Filed 5/8/20; Certified for Partial Publication 6/3/20 (order attached)

IN THE COURT OF APPEAL OF THE STATE OF CALIFORNIA

SECOND APPELLATE DISTRICT

DIVISION THREE

RISPERDAL AND INVEGA 

CASES

 B284315, B284002,

 B284317

 (Los Angeles County

 Super. Ct. Nos. BC562540,

 BC583302, BC604937)

 (JCCP No. 4775)

APPEALS from judgments of the Superior Court of Los 

Angeles County, William E. Highberger, Judge. Affirmed in part 

and reversed in part.

Bernstein Liebhard and Daniel C. Burke for Plaintiff and 

Appellant C.S.

Law Office of Martin N. Buchanan, Martin N. Buchanan; 

Engstrom, Lipscomb & Lack and Ann Howitt for Plaintiffs and 

Appellants J.D. and J.T.

Drinker Biddle & Reath, Rodney M. Hudson, William A. 

Hanssen; Faegre Drinker Biddle & Reath and Rodney M. Hudson

for Defendants and Respondents.

——————————
2

C.S., J.D., and J.T. (collectively plaintiffs) were adolescents 

who were prescribed the antipsychotic drug risperidone after it 

was approved by the Food and Drug Administration (FDA) to 

treat behavioral symptoms in children with autism. They allege 

that risperidone caused them to develop gynecomastia, a 

condition characterized by the enlargement of male breast tissue. 

Plaintiffs sued risperidone’s manufacturers and distributors, 

Janssen Pharmaceuticals, Inc.; Janssen Research and 

Development, LLC; Johnson & Johnson; and McKesson 

Corporation (collectively and interchangeably, Janssen) for 

failure to adequately warn of the risk of gynecomastia on the 

drug’s label. Janssen moved for summary judgment on federal 

preemption grounds against plaintiffs. Janssen also moved for 

summary judgment against the individual plaintiff, C.S., on the 

ground that he could not raise a triable issue of fact under New 

York’s proximate cause standard, which requires the patient to 

show that the treating physician would have changed her 

prescribing behavior had she had an adequate warning. The trial

court granted both motions. For the reasons set forth below, we 

affirm the summary judgment against C.S., but reverse the 

summary judgment decided on preemption grounds.

BACKGROUND

I. Janssen researches a pediatric indication for risperidone

Risperidone1 is an antipsychotic medication that was first 

approved by the FDA in 1993 for managing manifestations of 

psychotic disorders in adults. Risperidone elevates blood levels of 

prolactin, a hormone produced by the pituitary gland. Elevated 

1 Risperdal is the brand name for risperidone.
3

levels of prolactin (hyperprolactinemia) are associated with 

gynecomastia.

After risperidone was approved for use in adults, Janssen 

sought a pediatric indication to treat irritability associated with 

autism in children. Before it sought FDA approval for pediatric 

use, Janssen conducted five studies of prolactin levels and 

prolactin-related side effects in 592 children who took risperidone 

for disruptive behavior disorders. The combined results of these 

five studies showed that the prolactin levels of children elevated 

quickly after being put on risperidone, peaked during weeks four 

through seven, then gradually declined. At weeks four through 

seven, 70.5 percent of children had elevated prolactin levels. 

Thirty of the 592 children, or five percent, developed prolactinrelated side effects, with gynecomastia being the most common.

The largest of the pediatric studies was an open label 

risperidone only use study known as RIS-INT-41 (study 41). 

(Croonenberghs et al., Risperidone in Children With Disruptive 

Behavior Disorders and Subaverage Intelligence: A 1-Year, OpenLabel Study of 504 Patients (Jan. 2005) 44 Journal of the 

American Academy of Child and Adolescent Psychiatry 64.) It 

followed 504 children between the ages of five and 14 who used 

risperidone over the course of one year. The results of study 41 

showed that 5.5 percent of the boys in the study developed 

gynecomastia. Janssen also conducted an extension study of 

study 41 that followed 48 of the children who continued to take 

risperidone for a second year known as RIS-INT-70 (study 70). 

(Reyes et al., Long-Term Use of Risperidone in Children with 

Disruptive Behavior Disorders and Subaverage Intelligence: 

Efficacy, Safety, and Tolerability (2006) 16 Journal of Child and 
4

Adolescent Psychopharmacology 260.) Study 70 showed that 14.3 

percent of the children developed gynecomastia.

The pooled results of the five pediatric studies were 

published in a 2003 article in the Journal of Clinical Psychiatry. 

(Findling et al., Prolactin Levels During Long-Term Risperidone 

Treatment in Children and Adolescents (Nov. 2003) 64 Journal of 

Clinical Psychiatry 1357.) The purpose of the article was to 

investigate prolactin levels in children taking risperidone and to 

explore any relationship to “side effects hypothetically 

attributable to prolactin” or “SHAP”, which included 

gynecomastia.2 For the article, Janssen commissioned a 

statistical analysis of the five pediatric studies that generated a 

number of tables. One of those tables was table 21, which 

compared subjects with elevated prolactin levels and those with 

normal prolactin levels for different study time periods. For 

children prescribed risperidone for a period of eight to 12 weeks, 

table 21 showed that those with elevated prolactin levels were 2.8 

times more likely to have suffered prolactin-related side effects, 

particularly gynecomastia. 

A July 2002 draft manuscript of the article circulated 

internally within Janssen referred to the statistically significant 

association between elevated prolactin in risperidone users and 

prolactin related adverse events during weeks eight through 12. 

In internal emails, Janssen officials expressed concerns about 

how to deal with the table 21 statistics. One Janssen 

representative stated, “I think we need to include the lack of 

association between . . . [prolactin] level or SHAP, as our advisors 

tell us that this is one serious concern about prolactin. If we can 

2 SHAP is an acronym invented by Janssen. Gynecomastia 

is the only prolactin-related side effect in males. 
5

demonstrate that the transient rise in [prolactin] does not result 

in abnormal maturation or SHAP, this would be most reassuring 

to clinicians.” Another Janssen representative stated, “Key 

message—prolactin rise is transient and not related to side 

effects hypothetically attributed to prolactin.” Janssen then 

commissioned a revised statistical analysis, which excluded all 

findings of prolactin-related side effects in males 10 years or 

older. With the revised data set, Janssen created a new table, 

which was similar to table 21; however, it no longer showed any 

statistical significance for prolactin-related side effects at weeks 

eight through 12.

