05/06/20ll

SEE REVERSE
OF THIS PAGE Zache1y
I I'JJA
(b) (4)
HEALTH AND HUMAi\'
D DRUG ADMIN! STRATJON
- 05/06/2011
vi ce Pre.sider'lt
Boul eva.rd
Broomfield CO
This document lists observmions made by. the FDA during the inspection ofyom facility. They are inspcctional
observati ons, and do Jloi represent a iinal Agency determination regaiding your compliance. If yon have an regarding an
observation, or hnve implemented, or plan to implement. corn:ctive action in response to an observation, you may the oqjection or
action with tht: FDA representntive(s) dlll'ing the inspection or submi l this information to FDA at the add ress above. If you have any
questions, please contact FDA al the phone number and address above.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:
OBSERVATION 1
Control procedures are not established which vaiidate the performance of those manufactnring processes that may be
responsible for causing variability in the characteristics of in-process material and the drug product.
Specifically,
L
(b) (4)
(b) (4)
I blenders, were used
jnterchangeab1y for the production of Triamtererre and Hvdr ochlorothiazide (50/25_LCapsules between

(b) (4)
(b) (4)
Blenders
(b) (4)
re identical in the- construction. Blende1 used for the
(b) (4)
process validation of Triamterene and Hydrochlorothiazide (50/25) Capsules. BlenderO .'as
equipped with a
(b) (4)
was removed for the roduction of
,
:
Triamterene and Hydrochlorothiazide (:50/25) Capsules, leaving . .

(b) (4)
'The average finished product dissolutio11 history documented a
downward trend for Triamterene and Hydrochloiothiazide (50/25) Capsules deviutiun # 1 0-0065, .
(b)
dated 02/11/2010, and was attributed by the firm as being "directly associated witb the use of blender
(4)
based on review of product history." "It is suspected that the blencting of i material is
optimizec} with the use ofblendeJD
(b)
rhich does not have the
(b) (4)
. In 2007,
(4)
(b) (4)
blende1
(b) (4)
was removed from service. Blender - were used interchangea 1998-
2007 without any form of process validation for the productioi1 of Triamterene and Hydrochlorothiazide
(50/25) Capsules with blender
(b)
(4)
Currently manufactured products blended with blenders that ' :vere not' validated for the product during
process validation include:
SEE REVERSE
a OF THIS PAGE
SIGNATURE
Er ika V. But ler , Investigator , .,_ .
I<: imbel-ley A. Hoefen , Investigator of}:>r-\
Zachery L. Mil ler,
0 5 /06/2011
DATEJSSU;:O
JNSPeCTJO!\AL OBSER\ ATIONS __ .. _______ ._. _. - ..:. I',;,;AGE l OFY I'AGES--
.,
(b) (4)
J_:..:...:.:..:..::..:..!:.=::.:::.:..:.::....:_ _ __ ,.,.. __ ... - ...,... _ .. ... -- -
- ------- - -----------

x:.rr---
DEPART/I'IEIW OF HEALTB AND HUMAr\ SEHVi CE.S . !
FOOD AND DRUG ADJvi!NtSTRATIOl'
I OAE(SJ INSPECTION j
5th r,, Kipling st . (P.O. Box 250 87 ) - 05 / 06/2011
Denver, CO 80225-00 87 j .dhUMBi:R li-
DJSTAI:;i AODP.ESS AND NUMBER
( 3 b 3) 2 3 6- 3 0 0 0 Fax: ( 3 0 3) 2 3 6- 3 1 0 0 ' l 7l 7 7 59
: I ndust ::-y Information: www.da. gov / oc/ i ndust ry

' TO : Gaspar . p._. Zunga .. Vice Pr esident: of TechnicEl.l Opel-a-ci on.s
fiP.MNf\Mi:. STRE:T ADDRESS
Sandoz ________________ -il
CITY, STATE, Zl? CODE, COUNTRY TYP::: ESTABliSHMENT
Broomfiel d, CO 80020-1632 Drug Manuf actu::er

