Generic, Brand Companies Have Concerns About FDA's Proposed Drug Shortage Rule

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By Bronwyn Mixter  

Jan. 6 --In comments to the Food and Drug Administration, generic and brand drug companies said although they support the idea of notifying the agency of potential drug shortages, they have concerns with the agency's proposed rule.

On Oct. 31, the FDA proposed a rule that would require drug manufacturers to report any supply chain disruptions (11 PLIR 1339, 11/8/13). The proposed rule, Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products, was called for under the FDA Safety and Innovation Act of 2012 (FDASIA).

It was published in the Federal Register Nov. 4 (78 Fed. Reg. 65,904, Nov. 4, 2013), and comments were due Jan. 3. The FDA will take the comments into consideration as it finalizes the rule.

Generic Industry's Concerns

The Generic Pharmaceutical Association (GPhA) in comments submitted Jan. 3 pointed to the requirement that manufacturers notify the FDA of a permanent discontinuance or an interruption in manufacturing at least six months in advance, but not later than five business days after the discontinuance or interruption occurs.

“We are concerned that in some instances it may not be feasible for the manufacturer of a drug to comply with this,” GPhA said. “In addition, it could have the unintended consequence of forcing drug manufacturers to report an interruption in manufacturing at the 5 business day mark even if at that time the manufacturer does not have sufficient information to determine whether the interruption is likely to lead to a meaningful disruption in the supply of that drug in the United States.”

FDASIA mandates that companies report to the FDA “as soon as practicable,” versus a fixed period of days.

GPhA said “the more flexible timing provided by Congress takes into consideration supply chain reliability and vulnerability as a whole and minimizes the opportunity for over-reporting as is the case with FDA's proposed 5 day reporting requirement.”

Additionally, GPhA said market dynamics and the duration of a drug shortage should be considered and used as filters when manufacturers report shortages.

GPhA said that for market dynamics, the FDA should consider the number of active suppliers for a particular drug and the percentage of market supplied by the active suppliers. “Using this as a filter would help alert the FDA to identify suppliers that are providing a significant percent of the market and that truly have the potential to create a drug shortage,” the group said.

The duration of a drug shortage also might be taken into consideration and used as a filter, GPhA said. An active supplier may have a supply disruption for 30 days, but “the market may not experience a drug shortage given the inventory levels in the retail and wholesale channels.”

GPhA proposed a 60-day potential supply disruption as the minimum duration for drug shortage reporting “to avoid chances of inventory hoarding and artificial increases to market demand that ultimately undermines the intent of FDASIA.”

PhRMA Weighs In

The Pharmaceutical Research and Manufacturers of America (PhRMA) said Jan. 3 in comments that it supports “the collaborative approach FDA has taken towards identifying and mitigating drug shortages, particularly the open communication and regulatory flexibility that the agency has exhibited since the signing of the President'sExecutive Order 13588--Reducing Prescription Drug Shortages, in October 2011.”

The executive order directed the FDA to broaden reporting of potential shortages of certain prescription drugs and to expedite regulatory reviews that can help prevent or respond to shortages (9 PLIR 1386, 11/4/11).

“We strongly believe that retaining a flexible framework that allows FDA and manufacturers to interact and discuss potential drug shortages, combined with FDA's careful and appropriate public disclosure of that information in a manner that prevents hoarding and other negative consequences, is the best way to serve patients,” PhRMA said.

PhRMA said the definitions of the types of drugs covered by the proposed rule are too broad and this might cause the agency to be over-notified. The group requested that the FDA offer additional clarity in the final rule about the specific types of drugs included or not included under the rule.

Drug Compounding

PhRMA also said the recently passed Drug Quality and Security Act permits a drug compounder to begin manufacturing a drug once it is on the shortage list, and a broad definition of the term product “may allow drug compounders to begin manufacturing a specific drug before it is actually necessary, at the possible peril of public health.”