In October 2002, Janssen prepared another draft of the 

article based on the revised statistics. The draft manuscript 

claimed that there “was no statistical difference in the percentage 

of patients who reported SHAP for any analysis time period, 

whether or not prolactin levels were normal or above the ULN 

[upper limit of normal] (range).” The final published version of 

the article again omitted all prolactin-related side effects in boys 

10 years of age or older, and did not mention or include the 

original analysis results for weeks eight through 12. Table 21 

was not disclosed by Janssen to the outside authors of the article.

II. The FDA approves risperidone’s label and pediatric 

indication 

In 2003, Janssen submitted a supplemental new drug 

application seeking a pediatric indication for risperidone to treat 

children with autism. Janssen submitted the pooled pediatric 

safety data to the FDA. Janssen described the data pooling 

portion of Janssen’s proposed statistical analysis plan, which 

included data from autism studies as well as data from pediatric 
6

disruptive behavior disorder studies. Janssen did not submit 

table 21 as part of its application. 

In July 2006, the FDA sent Janssen an approvable letter 

for its application and attached proposed labeling that included 

language describing the method for pooling pediatric safety 

data.3 The FDA requested that Janssen specify the number of 

pediatric patients in the studies. Janssen responded with two 

proposals for calculating the number of patients for adverse event 

purposes. The FDA found discrepancies in Janssen’s calculation, 

noting that the “proposed labeling uses 1348 as the denominator 

for the calculation of the rate of . . . ( . . . adverse events) in 

pediatric clinical trials” while the other events observed during 

the premarketing evaluation of risperidone section states that 

risperidone was studied in 1,923 children. The FDA asked 

Janssen to clarify the total number of patients exposed to 

risperidone and to provide an updated percentage for 

gynecomastia. 

Janssen explained that the number of risperidone-treated 

subjects across all studies of children and adolescents with 

autism or disruptive behavior disorders was 1,348. The FDA 

asked Janssen to include any new serious adverse events 

experienced by children to the list of events observed during 

premarketing evaluation and to include all pediatric studies 

beyond autism and disruptive behavior disorders. These 

3 An approvable letter is a written communication to an 

applicant from the FDA stating that the agency will approve the 

application if specific additional information or material is 

submitted or specific conditions are met. (21 C.F.R. § 314.110(a) 

(2019); see id. § 814.44(e)(2019) [describing approvable letters for

medical devices].) 
7

additional studies brought the total number of risperidonetreated subjects to 1,923. 

The FDA’s revised label included 1,923 patients as a 

denominator and a proposed calculation for the reported incident 

rate specific to gynecomastia in the label. The FDA revised the 

reported rate of gynecomastia from .03 percent to 2.7 percent. 

Janssen responded to the FDA’s proposal by explaining that 

1,923 pediatric patients was an accurate number; however, 

38 patients were in an ongoing clinical study and full safety data 

were not yet available. Janssen proposed a rate based on 1,885 

patients, excluding the 38 patients from the ongoing study. This 

brought the rate of gynecomastia to 2.3 percent. The 2.3 percent 

rate included the results from studies 41 and 70. 

In October 2006, the FDA approved the pediatric use of 

risperidone for irritability associated with autistic disorder with 

an updated label. Under the precautions section for pediatric 

use, the label stated, “The efficacy and safety of [risperidone] in 

the treatment of irritability associated with autistic disorder

were established in two 8-week, placebo-controlled trials in 

156 children and adolescent patients, aged 5 to 16 years. . . . 

Additional safety information was also assessed in a long-term 

study in patients with autistic disorder, or in short- and longterm studies in more than 1200 pediatric patients with other 

psychiatric disorders who were of similar age and weight, and 

who received similar dosages of [risperidone] as 

patients . . . treated for irritability associated with autistic 

disorder.” 

The precautions section also contained a section on 

hyperprolactinemia, stating, “As with other drugs that 

antagonize dopamine D2 receptors, risperidone elevates prolactin 
8

levels and the elevation persists during chronic administration. 

Risperidone is associated with higher levels of prolactin elevation 

than other antipsychotic agents. [¶] . . . [G]ynecomastia . . . ha[s] 

been reported in patients receiving prolactin-elevating 

compounds.” The label went on to state that “[r]isperidone has 

been shown to elevate prolactin levels in children and adolescents 

as well as in adults (see PRECAUTIONS—Hyperprolactinemia). 

In double-blind, placebo-controlled studies of up to 8 weeks 

duration in children and adolescents (aged 5 to 17 years), 49% of 

patients who received risperidone had elevated prolactin levels 

compared to 2% of patients who received placebo. [¶] In clinical 

trials in 1885 children and adolescents with autistic disorder or 

other psychiatric disorders treated with 

risperidone, . . . gynecomastia was reported in 2.3% of risperidone 

treated patients. [¶] The long-term effects of risperidone on 

growth and sexual maturation have not been fully evaluated.” 

Under adverse reactions and other events observed during the 

premarketing of risperidone, the label stated that during 

premarketing assessment, risperidone was administered to 2,607 

adult patients and 1,923 pediatric patients. That same section 

listed gynecomastia as “rare” and defined rare events to mean 

those occurring in fewer than one in 1,000 patients.

III. Citizens petition

In July 2012, Sheller P.C. (Sheller), a law firm representing 

hundreds of individuals who had taken risperidone, petitioned 

the FDA to immediately revoke the pediatric indication for 

risperidone unless and until the long-term safety of the drug

could be demonstrated, or in the alternative, require that the 

risperidone label include a box warning based on the lack of 
9

sufficient safety data (citizens petition).

