Marcus v. Forest Pharmaceuticals, Inc., 1st Cir. (2015)

7/26/2019 Marcus v. Forest Pharmaceuticals, Inc., 1st Cir. (2015)

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United States Court of AppealsFor the First Circuit

No. 141290I N RE: CELEXA AND LEXAPRO MARKETI NG AND

SALES PRACTI CES LI TI GATI ON

RANDY and BONNI E MARCUS, on behal f of t hemsel ves and al l ot herper sons si mi l ar l y si t uat ed,

Pl ai nt i f f s , Appel l ant s,

v.

FOREST LABORATORI ES, I NC. and FOREST PHARMACEUTI CALS, I NC. ,

Def endant s, Appel l ees.

APPEAL FROM THE UNI TED STATES DI STRI CT COURTFOR THE DI STRI CT OF MASSACHUSETTS

[ Hon. Nat hani el M. Gor t on, U. S. Di st r i ct J udge]

Bef or e

Lynch, Chi ef J udge,Sel ya and Kayat t a, Ci r cui t J udges.

R. Br ent Wi sner , wi t h whom Baum, Hedl und, Ar i st ei & Gol dman,P. C. and Pendl ey, Baudi n & Cof f i n, LLP wer e on br i ef , f orappel l ant .

Edwi n G. Schal l er t , wi t h whom Debevoi se & Pl i mpt on LLP andSugarman, Roger s, Barshak & Cohen, P. C. were on br i ef , f or

appel l ee.

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KAYATTA, Circuit Judge. Thi s appeal ar i ses out of a

put at i ve cl ass act i on agai nst For est Phar maceut i cal s, t he

manuf act ur er of Lexapr o, an ant i depr essant medi cat i on. Pl ai nt i f f s

cl ai m t hat Lexapr o' s FDA- appr oved dr ug l abel mi sl eads Cal i f or ni a

consumer s by omi t t i ng mat er i al ef f i cacy i nf or mat i on, i n vi ol at i on

of Cal i f or ni a' s Consumer Legal Remedi es Act ( "CLRA") , Cal . Ci v.

Code 1750 et seq. , Fal se Adver t i si ng Law ( "FAL") , Cal . Bus. &

Prof . Code 17500 et seq. , and Unf ai r Compet i t i on Law ( "UCL") ,

Cal . Bus. & Pr of . Code 17200 et seq. The di st r i ct cour t

di smi ssed t hese cl ai ms, f i ndi ng t hem bar r ed by Cal i f or ni a' s saf e

har bor doct r i ne. See I n r e Cel exa & Lexapr o Mkt g. Sal es Pr act i ces

Li t i g. ( Mar cus v. For est Labs. , I nc. ) , No. 1311343NMG, 2014 WL

866571 ( D. Mass. March 5, 2014) . See gener al l y Cel - Tech Commc' ns,

I nc. v. L. A. Cel l ul ar Tel . Co. , 20 Cal . 4t h 163, 182 ( 1999)

( out l i ni ng Cal i f or ni a' s saf e har bor doct r i ne) .

Expr essi ng no vi ew on t he Cal i f or ni a saf e har bor

doctr i ne' s appl i cabi l i t y her e, we i nst ead f i nd t hat f eder al l aw

i mpl i edl y pr eempt s t hese cl ai ms because t he Feder al Food, Dr ug, and

Cosmet i c Act ( "FDCA") , 21 U. S. C. 301 et seq. , pr ohi bi t s For est

f r om i ndependent l y changi ng i t s FDA- appr oved l abel as pl ai nt i f f s

cl ai m Cal i f or ni a l aw r equi r es. See PLI VA, I nc. v. Mensi ng, 131

S. Ct . 2567, 258081 ( 2011) . Ther ef or e, we af f i r m t he j udgment

di smi ssi ng t he compl ai nt .

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I. Background

Lexapr o bel ongs t o a cl ass of ant i depr essant s known as

sel ect i ve ser ot oni n r eupt ake i nhi bi t or s. For est al so manuf act ur es

Cel exa, a dr ug wi t h a chemi cal composi t i on cl osel y r el at ed t o

Lexapr o. I n 2002, t he FDA f i r st appr oved Lexapr o t o t r eat adul t s

f or depr essi on. I n 2008, For est sought FDA appr oval f or t he use of

Lexapr o t o t r eat maj or depr essi ve di sorder i n adol escent s.

A. FDA's Drug Approval Process

The FDA drug appr oval process i s "onerous and l engt hy. "

Mut . Phar m. Co. , I nc. v. Bar t l et t , 133 S. Ct . 2466, 2471 ( 2013) .

The FDCA r equi r es t hat drug manuf act urer s gai n FDA appr oval pr i or

t o mar ket i ng or sel l i ng a dr ug i n i nt er st at e commer ce. See 21

U. S. C. 355( a) . To gai n FDA appr oval , a dr ug manuf act ur er must

submi t ei t her a new- dr ug appl i cat i on ( "NDA") , f or a new dr ug, or a

suppl ement al new- dr ug appl i cat i on ( "sNDA") , f or a new t r eatment .

See 21 C. F. R. 314. 1 et seq. NDAs and sNDAs are subj ect t o t he

same approval r equi r ement s. See i d. The NDA or sNDA must i ncl ude

"f ul l r epor t s of [ al l cl i ni cal ] i nvest i gat i ons whi ch have been made

t o show whet her . . . such dr ug i s ef f ect i ve i n use. " 21 U. S. C.

