Judge: David S. Cunningham, Case: JCCP4962, Date: 2023-01-24 Tentative Ruling
Case Number: JCCP4962 Hearing Date: January 24, 2023 Dept: 11
JCCP 4962 (Zostavax Product Cases)
Tentative Ruling Re: Motion for Summary
Judgment/Adjudication
Date: 1/24/23
Time: 10:30
am
Moving Party: Merck & Co., Inc., et al.
(jointly “Defendants”)
Opposing Party: Barbara Gregory, et al. (jointly “Plaintiffs”)
Department: 11
Judge: David S. Cunningham III
________________________________________________________________________
TENTATIVE RULING
Defendants’ Request for Judicial Notice
Defendants’ request for judicial notice is granted in full. The documents are court records.
Defendants’ Evidentiary Objections
Objections 1 and 2 are sustained.
The rebuttal report and the addendum were filed late.
Objections 3 through 115 are overruled.
Undisputed material facts are not evidence.
Objections 116 through 196 are overruled.
Defendants contend the documents contain irrelevant, prejudicial, and
hearsay material. The objections are
overbroad as applied to the entire documents.
Defendants’ Objections Re: Dr. Darren Scheer
Except for objections 1 and 2
above, the Court declines to decide the objections to Dr. Scheer’s evidence at
this time. The Court will determine at
the hearing whether an Evidence Code section 402 hearing should be held before
ruling on the objections.
New Information from Zostavax Post-Marketing Studies
Defendants shift the burden as to
the Protocol 022 evidence, and Plaintiffs fail to raise a triable issue.
The Court intends to discuss the
AN1030166 evidence with the attorneys during oral arguments, especially
regarding whether Defendants previously submitted it to the Food and Drug
Administration (“FDA”).
New Information from
Adverse Events Reporting
The Court also intends to discuss
the European Medicines Agency’s (“EMA”) 2008 report at the hearing. In part, the Court is interested in
Defendants’ assertion that Zostavax use did not cause the high rate of shingles-like
rashes or that the high rate was simply reflective of Zostavax’s efficacy
rate. What evidence supports the
assertion?
Defendants shift the burden as to
the 2014 EMA report, and Plaintiffs fail to raise a triable issue.
Defendants shift the burden as to
the Varicella Zoster Virus Identification Program (“VZVIP”) evidence, and
Plaintiffs fail to raise a triable issue.
New Information Re:
Recombination
Defendants shift the burden
shifted as to the recombination evidence, and Plaintiffs fail to raise a
triable issue.
2014 Label Change
Defendants shift the burden as to
the 2014 label change, and Plaintiffs fail to raise a triable issue.
BACKGROUND
Shingles and Zostavax
“After a person contracts chickenpox, the Varicella Zoster Virus
(‘wild-type’ virus) remains in a person’s nervous system for life. When a person’s immune competence declines,
usually with advancing age, the virus can reactivate . . . in the form of”
herpes zoster, more commonly known as shingles.” (Plaintiffs’ Response Separate Statement,
Undisputed Material Fact (“UMF” 1.)
“Chickenpox and shingles are both caused by the varicella zoster
virus. Chickenpox and shingles are
discrete clinical entities that involve different symptoms, different clinical
presentations, and different diagnoses.”
(Id. at UMF 2.)
Defendants manufacture Zostavax, a vaccine utilized to prevent
shingles. In 2005, they applied to the FDA
for approval. “The FDA’s Vaccine and Related Biological Products Advisory
Committee unanimously determined that Zostavax is safe and effective for use in
preventing shingles in adults over the age of 60.” (Defendants’ Separate Statement, UMF 5 [adding
that “the FDA extended the eligible population to adults over the age of 50” on
3/24/11].)
“When the FDA approved Zostavax as safe and effective,” it “also approved
the vaccine’s labeling, including warnings and adverse reactions.” (Plaintiffs’ Response Separate Statement, UMF
6.) “That label included the following
FDA-approved language: ‘Zostavax significantly reduced the risk of developing
[shingles] when compared with placebo.’”
(Ibid.) “As to adverse events,
the initial label identified ‘noninjection-site [shingles]-like rashes’ as well
as chicken-pox like rashes, and explained that the vaccine-strain of the virus
was detected in ‘two subjects who reported’ chickenpox ‘like rashes.’” (Ibid.)
“Zostavax was the first FDA-approved vaccine for the prevention of
shingles. Since its approval, more than
47 million doses of Zostavax have been distributed worldwide.” (Id. at UMF 7.)