4 The citizens petition 

alleged that the risperidone label did not reflect the long-term 

safety data used to support risperidone’s pediatric indications 

and it did not reflect the true risks posed by the drug. The 

citizens petition alleged that the portion of the risperidone label 

stating that gynecomastia was reported in 2 to 3 percent of 

risperidone-treated patients was misleading and that the actual 

rate of gynecomastia was five percent. The citizens petition also 

alleged that the risperidone label failed to recommend that 

physicians should closely monitor their adolescent patients’ 

prolactin levels, routinely examine them for abnormal breast 

growth, and discontinue risperidone use at the first sign of any of 

those symptoms. 

In addition to requests for a box warning and revocation of 

the pediatric indication, the citizens petition indicated that 

Janssen was in possession of documents that substantiated the 

allegations. However, those documents were subject to 

confidentiality orders in other risperidone litigation and 

petitioners were unable to supply those documents to the FDA. 

The petition requested that the FDA obtain the documents 

directly from Janssen or to release petitioners from the 

confidentiality orders. In response, the FDA requested Janssen 

to submit any data in its possession relevant to the use of 

risperidone in children and adolescents that it had not previously 

provided. Janssen responded that it had not identified any data 

4 The FDA generally requires special problems with a drug, 

particularly those that may lead to death or serious injury, to be 

placed in a prominently displayed box on the label. (21 C.F.R. 

§ 201.80(e) (2019).)
10

that it was required to submit pursuant to its statutory and 

regulatory obligations. 

The FDA denied the citizens petition, disagreeing with the 

assertion that a lack of long-term safety data is a basis for either 

revoking the pediatric indications for risperidone or adding a new 

boxed warning. The FDA was concerned that revoking 

risperidone’s pediatric indications until long-term safety could be 

demonstrated “would be tantamount to a long-term or permanent 

withdrawal, thereby removing an important and beneficial 

therapeutic option for many children and adolescents with these 

disorders.” The FDA stated that based on reviews of clinical data 

submitted by Janssen, published literature, and postmarketing 

surveillance, there was no evidence that risperidone was unsafe 

or anything else that warranted revoking the pediatric indication 

of the drug. The FDA also stated, “Gynecomastia is a common 

clinical manifestation of hyperprolactinemia, regardless of 

cause,[fn. omitted] and does not represent a serious adverse 

event” as defined in 21 Code of Federal Regulations, 

section 312.32 (a) (2019).5 

5 “An adverse event . . . is considered ‘serious’ if . . . it 

results in any of the following outcomes: Death, a lifethreatening adverse event, inpatient hospitalization or 

prolongation of existing hospitalization, a persistent or 

significant incapacity or substantial disruption of the ability to 

conduct normal life functions, or a congenital anomaly/birth 

defect. Important medical events that may not result in death, 

be life-threatening, or require hospitalization may be considered 

serious when, based upon appropriate medical judgment, they 

may jeopardize the patient or subject and may require medical or 

surgical intervention to prevent one of the outcomes listed in this 

definition.” (21 C.F.R. § 312.32 (a) (2019).) 
11

Further, the FDA found no basis for requiring a box 

warning about the lack of long-term safety data associated with 

pediatric use of risperidone. In response to the petitioner’s box 

warning request, the FDA noted that risperidone is “known to 

elevate blood levels of prolactin, a naturally occurring hormone 

produced by the pituitary gland in the brain. Elevated levels of 

prolactin (hyperprolactinemia) from any cause can be associated 

with a number of clinical effects, including breast enlargement 

(also called gynecomastia).” “The risk of hyperprolactinemia 

associated with certain antipsychotics has been basic textbook 

knowledge in psychiatry for many years.”

In its denial, the FDA noted that it was not responding to 

any labeling requests other than the request for a box warning 

and the revocation of the pediatric indication. “Although your 

petition includes an extensive discussion of the current labeling 

of [risperidone], you do not make specific labeling requests other 

than . . . that FDA require a new boxed warning for Risperdal 

and all generic versions of risperidone. We therefore do not 

respond to your specific contentions regarding the current 

labeling of these products.” 

IV. C.S.

C.S. is a New York resident who was diagnosed with 

autism and attention deficit hyperactivity disorder as a child. He

exhibited aggressive behavior including screaming, tantrums, 

and physical aggression. C.S. and his mother consulted a child 

psychiatrist to treat these behavioral symptoms. The 

psychiatrist prescribed risperidone to C.S. from April 2009 to 

July 2010. 

Before prescribing a particular medication, the 

psychiatrist’s practice was to review the risks and benefits with 
12

her patients. At the time she prescribed risperidone to C.S., her 

custom was to mention gynecomastia in “passing” but she did not 

“delve into” it the way she would have with other side effects. 

When presented with the results of study 70 which showed a 

gynecomastia rate of 12.5 percent, the psychiatrist stated she 

would have emphasized gynecomastia as a side effect to C.S.’s 

mother and would have included it as part of her risk-benefit 

analysis. She currently informs her patients that gynecomastia 

is a potential side effect of risperidone use, but still emphasizes 

other side effects more. 

The psychiatrist’s records do not indicate that she 

mentioned gynecomastia to C.S.’s mother or observed the 

condition in C.S. The psychiatrist would have noted 

gynecomastia in C.S.’s medical records if she had observed the 

condition, or if either C.S. or his mother had mentioned it. 

Indeed, C.S.’s medical records do not mention gynecomastia, 

breast growth, or elevated prolactin during risperidone use. A 

few months after C.S. stopped using risperidone, another 

physician examined C.S. and found his chest to be “ ‘normal 

contour, normal shape and expansion, clear to auscultation’ ” and 

made the same observation five months later. 

Two months after discontinuing risperidone, C.S. was 

prescribed, haloperidol, another antipsychotic associated with 

elevated prolactin. Haloperidol’s prescribing information in effect 

at the time stated, “[a]ntipsychotic drugs elevate prolactin levels; 

the elevation persists during chronic administration.” C.S. used 

haloperidol from September 2010 through 2016. In November 

2011, over a year after C.S. discontinued risperidone, a physician 

noted C.S. had abnormal breast growth. In February 2015, C.S. 

was diagnosed with idiopathic gynecomastia.
13

V. Procedural history

Plaintiffs, along with thousands of other individuals sued 

Janssen, alleging that they developed gynecomastia from their 

use of risperidone and that Janssen failed to adequately warn of 

the risk. The complaints were coordinated and assigned to a 

single trial court. 