)
This is a repeat observation from the 5/28/2010 FDA inspection.
OBSERVATION 2
Investigations of an unexplained discrepancy di d not extend to other batches of the same drug product and other drug
products that may have been associated with the specific fai lure or discrepancy.
Specifically,
14 out of 79 (18%) laboratory investigations (LBINV) lacked documentati on of an investigation into
other batches or products or the estabiishment of a corrective action:
a) In-process specification for blend uniformity was not met for validated processes, incl uding:
wu; /f./.
Kipling St. (P.O. Box 25087)
80225-0087
Fax: (303) 236-3100
ViV.,TW. fda.
Vice Presi
ted
co 80020-1632
04
1717759
of rations
Boulevard
l\1anufacturer
011
SEE REVERSE
OF THIS [>AGE
Erika V. Butler, Investigator
Kimberley A. Hoe:Een, Investigator
Zacl1ery L. Miller, Investigator
~ ~ ~ - ~ -
i.'
05/06/2011
- - - - ~ - - ~ - - ~ ~ ~ ~
SEE REVERSE
. OF THIS PAGE
EMPLOYi:C:(SJ SIGNATUR;
Erika V. Investigator
Kimber l ey A. Hoefen,
Zacher y L. Mi l ler, Investigator
l'it!:Vidus Euni0i{01JSOLUT.
I .. -ololat.WI .
DATCtSSVEO
05/06/2011
(b) (4)
(b) (4)
APl identity out of specifications for
(

(
03/ 15/201 1 and finished product related compound
__ J
on 12/07/2011 '"'ere rerun without the establishment of root cause 0._1 __ -co- I-.1.e - -ct...,i_v_e_a_c_tl.,... o_. ns.
t _.....,_ -- OF HEALTH AND SERV!CEsu -
i FOOD AND DRU(i ADMINlSTRATIU!'\
' OISTRlCT ADDRESS AND Pt-K>N: I\1JMBR
6th & Kipl ing St. (P.O. Box 25087 )
Denver, CO 80 225-0087
(303) 23 6 -30 00 Fax: {30 3) 236 -3100
DATE(SI 0" INSPECTION
04/19/2011 - 05 /06/ 2011
FC:INUMBEP.
1717759
::!::1dustry I rtforma'.: ion: www. fda. gov f oe/industry
i NAM!:. AND TITL:: OF INOfVIOUAl. 10 WtiOM REPOP.T SUED
TO: Gaspa r "P.. Zunga , Vice ?residen:. of Technical Operations
Sandoz Incorporated
CITY. STATE. ZIP CODE. COUNTRY
Broomfield, CO 8002.0 - 1 632
I STREET AOOr<ESS
i 2535 vJest Midw;:..y Boulevard
., . TYPE E:STA13LtGI-tM::NT 1NSPEG1ED
Drug l'1anufacturer
=
-,
c) The purified water in the laboratory failed specification for microbiology testing on 02/07/201 1
(b) (4) (b) (4)
for \Vater sampling point on 02/14/201 1 for water sampllng pointc=J Q.u_Q2/22/20 11
(b) (4)
(b) (4)
for water sampling point and on 03/07/201 1 for water sampling point! JTb.e
laboratory investigation stated that "the assignable cause is biological contamination due to
stagnation of water in a DOn-circulating branch of the water system." "Laboratory water is not a
product ingredient and does not affect product quality." Each time the problem was fixed with
flushing of the system and retesting. Investigations were not performed on any impact the purified
water might have had on the laboratory tests performed between the previous check and the one that
was out of specification.
This is a repeat from the 5/28/2010 FDA inspection.
OBSERVATION 3
The quality control unit lacks authority to fully investigate errors that have occurred.
Specifically,
a) On 6/30/2010, a report was received from your contract packager that black specks were
observed on tablets while blister packaging Loratadine 10 mg batches j 95524, 195525 and
195529. Yom investigati on found an
11
excess amount of the acti ve" present in the extracted dark
particles. The Quality Assurance evaluation concluded the dark spots are characteristic of the
material and closed the investigation on 7/9/201 0. There '"'as no investigation as to the potency
or purity of the speckled tablets or if they would pose harm to the consumer. The finished
product lots were released and distributed.

