Lawmakers Express “Grave Concerns” with Generic Drug Labeling Proposal; Demand Answers from FDA

January 22, 2014

By Kurt R. Karst – 

In a Januarry 22, 2014 letter to FDA Commissioner Margaret Hamburg, M.D. signed by 28 members of Congress, lawmakers express “grave concerns” about FDA’s November 2013 proposed rule to allow generic drug manufacturers to independently update product labeling (with respect to product safety) through the changes being effected (“CBE-0”) supplement process that is currently only available to brand-name drug manufacturers whose products are approved under an NDA.  As we previously reported, the proposal is quite clearly intended to undercut generic drug labeling preemption arguments and was made in response to various U.S. Supreme Court rulings, and in particular the Court’s ruling in PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011).

“We strongly believe that such a rule would conflict directly with the statute, thwart the law’s purposes and objectives, and impose significant costs on the drug industry and healthcare consumers,” write the lawmakers, who request that FDA “explain and reconsider this departure from decades of settled practice.”  House Energy and Commerce Committee Chairman Fred Upton (R-MI) reiterated this message in a press release announcing the letter to FDA.  (A similar press release was issued by Senator Lamar Alexander (R-TN), the senior Republican on the Senate health committee.) The letter goes on to note that a bedrock principle of generic drug approval has been the same labeling requirement, which FDA has adhered to for decades and that “Congress has also embraced . . . , as we have declined to change it in every food and drug law we have passed since 1992.” 

But even putting the same labeling requirement to one side for a moment, the lawmakers say that FDA’s proposal threatens to undermine the purpose of the Hatch-Waxman Amendments:

Allowing generic manufacturers to unilaterally change their labeling means potentially dozens of drugs that are chemically and biologically identical might nonetheless bear different safety information, confusing patients and prescribers alike.  The labeling on the generic products should be ide tical to the labeling on the branded product so providers and patients are comfortable with the risks and benefits of the product they are using regardless of the name of the company on the bottle or vial.

In a move that is likely to provide much fodder for comment on FDA’s proposal (as well as in any litigation that might ultimately result if FDA finalizes the proposal), the lawmakers ask that FDA respons to a series of questions by Febryary 5, 2014:

1. For the period of time after a generic drug has submitted a CBE-0 supplement, please explain how the generic drug’s label will be “the same as the labeling approved for the requirements included in sections 505(j)(2)(A)(i)-(v) of the Hatch-Waxman Act extend beyond the date of approval?

2.  Please explain the benefit of having proposed label changes published on a public website before FDA consideration, undermining FDA’s current role as the gatekeeper and deciding authority for changes to a drug’s label.

3.  Please provide the names of any executive branch employees outside the FDA who were involved in the decision to proceed with this proposed rule or who participated in drafting or reviewing it.

4.  What is FDA’s policy on when an adverse event needs to be listed on the label?  Are there standards around the prevalence or severity of the adverse event that are necessary before it rises to a labeling change?

5.  What is the expected cost to the FDA to review the CBE-0 submissions in a timely manner and establ sh and update the website, and from where does the FDA propose drawing resources to meet these costs?  How will the agency prioritize submissions and what is the estimated time or review?

6.  Please describe in detail how FDA arrived at the estimated cost orthe rule of $4,237 to $25,852 per year and estimates it will receive 20 CBE-0 supplements annually from approximately 15 ANDA holders.  Please explain how the agency derived these estimates.  Did FDA conduct any analysis of how long it takes a manuhlcturcr to prepare a CBE supplement and how much it costs?  Did FDA conduct any analysis of what it will cost manufacturers to institute new procedures for monitoring safety and enectivencss of drugs?  Did FDA conduct any analysis of the effect the proposed rule will have on drug prices?  Please provide all documents and communications regarding the cost-benefit analysis.

7. Generic drug manufacturers can currently propose labeling changes with FDA as a result of newly acquired safety information.  Please provide statistics for how many times this is done in comparison to brand name manufacturers and the current causes of any delay when using that process.  Please provide any evidence that would indicate generic drug manufacturers are not submitting required adverse event reports or otherwise not meeting their post-market surveillance requirements[.]

8.  The proposed rule notes a 2010 study of FDA safety-relatcd drug labeling changes that found the me ian time from initial approval of the drug product to label change was 11 years.  Please provide this study and all support ing documentation to the Committee(s).  Please also provide statistics showing how long it takes FDA to make a decision once a label change is suggested.

9.  Please explain why the prior approval supplement process alone cannot be used effectively to change generic and brand drug labels, and the current causes of any delay when using that process.  Please provide any evidence that would indicate generic drug manufacturers are not updating their label upon FDA approval of a change to the label of the reference brand drug.

10.  As an alternative approach, did the FDA consider permitting generic drug manufacturers to use a modified CBE process by which the agency has an opportunity to assess a proposed labeling change before introducing it into the market?  What does the agency believe would be the pros and cons of using this approach as opposed to the CBE-0?  Did the agency conduct a cost benefit analysis of such an approach?

11.  Did the agency consider the impact the proposed rule would have on over-the-counter (OTC) drugs?  If so, please submit any such analysis and explain how FDA envisions the proposed regulation applying to OTC drugs.

The letter closes on a strong note expressing the lawmakers’ disdain of the FDA proposal and the process undertaken by the Agency to move forward with a “solution” to the “problem” resulting from the U.S. Supreme Court’s ruling:

A number of processes already exist through which generic drug manufacturers can share new safety information and propose a label change to FDA without disrupting the market.  If the agency believes those methods are inadequate, it cannot simply ignore written statute.  FDA has an obligation to share those concerns with Congress and work together on a legislative solution.

Indeed, that’s exactly what the last line of the Court’s decision in PLIVA said: “Congress and the FDA retain the authority to change the law and regulations if they so desire” (emphasis added).