BIO Argues Changes Needed to FDA's Drug Shortage Rule to Account for Vaccines

Should vaccines be considered under the US Food and Drug Administration's (FDA) recent drug shortages rule? No, argues the Biotechnology Industry Organization (BIO), which explained in a recent letter to FDA that the Centers for Disease Control and Prevention (CDC) has been able to adequately handle shortages of vaccines on its own for at least the last decade.

Background

Drug shortages emerged as a major issue in 2011 and 2012, with many generic sterile injectable drugs experiencing supply shortages. Investigations into the matter brought to light a number of reasons for the shortages, including gray market pharmacies, government reimbursement policies, low profit margins, quality manufacturing problems and overly aggressive inspections by FDA.

In response to these challenges, FDA has taken a number of actions intended to mitigate the effects of drug shortages over the course of the last year. Among them:

• allowing the import of certain unapproved drugs to ease especially dire shortage situations
• asking manufacturers to notify FDA of any impending supply problems or disruptions
• working one-on-one with manufacturers experiencing problems
• approving novel manufacturing agreements for some facilities to allow them to release some products for further processing or quality checks-a significant deviation from the usual quality-by-design parameters of current good manufacturing practices (CGMP)
• expediting the reviews of substitute medications
• formulating a strategic plan on drug shortages, as required by Title X, Section 506D of the Food and Drug Administration Safety and Innovation Act (FDASIA)

But the biggest response by FDA came in October 2013, when FDA released a long-awaited rule intended to require companies to report any drugs that were actively experiencing shortages or that would conceivably encounter shortages in the near future.

FDASIA Statute

FDA's authority for the rule was authorized under Title X of FDASIA, in which FDA was explicitly given the authority to include biological products in its rule, such as plasma products and the like.

But legislators also gave FDA a choice: They could choose to bring vaccines under their drug shortage rule, or they could defer to the CDC's existing vaccine shortage notification program.

Specifically: "If the secretary applies this section to vaccines pursuant to subparagraph (A), the secretary shall (i) consider whether the notification requirement under subsection (a) may be satisfied by submitting a notification to the CDC under the vaccine shortage notification program of such Centers, and (ii) explain the determination made by the Secretary under clause (i) of the regulation."

FDA: Bring Vaccines under Shortage Rule

FDA ultimately decided that it would bring vaccines under its drug shortage notification program.

"Like drug shortages, shortages of biological products can have serious negative consequences for patients who rely on these products for their treatment," FDA wrote. Since the CDC's vaccine shortages program only covered "certain vaccines"-approximately 70% by FDA's estimation-it would be easier to bring the program under FDA's control.

Further, FDA noted that even among vaccines in the CDC program that are required to report, the program does not necessarily require six months of advance notice of a permanent discontinuance or interruption in manufacturing. "Early notice of permanent discontinuances and interruptions is critically important to the prevention of drug shortages," FDA wrote.

"Although FDA and its HHS partners work together closely on vaccine supply issues, and the current framework for CDC notification is useful for contractual purposes, FDA believes including vaccines within the scope of this rulemaking is necessary to fully support FDA's efforts to identify, address, prevent, or mitigate a vaccine shortage and would not be duplicative of existing notification systems," it concluded.

BIO: CDC Program is Fine

However, in comments to FDA, biotechnology trade group BIO argued that the CDC program was sufficient and had a lengthy and proven track record. Over the course of the program, CDC and industry have "successfully partnered … to reduce, if not eliminate completely, impacts to public health that may arise due to a supply shortage," BIO wrote. Industry has also "voluntarily strived" to meet the minimum six-month reporting requirements, BIO added, though the group did not mention how successful those attempts had been.

Either way, BIO wrote, "The existing system fundamentally works and, therefore, BIO believes no additional FDA regulation is necessary."

But Just in Case…

But just in case FDA still wants to include vaccines in the program, BIO said a few changes would benefit the agency's proposed drug shortages rule.

First, if "alternate presentations" of the same vaccine exist, the manufacturer should not have to report a disruption to FDA under the "meaningful disruption" clause.

Further, BIO noted that some vaccines, such as the influenza vaccine, are meant to be taken out of circulation on a regular basis because they are seasonally available. "BIO requests FDA clarify that the proposed rule does not apply to vaccines that have such intentionally restricted availability."

Additionally, BIO asked that FDA apply its shortage rule only to non-Vaccines for Children (VCF), as vaccines in the VCF program are already stockpiled by the CDC to account for shortages. "Since the FDA does not have the authority to maintain comparable stockpiles, broader application of this successful approach would require expanding the stockpiles held by CDC, or for the FDA to encourage creation and funding of other government stockpiling programs for non-VFC vaccines and other life-saving products," BIO wrote.

The existence of a stockpile should also be taken into account when considering if an interruption is "reasonably likely to disrupt supply chains," BIO added.

Finally, CDC should continue to act as a "confidential facilitator of critical supply information" to allow them to use information to "fill the gap in the event of an imminent shortage" using other manufacturers.

BIO Comments