The trial court divided the cases into four separate groups: 

individuals who used risperidone as children before the October 

2006 label change; individuals who used risperidone as children 

after the October 2006 label change; individuals who used 

risperidone as children before and after the October 2006 label 

change; and individuals who used Invega, but not risperidone.6 

Plaintiffs are from the second group of individuals who used 

risperidone after the October 2006 label change.

Janssen moved for summary judgment against six of the 

plaintiffs who took risperidone after the 2006 label change, 

including J.D., J.T., and C.S. Janssen asserted that their claims 

were preempted by federal law governing prescription 

medication. Janssen also moved for summary judgment on 

nonpreemption grounds against C.S, arguing that C.S. could not 

raise a triable issue of fact under New York’s proximate cause 

standard. The trial court granted both motions. 

J.D., J.T., and C.S. filed individual appeals. We 

consolidated the appeals, ordered J.D. and J.T. to file joint 

briefing on the preemption issue, and allowed C.S. to join in that 

briefing and to file separate briefing on the nonpreemption issues 

raised in the case-specific motion for summary judgment. After 

6 Invega is a risperidone-related drug. Individuals who 

took Invega are not the subject of this appeal.
14

the appeals were fully briefed, the United States Supreme Court 

decided Merck Sharp & Dohme Corp. v. Albrecht (2019) ___ U.S. 

___, ___ [139 S.Ct. 1668] (Merck Sharp), addressing the same 

preemption question at issue here. Janssen, J.D., and J.T. filed 

supplemental briefs discussing Merck Sharp. 

DISCUSSION

As noted above, there are two motions for summary 

judgment at issue: one entered against a group of plaintiffs who 

used risperidone after the FDA approved the 2006 label and 

another on case-specific grounds against C.S. Regarding the 

preemption issue, the parties dispute whether the trial court had 

authority to determine the preemption question as matter of law 

or whether it was required to submit underlying factual disputes 

to a jury. On the merits, the parties contest whether Janssen 

met its burden to show that plaintiffs’ claims were preempted. 

With respect to the case-specific summary judgment against C.S., 

the parties dispute whether there is a triable issue of fact that 

risperidone’s label proximately caused C.S. to develop 

gynecomastia. We address each issue in turn. 

I. Preemption

A. Preemption is decided as a matter of law 

The parties’ first dispute is whether the trial court had 

authority to decide the preemption issue as a matter of law. 

Plaintiffs argue that the trial court overstepped its authority by 

deciding the preemption issue in the face of underlying factual 

disputes that should have been submitted to a jury. However, 

the United States Supreme Court in Merck Sharp, supra, 

139 S.Ct. 1668 rejected this argument. “[J]udges, rather than lay 

juries, are better equipped to evaluate the nature and scope of an 
15

agency’s determination. Judges are experienced in ‘[t]he 

construction of written instruments,’ such as those normally 

produced by a federal agency to memorialize its considered 

judgments. [Citation.] And judges are better suited than are 

juries to understand and to interpret agency decisions in light of 

the governing statutory and regulatory context. [Citations.] To 

understand the question as a legal question for judges makes 

sense given the fact that judges are normally familiar with 

principles of administrative law.” (Id. at p. 1680.) Merck Sharp

acknowledged that “brute facts will prove relevant to a court’s 

legal determination about the meaning and effect of an agency 

decision”; however, these factual questions are “subsumed within 

an already tightly circumscribed legal analysis.” (Ibid.) They do 

not “warrant submission alone or together with the larger preemption question to a jury.” (Ibid.) Accordingly, the trial court 

was correct to decide the issue without submitting any purported

underlying factual questions to a jury.

B. Plaintiffs’ claims are not preempted 

Although the trial court had authority to decide the issue, 

in light of Merck Sharp, it came to the wrong conclusion. Janssen 

did not meet its burden to establish its preemption defense. 

To understand plaintiffs’ theory of the case and Janssen’s 

preemption defense, we provide an overview of FDA regulations 

and the process followed by drug manufacturers to appropriately 

label their drugs. “The FDA regulates the safety information 

that appears on the labels of prescription drugs that are 

marketed in the United States. [Citation.] Although we 

commonly understand a drug’s ‘label’ to refer to the sticker 

affixed to a prescription bottle, in this context the term refers 

more broadly to the written material that is sent to the physician 
16

who prescribes the drug and the written material that comes 

with the prescription bottle when the drug is handed to the 

patient at the pharmacy. [Citation.] These (often lengthy) 

package inserts contain detailed information about the drug’s 

medical uses and health risks.” (Merck Sharp, supra, 139 S.Ct. 

at pp. 1672–1673.) 

Federal regulations set out the requirements for the 

content, format, and order of the safety information on a drug’s 

label. (21 C.F.R. § 201.57(c) (2019).) The labels must include: 

“(1) prominent ‘boxed’ warnings about risks that may lead to 

death or serious injury; (2) contraindications describing any 

situation in which the drug should not be used because the risk of 

use outweighs any therapeutic benefit; (3) warnings and 

precautions about other potential safety hazards; and (4) any 

adverse reactions for which there is some basis to believe a causal 

relationship exists between the drug and the occurrence of the 

adverse event.” (Merck Sharp, supra, 139 S.Ct. at p. 1673.) The 

section where a particular risk appears on a drug label is an 

indicator of the likelihood and severity of the risk, ensuring that 

less important information does not overshadow more important 

information. (Ibid.) It prevents over exaggeration of risk and 

excludes speculative or hypothetical risks such that appropriate 

use of an otherwise beneficial drug is discouraged. (Ibid.) 