,
(b) (4)
(b) (4)
b) On 04/19/2011 the ocated in suite was "On Hold" as noted in the
E Use and Cleaning Log for
11
011 hold for rust and paint bubble. Previously

(b) (4)
investigation was not performed to evaluate any
impact on previously run drug products.
(b) (4) (b) (4)
(b) (4)
DEPARTMENT OF
F()OLJ AN
(P.O. Box 25087)
o::: / indust
, . Vic?. President o
Broomfield, CO 80020 - 1632.
- 05 / 06/2011
Boulevard
SEE REVERSE
OF THIS PAGE
Erika V. Butler, I nvestigator
Kimberl ey P,_. Hoe:Een, I nv e stigator
Zachery L. rhl ler, Investigator
05/06/2011
OBSERVATION 4
and utensils are not cleaned and sanitized at appropriate intervals to prevent contamination that would alter the
safety, identity, strength, qLtality or purity of the drug product.
Specifically,
Equipment was observed not clean and in sanitary condition. Below is a list of the unclean equipment
observed:
'
(b) (4) Complete Clean accompiished and
verified, equipment is on hold status.
Complete Clean accompli shed and
verified, ready to use.
Diclofenac 75 mg Tablets_ Batch
(b) (4)
- was c;ated pri;r to the
complete clean.
Observed a thick (approximate l inch) build-up of pink Complete Clean accomplished and
coating material adhering to the exhaust bypass vaives.
Exhaust valve is located within the confines of the
verified, ready to use. Diclofenac 75
(b) (4)
mgT ablets, Batch
porous coating pan. coated prior to the
(b) (4)
Observed Kettle a parts cart had incorrect Room labeled "Complete Clean," on
status labeling, indicating "in:.process" instead ofthe 4/25/11.
"complete clean" performed status.
Observed a cleaned processing hose return line stored on
the floor after "complete clean" had been performed.
Hose transfers coating material from mixer into the
tablet coater
Observed a dirty cloth wipe underneath the tablet coater
after the room had been labeled, "complete clean."
DE!'ARTJ\IE!'\T OF HEALTH AND HUMAl\' SERVICES
I FOOD AND DIWG ADMINISTRATION
1
CIS 1 RICT ADDRESS'AI\!D PHONE NUM!ER l OATE.(SJ Of= 11 \!SPi:. CTION
6th 0: Kipl i ng St . (P.O. Box 2 5 0 87) i 04/19 / 20l l - 05/06 / 2 011
Denver, co 80225- 0087
. I FEI N'JI.iiEP. I
(303) 236 -3 000 Fa ): : ( 3 03) 236 - 31 00 1 717759
I ndustry Information: wwv1. fda . gov /oc/industr:y
, AND OF INDIVIDUAL TO WHOM ISSUED
TO : G.p.spar _.h.. Zunga , Vi ce Pr esident of Technical Operat ions
FIRM NAJ<. E I sr?.=Er )
Sandoz I ncorporated
2555 West l
1
1idway Boulevard
(
CITY. S1 ATE, ZIP coo=. COUNTRI' I T:PE '
Broomfield, co 8 0020- 1 632 Drug f\1anur
l
i
OBSERVATION 5
l
An NDA-Field Alert Report was not submitted within three working days of receipt of information concerning signi ficant
chemi cal , physical, or other change or deterioration in a distributed drug product.
:
Specifically,
On 12/29/201 0, your firm received a complaint from a pharmacist who reported finding a
Methazolamide 50 mg tablet (batch number 191103 2 that appeared to look "twice as large as the others.
1
'
(b) (4)
Your investigation found the weigl: edl . "' . .
(b) (4)

