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PLAINTIFFS’ USE OF THE
CHANGES BEING EFFECTED
(CBE) PROVISIONS
Challenges and Best Practices
for Defendants
http://delvacca.acc.com
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Changes Being Effected (“CBE”) Is A
Narrow Exception
• The general rule is that all product labeling must be
approved by the FDA.
• CBE regulation creates a narrow exception to this rule
and allows a manufacturer to amend labeling:
• To reflect newly acquired information, or
• To add or strengthen a contraindication, warning, precaution, or
adverse reaction,
• If there is sufficient evidence of a causal association with the drug.
• Plaintiffs use this exception to argue that labels can be
changed at any time based on any information.
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Focus of Today’s Presentation
• What is the CBE regulation and how is it used?
• What are some common strategies used by plaintiffs to
support their claims?
• How have emails and other communications added to the
defense challenge?
• How can companies make it less appealing for plaintiffs?
• How can companies help their employees prepare for the
deposition process?
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What Is The CBE Regulation?
(c)(6) [T]he holder of an approved application may
commence distribution of the drug product involved upon
receipt by the agency of a supplement for the change:
***
(iii) Changes in the labeling to reflect newly acquired
information, except for changes required in § 201.57(a) of
this chapter . . . to accomplish any of the following:
(A) To add or strengthen a contraindication, warning,
precaution, or adverse reaction for which the evidence of
a causal association satisfies the standard for inclusion
in the labeling under § 201.57(c) of this chapter.
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What Does FDA Say About CBE?
• 2008 Amendment to § 314.70(c) was implemented “to
codify the agency’s longstanding view on when changes
on labeling of an approved drug may be made in advance
of the agency’s review of such change.”
• CBE applications are appropriate to amend the labeling
only to reflect newly acquired information and only if there
is sufficient evidence of a causal association with the
drug.
• FDA maintains that “[a]llowing sponsors to unilaterally
amend the labeling for approved products without
limitation – even if done to add new warnings – would
undermine the FDA approval process required by
Congress.”
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What The CBE Regulation Is NOT:
• The CBE regulation does NOT require a manufacturer to
update a package insert based simply on “available
information.”
• Rather, a manufacturer may update a package insert via
CBE only when it has (i) “newly acquired information” that
(ii) constitutes “evidence of a causal association,” as
defined by § 201.57(c).
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What Is Newly Acquired Information?
• The FDA made clear that what constitutes “newly
acquired information” is very limited:
• “The definition of ‘newly acquired information’ has been revised to
clarify that data, whether derived from new clinical studies, reports
of adverse events, or new analyses of previously submitted data
(e.g., meta-analyses) needs to be of a ‘different type or greater
severity or frequency than previously included in submissions to
FDA.’”
Source: 73 Fed. Reg. 49604 (Aug. 22, 2008)
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What Constitutes “Evidence of a Causal
Relationship”?
• A little less clear
• Nonetheless, FDA did discourage manufacturers from
including speculative risk information in the label:
• “Exaggeration of risk, or inclusion of speculative or hypothetical
risk, could discourage appropriate use of a beneficial drug, biologic,
or medical device or decrease the usefulness and accessibility of
important information by diluting or obscuring it. . . . [L]abeling that
includes theoretical hazards not well grounded in scientific
evidence can cause meaningful risk information to lose its
significance.”
Source: 73 Fed. Reg. 2848 (Jan. 16, 2008)
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What Constitutes “Evidence of a Causal
Relationship”? (cont’d)
• Section 201.57(c)(6) states that “there need be only
‘reasonable’ evidence of a causal association with the
drug, a standard that could be met with a wide range of
evidence.”
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What Changes Cannot Be Made Through
CBE Submission?
• Addition of boxed warnings
• Changes to the size or color of the text
• Changes to the “Highlights” section
• Changes in pregnancy categories
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How Do Plaintiffs Use CBE?
• Plaintiffs frequently use the CBE regulation to try to
convince a court that the manufacturer can change a label
at any time, for any reason.
• Based on “available information”
• Can be as little as one study that is consistent with prior studies
• Adverse event reports that are similar in number, severity and
frequency as those previously reported
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What Do Courts Say?
• Wyeth v. Levine, 555 U.S. 555 (2009)
• “[A]bsent clear evidence that the FDA would not have approved a
change in Phenergan’s label, we will not conclude that it was
impossible for Wyeth to comply with both federal and state
requirements.”
• Dobbs v. Wyeth Pharms., 797 F. Supp. 2d 1264 (W.D.
Okla. 2011)
• Because the defendant “regularly submitted to the FDA the
required reports reflecting suicide-related events,” and FDA
rejected “enhanced suicidality warnings . . . finding insufficient
scientific evidence” to support the change,” the plaintiff’s claims
were preempted.
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What Are Plaintiffs’ Strategies?
• Getting company employees to agree that there was a
“signal” before the information appeared in the label
• Trolling through company documents to find something
that suggests that the company was aware of a previously
undisclosed risk
• Unpublished studies
• Drafts of unpublished/revised articles
• Communications showing a difference of opinion
• Emails setting forth one person’s views
• New employee “syndrome”
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How Have Emails Added To The Defense
Challenge?
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What Can Companies Do?
• How can companies make it less appealing for plaintiffs to
pursue these theories?
• Should companies submit more CBE applications?
• How can companies counsel their employees – and
through what avenues – to help thwart plaintiffs’ efforts?
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How Can You Prepare For Depositions?
Empathize
• Employees are not in the business of litigation
• Employees are frequently nervous that they are on the
“chopping block”
• Employees fear being singled out or scapegoated
Educate
• Explain the role of counsel
• Encourage employees to be fully cooperative
• Provide company perspective on litigation
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Presenter Information
Lisa Warren, Esquire
Johnson & Johnson
Office of General Counsel
One Johnson & Johnson Plaza
New Brunswick, NJ 08933
Kenneth A. Murphy, Esquire
Melissa A. Graff, Esquire
Drinker Biddle & Reath LLP
One Logan Square, Suite 2000
Philadelphia, PA 19103