FDA Issues Temporary Guidance on Resuming Normal Drug Manufacturing

The FDA is urging drugmakers to develop a “resumption plan” to help them prioritize as they get back to normal operations and resume current good manufacturing practice (CGMP) activities that were modified or delayed due to COVID-19.

The 12-page straight-to-final guidance released Friday, which is temporary because it only pertains to the coronavirus pandemic, advises manufacturers to prioritize drugs and biological products that are in shortage or susceptible to shortage, as well as activities related to restarting batch production.

The agency said manufacturers should identify any deviations from established CGMP activities that were made in response to the pandemic and outline any actions needed for remediating them, as part of a comprehensive risk management plan.

Drug manufacturers that have not established a resumption plan prior to the pandemic “may find themselves in the suboptimal position of having to quickly develop and execute a plan at the same time; this can lead to errors and poor decisions,” the agency said. “We encourage drug manufacturers to develop a resumption plan, in conjunction with an emergency plan, if one is lacking especially due to the possibility of additional waves of COVID-19.”

“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 agency said.

The guidance lists examples of areas where remediation may be needed. For example, if a manufacturer has prepandemic investigations for noncritical products or process discrepancies and deviations that haven’t been resolved, it should answer the following questions to see if any actions are needed:

• Should the investigation’s scope be widened to supplement information missing because staff were not fully present to gather information or because the problem was worsened by a delay in response?
• Were short-term changes to normal operations implemented that may have increased the risk to product quality, such as a change in material flow or personnel flow?
• Are the firm’s procedures for discrepancy, deviation and nonconformance investigations suitable during the pandemic or should they be updated?

The guidance also recommends that manufacturers consider the following if there has been incomplete or insufficient testing during the pandemic to determine if additional measures are necessary to conclude a batch is suitable for release:

• For delayed or reduced testing that indirectly measures a batch operation, such as certain types of in-process tests, what was the impact on drug quality?
• For delayed or reduced testing not associated with a batch (such as microbiological testing of environmental monitoring plates from low-criticality areas or routine stability testing supporting a marketed drug with a history of minimal degradation), should there be additional tests to ensure the facility is appropriate to manufacture quality drugs?
• Were operations or materials used in drug production changed in any way that might impact quality or availability of the finished drug product? If so, was the change evaluated and implemented under the change management program? Is an investigation needed to determine if an associated batch is suitable for release? Should the testing or monitoring program be modified to gauge any long-term adverse effects on product quality, such as conducting additional stability testing?

Comments on the guidance may be made at any time.

Read the full guidance here: www.fdanews.com/09-11-20-Guidance.pdf. — James Miessler