“Administration of Zostavax does not guarantee protection against
shingles.” (Id. at UMF 9.) “Since approval, the Warnings and Precautions
section of the Zostavax label has stated: ‘Vaccination with ZOSTAVAX does not
result in protection of all vaccine recipients.
The duration of protection beyond 4 years after vaccination with
ZOSTAVAX is unknown.’” (Ibid.) “It has also stated that that efficacy
‘decline[s] with increasing age.’”
(Ibid.)
“Zostavax is approved for administration only in individuals with a
healthy immune system because Zostavax ‘may result in a more extensive
vaccine-associated rash or disseminated disease in individuals who are
immunosuppressed.’” (Id. at UMF 10.)
Defendants “submitted a Changes Being Effected (‘CBE’) application to the
FDA” on 2/26/14 “to add ‘[h]erpes zoster (vaccine strain)’ under ‘Infections
and infestations’ in the ‘Post-marketing Experience’ section of the Zostavax
labeling.” (Id. at UMF 18.)
On 8/28/14, “after reviewing the data, the FDA approved [Defendants’] CBE
application for a labeling change, agreeing that ‘[h]erpes zoster (vaccine
strain)’ should be placed in the Postmarketing Experiences section of the
label.” (Ibid.)
Plaintiffs claim Defendants should have made additional label
changes. They assert that Zostavax can
cause shingles and that Defendants should have amended the label to provide
such information.
The Instant Action
The instant action is a coordinated proceeding with more than 20
underlying cases. The
operative complaints allege several causes of action, all grounded in
failure-to-warn theories.
On 8/2/22, the Court denied Defendants’ first motion for summary
judgment/adjudication without prejudice due to procedural defects.
At issue here is Defendants’ second motion for summary
judgment/adjudication. The parties appear to agree that the
motion applies to all causes of action remaining in the operative
complaints. (See Motion, p. 2; see also
Opposition, pp. 11-12; Reply, p. 1.) Defendants contend the motion should be
granted because the causes of action are preempted.
LAW
Summary
Judgment
A defendant or
cross-defendant has met his or her burden of showing that a cause of action has
no merit if the party has shown that one or more elements of the cause of
action, even if not separately pleaded, cannot be established, or that there is
a complete defense to the cause of action.
(Cal. Code Civ.
Proc. § 437c, subd. (p)(2).)
“The ‘tried and true’ way for defendants to meet their burden
of proof on summary judgment motions is to present affirmative evidence
(declarations, etc.) negating, as a matter of law, an essential element of
plaintiff's claim.” (Weil & Brown,
Cal. Prac. Guide: Civ. Proc. Before Trial (The Rutter Group 2022) ¶ 10:241,
emphasis in original.) “A cause of
action ‘cannot be established’ if the undisputed facts presented by defendant
prove the contrary of plaintiff's allegations as a
matter of law.” (Id. at ¶
10:241.10, emphasis in original.) “The
moving party's declarations and evidence will be strictly construed in
determining whether they negate (disprove) an essential element of plaintiff's
claim ‘in order to resolve any evidentiary doubts or ambiguities in plaintiff's
[opposing party's] favor.’” (Id. at ¶
10:241.20.)
A second way to meet the initial burden “is to ‘show’ that an
essential element of plaintiff's claim cannot be established.” (Id. at ¶ 10:242.) “Defendant does so by presenting evidence that plaintiff ‘does not possess
and cannot reasonably obtain, needed evidence . . .
.” (Ibid., emphasis in original.) The moving party must present evidence
of discovery admissions and/or factually devoid “all facts” discovery
responses. (See id. at ¶¶
10:244-10:245.27.)
The third way is to show a
complete defense. (See id. at ¶
10:246.) “To ‘show’ a complete defense, defendant must present admissible
evidence of each essential element of the
defense upon which it bears the burden of proof at trial.” (Id. at ¶ 10:247, emphasis in original.) “Thus, where a defense has several elements,
lack of substantial evidence on any element
bars relief, ‘even if the plaintiff failed to introduce a
scintilla of evidence challenging that element.’” (Ibid., emphasis in original.)
Once one of these burdens is met, it “shifts to plaintiff to prove the existence of a
triable issue of fact regarding that element of its cause of action or that
defense. If plaintiff is unable to do
so, defendants are entitled to judgment as a matter of law.” (Id. at ¶ 10:240, emphasis in original.)
Summary
Adjudication
“A motion for summary adjudication asks
the court to adjudicate the merits of a particular cause of action, affirmative
defense, issue of duty or claim for damages, including a punitive damage
request.” (Id. at ¶ 10:1, emphasis in
original.)