A “central premise of federal drug regulation [is] that the 

manufacturer bears responsibility for the content of its label at 

all times.” (Wyeth v. Levine (2009) 555 U.S. 555, 570–571.) While 

drug manufacturers work with the FDA to develop an 

appropriate label when they apply for approval of a new drug, the 

drug manufacturer, not the FDA, is responsible for crafting an 

adequate label and ensuring that the warnings remain adequate 
17

while the drug is on the market. (Ibid.; 21 U.S.C.S. § 355(a), (b), 

& (d); 21 C.F.R. § 314.125(b)(6) (2019).) The drug manufacturer 

has a duty to conduct postmarket surveillance and revise the 

label as soon as there is reasonable evidence of an association of a 

serious hazard with a drug. (21 C.F.R. §§ 201.80(e) (2019), 

314.80(b) (2019).) 

FDA regulations account for changes to drug safety 

information changing over time that necessitate revisions to a 

drug’s label. (21 C.F.R. §§ 314.80(c) (2019), 314.81(b)(2)(i) 

(2019).) Substantive label changes generally require advance 

FDA approval. However, an FDA regulation called the “ ‘changes 

being effected’ ” or “ ‘CBE’ ” regulation permits drug 

manufacturers to change a label without advanced approval if the 

change is designed to add or strengthen a warning where there is 

“ ‘newly acquired information’ ” about the “ ‘evidence of a causal 

association’ ” between the drug and a risk of harm. (Merck 

Sharp, supra, 139 S.Ct. at p. 1673; 21 C.F.R. § 314.70(c)(6)(iii)(A) 

(2019).) “Newly acquired information is data, analyses, or other 

information not previously submitted to the Agency, 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(b) (2019).) Manufacturers cannot propose a 

label change that is not based on newly acquired information and 

supported by reasonable evidence of a causal association with the 

drug. (21 C.F.R. §§ 314.70(c)(6)(iii)(A) (2019), 201.57(c)(6)(i) 

(2019).) The FDA reviews CBE submissions and can reject label 
18

changes even after the manufacturer has made them. (See 

21 C.F.R. § 314.70(c)(6), (7) (2019).)

The FDA, however, has limited resources and

“manufacturers have superior access to information about their 

drugs, especially in the postmarketing phase as new risks 

emerge.” (Wyeth v. Levine, supra, 555 U.S. at pp. 578–579.) To 

fill the void, “[s]tate tort suits uncover unknown drug hazards 

and provide incentives for drug manufacturers to disclose safety 

risks promptly.” (Id. at p. 579.) These lawsuits are a 

complementary form of drug regulation and offer an important 

layer of consumer protection. They also support the premise that 

manufacturers always bear ultimate responsibility for their drug 

labeling. (Ibid.) 

In Wyeth v. Levine, supra, 555 U.S. at page 572, a patient 

sued a drug manufacturer for a failure-to-warn claim after she 

developed gangrene and her arm had to be amputated as a result 

of her use of an antinausea drug. A physician’s assistant 

administered the drug using the “IV-push method” whereby the 

drug is injected directly into the patient’s vein. Using this 

method greatly increased the risk that the drug could enter a 

patient’s artery and cause irreversible gangrene. (Id. at p. 559.) 

The drug manufacturer argued that the patient’s state-law 

claims were preempted because it would have been impossible to 

comply with both its state-law duties and federal labeling duties, 

which require FDA approval of the exact text of a drug label. (Id. 

at p. 568.) The United States Supreme Court observed, however, 

that while typically, a manufacturer may only change a drug 

label after it gets FDA approval for the change, the CBE 

regulation makes an exception, permitting a manufacturer to 

make certain changes to its label before receiving the FDA’s 
19

approval. (Ibid.) For example, a manufacturer can “add or 

strengthen a contraindication, warning, precaution, or adverse 

reaction” without waiting for the FDA to approve the change. 

(21 C.F.R. § 314.70(c)(6)(iii)(A) (2019).) Therefore, a drug 

manufacturer can be held liable for a state law failure-to-warn 

claim if it could have revised its label using the CBE process but 

failed to do so. (See Merck Sharp, supra, 139 S.Ct. at pp. 1677–

1678.) Levine concluded that state-law failure-to-warn claims 

concerning prescription drugs are preempted only where there is 

clear evidence that the FDA would have rejected the proposed 

label change. (Levine, at pp. 571–572.) 

“ ‘[C]lear evidence’ is evidence that shows the court that the 

drug manufacturer fully informed the FDA of the justifications 

for the warning required by state law and that the FDA, in turn, 

informed the drug manufacturer that the FDA would not approve 

a change to the drug’s label to include that warning.” (Merck 

Sharp, supra, 139 S.Ct. at p. 1672.) In this context clear evidence 

is not a typical standard of proof. (Id. at p. 1679.) “Standards of 

proof, such as preponderance of the evidence and clear and 

convincing evidence, have no place in the resolution of this 

question of law.” (Id. at p. 1685 (conc. opn. of Alito, J.).) “The 

underlying question . . . is whether federal law (including 

appropriate FDA actions) prohibited the drug manufacturer from 

adding any and all warnings to the drug label that would satisfy 

state law. And, of course, in order to succeed with that defense 

the manufacturer must show that the answer to this question is 

yes.” (Id. at p. 1678.) 

This type of impossibility preemption is a demanding 

defense. (Wyeth v. Levine, supra, 555 U.S. at p. 573.) Because 

the CBE regulation permits changes, “a drug manufacturer will 
20

not ordinarily be able to show that there is an actual conflict 

between state and federal law such that it was impossible to 

comply with both.” (Merck Sharp, supra, 139 S.Ct. at p. 1679.) 

“[T]he very idea that the FDA would bring an enforcement action 

against a manufacturer for strengthening a warning pursuant to 

the CBE regulation is difficult to accept.” (Levine at p. 570.) 

Plaintiffs assert that Janssen could have used the CBE 

process to revise the risperidone label by: (1) warning of a direct 

correlation between risperidone use and gynecomastia; (2) adding 

a recommendation for regular monitoring of prolactin levels and 

physical examinations of children taking the drug; (3) deleting 

language on the label referring to gynecomastia as a rare event 

occurring in fewer than 1/1000 patients; and (4) disclosing the 

results of studies 41 and 70. 