355( b) ( 1) ( A) . The FDA may onl y approve t he dr ug i f t he NDA or

sNDA pr ovi des " subst ant i al evi dence t hat t he dr ug wi l l have t he

ef f ect i t . . . i s r epr esent ed t o have. " I d. 355( d) ( 5) . As par t

of i t s showi ng t hat i t has pr ovi ded such subst ant i al evi dence, a

manuf act ur er submi t s t he r esul t s of "adequat e and wel l - cont r ol l ed

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i nvest i gat i ons, i ncl udi ng cl i ni cal i nvest i gat i ons, by exper t s

qual i f i ed by sci ent i f i c t r ai ni ng and exper i ence t o eval uat e t he

ef f ect i veness of t he dr ug i nvol ved. " I d. 355( d) ( 7) .

I n i t s eval uat i on of an NDA or sNDA, t he FDA has

di scr et i on t o det er mi ne t hat dat a f r om "one adequat e and wel l -

cont r ol l ed cl i ni cal i nvest i gat i on, " al ong wi t h ot her " conf i r mat or y

evi dence, " ar e "suf f i ci ent t o est abl i sh ef f ecti veness. " I d. ; see

21 C. F. R. 314. 105( c) ( "[ The] FDA i s r equi r ed t o exer ci se i t s

sci ent i f i c j udgment t o det er mi ne t he ki nd and quant i t y of dat a and

i nf or mat i on an appl i cant i s r equi r ed t o pr ovi de f or a par t i cul ar

dr ug t o meet t he st at ut or y st andar ds. " ) The FDA wi l l not appr ove

a dr ug i f t he NDA or sNDA l acks "subst ant i al evi dence t hat t he dr ug

wi l l have t he ef f ect i t pur por t s or i s r epr esent ed t o have. " 21

U. S. C. 355( d) ( 5) .

The drug manuf act urer must al so submi t " t he l abel i ng

pr oposed t o be used f or such dr ug. " I d. 355( b) ( 1) ( F) ; 21 C. F. R.

314. 50( c) ( 2) ( i ) . The appl i cat i on must i ncl ude t he pr oposed

l abel ' s t ext "wi t h annot at i ons t o t he i nf or mat i on i n t he [ dr ug

appl i cat i on] t hat suppor t t he i ncl usi on of each st at ement [ on t he

l abel ] . " 21 C. F. R. 314. 50( c) ( 2) ( i ) . I n or der t o appr ove an NDA

or sNDA, t he FDA must det er mi ne, "based on a f ai r eval uat i on of al l

mat er i al f act s, " t hat t he pr oposed l abel i s not "f al se or

mi sl eadi ng i n any par t i cul ar . " 21 U. S. C. 355( d) ( 7) ; 21 C. F. R.

314. 125( b) ( 6) . Af t er appr oval , t he manuf act ur er may di st r i but e

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t he dr ug wi t hout vi ol at i ng f eder al l aw as l ong as i t uses t he FDA-

appr oved l abel . See 21 U. S. C. 331( c) , 333( a) , & 352( a) , ( c) .

I n an ef f or t t o secur e FDA appr oval t o sel l Lexapr o f or

t he t r eat ment of maj or depr essi ve di sorder i n adol escent s, For est

submi t t ed t o t he FDA t he r esul t s of f our st udi es: Cel exa St udy

94404, Cel exa St udy 18, Lexapro St udy 15, and Lexapro St udy 32.

Cel exa Study 94404 and Lexapro St udy 15 showed no ef f i cacy. Cel exa

St udy 18 and Lexapr o St udy 32 f ound posi t i ve ef f i cacy t hat was

st at i st i cal l y si gni f i cant , but onl y bar el y so. I n Mar ch 2009, t he

FDA never t hel ess appr oved t he sal e of Lexapr o t o t r eat maj or

depr essi ve di sorder i n adol escent s based on a f i ndi ng t hat

subst ant i al evi dence suppor t ed t he ef f i cacy of t hat use. I n maki ng

t hi s f i ndi ng, t he FDA "ext r apol at e[ d] on t he basi s of a pr evi ousl y

r evi ewed posi t i ve study wi t h [ Cel exa] , " al ong wi t h t he posi t i ve

st at i st i cal ef f i cacy r esul t s f r omLexapr o St udy 32. As requi r ed by

t he FDCA, i n appr ovi ng t he sNDA, t he FDA made a speci f i c f i ndi ng

t hat Lexapr o' s l abel was not " f al se or mi sl eadi ng i n any

par t i cul ar . " 21 U. S. C. 355( d) ( 7) ; 21 C. F. R. 314. 125( b) ( 6) .

That appr oved l abel i ncl uded t he f ol l owi ng:

Cl i ni cal St udi es, Maj or Depr essi ve Di sor der - -Adol escent s

The ef f i cacy of Lexapr o as an acut e t r eat mentf or maj or depr essi ve di sorder i n adol escentpat i ent s was est abl i shed i n an 8- week,f l exi bl e- dose, pl acebo- cont r ol l ed st udy t hatcompar ed Lexapr o 10- 20 mg/ day t o pl acebo i nout pat i ent s 12 t o 17 year s of age i ncl usi vewho met DSM- I V cr i t er i a f or maj or depr essi ve

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di sor der . The pr i mary out come was change f r ombasel i ne t o endpoi nt i n t he Chi l dr en' sDepr essi on Rat i ng Scal e - - Revi sed ( CDRS- R) .I n t hi s st udy, Lexapr o showed st at i st i cal l ysi gni f i cant great er mean i mprovement compar edt o pl acebo on t he CDRS- R.