On Nov. 27, President Barack Obama signed into law a bill (H.R. 3204) that clarifies the FDA's authority over compounding pharmacies (11 PLIR 1438, 12/6/13). The Drug Quality and Security Act (Pub. L. No. 113-54) defines the FDA's role in the oversight of “outsourcing” or large-scale compounding facilities.

“PhRMA strongly believes widespread compounding is not a sensible public health approach to dealing with drug shortages, as the practice exposes patients to unapproved products made in facilities that have not been subject to a pre-approval inspection,” the group said.

PhRMA said the preamble to the final rule should say that the FDA won't list FDA-approved drugs on its shortage list if the possible consequences outweigh the public health benefit of doing so.

The group also said the FDA should provide additional clarity on how it will determine at what point a drug shortage or interruption is triggered.

“We suggest that the appropriate trigger to start the notification 'clock' is the date on which information becomes available to the applicant from which it could be reasonably determined that a meaningful disruption is likely to occur,” PhRMA said. “Because the manufacturer may not know that a given issue is likely to lead to a drug shortage on the date that the issue arises, the date that the applicant becomes aware or reasonably should have become aware that the issue will lead to a meaningful disruption is a more appropriate standard.”

PhRMA said the five business days' limit for notifying the FDA isn't required by statute and it believes it is sufficient to require notification “as soon as practicable” after the information becomes available. The group said that if the FDA requires a specific time period for reporting, it should be no shorter than 15 business days, “which is a more reasonable timeframe for manufacturers to investigate and confirm how the actions taken in response to the interruption will affect the ability of the manufacturer to fill orders or meet expected demand.”

Noncompliance Letters

The proposed rule also requires the FDA to issue a letter of noncompliance to manufacturers that fail to notify the agency of a potential drug shortage within the required time frame.

PhRMA said noncompliance letters should be issued only after a discussion between the manufacturer and the FDA, and manufacturers should be given sufficient opportunity to appeal the agency's determination of noncompliance.

“Because the proposed rule only provides vague guidance about how FDA would handle and adjudicate letters of noncompliance, we recommend FDA specify in the preamble to the final rule: how the agency anticipates issuing these letters in practice; a process through which manufacturers can appeal any decisions to issue noncompliance letters; and that the agency will retract and remove any non-compliance letter from the public website if the appeal is successful,” PhRMA said.

It also said the FDA should provide the following in the final rule:

• greater clarity on whether applicants still will be able to submit information in a nonspecified format via e-mail, and if not, whether the agency will specify a uniform process for applicants to follow when submitting notifications;

• what should be listed in a notification for manufacturers of drugs marketed without an approved application; and

• confirmation that the agency will continue to work with applicants to avoid disclosure of proprietary information or any information that might lead to hoarding and other unwanted consequences.


Amgen's Comments

Amgen Inc. said in comments submitted Dec. 16, 2013, that it “supports the requirements in the proposed rule for advance notification of situations and events that may result in drug shortages of innovative and generic drugs alike” and supports including biologic drugs in the proposed rule.

However, Amgen said the FDA should carefully consider the unintended consequences if it makes information about potential drug shortages available to the public.

“This may lead to hoarding by distributors, pharmacies, hospitals and other purchasers and may cause or exacerbate a situation that otherwise could have been manageable,” the company said. “Also under these conditions, patients may not take their medications as prescribed, decreasing the dosage to make the prescribed amount last for a longer time, leading to potentially ineffective course of therapy.”

Amgen also said information on a potential shortage may “facilitate introduction of counterfeit drugs or drugs from questionable sources into the supply chain.”

The company also said the FDA should make sure the definitions in the rule have sufficient clarity to prevent both under-reporting and over-reporting.

“With regard to the consequences of failure to report an impending drug shortage or discontinuation, we suggest that FDA provide notice of such non-compliance to the major news services as well as posting the information on the FDA web site,” Amgen said. “In this way, consumers, distributors, and payers will have the knowledge of which companies have not complied with this requirement.”

To contact the reporter on this story: Bronwyn Mixter in Washington at

To contact the editor responsible for this story: Lee Barnes at

GPhA's comments are at; PhRMA's comments are at; and Amgen's comments are at