In support of their labeling contentions, plaintiffs argue 

that table 21, studies 41 and 70 constitute newly acquired 

information for purposes of the CBE regulation. 

As an initial matter, we do not agree with plaintiffs that 

studies 41 and 70 constitute newly acquired information. By 

definition, newly acquired information is “information not 

previously submitted to the [FDA].” (21 C.F.R. § 314.3(b)(4) 

(2019).) The plaintiffs do not dispute that Janssen submitted the 

results of both studies to the FDA as part of its application for a 

pediatric indication. Thus, because the FDA had the results of 

studies 41 and 70, they cannot serve as the basis for a CBE 

submission. Further, to the extent plaintiffs argue that the 

results of these studies demonstrated a higher rate of 

gynecomastia than the 2.3 percent indicated on the label, the 

FDA made clear in its discussions with Janssen during the 

labeling process that it wanted adverse events, such as 
21

gynecomastia, to be calculated from all sources and pooled to 

ensure that all events across multiple studies were captured. 

Because the FDA had studies 41 and 70, and it expressly asked 

for the rate of gynecomastia to be calculated using pooled results 

from all studies (not just the select few identified by plaintiffs), 

there is clear evidence that the FDA was fully informed and 

required Janssen describe the risk of gynecomastia in the 

manner that it did. 

Plaintiffs’ argument that the risperidone label was 

inadequate because a section listed gynecomastia as a rare event 

occurring in less than one in 1,000 patients, thus contradicting 

the results of the pediatric studies, is also without merit. The 

term “rare” appears in the section, other events observed during 

the premarketing evaluation of Risperdal which states that 

Risperdal was administered to 2,607 adult patients and 

1,923 pediatric patients. The section goes on to state that events 

are categorized by body system and listed in order of decreasing 

frequency according to the following definitions: “frequent 

adverse events are those occurring in at least 1/100 patients (only 

those not already listed in the tabulated results from placebo–

controlled trials appear in this listing); infrequent adverse events 

are those occurring in 1/100 to 1/1000 patients; rare events are 

those occurring in fewer than 1/1000 patients.” Thus, it appears 

this gynecomastia rate was in reference to all patients, not just 

children. Plaintiffs have cherrypicked this language as well as 

the pediatric studies to create a purported discrepancy in the 

reported rate of gynecomastia on the risperidone label.

We are thus left with table 21 as a basis to support a 

potential label change via the CBE regulation. It is undisputed 

that Janssen did not submit table 21 during the application or 
22

labeling process.7 Nevertheless, Janssen offers several 

arguments why table 21 does not preclude its preemption 

defense. First, table 21 is not newly acquired information 

because it did not reveal risks of a different type or greater 

severity or frequency and the analysis was based on the studies 

submitted to the FDA. Janssen argues that the label warned of 

the exact type of risk, gynecomastia, and table 21 does not change 

the 2.3 percent rate. While it is true that table 21 does not 

change the rate of gynecomastia reported on the label, Janssen’s 

position overlooks the fact that table 21 provided additional 

information with respect to elevated prolactin levels during 

different time periods. Specifically, table 21 tended to show that 

children who had elevated prolactin after taking risperidone for 

eight to 12 weeks were 2.8 times more likely to develop prolactinrelated side effects, including gynecomastia. As the risperidone 

label made no mention of the likelihood of developing side effects 

related to elevated prolactin levels for different time periods, this 

information demonstrated a risk of greater frequency then 

reported on the label.

Second, Janssen argues that table 21 is not new and does 

not support a label change because the FDA confirmed that 

Janssen submitted all the necessary data and information to 

conclude that risperidone was appropriately labeled. In support, 

Janssen refers to the FDA’s statement in a reply brief filed in a 

separate litigation between the FDA and Sheller, the law firm 

that filed the citizens petition. The statement is of little value 

here. Sheller sued the FDA, asserting it had to expend 

unnecessary resources in various forums where it was suing 

Janssen for risperidone-related injuries. The primary issue in 

7 The FDA did not receive table 21 until October 2015. 
23

the brief cited by Janssen was whether the law firm had standing 

to sue the FDA for denying the citizens petition. This statement 

is not clear evidence that the FDA would have rejected a CBE 

submission based on table 21. Not only was it made in a wholly 

different context, but “the only agency actions that can determine 

the answer to the pre-emption question, . . . are agency actions 

taken pursuant to the FDA’s congressionally delegated 

authority.” (Merck Sharp, supra, 139 S.Ct. at p. 1679.) The FDA 

can communicate its disapproval of a warning by means of noticeand-comment rulemaking setting forth labeling standards, (see, 

e.g., 21 U.S.C.S. § 355(d); 21 C.F.R. §§ 201.57 (2019), 314.105 

(2019)); by formally rejecting a warning label that would have 

been adequate under state law, (see, e.g., 21 C.F.R. §§ 314.110(a) 

(2019), 314.125(b)(6) (2019)); or with other agency action carrying 

the force of law (cf., e.g., 21 U.S.C.S. § 355(o)(4)(A)). The FDA’s 

reference in a reply brief filed in a separate lawsuit in which the 

agency is seeking to avoid liability, is not the type of official 

action required by Merck Sharp. 

Third, Janssen contends that, to the extent table 21 

supports a monitoring recommendation, the CBE process does 

not allow Janssen to unilaterally change an FDA-approved label 

to make a monitoring recommendation. Janssen reasons that, 

because monitoring recommendations are included in the 

highlights section of a drug label (21 C.F.R. § 201.57(b)(2)(v)(C) 

(2019)) and a change to that section requires prior approval from

the FDA, Janssen could not make that change via the CBE 

process. Janssen’s argument misses the mark. Although the 

highlights section may indicate certain “recommendations for 

patient monitoring that are critical to safe use of the drug” 

(21 C.F.R. § 201.57(a)(10) (2019)), it does not have to include all 
24

of the same monitoring recommendations contained in the full 

prescribing information, which need only be “helpful in following 

the patient’s response or in identifying possible adverse 

reactions.” (21 C.F.R. § 201.57(c)(6)(iii) (2019).) The highlights 

section includes warnings and precautions and adverse reactions. 

