FDA rule requires drugmakers to report manufacturing disruptions six months in advance

08-Jul-2015 - Last updated on 08-Jul-2015 at 21:38 GMT

A new final rule from the US FDA now requires all drug and biologic manufacturers to notify the agency electronically of a permanent discontinuance or an interruption in manufacturing six months in advance, or as soon as is practical, before the disruption causes a shortage.

The rule comes as shortages of critical drugs used to treat cancer, provide required parenteral nutrition, or to address other serious medical conditions rose earlier this decade but have since normalized. According to the FDA’s shortages databases, the number of shortages quadrupled from about 61 in 2005 to more than 250 shortages in 2011, but then significantly decreased in 2012 to 117 shortages, and fell again in 2013 to 44 shortages.

Still, shortages can result in delayed treatment for patients and can cause providers to prescribe second-line alternatives, which may be less effective or higher risk than first-line therapies, according to the FDA.

Under the final rule, the FDA lays out what it deems to be reportable discontinuances or interruptions in manufacturing, which at the very latest must be disclosed five business days after interruption occurs. The agency defines a "significant disruption" as one that would affect 20% or more of an drugmaker's supply over a one-month period.

As an example of a case where a manufacturer might not be able to provide six months advance warning to the FDA, the agency points to fungal contaminations that require immediate, temporary shutdown of a manufacturing plant. Other possible issues that could cause an interruption include:

A business decision to permanently discontinue manufacture of a covered drug or biologic;
A delay in acquiring APIs or inactive ingredients likely to lead to a meaningful disruption in the applicant's supply of a drug or biologic while alternative API suppliers are located;
Equipment failure or contamination affecting the quality of a treatment;
Manufacturing shutdowns for maintenance or other routine matters that extend for longer than anticipated;
A merger of firms or transfer of an application for a covered drug or biologic to a new firm that leads to a meaningful disruption in the applicant's supply of the product; and
An interruption in manufacturing (e.g., contamination of a manufacturing line) that in the applicant's view may not meaningfully disrupt the market supply of the covered drug or biologic but that is likely to lead to a meaningful disruption in its own supply.

As far as vaccines are concerned, FDA recognizes that the CDC (Centers for Disease Control) includes language in its contracts with vaccine manufacturers requiring the manufacturer to notify CDC of supply issues but only about 30% of the vaccines licensed in the US are subject to that notification.

The FDA adds that the rule imposes annual reporting costs of up to $16,827 on drugmakers affected, and up to $441,000 on FDA in review costs.