In our prior blog post of the same title on July 5, 2013, we predicted that the protection from product liability/failure to warn litigation for generic manufacturers as a result of the Supreme Court decision in Mutual Pharmaceutical Co., Inc. v. Bartlett, 133 S. Ct. 2466 (2013) might be short-lived.  FDA, in a Federal Register notice dated November 13, 2013, has proposed to allow holders of Abbreviated New Drug Applications (“ANDA’s”) for generic drugs to file supplements for labeling changes that might cause its labeling – on at least a temporary basis – to differ from the labeling of its Reference Listed Drug.  The proposed rule was published at 78 Fed. Reg. 67,985 and allowed for comments to be filed by January 13, 2014.  By notice of Federal Register of December 27, 2013, 78 Fed. Reg. 78,796, FDA extended the comment date to March 13, 2014.  What generic manufacturers need to know about this proposed rule is not only would it eliminate product liability protection, but it would increase their regulatory burdens.

Under this proposal, any applicant – either of an approved New Drug Application (“NDA”) or ANDA – could file a CBE-0 Supplement, notifying FDA that it has commenced distribution of a drug product with revised labeling due to newly acquired information as to the safety of the drug product.  Alternatively, the applicant could file a CBE-30 Supplement, which would permit the applicant to distribute products with the labeling change if FDA did not object within the thirty (30) day period.  In either case, if the FDA issues a Complete Response Letter, the manufacturer may be ordered to cease distribution of their product with the revised labeling.

Such a supplement would need to contain:

  1. The application number;
  2. A description of the labeling change;
  3. The basis of the labeling change, and all of the data supported by the change; and
  4. A copy of the final printed labeling with the change and an annotated copy of the labeling showing the change(s).

If the supplement is filed by an ANDA holder (as opposed to an NDA holder), the ANDA holder must send notice of the change to the NDA holder for the Reference Listed Drug.  Once such a supplement is submitted, FDA will post on its website information regarding the proposed labeling change.  Once the labeling of the Reference Listed Drug has been amended, any other ANDA holder must file a supplement to make the same change.

The proposed changes do not result from any legislative change, but from FDA’s interpretation of its rulemaking authority.  See Legal Authority, 78 Fed. Reg. 67995, and specifically:

FDA’s legal authority to modify §§ 314.70, 314.97, 314.150, and 601.12 arises from the same authority under which FDA initially issued these regulations. The FD&C Act (21 U.S.C. 301 et seq.) and the PHS Act (42 U.S.C. 201 et seq.) provide FDA with authority over the labeling for drugs and biological products, and authorize the Agency to enact regulations to facilitate FDA’s review and approval of applications regarding the labeling for those products.

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The changes proposed in this rulemaking are authorized under the FD&C Act, which provides authority for FDA to permit NDA holders and BLA holders to change their product labeling to include certain newly acquired safety-related information through submission of a CBE–0 supplement.

For the time being, generic manufacturers may continue to be protected by Mutual, and prior cases such as Pliva, Inc. v. Mensing, 131 S. Ct. 2567 (2011) and Wyeth v. Levine 555 U.S. 555 (2009).  Once the regulations are finalized, such protection may evaporate-and indeed that was the express rationale given by FDA for the proposed rule.  It explained:

As a result of the decisions in Wyeth v. Levine and Pliva v. Mensing, an individual can bring a product liability action for failure to warn against an NDA holder, but generally not an ANDA holder, and thus access to the courts is dependent on whether an individual is dispensed a brand name or generic drug. The Mensing decision alters the incentives for generic drug manufacturers to comply with current requirements to conduct robust postmarketing surveillance, evaluation, and reporting, and to ensure that the labeling for their drugs is accurate and up-to-date. We are proposing to change our regulations to expressly provide that ANDA holders may distribute revised labeling that differs from the RLD upon submission of a CBE–0 supplement to FDA. FDA’s proposed revisions to its regulations would create parity between NDA holders and ANDA holders with respect to submission of CBE–0 supplements for safety-related labeling changes based on newly acquired information. This proposal is also intended to ensure that generic drug companies actively participate with FDA in ensuring the timeliness, accuracy, and completeness of drug safety labeling in accordance with current regulatory requirements. If this proposed regulatory change is adopted, it may eliminate the preemption of certain failure-to-warn claims with respect to generic drugs.

Once the rule is finalized, it may pose new burdens on generic manufacturers as to postmarket surveillance, pharmacovigilance, literature review and reviewing and revising product labeling on a pro-active as opposed to reactive basis, as is largely the case under current practice.  While the proposed rules may have little effect on innovator companies, they have the potential to increase the regulatory  burden on generic manufacturers.