(b) (4)
ilirn the targeted
tablet weight ofl jrl11S exceeaed your upper specmcCl.t10n lnmt of grams. The FDA
Denver District was not notified of this out of specification.
!
E
OBSERVATiON 6
l
Not all adverse drug experiences that are both serious and unexpected have been reported to FDA within 15 calendar days of
initial receipt of the information.
Speciftcally, - - .
-
Since 1 0/2008 until 04/1512010, there were 6082 Serious and Unlisted Adverse Drug Experience Ale1i
Reports submitted to FDA by your firm, of which 116 were not submitted in a timel y manner. For
example the foll owing is a list of ADE reports submitted past the 15 day time frame:
I
'
Case Number Product Day Submitted to Manufacture Number of days
FDA Receipt date of Late to FDA
ADE
GXKR2009GB 12154 Citalopram/Lamotringine I 1/ 11/2010 11/4/2009 53
CHNY2008GBOI J 14 Ibuprofen 3/1 9/2010 3/3/2008 731
GXKR2009GB07550 Omeprazole 3/30/20 I 0 7/1 /2009 257
I
GXKR201 0USI 0030 Carisoprodol 10/25/2010 9/3/201 0 37
This is a repeat obsen'ation from the 10/08/2008 FDA inspection.
SIGfo/A7URf
g t--.(;{_t"--
OAT!: ISSUED
Erika. v. But le:::-, Investigator
SEE REVERSE Kimberley 1' . Hoef en, Inves tigator
\!);, \J,
O(THIS PAGE Zachery L . Mi l l er ,
05 / 06/ 2011 ' '
-----
I
/
.. .. r mx <o9TORJ
..
rP.ovu;,us r.orntr.< INSPECf!O!':AL OBSERVATIO!I:S- _,, M > ' ' ..
. -... .
w ""//.
DEPAHTi'I'IENT OF HEALTH AN
FOOD AND DRUG /\Divil
( P . 0 _ Box. 2 5 0 8 7 )
Vice President of
05 /06 2011
Boulevard
Broomfield co 80020- 1632
TION 7
Equipment used in the manufacture, processing, packing or holding of drug products is not of appropriate design to fac ilitate
operations for its cleaning and inaintenance.
Specifically, observed. the following equipment not maintained.
.. , : , ...
(b) (4) Observed too numerous to count Complete Clean accompl ished and verified,
ready for use.
metal lters in disrepair, j agged
stl'ands protruding from filtering surface.
Complete Clean accomplished and verified.
Previous! ' run procluct was Orphenadrine, lot#
(b) (4)
This is a r(;! eat observation from the 5/28/2010 FDA ins ou.
OBSERVATION 8
Buildings used in the manufacture, processing, packing or hol ding of drug products are not maintained in a clean and sanitary
condition.
Specifically,
Multiple production rooms were observed not clean and in sanitary condition after a "Complete Clean"
was accomplished and verified, including:
! 0
. '
(b) (4)
Observed a used pipe seal, and piece a paper
approximately 2 X 2 inches located underneath a vertical
"Complete Clean," on
mixer after coinplete clean. 4/2511 1.
Observed a pool of standing water on the fioor, directly
under mixer and below mixer outlet contained within an
2 X 2 foot fl oor stain.
(b) (4) Observed a nest of packaging
(b) (4)
debris undemeath
SEE REVERSE
OF THIS PAGE
Erika V. Butler, Investigator
Kimberley A. Hoefen, Investigator
Zachery L. Mil ler , Investigat
' i'fii::VIOU3 EfJITIO:o: OUSOl=lE
05 /06 / 2011
!'AGE 7..0f
- ---------
6t- & ..... . . Box ::> I} 4
i
l _
- 5/06 2011
Denver, co 80225-0087
I FEINUMilER
I
(303) 236 - 3000 Fax: (303) 236 -3100 1 71 775 9
Industry I nformation: vJWV.. fda. gov / oc/ industry-.
. '
NAM:. AND TITLE INDIVI DUA!. TO WliOM REPORT ISSV::C.
'
'
TO: Gaspar A. Zunga, Vi ce Pres ident of 'l'echni cel Ope!a t: ior"s
FlRMNAN.:.
I t
Sandoz Incorporated rHdv1ay Bouleve.rd
CITY, STA E. Z.IP COO;, COUNTRY ' ' ' ! f)'PE
I
:Sroomfi eld, co 80020 - 1632 j Drug !'1anu:Eacturer
'
components- cleaned weekly. 4/26/ ll .
(b) (4)
Observed plastic packaging debris throughout. Room labeled,
"Complete Clean," on
;
Observed clumped debri s (approximate Y:, inch in si ze) 4/26/11.
along NE corner of room.
i
Observed a dirt/rust rype substance, covering a 2 inch

sg_uare surface on the floor, in the NE corner ofrocnn.
I
I
.I
OBSERVATION 9
Deviations from written laboratory mechanisms are not recorded.