The ef f i cacy of Lexapr o i n t he acut e t r eat mentof maj or depr essi ve di sorder i n adol escent swas est abl i shed, i n par t , on t he basi s ofext r apol at i on f r om t he 8- week, f l exi bl e- dose,pl acebo- cont r ol l ed st udy wi t h r acemi cci t al opr am [ i . e. , Cel exa] 20- 40 mg/ day. I nt hi s out pat i ent st udy i n chi l dr en andadol escents 7 to 17 years of age who met DSM-I V cri t er i a f or maj or depr essi ve di sor der ,ci t al opr am t r eat ment showed stat i st i cal l ysi gni f i cant gr eat er mean i mpr ovement f r ombasel i ne, compared t o pl acebo, on t he CDRS- R;t he posi t i ve resul t s f or t hi s t r i al l argel ycame f r om t he adol escent subgr oup.

Two addi t i onal f l exi bl e- dose, pl acebo-cont r ol l ed MDD st udi es ( one Lexapr o st udy i npat i ent s ages 7 t o 17 and one ci t al opr am[ Cel exa] st udy i n adol escent s) di d notdemonst r at e ef f i cacy.

Al t hough mai nt enance ef f i cacy i n adol escentpat i ent s has not been syst emat i cal l yeval uated, mai nt enance ef f i cacy can beext r apol at ed f r om adul t dat a al ong wi t hcompar i sons of esci t al opr am phar macoki net i cpar amet er s i n adul t s and adol escent pat i ent s.

B. Changing The Label

Ther e ar e t wo ways pert i nent t o t hi s l awsui t i n whi ch a

manuf act ur er of a br and name pr escr i pt i on dr ug can change t he

dr ug' s l abel . Fi r st , t he def aul t r ul e i s that a manuf act ur er must

secur e FDA appr oval f or a pr oposed change pr i or t o di st r i but i ng t he

pr oduct wi t h t he changed l abel . 21 C. F. R. 314. 70( b) ( 2) ( v) ( A) .

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Second, under what i s known as t he Changes Bei ng Ef f ect ed ( "CBE")

r egul at i on, i d. 314. 70( c) ( 6) ( i i i ) , a manuf act ur er can make

cer t ai n t ypes of changes t o i t s l abel , wi t hout pr i or FDA appr oval ,

by sendi ng t he FDA a "suppl ement submi ss i on. "

To make a change under t he CBE r egul at i on, t he

manuf act ur er must sat i sf y at l east t wo r equi r ement s. Fi r st , t he

change must " r ef l ect newl y acqui r ed i nf or mat i on. " I d. ; see al so

i d. 314. 3( b) ( def i ni ng "newl y acqui r ed i nf or mat i on" ) . Second,

t he change must be f or t he pur pose of accompl i shi ng at l east one of

t he f i ve f ol l owi ng obj ecti ves:

( A) To add or st r engt hen acont r ai ndi cat i on, war ni ng, pr ecaut i on, oradver se react i on f or whi ch t he evi dence of acausal associ at i on sat i sf i es t he st andar d f ori ncl us i on i n t he l abel i ng . . . ;

( B) To add or st r engt hen a st at ementabout dr ug abuse, dependence, psychol ogi calef f ect , or over dosage;

( C) To add or st r engt hen ani nst r uct i on about dosage and admi ni st r at i ont hat i s i nt ended t o i ncr ease t he saf e use oft he dr ug pr oduct ;

( D) To del et e f al se, mi sl eadi ng, orunsuppor t ed i ndi cat i ons f or use or cl ai ms f oref f ect i veness; or

( E) Any l abel i ng change nor mal l yr equi r i ng a suppl ement submi ss i on and appr ovalpr i or t o di st r i but i on of t he dr ug pr oduct t hatFDA speci f i cal l y r equest s be submi t t ed undert hi s pr ovi si on.

I d. 314. 70( c) ( 6) ( i i i ) .

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C. The Complaint

Accor di ng t o t he compl ai nt , i n Apr i l 2009, Randy and

Bonni e Mar cus, t he pl ai nt i f f s, pur chased Lexapr o to t r eat t hei r

adol escent son' s depr essi on. Based on t hei r r eadi ng of Lexapr o' s

FDA- appr oved l abel , t hey and t hei r son' s physi ci an over est i mat ed

Lexapr o' s ef f ect i veness. As a r esul t , t hey spent money pur chasi ng

a dr ug t hat t hey descr i be as no mor e cl i ni cal l y ef f ect i ve t han a

pl acebo. On behal f of al l ot her Cal i f or ni ans who pur chased Lexapr o

f or an adol escent f r om Mar ch 2009 unt i l pr esent , t hey cl ai m t hat

For est Phar maceut i cal s omi t t ed mat er i al ef f i cacy i nf or mat i on, i n

vi ol at i on of Cal i f or ni a st at e consumer pr ot ect i on l aws: t he CLRA,

FAL, and UCL.