A defendant (or
cross-defendant) moving for summary [adjudication] must “show” that either:
* one or more elements of
the “cause of action … cannot be established”;
OR
* there is a complete defense to that cause of action. [Citation.]
This means that where
plaintiff has the burden of proof at trial by a preponderance of evidence,
defendant “must present evidence that would require a reasonable trier of
fact not to find any underlying material fact more
likely than not—otherwise, he [defendant]
would not be entitled to judgment as a matter of law,
but would have to present his evidence
to a trier of fact.” [Citation.]
The import of “more likely
than not” in the foregoing quote is that a moving defendant must generally
present evidence that, if uncontradicted, “would constitute a preponderance of
evidence that an essential element of the plaintiff's case cannot be
established … The same is true when a moving defendant seeks to secure
dismissal of the complaint based on an affirmative defense.” [Ciation.]
. . . Once defendants meet this burden, the burden shifts to plaintiff to prove the existence
of a triable issue of fact regarding that element of its cause of action or
that defense. If plaintiff is unable to do so, defendants are entitled to
judgment as a matter of law. [Citations.]
. . . If defendants fail to meet their burden, their motion
must be denied; plaintiff need not make any showing at all. [Citation.]
(Id. at ¶ 10:240, emphasis
in original.)
Preemption Re: Food,
Drug, and Cosmetic Act (“FDCA”), 21 U.S.C. Section 301 et seq.
“The federal government
regulates the manufacture, labeling, and sale of pharmaceuticals pursuant to
the FDCA.” (Gibbons v. Bristol-Myers
Squibb Co. (2d Cir. 2019) 919 F.3d 699, 707.) “To bring a drug to market, a manufacturer
must file a new drug application, which must explain the drugmaker's tests and
studies, demonstrate that the drug is ‘safe for use under the conditions
prescribed,’ and include proposed labeling language.” (Ibid.) “The [Food and
Drug Administration’s (‘FDA’)] premarket approval of a new drug application
includes the approval of the exact text in the proposed label.” (Ibid.)
“The FDA can direct a pharmaceutical
manufacturer to change a drug's label after it has entered the market, [citation], but ‘manufacturers, not the FDA, bear primary
responsibility for their drug labeling at all times,’ [citation].” (Ibid.) “Nevertheless, drug manufacturers are limited
in their ability to unilaterally change the labels on their products. Specifically, to make a change on their own, a
manufacturer must comply with the ‘changes being effected’ (‘CBE’) regulation,
set forth at 21 C.F.R. [section] 314.70(c)(6)(iii).” (Ibid.)
The CBE “allows drug manufacturers to change [a label] without the FDA’s
preapproval if the changes ‘add or strengthen a contraindication, warning,
precaution, or adverse reaction,’ or ‘add or strengthen an instruction about
dosing and administration that is intended to increase the safe usage of the drug
product,’ in order to ‘reflect newly acquired information.’” (Ibid.)
“‘Newly acquired information’ can include either new data or new
analyses of previously submitted data.”
(Ibid.) “The rule accounts for
the fact that risk information accumulates over time and that the same data may
take on a different meaning in light of subsequent developments[.]” (Wyeth v. Levine (2009) 555 U.S. 555,
569 [“[I]f the sponsor submits adverse event
information to FDA, and then later conducts a new analysis of data showing
risks of a different type or of greater severity or frequency than did reports
previously submitted to FDA, the sponsor meets the requirement for ‘newly
acquired information.’”].)
“The Supremacy Clause
establishes that federal law ‘shall be the supreme Law of the Land . . . any
Thing in the Constitution or Laws of any State to the Contrary
notwithstanding.’” (PLIVA, Inc. v.
Mensing (2011) 564 U.S. 604, 617.) “Where
federal and state law conflict – that is, where it is impossible for a party to
follow both federal and state law – state law must give way.” (Gibbons, supra, 919 F.3d at
708.) “Because manufacturers may
unilaterally update a drug's label if the change complies with the CBE
regulation, a state law failure-to-warn claim that depends on newly acquired
information – information that Defendants could have added to their label
without FDA approval – is not preempted.”
(Ibid. [citing Wyeth, supra, 555 U.S. at 568-572 and In re
Celexa & Lexapro Mktg. & Sales Practices Litig. (1st
Cir. 2015) 779 F.3d 34, 40-41].)
“[T]he Courts of Appeals
have synthesized the requirements to properly plead and then prove a state law
failure-to-warn claim based on post-drug-release information.” (Ibid.)
“Thus, to state a claim for failure-to-warn that is not preempted by the
FDCA, a plaintiff must plead ‘a labeling deficiency that [Defendants] could
have corrected using the CBE regulation.’”