Specifically,
(b) (4)
Standards requiring storage at - emperature were not documented to be returned on the day of
analysis between 2010-2010.

(b) (4) 09/30/2010 I Not listed
I
I
10/07/2010
I0/22i201 0
11 /29/2010
Not listed
I
Not listed
Not li sted
I 1/2912010 Not listed
11 /29/2010
I
Not listed
I
l
12/01/20 l 0 Not listed
I
12/01/2010 Not listed
12/16/2010 Not listed
12/ 16/20 10 Not listed
0 Ill 1/2011 Not li sted
Ol /20/2011 Not listed
02/15/201 1 Not listed
02/15/201 1 Not listed
02/24/201 J Not listed
02/21/2011 04/18/2011
.. ---

-
--
I
E.MPLOYE(Si
--1/.
DATE ISSUED
Eri ka v . Butler, Investigator
SEE REVERSE Kimber l ey A. Hoe fen, Investigator
i-\
05/06/2011
OF THIS PAGE zache:ry L. Miller,

I
I I

. -. . '
JIH!:VIOCS f!t>ll'IOP: ' . I NSJ'CCTIONAI.. OBSERVATIONS

- ,. .. .
- !'AGE t .OF !'.\G!!S .
--
(b) (4)
02/24/20 I I Not listed
03/03/20 J J Not listed
0 3/1 4/20 I J Not listed
04/07/201 I
04/J 3/20 I I
No! listed
I 04/1 4/2011
DEPARTivlENT OF HEALTH AND m JMAN SEHVICS
FOOD AND DRU(i ADMINiSTRATION
OtSTRICT AOORESS AND NUMBER Dl,TE<SJ INS>ECTION
6th &: Kipling st. (P.O; Box 25 087) 04 / 19/ 2011 - 05/06/2011
Denver , co 80225-0087
i=CI NUJABER
(303) 236 - 3000 Fa):: ( 3 03) 236 - 3100
11717759
'
Indus try I nformat ion: www. fda.gov/oc/ indus try
1
NAV.E AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED
TO : Gaspar
_1.>,. _ Zun ga, Vice President of Teclu1ical
! STREC:T ADDRESS
I
, Sa11doz Incorpo ra. t ed
I
2555 West Boul evard
CtTl'. ZIP Coo:. COUNTR\' I INSPECTED .
;
. Br oomfield, co 80020 - 1632 Drug Manufacturer
OBSERVATION "i O
.
Established laboratory control mechanisms are not followed .
S pecifi call y,
SOP MATA008 "Laboratory Reference Stru1dards", revision 09, validity date 08/30/2010, was not
foll()wed in that there ,;o,,as no documentation for:
(b) (4)
OBSERVATiON 'I 1
-
.. _
...
-
..
. -- -
...
There is a lack of rotation so that the oldest approved stock of components is used first.
Specifically,
l
(b) (4)
For at least two producti ons of metformin tablets 1. multiple older lots of
metformin API
(b) (4)
lwere available for use
and a newer lot of APl l
(b) (4)
I was selected by warehouse personnel to send to production.
EMptOYEE(S) SIGNATURE
v: [Jdffi___
Dlo.I: ISSUEO
Erika v. But ler, Investigator
,t"
\' \
\ \
tJ {; .; (./(\
SEE REVERSE Ki mberley Jo . Hoe fen , Invest igator
05/06/ 20ll
OF THIS PAGE Zachery L. Miller , Investigator
I
/
- -I
FlM IS)'(U,/OS) rru::v10t.'S I:!Dinm: oosou;:rc- -
..
... !NSl'ECTIOI'\AL OBSERVATIONS. . .... . . . . ... ... . OF P .:\G!!S i
J
I
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