The CLRA prohi bi t s unf ai r met hods of compet i t i on and

unf ai r or decept i ve act s t hat r esul t i n t he sal e of goods t o any

consumer . Cal . Ci v. Code. 1770( a) . The compl ai nt al l eges t hat

For est vi ol at ed f our di f f er ent pr ovi si ons of t he CLRA, speci f i cal l y

1770( a) ( 2) ( "Mi sr epr esent i ng t he sour ce, sponsorshi p, appr oval ,

or cer t i f i cat i on of goods or ser vi ces. ") ; 1770( a) ( 5)

( "Repr esent i ng t hat goods or servi ces have sponsorshi p, appr oval ,

. . . , [ or ] benef i t s , . . . whi ch t hey do not have . . . . " ) ;

1770( a) ( 7) ( "Repr esent i ng t hat goods . . . ar e of a par t i cul ar

st andar d, qual i t y, or gr ade, . . . i f t hey ar e of anot her . ") ; and

1770( a) ( 9) ( "Adver t i si ng goods . . . wi t h i nt ent not t o sel l t hem

as adver t i sed. " ) . The FAL pr ohi bi t s compani es f r om di ssemi nat i ng

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"unt r ue or mi sl eadi ng" st atement s. Cal . Bus. & Prof . Code.

17500. And t he UCL pr ohi bi t s "unf ai r or f r audul ent busi ness

act [ s] or pr act i ce[ s] and unf ai r , decept i ve, unt r ue or mi sl eadi ng

adver t i si ng. " I d. 17200.

I n suppor t of t hese st at e l aw cl ai ms, t he compl ai nt t akes

i ssue wi t h " t he FDA[ ' s] accept [ ance of ] t he quest i onabl e dat a f r om

Lexapr o St udy 32 and the f l awed data f r om Cel exa St udy 18 t o

concl ude that For est met i t s r egul at or y requi r ement of pr ovi di ng

t wo wel l - cont r ol l ed st udi es showi ng t hat Lexapr o was ef f ect i ve f or

t he t r eat ment of adol escent [ depr essi on] . " Expr essi ng di spl easur e

wi t h f eder al l aw as wel l as t he FDA, t he compl ai nt f ur t her not es

t hat t he FDA' s "st andards f or appr ovi ng ant i depr essant s are mi ni mal

accor di ng t o the l aw. "

The compl ai nt gi ves a di f f er ent r ead t o Cel exa St udy 18

t han di d t he FDA' s expert s, who f ound t hat t he st udy showed a

st at i st i cal l y si gni f i cant di f f er ence bet ween Cel exa and a pl acebo

f or an acut e t r eat ment of maj or depr essi ve di sorder i n adol escent s.

The compl ai nt di sagrees, and asser t s i nst ead t hat " [ a] cl ose

eval uat i on of t he unpubl i shed ver si on of Cel exa St udy 18 r eveal s

t hat dat a was mani pul at ed t o creat e t he appear ance of st at i st i cal

si gni f i cance. " I n sum, t he compl ai nt char act er i zes Cel exa St udy

18' s r esul t s as "f r audul ent and mi sl eadi ng. "

The compl ai nt al so r eads Lexapr o St udy 32 di f f er ent l y

t han di d t he FDA' s exper t s, who f ound t hat t hi s st udy al so showed

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a st at i st i cal l y si gni f i cant di f f er ence bet ween Lexapr o and pl acebo

f or an acut e t r eat ment of maj or depr essi ve di sorder i n adol escent s.

As wi t h Cel exa St udy 18, t he compl ai nt quest i ons t he st udy' s

f i ndi ng of st at i st i cal si gni f i cance, and under scor es t he f act- -

known t o t he FDA at t he t i me of appr oval - - t hat t he di f f er ence

i ndi cat ed " i s not c l i ni cal l y s i gni f i cant . "

Based on t he f oregoi ng, t he compl ai nt argues t hat t he

"dr ug l abel f or Lexapr o i s mi sl eadi ng and i nadequat e. " I n i t s

pr ayer f or r el i ef , pl ai nt i f f s r equest t hat t he cour t "[ p] er manent l y

enj oi n[ ] For est f r om cont i nui ng t o sel l or mar ket Lexapr o wi t h i t s

cur r ent dr ug l abel and di r ect [ ] For est t o seek FDA appr oval of a

new [ dr ug] l abel . " Al t hough t he compl ai nt cont ai ns gener al

al l egat i ons of decept i ve mar ket i ng, and quot es a pr ess r el ease f r om

For est , 1 pl ai nt i f f s ( who seek t o r epr esent a cl ass) hi nge t hei r

cl ai ms and t he r el i ef t hey seek on t hei r chal l enge t o the adequacy

of t he ef f i cacy di scussi on i n t he FDA- appr oved l abel . For exampl e,

pl ai nt i f f s al l ege t hat "For est ' s mi sconduct was uni f or ml y di r ect ed

at al l consumer s and t hei r pr escr i bi ng heal t hcar e pr of essi onal s i n

Cal i f or ni a t hr ough t he use of a mi sl eadi ng dr ug l abel . Thus, al l

1 Par agr aph 53 of t he compl ai nt al l eges t hat For est i ssued a

pr ess r el ease i n whi ch For est ' s CEO st at ed, " [ w] e have l ongbel i eved t hat Lexapr o woul d be of benef i t f or t he t r eat ment ofdepr essi on i n adol escent s and that i s why we under t ook t he sever alst udi es descr i bed i n t he package i nser t . We are enormousl ygr at i f i ed t hat Lexapr o wi l l be avai l abl e f or depr essed adol escent swho so much r equi r e t he benef i t s whi ch Lexapr o has made avai l abl ef or depr essed adul t s f or t he past seven year s. "

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member s of t he [ cl ass] have a common cause of act i on . . . . "

Pl ai nt i f f s t hen al l ege t hat "t he quest i on of For est ' s conduct ,

i . e. , whet her t he dr ug l abel was mi sl eadi ng, pr edomi nat es over any

i ndi vi dual i ssues. "

D. Procedural History

Randy and Bonni e Marcus f i l ed t he compl ai nt i n May 2013,

seeki ng cl ass cer t i f i cat i on, i n t he Cent r al Di str i ct of Cal i f or ni a.