(Ibid.) “If the plaintiff meets
that standard, the burden shifts to the party asserting a preemption defense to
demonstrate that there is ‘“clear evidence that the FDA would not have approved
a change” to the [prescription drug's] label.’”
(Ibid.)
DISCUSSION
“Post-FDA approval preemption analysis proceeds in two
stages.” (Utts v. Bristol-Myers
Squibb Co. (S.D.N.Y. 2017) 251 F.Supp.3d 644, 661.) The first stage asks whether “newly acquired
information” existed that “support[ed] a [unilateral] labeling change [by
Defendants] under the CBE regulation[.]”
(Ibid.) If “newly acquired
information” existed, the second stage requires a “show[ing] by ‘clear
evidence’ that the FDA would not have approved the labeling change made on the
basis of this newly acquired information.”
(Ibid.)
Defendants only addresses the first stage; they do not
contend “Plaintiffs’ claims are preempted” because “the FDA would not have
approved a change to the vaccine’s label.”
(Motion, p. 11.)
“Newly acquired information” means:
[D]ata, analyses, or other information
not previously submitted to the [FDA], which may include (but is not limited
to) data derived from new clinical studies, reports of adverse events, or new
analyses of previously submitted data (e.g., meta-analyses) if the studies,
events, or analyses reveal risks of a different type or greater severity or
frequency than previously included in submissions to FDA.
(21 C.F.R. § 314.3, subd. (b).)
Plaintiffs’ opposition brief identifies three types of
information that Plaintiffs claim qualify as “newly acquired information” – new
information from Zostavax post-marketing studies, new information from adverse
events reporting, and new information regarding recombination. (See Opposition, pp. 17-20.) The Court’s analysis focuses on the three
types.
New Information from Zostavax Post-Marketing Studies
Plaintiffs argue:
One example [of
‘newly acquired information’] is Defendants’ Protocol 022, conducted from
October 2007 to January 2010, which included an “indeterminate” result from a
rash that presented on day 16 after vaccination that Merck described as
varicelliform. The PCR results from the indeterminate show that it was from a
rash that contained primarily Oka/Merck DNA but also contained wild-type
varicella DNA. [Citation.] When it was suggested there be retesting of the
indeterminate results to determine if subjects had Oka/Merck vaccine virus
strain or wild-type, Merck’s Allison Fisher was in favor of retesting, “if in
no way it calls into question the results for P022 and if there is no risk of
changing the conclusions.” Had this sample been retested, changes would have
been required to the clinical study report, Merck’s publication of the trial,
and notification to FDA. [Citations.] This was new information. Merck had many
missed signals during its post- marketing review that they chose to
ignore instead of implementing the proper testing and assessment.
Another example of
new information and Merck’s disregard for proper testing, is with “Subject
AN1030166” in the Zostavax arm of the Shingles Prevention Study (SPS). This
subject developed an infection site rash that lasted 21 days in which a swab
sample was taken [citation]. The swab was then PCR tested and the results
indicated Ct values were reached for Oka (vaccine) strain. [Citation.] The
subject however was reported in the study as having a VZV-negative PCR result. [Citation.]
This again is new information that Merck ignored.
(Opposition, pp. 17-18.)
Defendants assert:
First, Plaintiffs
argue that “an ‘indeterminate’ result from a rash” in Protocol
022 was “new information.” [Citation.] One study participant in Protocol 022, a
Phase III study designed to evaluate the safety and efficacy of Zostavax in the
50-59 age group, developed a rash 16 days after vaccination. The rash contained
varicella-zoster virus (“VZV”). But the type of virus strain (i.e.,
vaccine-strain or wild-type virus) could not be determined, and the results
were deemed inconclusive. As explained in Merck’s opening brief, [citation],
this event report is not “newly acquired information” for at least two reasons:
(1) it is undisputed that this event was submitted to the FDA and therefore cannot
be “new” under FDA regulation, and (2) the result was inconclusive and
therefore cannot, by definition, establish “reasonable evidence of a causal
association.” [Citations.] Plaintiffs’ opposition fails to address these
undisputed facts, or otherwise cite to any authority in support of their
interpretation of this single inconclusive event as meeting the federal
definition of “newly acquired information” reflecting “reasonable evidence of a
causal association.”
* * *
Next, Plaintiffs
point to a single chickenpox-like rash in the Shingles Prevention Study in
Subject AN1030166. Plaintiffs’ expert Dr. Scheer claims that “Oka strain was
the source of the rash.” [Citation.] As an initial matter, this newly disclosed
opinion is inadmissible on multiple grounds. Even if it were admissible, this
again involves an event that Plaintiffs do not allege to have experienced — a
chickenpox-like rash, not shingles. In addition, it is undisputed that Merck
correctly reported the test results from AN1030166, consistent with the study’s
predefined definitions and guidelines, as negative and the results of retesting
as inconclusive. Regardless, Merck then provided the raw data to the FDA.
