Amid the coronavirus disease 2019 (COVID-19) pandemic, the FDA issued guidance stressing the importance that manufacturers notify it of discontinuations and manufacturing interruptions so that the agency can implement contingency measures.
Taking into account the extraordinary conditions caused by the coronavirus 2019 (COVID-2019) pandemic, the FDA has issued guidance stressing the importance of notifying the agency about any current or anticipated stoppages or slowdowns in prescription and biologic drug manufacturing.
Based on the urgent need to plan for interruptions in supply, the FDA took the unusual step of issuing the guidance in advance of seeking public comment, although it said the guidance is not yet final and public comment will be accepted.
“FDA has been closely monitoring the medical product supply chain with the expectation that it may be impacted by the COVID-19 outbreak, potentially leading to supply disruptions or shortages of drug and biological products in the US,” the agency said in a statement.
On the Alert for Supply Interruptions
Manufacturers of biologics, including biosimilars, have been on the alert for possible supply chain disruptions, and industry analysts have companies with manufacturing sites overseas that are at risk for product interruptions that may affect the flow of medicines in the United States. The FDA has identified 20 drugs whose active pharmaceutical ingredients (APIs) are sourced from China, the origin of the pandemic.
On February 27, 2020, the FDA said it had been notified by a manufacturer about a shortage of a human drug. Since January, the FDA has been in touch with scores of manufacturers to remind them of FDA requirements for notification of any anticipated supply disruptions.
The fresh guidance describes reporting requirements under section 506C of the Federal Food, Drug and Cosmetic Act. Notifications must be submitted to the FDA at least 6 months in advance of permanent discontinuances or an interruption to manufacturing. If this is not possible, the FDA expects notice as soon as possible, but in no cases should notifications be filed later than 5 business days after a discontinuance or interruption occurs.
Situation updates should be provided every 2 weeks and should continue until the issues have been resolved.
In the COVID-19 climate, the FDA believes that “early, informative notifications are the best tools FDA has to help prevent a shortage from occurring and to mitigate the impact of an unavoidable shortage,” it said.
The guidance applies to manufacturers of prescription drugs and biological products that are considered life-supporting, life-sustaining, or intended for use in the prevention or treatment of a debilitating disease including those used for emergency medical care and surgery.
Clarifying the Grey Areas
The FDA also sought to clarify grey areas that might present difficulties for manufacturers trying to decide whether notice is required.
“When assessing whether a meaningful disruption in 229 supply is likely to occur, the relevant analysis is whether a change in production is likely to lead 230 to a reduction in the supply of a product by the manufacturer that is more than negligible and 231 would affect the manufacturer’s ability to fill orders or meet expected demand for its product, the FDA said.
“The manufacturer should not consider other manufacturers’ or competitors’ capacities or 234 assumed capacities, or what it understands about market demand for the product.”
In the event that a manufacturer is unsure what to do, the FDA said, the manufacturer should submit a notification, which would allow the FDA to make and assessment and take any necessary steps to shore up supply.
Notifications for manufacturing disruptions and discontinuations must include:
The FDA asks for notification providers to add any other additional information that could be related to shortages or manufacturing disruptions including:
“The more information manufacturers are able to provide on these topics, the better FDA is able to assist in preventing or mitigating a shortage,” the agency said.
Information can be updated at any time and therefore, “manufacturers should not delay notifying FDA until after production has ceased; FDA expects to be notified well before any decline in supply occurs,” the FDA noted. This will ensure the agency has ample time to review, monitor, and act accordingly for each case.
Additionally, “FDA asks that animal drug manufacturers voluntarily report information about animal drug shortages to the agency.”