The J udi ci al Panel on Mul t i di st r i ct Li t i gat i on subsequent l y

t r ansf er r ed t he case t o t he Di st r i ct of Massachuset t s as par t of

ongoi ng mul t i di st r i ct l i t i gat i on, I n r e Cel exa and Lexapr o

Market i ng and Sal es Pr act i ces Li t i gat i on, No. 09MDL2067NMG.

Forest moved t o di smi ss, r el yi ng on FDCA pr eempt i on and

Cal i f or ni a' s saf e har bor doctr i ne. Whi l e bot h par t i es f ul l y

br i ef ed For est ' s f eder al pr eempt i on def ense, t he di st r i ct cour t di d

not r each i t , r el yi ng i nst ead on i t s concl usi on t hat t he compl ai nt

f ai l ed under Cal i f or ni a' s saf e har bor doct r i ne.

II. Standard of Review

We gi ve de novo r evi ew t o t he di st r i ct cour t ' s gr ant of

For est ' s mot i on t o di smi ss f or f ai l ur e t o st at e a cl ai m. See,

e. g. , Cooper v. Chart er Commc' ns Ent m' t s I , LLC, 760 F. 3d 103, 106

( 1st Ci r . 2014) . We accept as t r ue al l f act s i n t he compl ai nt and

dr aw al l r easonabl e i nf er ences i n t he pl ai nt i f f s' f avor . I d.

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III. Analysis

A.

I n deci di ng whet her t he compl ai nt st at es a cl ai m upon

whi ch r el i ef may be gr ant ed, we ar e ur ged by pl ai nt i f f s t o r est r i ct

our i nqui r y t o det er mi ni ng whet her t he saf e har bor doct r i ne under

Cal i f or ni a l aw def eat s pl ai nt i f f s' cl ai ms. Hor nbook pr i nci pl es of

appel l at e pr ocedur e, however , gr ant us di scr et i on t o rel y on any

basi s made appar ent i n t he r ecor d f or af f i r mi ng a di st r i ct cour t ' s

deci si on. E. g. , Debnam v. FedEx Home Del i ver y, 766 F. 3d 93, 96

( 1st Ci r . 2014) .

I n movi ng t o di smi ss, For est r el i ed upon not j ust t he

Cal i f or ni a saf e har bor doct r i ne, but al so on pr i nci pl es of f eder al

pr eempt i on. The par t i es br i ef ed t he f eder al pr eempt i on i ssue i n

t he di st r i ct cour t . On appeal , For est r epeat s t hat argument ,

ur gi ng t hat we may af f i r m on t hat gr ound. Pl ai nt i f f s i n r esponse

concede t hat "unpacki ng how f eder al l aw i nt er act s wi t h st at e l aw i s

key" t o appl yi ng Cal i f or ni a' s saf e har bor doct r i ne. We agr ee. I t

t her ef or e makes mor e sense t o l ook f i r st at t hi s quest i on of

f eder al l aw r at her t han ski ppi ng f or war d t o f i gur i ng out - - or

cer t i f yi ng t o Cal i f or ni a' s Supr eme Cour t - - t he quest i on of whet her

Cal i f or ni a' s saf e har bor doct r i ne woul d shi el d For est even i f

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f eder al l aw di d not pr eempt t he Cal i f or ni a consumer pr ot ect i on

cl ai ms. 2

B.

The Uni t ed St at es Const i t ut i on' s Supremacy Cl ause

pr ovi des t hat f eder al l aw "shal l be t he supr eme Law of t he Land;

. . . any Thi ng i n t he Const i t ut i on or Laws of any stat e t o t he

Cont r ar y not wi t hst andi ng. " U. S. Const . , ar t . VI , cl . 2. Wher e

st at e l aw r equi r es a pr i vat e par t y t o vi ol at e f eder al l aw, t hat

st at e l aw i s "wi t hout ef f ect . " Bar t l et t , 133 S. Ct . at 247677

( i nt er nal quot at i on mar ks omi t t ed) . Feder al l aw i mpl i edl y pr eempt s

st at e l aw "wher e i t i s ' i mpossi bl e f or a pr i vat e par t y t o compl y

wi t h bot h st at e and f eder al r equi r ement s. ' " I d. ( quot i ng Engl i sh

v. Gen. El ec. Co. , 496 U. S. 72, 79 ( 1990) ) ; see al so Frei ght l i ner

Cor p. v. Myr i ck, 514 U. S. 280, 287 ( 1995) ( not i ng t hat conf l i ct

pr e- empt i on al so appl i es " wher e st at e l aw st ands as an obst acl e t o

