The Guidance, titled “Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency,” describes FDA’s suggestions for evaluating and prioritizing the remediation of CGMP activities that were necessarily delayed, reduced, or otherwise modified during the public health emergency in order to maintain production and the drug supply.

FDA explains that, if a drug manufacturer departed from established CGMP activities impacted by the COVID-19 public health emergency, the drug manufacturer should identify these deviations and any necessary remediation actions (see section I below). The drug manufacturer should evaluate these actions as part of their risk management approach (see section II). The results of the evaluation will help the drug manufacturer prioritize resumption activities (see section III).

I. Addressing Deviations from Established CGMP Activities

As explained by FDA “[r]emediation may be necessary for activities impacted by the COVID-19 public health emergency that were delayed, interrupted, or reduced in frequency.” “Remediation could include a modification to an activity, a new activity, or a more comprehensive program change that mitigates the risk of a drug quality issue due to the deviation from normal operation.” The Guidance identifies considerations for assessing the need for remediation in certain contexts, including:

• How to appropriately complete and document an unresolved investigation relating to a non-critical product or process deviation that occurred before or during the COVID-19 public health emergency.
• Whether additional measures are needed to determine a batch’s suitability for release in situations where testing was incomplete or was accomplished under conditions that may have compromised the accuracy of the test results.
• Whether additional measures are needed with respect to changes to, or difficulties in obtaining, materials used in drug manufacturing.
• Whether additional measures are needed to address facility and/or equipment changes or departures from scheduled maintenance activities.

II.  Risk Management and Other Important Elements of a Plan to Resume Normal Drug Manufacturing

FDA encourages drug manufacturers to develop a resumption plan, specific to their operations and organizational needs and which accounts for the possibility of additional waves of COVID-19 infections.

Once the drug manufacturer has identified the appropriate remediation priorities, these activities should be incorporated into its resumption plan. The plan should prioritize the manufacture of drugs at risk of shortage and activities related to restarting batch production (e.g., performance of equipment maintenance prior to restarting production lines) in addition to activities that were delayed, reduced in frequency, or otherwise modified.

A plan to resume normal drug manufacturing should:

• Include use of a risk management approach that identifies, evaluates, and mitigates factors that may impact product quality. These factors include activities performed, not performed, delayed, interrupted, or performed remotely; changes to procedures, processes, or programs; and associated outcomes. Findings and conclusions from the risk management process should be used to plan and prioritize remediation activities implemented when production activities resume.
• Include a timeline for implementing priorities.
• Specify that all changes be reviewed and approved by the drug manufacturer’s quality unit.
• Specify that drug manufacturers submit the required Field Alert Reports (FARs), Biological Product Deviation Reports (BPDRs), and animal drug product/manufacturing defect and adverse drug experience reports.
• Specify that if a drug manufacturer decides that a recall is needed, FDA should be notified as recommended in the Guidance “Product Recall, Including Removals and Corrections.”
• Specify that applicants and drug manufacturers notify FDA of a permanent discontinuance in the manufacture of certain products or an interruption in the manufacture of certain products that is likely to lead to a meaningful disruption in supply of that product in the United States.
• Be updated based on new information, as appropriate.

FDA notes that its CGMP regulations require manufacturers to assess whether novel pathogens—such as SARS-CoV-2—pose new risks to product safety or quality. As such, manufacturers should conduct a risk assessment to determine the potential impact of SARS-CoV-2 contamination on production materials, components, drug product containers and closures, in-process materials, and drugs. This risk assessment should be approved by the manufacturer’s quality unit and documented within the manufacturer’s quality management system.

III.  Prioritize Activities to Resume Normal Drug Manufacturing

According to FDA, drug manufacturers should use the findings and conclusions drawn from the risk management approach to plan and prioritize resumption activities. “High priority should be given to drugs that are in shortage or at risk of shortage.”

FDA also notes that returning to normal operations is often a fluid process. “When production priorities change or new information impacting priorities is obtained the drug manufacturer should update the resumption plan and reprioritize activities, as appropriate.”

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This guidance is effective immediately, but comments may still be submitted to the Agency for consideration. Except as otherwise noted in the guidance, this version of the guidance will remain in effect for the duration of the public health emergency declared by the Secretary of Health and Human Services. FDA may incorporate changes in the guidance, based on public comments received in response to this guidance.

If you have any questions concerning the material discussed in this client alert, please contact the following members of our Food, Drug, and Device Practice.