19 emergency remain unsolved, manufacturers should consider things such as: whether the scope of the investigation should be expanded to supplement information lost because staff were not present to fully observe or gather information about the incident or were otherwise delayed in response; if short-term changes to normal operations were implemented and whether these changes may have increased the risk to product quality; and what procedures govern investigations at present and whether these procedures cover discrepancies, deviations, and non-conformances suitable during the public health emergency.
FDA further encourages drug and biologics manufacturers to develop a resumption plan specific to their operations and organizational needs, and an emergency plan addressing the possibility of additional waves of COVID-19. Appropriate remediation should be incorporated into a manufacturer’s resumption plan, and the plan should state that the risk-management approach prioritized the manufacture of products at risk of shortage and activities related to restarting batch production.
Elements as considerations for developing a plan to resume normal drug manufacturing include identifying and mitigating factors that may impact product quality, considering the role of management leadership in the successful execution of the resumption plan, timelines for implementing priorities, and should also include a plan for recall, including FDA notification.