(21 C.F.R. § 201.57(a)(10), (11) (2019).) Thus, if the CBE process 

could not be used to add any information that could conceivably 

be included in the highlights section, the CBE process could 

never be used to add any new warning, precaution, or adverse 

reaction without FDA approval. This is contrary to the purpose 

of the CBE process and the holdings in Wyeth v. Levine, supra, 

555 U.S. 555. 

We also reject Janssen’s assertion that the denial of the 

citizens petition was clear evidence the FDA would have rejected 

a proposed label change based on the evidence presented in 

table 21. As stated above, the FDA did not have table 21 when it 

denied the citizens petition. Impossibility preemption requires 

the drug manufacturer to show that it fully informed the FDA. 

Janssen did not. Nevertheless, Janssen argues that, because the 

FDA rejected similar allegations in the citizens petition, the FDA 

would have also rejected plaintiffs’ claims here. But the citizens 

petition made a much broader request, asking the FDA to 

essentially take risperidone off the market or include the risk of 

gynecomastia in the box warning, the most serious type of 

warning on the label. (See 21 C.F.R. § 201.57(c)(1) (2019)

[requiring contraindications leading to death or serious injury be 

included in boxed warning].) In contrast, here, plaintiffs’ 

argument is that table 21 could have supported a label change 

that included a recommendation to monitor prolactin levels at 

certain periods while a patient was taking risperidone. The fact 
25

that the allegations in the citizens petition were similar and 

partly based on some of the evidence presented here does not 

change our conclusion that the claims are distinct. Hypothetical 

labeling changes and speculative future rejections are not clear 

evidence of an impossibility preemption defense. (See Merck 

Sharp, supra, at p. 1682 (conc. opn. of Thomas, J.).) 

Accordingly, Janssen did not meet its burden to show by 

clear evidence that it fully informed the FDA and, in turn, the 

FDA rejected a proposed label change. Plaintiffs’ claims based on 

the information in table 21 are not preempted. 

II. C.S. cannot establish causation

Turning to the merits of Janssen’s case-specific summary 

judgment against C.S., we find Janssen’s argument persuasive. 

C.S. failed to raise a triable issue of fact with respect to causation 

because there is no evidence that C.S.’s treating physician would 

have changed her prescribing behavior had she been given a 

different warning.

Summary judgment is proper when there are no triable 

issues of material fact and the moving party is entitled to 

judgment as a matter of law. (Code Civ. Proc., § 437c, subd. (c).) 

“The purpose of the law of summary judgment is to provide 

courts with a mechanism to cut through the parties’ pleadings in 

order to determine whether, despite their allegations, trial is in 

fact necessary to resolve their dispute.” (Aguilar v. Atlantic 

Richfield Co. (2001) 25 Cal.4th 826, 843.)

“A defendant who moves for summary judgment bears the 

initial burden to show the action has no merit—that is, ‘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 [that] cause of action.’ [Citation.] Once the defendant 
26

meets this initial burden of production, the burden shifts to the 

plaintiff to demonstrate the existence of a triable issue of 

material fact. [Citation.] ‘From commencement to conclusion, 

the moving party defendant bears the burden of persuasion that 

there is no triable issue of material fact and that the defendant is 

entitled to judgment as a matter of law.’ [Citation.] We review 

the trial court’s ruling on a summary judgment motion de novo, 

liberally construing the evidence in favor of the party opposing 

the motion and resolving all doubts about the evidence in favor of 

the opponent. [Citation.] We consider all of the evidence the 

parties offered in connection with the motion, except that which 

the court properly excluded.” (Grotheer v. Escape Adventures, 

Inc. (2017) 14 Cal.App.5th 1283, 1292–1293.)

Under New York law,8 a pharmaceutical “manufacturer’s 

duty is to warn of all potential dangers in its prescription drugs 

that it knew, or, in the exercise of reasonable care, should have 

known to exist.” (Martin v. Hacker (1993) 83 N.Y.2d 1, 8.) This 

duty to warn applies to the prescribing medical professional, not 

the individual patient. (Id. at p. 9.) The basis for this rule is that 

the physician acts as a learned intermediary between the 

manufacturer and the patient, evaluating the patient’s needs, 

assessing the risks and benefits of available drugs, and 

supervising their use. (Glucksman v. Halsey Drug Co., Inc., 

(1990) 553 N.Y.S.2d 724, 726.) A plaintiff must demonstrate that 

the warning was inadequate and that the failure to adequately 

warn of the dangers of the drug was a proximate cause of his or 

her injuries. (Ibid.) To establish proximate cause, “a plaintiff 

must demonstrate that had a different, more accurate warning[ ] 

8 As C.S. is a New York resident, the parties do not dispute 

that New York law applies.
27

been given, his physician would not have prescribed the drug in 

the same manner.” (Alston v. Caraco Pharm., Inc. (S.D.N.Y. 

2009) 670 F.Supp.2d 279, 285.) A defendant is entitled to 

summary judgment if the evidence establishes “that any given 

warning would have been futile—either because any such 

warnings would not have been heeded or because the injury 

would have occurred, regardless of the given warnings.” (Bee v. 

Novartis Pharms. Corp. (E.D.N.Y. 2014) 18 F.Supp.3d 268, 284.) 

C.S. argues that he is entitled to a heeding presumption, 

i.e., had Janssen given an adequate warning, C.S.’s physician 

would have followed it. Janssen counters that New York does not 

recognize a heeding presumption. The only New York case that 

is directly on point and contains a lengthy discussion of the 

heeding presumption is Castorina v. A.C. & S. (2017) 49 N.Y.S.3d 

238, a decision by the Supreme Court, New York County. 

Castorina at pages 242 and 243 found that the heeding 

presumption has not been unequivocally recognized as part of 

New York law and, even if there were a presumption required by 

state decisional law, there is authority that has restricted its use 

to where the individual who would have heeded the warnings is 

not available to testify. As Castorina is the only New York case 

on point, we adopt its rule that where, as here, the physician was 

available to and actually did testify, plaintiff must prove that an 

adequate warning would have been heeded.