2 I nexpl i cabl y, pl ai nt i f f s announced i n t hei r r epl y t hat t heydi d not have enough pages t o addr ess t he i ssue even t hough Forestpr oper l y r ai sed i t as an al t er nat i ve gr ound f or af f i r mance. Andi nst ead of aski ng f or a page ext ensi on, t hey pr esumed that we woul dei t her i gnor e t he i ssue, or post pone t he case t o sol i ci t mor ebr i ef i ng. We f ol l ow i nst ead t he nor mal cour se of not al l owi ng apar t y t o uni l at er al l y di ct at e a change i n cust omar y pr act i ce. We

al so not e t hat pl ai nt i f f s hedged t hei r bet , devot i ng t wo pages oft hei r r epl y br i ef t o an expr ess di scussi on of t he pr eempt i ondef ense, and anot her f our pages t o di scussi ng t he pi vot alpr eempt i on case, Wyet h v. Levi ne, 555 U. S. 555 ( 2009) . Fi nal l y, wehave r evi ewed t he f ul l br i ef on t he pr eempt i on i ssue f i l ed bypl ai nt i f f s wi t h t he di st r i ct cour t , and we addr essed t he i ssue wi t hcounsel at oral argument .

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t he accompl i shment and execut i on of t he f ul l pur poses and

obj ect i ves of Congr ess" ( i nt er nal quot at i on mar ks omi t t ed) ) .

Pl ai nt i f f s' compl ai nt seeks t o i mpose l i abi l i t y on For est

because of what Lexapr o' s FDA- appr oved l abel st ates or f ai l s t o

st at e. I n ot her wor ds, as t he compl ai nt r eads, For est woul d need

t o change Lexapr o' s l abel i n or der t o avoi d l i abi l i t y under st at e

l aw.

I n t wo r ecent cases, t he Supreme Cour t has addressed how

pr i nci pl es of f eder al pr eempt i on appl y t o such cl ai ms. See PLI VA,

131 S. Ct . 2567 ( 2011) ; Wyet h v. Levi ne, 555 U. S. 555 ( 2009) . We

t ur n to t hese opi ni ons t o f i nd the pr eempt i on r ul es t hat gui de our

deci si on her e.

I n Wyet h, a j ury f ound a brand name dr ug manuf act urer

l i abl e under Vermont l aw f or what t he j ur ors deemed t o be an

i nadequat e war ni ng of r i sks i n an FDA- appr oved l abel . 555 U. S. at

558. I n r ej ect i ng t he manuf act ur er ' s pr eempt i on def ense t o

l i abi l i t y under Ver mont l aw, t he Cour t poi nt ed t o t he CBE

r egul at i on, "whi ch bot h r ef l ect s t he manuf act ur er ' s ul t i mat e

r esponsi bi l i t y f or i t s l abel and pr ovi des a mechani sm f or addi ng

saf et y i nf or mat i on t o t he l abel pr i or t o FDA appr oval . " I d. at

571. "Thus, when t he r i sk . . . became apparent , Wyet h had a dut y

[ under f eder al l aw] t o pr ovi de a warni ng t hat adequat el y descr i bed

t hat r i sk, and t he CBE r egul at i on per mi t t ed i t t o pr ovi de such a

war ni ng bef or e r ecei vi ng t he FDA' s appr oval . " I d. Based on t hese

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obser vat i ons, t he Cour t f ound t hat a st at e l aw ef f ect i vel y

penal i zi ng t he manuf act ur er f or not havi ng exer ci sed i t s f eder al l y

sanct i oned abi l i t y t o i mpr ove t he l abel under t he CBE r egul at i on

was not preempt ed. I d. at 581.

Two years l at er , t he Supreme Cour t di st i ngui shed Wyet h i n

sust ai ni ng a pr eempt i on bar t o t he i mposi t i on of t or t l i abi l i t y on

a gener i c dr ug manuf act ur er f or f ai l ur e t o add a war ni ng of a r i sk

t o i t s l abel . PLI VA, 131 S. Ct . at 2581. The cour t obser ved t wo

di f f er ences i n t he f eder al "dr ug l abel i ng dut i es" t hat appl i ed t o

gener i c manuf act urers as compar ed t o brand name manuf act urer s. I d.

at 2574. Fi r st , a gener i c manuf act ur er "i s r esponsi bl e f or

ensur i ng t hat i t s war ni ng l abel i s t he same as t he br and name' s. "

I d. Second, " t he CBE pr ocess was not open t o [ gener i c

manuf act ur er s] . " I d. at 2575. Ther ef or e, t he gener i c dr ug

manuf actur er i n PLI VA coul d not have changed i t s l abel wi t hout

pr i or FDA appr oval , whi ch i t coul d onl y have obt ai ned by pr oposi ng

t hat t he FDA r equi r e a change i n t he cor r espondi ng br and name

l abel . I d. at 2576. Assumi ng t hat the manuf actur er had a dut y

under f eder al l aw t o make such a pr oposal , t he Cour t never t hel ess

f ound t hat t he possi bi l i t y t hat t he FDA woul d have agr eed t o

r equi r e such a change di d not pr ecl ude t he cour t f r om concl udi ng

t hat compl i ance wi t h both st at e and f eder al br andi ng r equi r ement s

was i mpossi bl e. I mpor t ant l y f or our pur poses, t he Cour t expl ai ned

t hat "[ t ] he quest i on f or ' i mpossi bi l i t y' i s whet her t he pr i vat e