(Reply, pp. 4-5, emphasis in
original, footnotes omitted; see also Motion, pp. 14-16.)
The Court agrees with Defendants
as to Protocol 022. Defendants represent
that they submitted the Protocol 022 event to the FDA. (See, e.g., Defendants’ Response to
Plaintiffs’ Separate Statement, Additional Material Fact (“AMF”) 68 [citing
evidence].) Unless Plaintiffs cite
evidence showing otherwise at the hearing, this fact is dispositive given that
the regulation expressly defines “newly acquired information” as “data, analyses, or other information not
previously submitted to the [FDA] . . . .” (21 C.F.R. § 314.3, subd. (b), emphasis
added.)
Also, Plaintiffs admit that the initial Protocol 022 finding
was inconclusive (see, e.g., Plaintiffs’ Separate Statement, AMF 68), and the
evidence they cite to show that a further test of the sample would have
required changes to “the clinical study, [Defendants’] publication of the
trial, and notification of the FDA” is speculative. (See id. at AMF 114.) The emails do not show that the outcome would
have changed. (See West Decl., Exh. 32.)
The AN1030166 evidence needs to
be addressed with the attorneys at the hearing.
Defendants say they provided the FDA with the raw data pertaining to
AN1030166’s rash. (See, e.g., Reply, p.
5.) This might be dispositive, but
Plaintiffs should receive an opportunity to respond, and it should be fleshed
out during oral arguments.
Plaintiffs’ assertion – the swab
sample in AN1030166’s case that was PCR tested “shows Oka strain was the source
of this rash, and no wild-type VZV was found” (Opposition, p. 18) – comes from
a late addendum to Dr. Scheer’s expert report.
(See Defendants’ Supp. Brief Re: Evidentiary Objections to Opinions of
Dr. Scheer, p. 3 [stating that the case management order required expert
reports to be filed by 5/14/21 whereas the addendum is dated 7/8/21]; see also
Reply, p. 5 [noting that Dr. Scheer testified that “he lacks expertise in PCR
testing”].) The objection to the
addendum is sustained. Do Plaintiffs have
any other supporting evidence?
If it is shown that the data was
not provided to the FDA, the Court will consider continuing the hearing for an
Evidence Code section 402 hearing. At
the 8/2/22 hearing, the Court
stated its inclination to order Dr. Scheer to appear for such a hearing before
issuing a final decision.
To summarize:
* Defendants
shift the burden as to the Protocol 022 evidence, and Plaintiffs fail to raise
a triable issue.
* The AN1030166
evidence needs to be evaluated at the hearing to determine whether Defendants
submitted it to the FDA. Depending on
the answer, the Court may continue the hearing and order a section 402 hearing.
New Information from
Adverse Events Reporting
Plaintiffs state:
Merck has a tendency
to neglect testing results that are not in their favor nor did they champion
for proper adverse events reporting with things like PCR testing. To claim that
no new information came from adverse events reporting is both false and only a
direct result of their own actions to avoid the proper protocol. In 2008, the [EMA]
Post-authorization Evaluation of Medicines for Human Use [] drafted a
Rapporteur Final Assessment Report (RFAR) evaluating (among other things) the
Post-marketing exposure and reporting of Zostavax [citation]. The Assessor
commented:
Post marketing
experiences and information coming from the 3 existing PSUR [Periodic Safety
Update Report] periods show that the incidence of reports on Herpes zoster-like
rashes and varicella like rashes is quite high. In PSUR #3: herpes zoster
(195), varicella (18) and secondary transmission (19). On the other hand in
very few cases specimen was available for an analysis of the strain (WT vs.
OKA/Merck). The current surveillance program for these cases in absolutely
insufficient. The MAH [Marketing Authorization Holders] is asked to show
the usefulness of this system with the next PSUR. [Citation.]
In January 2014, the
Pharmacovigilance Risk Assessment Committee (PRAC), which is the EMA’s
committee responsible for assessing and monitoring the safety of human
medicines, produced a Rapporteur PSUR update that indicated not only was the
adverse reactions reporting was still insufficient and should be
amended, but during the review period of January 11, 2013 to February 5, 2013,
“two samples of the positive vaccine virus strain” were detected in the PCR
samples. [Citation.] Based on this information the MAH was recommended to
change the risk for HZ/HZ-like and varicella/varicella-like rash from “an
important potential to an important identified risk.” [Citation.] The report
further stated: “The PRAC Rapporteur is of the opinion that the passive
surveillance proposed by the MAH is not sufficient and should be amended. The
quantitative risk of zoster development and its characterization caused by the
vaccination with this vaccine strain should be analyzed more actively.” [Citation.]
