Proposed Generic Drug Labeling “CBE” Rule Turned on its “EAR”?

Changes Being Effected (CBE)

As pharmaceutical consultants, PDG has reported extensively on FDA’s Proposed Rule entitled Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products. We even gave it our own abbreviated name: the “Generic CBE Rule”. We did so because the rule as originally proposed would allow generic manufacturers to implement safety label changes using the CBE process. However, it seems we may have to change the name to something along the lines of, well, the “EAR Rule”.

Changing to Expedited Agency Review?

EAR stands for Expedited Agency Review and is a joint proposal of GPhA and PhRMA. Basically, EAR would require NDA/ANDA holders to submit new safety information to FDA. FDA would then review the information in light of information in its Sentinel System and require changes based on the review. Quite a departure from the CBE, the proposal describes the EAR as replacing “the changes being effected process for safety related labeling changes now permitted under 21 CFR §314.70(c)(6)(iii)“. The proposal is described in a letter to the FDA Commissioner from PhRMA and GPhA dated November 14, 2014.

The Unpredictability when FDA Happens

The dynamic does not lend itself to predictability. Assuming (big assumption), the rule is finalized as scheduled in September 2015, just under a year will have elapsed since PhRMA and GPhA wrote to FDA with their joint proposal, and only six months since the March 2015 Public Hearing. While this may seem like plenty of time, the competing proposals are as different as night and day. Furthermore, the joint developers of the EAR rule are known for intense competition including members who routinely sue one another. Moreover, it was reported at one point that the generic industry had threatened FDA with a lawsuit over their proposal.

An Updated Chronology of Events as of August 2016 Here is our updated chronology of events related to the Generic CBE/EAR Rule, followed by links to our various reports on the topic:

August 29, 2011 – Public Citizen files a Citizen Petition calling for FDA to authorize ANDA holders to change approved generic labeling using the Changes Being Effected (CBE) and Prior-Approval Supplement (PAS) procedures. In addition, the petition called for changes in the regulations that “permit ANDA approval to be withdrawn if a generic drug’s approved labeling differs from that of the reference listed drug (RLD)…to specify that this regulation does not apply to ANDA holders permitted to supplement labeling through CBE or PAS procedures”.

November 8, 2013 – FDA responds to Public citizen noting that “FDA issued a proposed rule that would amend its regulations to revise and clarify procedures for application holders to change the labeling of an approved drug or biological product to reflect certain types of newly acquired safety-related information in advance of FDA’s review of the change (see “Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products)”.

November 13th, 2013 – Federal Register (78 FR 67985) announces FDA Notice of Proposed Rule Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products.

December 27, 2013 – FDA announces they are extending the comment period for the proposed generic CBE rule from January 13 to March 13, 2014.

January 13, 2014 – original end of comment period.

January 22, 2014 – Twenty-eight members of Congress, including ten Senators, write to FDA Commissioner Hamburg to express “grave concerns” with the new proposed rule allowing generics to “alter an abbreviated new drug application (ANDA) label without FDA approval”.

February 26, 2014 – FDA responds to Representative Joseph R. Pitts (including copy to colleagues) noting that “it is of course possible that FDA might adopt an alternative regulatory approach or that the final rule may differ in some respects from the proposal to reflect points made in the comments.”

March 12, 2014 – Twenty-two health industry organizations submit a comment urging the agency to re-examine the proposal. Organizations signing the letter included Walgreens, CVS Caremark, Rite Aid, Walmart and the National Association of Chain Drug Stores.

March 13, 2014 – The comment period closes with at least 64 public submissions from a variety of stakeholders including industry, GPhA, National Conference of State Legislators, Public Citizen and others.

April 1, 2014 – Janet Woodcock, M.D. Director, Center for Drug Evaluation and Research Food and Drug Administration issues a statement before the Subcommittee on Health, Committee on Energy and Commerce U.S. House of Representatives entitled “Examining Concerns Regarding FDA’s Proposed Changes to Generic Drug Labeling” In it, Dr. Woodcock outlines the purpose and summary of the proposed rule, and cites recent court decisions and legal authority. In closing she states that “this proposed rule, if finalized, is intended to improve the communication of important drug safety information about generic drugs to both prescribers and patients.”

November 2014 – GPhA/PhRMA write letter to FDA Commissioner Margaret Hamburg outlining a counter-proposal known as Expedited Agency Review (EAR). The EAR would replace the CBE for safety related labeling changes.

December 2014 – Originally Scheduled Final Rule publication date. On February 17, 2015, FDA announced a reopening the comment period in light of the significant interest and alternate proposals put forth by GPhA and PhRMA.

March 2015 – On March 27, 2015, a FDA Public Hearing was held to describe proposal that generic companies be responsible for updating their labeling whenever new safety information becomes available. April 2015 – FDA extends the comment period through April 27, 2015.

September 2015 – Final Rule to be issued per Federal Register Unified Agenda.

December 2015 – FDA pushes the date for finalization of the rule back to July 2016.

May 2016 – FDA pushes the date for finalization of the rule back to April 2017

December 23, 2016 – FDA announces in Federal Register (see item number 276) that April 2017 is still the target date for finalization of the rule.

April 2017 – Current Target Date for finalization. 

Topic Reports:

Generic drug manufacturers could face new regulatory requirements from FDA

Generic Pharmacovigilance/Safety Surveillance & CBEs

RAPS Reports Generic Drug Industry Threatens FDA With Lawsuit Over Drug Labeling Proposal

FDA Delays Publication of Generic Drug CBE Rule Until Fall 2015

PDG Can Help

Regardless of the final rule, PDG will be prepared to assist industry with compliance. For contingency planning assistance, contact us.

GPhA is a registered service mark of Generic Pharmaceutical Association, Inc. and PhRMA is a registered service mark of Pharmaceutical Research And Manufacturers of America.