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par t y coul d i ndependent l y do under f eder al l aw what st ate l aw

r equi r es of i t . " I d. at 2579 ( ci t i ng Wyet h, 555 U. S. at 573) . The

Cour t t hus l i mi t ed Wyet h to si t uat i ons i n whi ch t he dr ug

manuf act ur er can, "of i t s own vol i t i on, . . . st r engt hen i t s l abel

i n compl i ance wi t h i t s st at e t or t dut y. " PLI VA, 131 S. Ct . at

2581. 3

The l i ne Wyet h and PLI VA t hus draw bet ween changes t hat

can be i ndependent l y made usi ng t he CBE regul at i on and changes t hat

r equi r e pr i or FDA appr oval al so makes some pr agmat i c sense. CBE

changes r est on t he exi st ence of "newl y acqui r ed i nf or mat i on. " 21

C. F. R. 314. 70( c)( 6) ( i i i ) . A st at e l aw dut y t o i ni t i at e such a

change i s t her ef ore not by i t s nat ur e a second guess of an FDA

j udgment . Wyet h, 555 U. S. at 57879. To t he ext ent t hat t he

under l yi ng pol i cy i ssue i s one of who deci des whet her and how a

dr ug can be marketed, t he l i ne so dr awn l et s t he FDA be the

excl usi ve j udge of saf et y and ef f i cacy based on i nf or mat i on

avai l abl e at t he commencement of market i ng, whi l e al l owi ng t he

st ates t o reach cont r ary concl usi ons when new i nf ormat i on not

3 Most r ecent l y, i n Bar t l et t , 133 S. Ct . at 2478, t he Supr emeCour t r ever sed a deci si on of t hi s ci r cui t i n whi ch we r ej ect ed apreempt i on def ense because t he gener i c dr ug manuf act urer coul d have

compl i ed wi t h bot h f eder al and st at e l aw si mpl y by not sel l i ng t hedr ug f or use i n t hat st ate. The Supr eme Cour t r easoned t hat " anact or seeki ng t o sat i sf y bot h hi s f eder al - and st at e- l awobl i gat i ons i s not r equi r ed t o cease act i ng al t oget her i n or der t oavoi d l i abi l i t y. " I d. at 2477. "To hol d ot her wi se woul d r enderi mpossi bi l i t y pr eempt i on ' al l but meani ngl ess. ' " I d. at 2477 n. 3( quot i ng PLI VA, 131 S. Ct . at 2579) .

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consi der ed by t he FDA devel ops. The CBE r egul at i on, t oo, cover s

vi r t ual l y al l si t uat i ons i n whi ch new i nf or mat i on i ndi cat es new or

gr eat er r i sks, or mi sl eadi ng cl ai ms of ef f i cacy. By hi ngi ng

pr eempt i on on t he avai l abi l i t y of t hat pr ocedur e i n a par t i cul ar

case, Wyet h ef f ect i vel y reserves t he l aunch of new dr ugs t o the

exper t i se of t he FDA, but t hen pr eserves a wi de scope f or t he

st at es i n r equi r i ng manuf act ur er s t o r espond t o i nf ormat i on not

consi der ed by the FDA. 4

Our r evi ew of t he Supr eme Cour t opi ni ons di scussed above

makes cl ear t hat a necessar y st ep i n def eat i ng For est ' s preempt i on

def ense i s t o est abl i sh t hat t he compl ai nt al l eges a l abel i ng

def i ci ency that For est coul d have cor r ect ed usi ng t he CBE

r egul at i on. The compl ai nt pl ai nl y al l eges t hat For est i s a br and

name manuf act urer and Lexapr o i s a brand name drug. So t he

quest i on t o whi ch we now t ur n i s whet her t he CBE regul at i on al l ows

a br and name manuf act urer t o make t he par t i cul ar t ype of change

t hat pl ai nt i f f s say For est needed t o have made t o avoi d l i abi l i t y

under Cal i f or ni a l aw.

C.

The CBE procedure i s onl y avai l abl e t o make changes t hat ,

among other t hi ngs, are based on "newl y acqui r ed i nf ormat i on. " 21

C. F. R. 314. 70( c) ( 6) ( i i i ) .

4 Of cour se, i t woul d be easi er f or t he cour t s i f Congr esswoul d expr essl y i ndi cat e whet her t hi s i s t he l i ne i t want s dr awn.

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pl acebo. As pl ai nt i f f s' compl ai nt acknowl edges, i t cont ai ns no

di scussi on of ef f i cacy f or t he acut e t r eat ment of maj or depr essi ve

di sor der s i n adol escent s, f ocusi ng i nst ead on t he l ack of appar ent

ef f i cacy f or pat i ent s gener al l y when sympt oms of depr essi on are not

sever e. I n shor t , even assumi ng i t qual i f i es as "newl y acqui r ed

i nf or mat i on, " i t does not cont ai n t he i nf or mat i on t hat pl ai nt i f f s

say needs t o be added t o t he l abel i n or der t o cor r ect t he l abel ' s

di scussi on of ef f i cacy f or t r eat ment of maj or depr essi ve di sor der

i n adol escent s.