(Opposition, pp. 18-19.)
Defendants argue:
[T]he EMA’s report
notes only a high incidence of reports of shingles-like rashes after Zostavax
administration. This is not surprising. To the contrary, it is consistent with
Zostavax’s 50% efficacy rate — i.e., it is protective in approximately half of
the people to whom it is administered, and not protective in the other half. In
other words, the mere fact of shingles infections occurring in vaccine
recipients reflects the vaccine’s limited efficacy, not that the vaccine itself
must be causing shingles. Plaintiffs’ argument is the equivalent of arguing
that breakthrough COVID infections in vaccinated individuals is evidence that
the vaccine itself causes COVID.
The EMA later
updated its initial report to indicate that there had been “two samples of the
positive vaccine virus strain.” [Citation.] But Plaintiffs omit critical
information about both samples that make it clear these cannot amount to “newly
acquired information.” The first sample identified is the June 2013 case that
Merck identified in its CBE to add vaccine-strain shingles to the Post
Marketing Experience section of Zostavax’s label. So it is uncontroverted that
the FDA knew of this report and approved Merck’s proposed label update. The
second of these infections occurred in an immunocompromised patient for whom
Zostavax is contraindicated. Specifically, the patient had rheumatoid arthritis
and was receiving a particular steroid treatment that was “considered a risk
factor for vaccine strain caused” shingles.
Plaintiffs’
Opposition claims that Merck’s [VZVIP], through which patients could provide
rash samples for testing, “provided an inaccurate” picture of adverse events
because private clinicians only submitted “a small portion of lesions” to this
voluntary post-marketing surveillance program. [Citation.] To begin with, it is
undisputed that Merck timely submitted all vaccine-strain shingles cases
identified in the VZVIP to the FDA. [Citation.]
Plaintiffs’
arguments regarding the VZVIP boil down to the supposition that including
information about the VZVIP in the Zostavax labeling might have prompted
healthcare providers to submit more samples that might have tested positive for
vaccine-strain shingles.12 Those allegations are speculative leaps of logic,
not actual “newly acquired information” reflecting scientific evidence of a
causal association between Zostavax and shingles. [Citation.]
Even assuming that
hypothetical additional cases could constitute “newly acquired information,”
courts uniformly have rejected similar allegations that would allow “any
litigant” to defeat preemption “by merely alleging that a manufacturer should
have created the ‘newly acquired information.’” [Citation.] In short,
Plaintiffs’ arguments about “the wisdom and reliability” of the VZVIP protocol
are “irrelevant to whether” Merck “failed to submit newly acquired information
that could support a CBE label change.” [Citation.]
(Reply, pp. 7-8, footnotes
omitted; see also, e.g., Motion, pp. 16-18.)
It is unclear whether Plaintiffs meant
to argue that the 2008 EMA report constitutes “newly acquired
information.” Assuming they did, the
Court notes that Defendants filed objections to the report. (See Defendants’ Evidentiary Objections, Obj.
190 [irrelevant, prejudice, hearsay].)
The Court is inclined to overrule them because they target the entire
document (it is overbroad to say the entire document is irrelevant, etc.).
Even if admissible, Defendants
contend the 2008 report is unhelpful to Plaintiffs because it merely shows “a
high incidence of reports of shingles-like rashes after Zostavax
administration[,]” which is “consistent with Zostavax’s 50% efficacy rate[.]” (Reply, p. 6.)
The contention might be true, but
it might be true instead that Zostavax use caused the shingles-like
rashes. What is Defendants’ evidence
that it did not? What is Defendants’
evidence that the “high incidence” was simply reflective of the efficacy
percentage? (Ibid.) The reply fails to cite particular
declarations or exhibits. (See ibid.
[citing no evidence].) Satisfying the
initial burden arguably requires more than just asking the Court to assume one
conclusion over the other, so the Court expects to discuss this issue with the
attorneys.
If Defendants end up shifting the
burden as to the 2008 report, Plaintiffs will need to show a triable
issue. Do they? The answer arguably is no because:
* “‘Newly
acquired information’ can include either new data or new analyses of previously
submitted data.” (Gibbons,
supra, 919 F.3d at 707, emphasis in original.)
* Plaintiffs do
not assert that the 2008 report was previously submitted.