This leads us to Janssen’s argument that C.S. failed to 

raise a triable issue with respect to whether his treating 

physician would have heeded a different warning and not 

prescribed risperidone in the same manner. According to 

Janssen, C.S. must show that his psychiatrist would not have 

prescribed risperidone had she been given a different warning. 
28

C.S., on the other hand, suggests that any alteration to his 

psychiatrist’s prescribing behavior is enough. Based on the 

authorities relied on by both parties, the answer lies somewhere 

in between.

In another risperidone case, Chandler v. Janssen Pharms., 

Inc. (E.D.N.Y. 2018) 322 F.Supp.3d 314, the trial court granted 

summary judgment in favor of Janssen. The plaintiff’s treating 

physician testified that he was not sure he would have changed 

his decision even if he knew the risk of gynecomastia was higher 

than the rate on the drug label. (Id. at p. 328.) Just as testified 

here, the physician stated he would have done a risk-benefit 

analysis and considered gynecomastia as a potential risk and 

weighed it against the potential benefits of keeping his patient on 

the drug. (Ibid.) These statements were not enough to defeat 

summary judgment.

In contrast, in Bee v. Novartis Pharms. Corp., supra,

18 F.Supp.3d 268, the trial court found genuine issues of material 

fact existed as to whether the patient’s prescribing and treating 

physicians would have acted differently if the drug manufacturer 

had provided a different warning. There, the patient alleged that 

he developed osteonecrosis of the jaw (bone death caused by poor 

blood supply) because the drug manufacturer failed to warn 

about the risk that tooth extraction, or other forms of invasive 

dental work, would trigger the condition. (Id. at pp. 273, 286.) 

The physician testified that, since he learned of the drug’s side 

effects, he distributes handouts about the drug, informs his 

patients about the benefits of the drug, discusses the risk of 

developing the condition, provides patients with instructions for 

their dental providers, and warns patients not to undergo dental 

work until they have stopped taking the drug unless it is an 
29

absolute emergency. (Id. at pp. 293–294.) This testimony was 

sufficient to raise a triable issue of fact with respect to proximate 

cause as there was a question of whether a different label altered 

the treating physician’s behavior. 

In Davids v. Novartis Pharms. Corp. (E.D.N.Y. 2012) 

857 F.Supp.2d 267, a case involving the same drug as Bee, the 

trial court found a genuine issue of material fact as to whether 

the patient’s treating physician would have prescribed the drug 

had she been given a different warning. Again, the treating 

physician testified that she would have referred the patient to a 

dental specialist to evaluate his dental health before making her 

prescribing decision. (Davids, at p. 288.)

In McDowell v. Eli Lilly and Co. (S.D.N.Y. 2014) 58 

F.Supp.3d 391, the trial court granted summary judgment in 

favor of the drug manufacturer finding that the discontinuation 

warning on the label of an antidepressant was not the proximate 

cause of the plaintiff’s injuries. The plaintiff’s treating physician 

stated that he preferred that particular antidepressant over other 

medications used to treat the same conditions. He also testified 

that knowing incident rates of certain withdrawal symptoms 

would not have changed his decision to prescribe the drug. The 

only thing that the doctor would have changed was that he would 

have emphasized the withdrawal symptoms. This was not 

enough to raise a triable issue under New York’s proximate cause 

standard.

We find the above district court cases instructive and 

conclude that the psychiatrist’s testimony dooms C.S.’s claim. 

When presented with the results of the individual studies that 

showed a higher rate of gynecomastia among pediatric patients, 

the psychiatrist did not indicate whether her decision to prescribe 
30

risperidone would have changed. Rather, the psychiatrist 

equivocated, stating that, while she would include the higher rate 

in her risk-benefit analysis, risperidone may have still been the 

best choice for C.S. At the time, there were only two medications 

on the market approved to treat C.S.’s symptoms. The 

psychiatrist stated that she would still have to balance the side 

effects of risperidone with the only other available drug that had 

the side effect of making “kids feel[ ] like they’re jumping out of 

their skin.” When presented with the results of study 70, the 

psychiatrist said, “[i]t may or may not have changed the choice of 

medicine.” The psychiatrist acknowledged that she “was treating 

a really sick kid and I felt I did right by that kid, so I just don’t 

want to mix things up. I didn’t know—I didn’t know this 

information at the time. But I was aware that gynecomastia 

could be a side effect.” The psychiatrist’s statements are not 

enough to raise a triable issue of fact with respect to whether she 

would have altered her behavior. C.S. had to show something 

more than the psychiatrist’s ambiguous statements that she may 

have still prescribed risperidone and would have spent more time 

explaining gynecomastia as a side effect. 

C.S. failed to carry his burden to establish that his 

physician would have heeded the warning. Therefore, summary 

judgment was correctly entered against C.S. 
31

DISPOSITION

The judgments entered against J.D. and J.T. are reversed. 

The judgment entered against C.S. is affirmed. The parties are 

to bear their own costs on appeal.

DHANIDINA, J.

We concur:

LAVIN, Acting P. J.

EGERTON, J.
Filed 6/3/20

CERTIFIED FOR PARTIAL PUBLICATION*

IN THE COURT OF APPEAL OF THE STATE OF CALIFORNIA

SECOND APPELLATE DISTRICT

DIVISION THREE

RISPERDAL AND INVEGA 

CASES

 B284315, B284002,

 B284317

 (Los Angeles County

 Super. Ct. Nos. BC562540,

 BC583302, BC604937)

 (JCCP No. 4775)

 CERTIFICATION AND

 ORDER FOR PARTIAL

 PUBLICATION

The opinion in the above-entitled matter filed May 8, 2020, 

was not certified for publication in the Official Reports. For good 

cause it now appears that the opinion should be partially published 

in the Official Reports and it is so ordered.

DHANIDINA, J. LAVIN, Acting P. J. EGERTON, J.

* Pursuant to California Rules of Court, rules 8.1105 and 8.1110, 

this opinion is certified for publication with the exception of part IV 

of the Background and part II of the Discussion.