The second i s a 2011 ar t i cl e cr i t i ci zi ng t he FDA' s

appr oval of Lexapr o. Thi s st udy i s an opi ni on pi ece i n whi ch t he

aut hor l ooks at t he same i nf ormat i on t hat t he FDA had i n appr ovi ng

Lexapr o. I t si mpl y argues t hat t he FDA shoul d not have appr oved

Lexapr o on t he basi s of t hat i nf or mat i on. As descr i bed by t he

compl ai nt , t he onl y pi ece of r el evant i nf or mat i on i n t he ar t i cl e i s

an asser t i on t hat a medi cal communi cat i on company act i ng on behal f

of For est was a cont r i but or t o t he publ i shed ar t i cl e di scussi ng

Lexapr o St udy 32. Pl ai nt i f f s do not ar gue, however , t hat t he FDA

was unawar e of t hi s f act, or t hat For est i s l i abl e f or f ai l i ng t o

seek a change addi ng t hi s f act t o t he l abel . Rat her , pl ai nt i f f s

argue t hat t hi s f act means t hat FDA appr oval of Lexapr o was

premat ure. 5

5 We not e al so t hat nei t her ar t i cl e di scl oses "r i sks of adi f f er ent t ype or gr eat er sever i t y or f r equency t han pr evi ousl yi ncl uded i n submi ssi ons t o [ t he] FDA. " 21 C. F. R. 314. 3; see al so

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We have al so exami ned t he compl ai nt ' s al l egat i ons

cl ai mi ng t hat t he posi t i ve st at i st i cal ef f i cacy r esul t s of Cel exa

St udy 18 hi nged i n par t on t he i nappr opr i at e i ncl usi on of some

subj ect s i n t he dat a pool . 6 Thi s i s t he basi s of pl ai nt i f f s '

al l egat i on t hat Cel exa St udy 18 was "mani pul at ed. " Pl ai nt i f f s make

no cl ai m, however , t hat t hi s i nf ormat i on was unknown t o t he FDA

pr i or t o l abel appr oval .

Fi nal l y, or al ar gument conf i r med t hat t he change

pl ai nt i f f s seek i n t he l abel i s i ndeed based on i nf or mat i on

concer ni ng t he mar gi nal ext ent of Lexapr o' s ef f ect i veness t hat was

pl ai nl y known t o the FDA pr i or t o appr ovi ng t he l abel :

Court: What speci f i c st atement do you say t hatFor est shoul d have added t o i t s descr i pt i on oft he dr ug?

i d. 314. 70(c ) ( 6) ( i i i ) .

6 Accor di ng t o t he compl ai nt :

Dur i ng t he st udy, t he f i r st ni ne ( 9) par t i ci pant s wer egi ven ' 1 week of medi cat i on wi t h pot ent i al l y unbl i ndi ngi nf or mat i on ( t abl et s had an i ncor r ect col or coat i ng) . 'When t he data f or Cel exa St udy 18 was f i r st anal yzed, t her esear cher s cor r ect l y excl uded t he dat a f r om t heunbl i nded par t i ci pant s, r eal i zi ng i t was unr el i abl e. Ther esul t s of t he i ni t i al stat i st i cal anal ysi s showed . . .[ t hat ] Cel exa St udy 18 was negat i ve f or ef f i cacy.However , f aced wi t h havi ng a cl i ni cal t r i al show t hat

Cel exa f ai l ed t o si gni f i cant l y out per f or m pl acebo f ort r eat i ng pedi at r i c depr essi on, t he r esear cher s deci ded t oi ncl ude t he dat a f r om t he unbl i nded par t i ci pant s. Byaddi ng t he unbl i nded pat i ent s' dat a, Cel exa St udy 18 wasabl e t o f i nd st at i st i cal si gni f i cance bet ween t het r eat ment and pl acebo- cont r ol gr oup- - even i f onl ymargi nal .

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Plaintiffs' counsel: I bel i eve t he dr ug l abel. . . shoul d have di scl osed how Lexapr oper f or med compar ed to pl acebo.

. . . .

Plaintiffs' counsel: . . . We ar e not t r yi ngt o cont r adi ct t he i nf or mat i on on t he l abel .. . . We ar e si mpl y havi ng t hem say . . .[ Lexapr o] has been shown t o be ef f ect i ve i n acl i ni cal t r i al by one poi nt . The di f f er encebet ween [ Lexapr o] and a pl acebo i s cl i ni cal l yi nsi gni f i cant . Meani ng a pat i ent , a doct or ,woul dn' t be abl e t o t el l t he di f f er ence.

Court: But t hat "by one poi nt " - - t hat was knownt o the FDA at t he t i me of t he appr oval ?

Plaintiffs' counsel: Absol ut el y.

We can f i nd no pr ecedent - - and pl ai nt i f f s poi nt t o none- -

t hat woul d have al l owed Forest t o use t he CBE pr ocedur e t o al t er

t he FDA l abel i n t he manner t hat pl ai nt i f f s al l ege i s necessary so

as t o r ender i t not "mi sl eadi ng. " I ndeed, pl ai nt i f f s seem t o

concede t hi s i n t hei r pr ayer f or r el i ef , as t hey ask t he Cour t t o

"di r ect [ ] For est t o seek FDA appr oval of a new [ dr ug] l abel . "

Pl ai nt i f f s ar e t hus st ymi ed: For est coul d not

i ndependent l y change i t s l abel t o r ead as pl ai nt i f f s say i t shoul d

have r ead i n or der t o compl y wi t h Cal i f or ni a l aw. That

const r uct i on of Cal i f or ni a l aw upon whi ch pl ai nt i f f s r el y- - even

assumi ng i t i s cor r ect not wi t hst andi ng t he saf e har bor doct r i ne- - i s

t her ef or e pr eempt ed by f eder al l aw. PLI VA, 131 S. Ct . at 2581.

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IV. Conclusion

Fi ndi ng pl ai nt i f f s' cl ai ms pr eempt ed by the FDCA, we

af f i r m t he di str i ct cour t ' s gr ant of For est ' s mot i on t o di smi ss.

So order ed.

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