* Whether treated
as new data or new analysis of previously submitted data, Plaintiffs do not
demonstrate that analysis of the report “reveal[s] risks of a different type or greater severity or frequency
than previously included in submissions to FDA” – e.g., there is no analysis
cited that shows, based on the report, that the vaccines actually caused the
rashes. (21 C.F.R. § 314.3, subd. (b),
emphasis added; see also Opposition, pp. 18-19.)
Ultimately, the Court finds that
both issues – burden shifting and raising a triable issue – should be addressed
at the hearing.
Next up is the EMA’s 2014 updated
report. Plaintiffs claim the report
notes that “‘two samples of the positive vaccine virus strain’ were detected in
the PCR samples.” (Opposition, p.
19.)
Defendants say the FDA knew about
the first sample because Merck identified it in the CBE regarding the “Post
Marketing Experience section of Zostavax’s label.” (Reply, pp. 6-7 [asserting that the FDA
approved the “proposed label update”].)
The fact that Defendants provided
the information to the FDA makes it not “newly acquired information.” Unless Plaintiffs show at the hearing that it
was not provided to the FDA, the Court anticipates finding that
Defendants shift the burden as to the first sample, and Plaintiffs fail to show
a triable issue of fact.
Defendants contend the second
sample goes against Plaintiffs’ position because it relates to an
“immunocompromised patient for whom Zostavax is contraindicated.” (Reply, p. 7.)
The Court agrees with Defendants.
“Contraindicated” means “not advised as a course of treatment or
procedure.” (https://www.merriam-webster.com/dictionary/contraindicated.) As Defendants note, the 2014 report states
that the patient was receiving “corticosteroid treatment” – i.e., steroid
treatment – for rheumatoid arthritis.
(West Decl., Exh. 174, p. MRK100104777; see also https://www.merriam-webster.com/dictionary/corticosteroid.) The report also points out that the treatment
was “considered a risk for vaccine strain caused HZ” – i.e., shingles. (West Decl. ,Exh. 174, p. MRK100104777.) These details support Defendants’ position
that the second sample is not “newly acquired information,” so the Court finds
the burden shifted as to the second sample, and there is no triable issue.
Plaintiffs seem to argue that the
2008 and 2014 reports establish that Defendants’ surveillance program – the
VZVIP – was “insufficient” and “provided an inaccurate and incomplete picture
of the adverse effects from Zostavax.” (Opposition, pp. 1, 19; see also id. at pp.
8-9.)
Defendants started the VZVIP in
1995. (See Defendants’ Response to
Plaintiffs’ Separate Statement, AMF 39.)
The parties agree that the program “was made available to healthcare
providers for collecting and analyzing samples taken from vaccinees who
experienced specific adverse events” after vaccine administration. (Opposition, p. 8; see also Defendants’
Response to Plaintiffs’ Separate Statement, AMF 40 [stating that the VZIP
“‘offer[s]’ ‘healthcare providers’ the opportunity to submit samples from
certain adverse experiences following vaccine administration for genetic
analysis”].) In 2006, Defendants
expanded the VZVIP to test samples from vaccinees who took Zostavax. (See Opposition, p. 8; see also Defendants’
Response to Plaintiffs’ Separate Statement, AMF 39.)
The Court’s understanding is that
participation in the VZVIP was voluntary.
While the 2008 and 2014 reports opine that the participation rate was
low, it is conjecture on Plaintiffs’ part to suggest that amending the Zostavax
label to include information about the program would have resulted in more
healthcare providers submitting more samples that would have tested
positive. The Court agrees with
Defendants that Plaintiffs’ argument involves “speculative leaps of logic, not
actual ‘newly acquired information’ reflecting scientific evidence of a causal
association between Zostavax and shingles.”
(Reply, p. 7.) The burden is
shifted as to the VZVIP evidence, and Plaintiffs fail to raise a triable issue.
To summarize:
* The Court
intends to address the 2008 EMA report during oral arguments.
* Defendants
shift the burden as to the 2014 EMA report, and Plaintiffs fail to raise a
triable issue.
* Defendants
shift the burden as to the VZVIP evidence, and Plaintiffs fail to raise a
triable issue.
New Information Re:
Recombination
Plaintiffs claim:
Recombination was
presented to Merck as early as August 2008 by the CDC who had a confirmed Oka
strain and wild-type recombination from 2007. At the same time, the CDC raised
questions such as Zostavax’s effect on recombination rate, recombination’s
impact on adverse events, and how this issue might affect herpes zoster
severity and transmission. Merck even had a potential recombinant case in 2014;
however, as described in the facts, Dr. [Anne] Gershon noted that the sample
sent to the London lab for testing was purportedly “lost.” [Citation.] This is
all new information.
(Opposition, p.
19.)
Defendants
assert:
As a threshold
matter, the “recombination” theory does not meet the definition of “newly
acquired information.” [Citation.] “[T]here is no reliable evidence or
documentation” of recombination of the vaccine-strain virus and wild-type
virus. And Plaintiffs offer no data in support of their contention that the
recombination theory may suffice as newly acquired information. “[L]abeling
that includes theoretical hazards not well-grounded in scientific evidence,” —
here, recombination — “can cause meaningful risk information to lose its significance.”
[Citation.] In any event, a potential recombinant case is not reasonable
evidence of a causal association. Indeed, Dr. Gershon, the lab director,
explained that because this unidentified sample was lost “we will never know
about that one,” and confirmed that the lab had “not seen any
recombinants.” Plaintiffs’ unsubstantiated speculation cannot constitute
“newly acquired information.” [Citation.] “[I]nconclusive” results do “not
justify a unilateral label change.” [Citation.]
(Reply, p. 8,
emphasis in original, footnotes omitted; see also Motion, pp. 15-16.)
The Court agrees with
Defendants. Dr. Gershon’s email states
that the sample was lost when it was sent to London for testing. (See Beamer Decl., Exh. 27 [“With Merck’s
permission, we sent the DNA specimen to Dr. Judith Breuer in London for deep
sequencing, where after along series of events it was lost. So we will never know about that one.”],
emphasis added.) A potential recombinant
case linked to a lost sample that never got tested enough to achieve a final
result is not “newly acquired information.” The situation is too inconclusive to “justify
a unilateral label change.” (McGrath
v. Bayer HealthCare Pharmaceuticals Inc. (E.D.N.Y. 2019) 393 F.Sup.3d 161,
169.) The Court finds the burden shifted,
and Plaintiffs fail to raise a triable issue.
2014 Label Change
Plaintiffs contend:
Defendants present
in their motion the fact that a label change regarding shingles was made in
2014, eight years after the initial product launch. [Citation.] Merck presented
to the FDA what it claims to describe as a report of a reactivation of shingles
due to the zoster vaccine, but the risk appeared to be extremely low. This
label change was made to the Post-Marketing Experience section, but never added
to the Warnings and Precautions. Defendants themselves are presenting this new
information that should have been added to the warnings label, as well as
adequately tested in post marketing. [Citation.]
(Opposition, p.
20.)
Defendants
state:
Plaintiffs
acknowledge that the Zostavax label was updated in 2014 based on the first
report of vaccine-strain shingles in an immunocompetent individual. [Citation.]
Yet Plaintiffs quibble about whether this information should have been added to
a different section of the label. [Citation.] First, the authors who reported
that case themselves explained that, despite the report, the risk of developing
vaccine-strain shingles after Zostavax administration remained “extremely low.”
Regardless, Plaintiffs do not — because they cannot — provide an answer to the
FDA’s clear guidance that the Warnings and Precautions section must be reserved
for only the most serious risks in order to “‘prevent overwarning’” and the
“‘exaggeration of risk, or inclusion of speculative or hypothetical risks.’”
[Citation.] Indeed, the FDA has specifically adopted a “cautious approach to
drug labeling” to avoid discouraging “appropriate use of a beneficial drug.”
[Citation.] Plaintiffs fail to establish that Merck’s 2014 label update,
reviewed and approved by the FDA, somehow reflects “newly acquired information”
that would require a different, additional CBE submission. Plaintiffs also do
not allege that any subsequent cases “reveal risks of a different type or
greater severity or frequency” than this initial submission. [Citation.]
(Reply, pp.
8-9, footnotes omitted.)
The Court agrees with
Defendants. The burden is shifted – and
there is no triable issue – because:
* Defendants
submitted the reactivation information to the FDA. (See 21 C.F.R § 314.3, subd. (b) [limiting “newly acquired information” to
“data, analyses, or other information not previously
submitted to the [FDA]”], emphasis added.)
* The FDA
approved the label change and, necessarily, the inclusion of the reactivation
information in the Post-Marketing Experience section.
* Plaintiffs
fail to cite authority holding that reactivation information contained in an
amended label approved by the FDA can constitute “newly acquired information”
when it appears in the Post-Marketing Experience section.
* Plaintiffs
fail to show new analysis of the reactivation information that “reveal[s] risks of a different type or
greater severity or frequency than previously included in submissions to FDA.”
(21 C.F.R. § 314.3, subd. (b); see also Opposition, p. 20; Plaintiffs’ Separate
Statement, AMFs 71-72.)