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_ .._ ,.__ · --- · A. --1 "~ _ _,, . , _:;.,,r ..-, ., _. ...._ ... . ..- . "'-----,, .. ~ .. ~--· ........_.._.-

DEPARTME~I OF HEAUH A'.\'D Hl:MAN SERVICES

FOOD A~D DRUG ADMl~ISTRATIO~
DISTRICT ADDRESS ANO PHONE NUMBER OATE(S) ~ INSPECTIOH

12420 Par kl awn Drive, Room 2032 6/ 3/ 2019- 6 /11/201 9*

FEI NUMBE R
Rockvil l e, MD 20857
3002809586

NAME AHO Tm.E OF INONIOUA.L. TO WHOM REPORT ISSUED

Pradipta K. Swain, Vice Preside nt of Operations

FIRM MAME STREET AOORESS

Sun Pha r mac eutic a l Indu stries Ltd . Hal ol - Baroda Highway
CITY. ST...TE. ZP COOE. COO>ITRY TYPE ESTA8USHMEHT INSPECTED

Ha l ol, Gu j ara t, 38 9350 I ndia Manu f acturer

This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional
observations. and do not represent a final Agency dete rmination regarding your compliance. Ifyou have an objection regarding an
observation, or have implemented, or plan to implement., corrective action in response to an observation, you may discuss the objection or
action with the FDA representative(s) during the inspection ·or submit this information to FDA at the address above. If you have any
questions, please contact FDA at the phone number and address above.

The observations noted in this Form FDA-483 are not an exhaustive listing ofobjectionable conditions. Under the law, your
firm is responsible for conducting internal self-audits to identify and correct any and all violations ofthe quality system
requirements.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

Production

OBSERVATION 1
Procedures designed to prevent microbiological contamination of drug products purporting to be sterile
are not followed.

The Aseptic Process Validation Master Plan was not followed during execution of media fill run~b><4>--i_

Specifically,

A mecr1a fi1II f a1·1ure on rme KbH4 >

or the > LH4
~esulted in media fill failure with overffi.yo media
batch contamination in the filled, incubated units. An investigation into the media fill failure determined that
several ' new' operations occurred during this media fill run. These included the following that were either not
recorded in detail as performed or not performed per written batch instructlons:

AM ENDMENT 1

SEE REVERSE
OF THIS PAG E
E"""-0V£EIS! lllGl<ATUAE

E'arhana Khan, Investi gator

Monica c Burgos Garc ia, I nvestigator
Kejun Cheng , E'DA Cente r Employee or
Employee o f Othe r Federal Agenc ies
12-~DS
)(
_
.............
...
~";.~-=-~',~••, ._,,,
~TE ISS<.ti>

6 / 11 / 2 0 19

Rebecca E Dombrows ki , f'IJA Center Emp l oyee /.Ze_r--chJ

o r Empl oyee of Othe r F'ederal Aqe n.:: i.es
FORM FD.\ 4J 1!111\1111 1·~ 1 \' ll•l ' I •J l l 1• ~· • .11:.t •1 1 ll l 'iSl't:<'l"ltl'i \I OOSt"lt\".U IO'.'iS P~G€ 1 of ~ P"G€S

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~
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DEPARTMENT OF llEALTll Ai'iD Ht:MAN SERVICES

FOOD AND DRUG ADMINISTRATION
DISTRICT AOOR£SSAHOPHOOE NUMllER 0Af'E(S) OF'INSP£vtevN

12420 Park lawn Drive, Room 2032 6/3/2019-6/ 11/2019*

..-• Rockville, MD 20857 F'EI NVM8€R
3002809586
.'
.. ~

, _E N<O nTlEOf INCMOUM. TO WHO.. REPORT ISSUED

·; Pradipta K. Swain, Vice President of Operation s
·.1
·: ~--
STREET ADDRESS

... Sun Pharmaceutical I ndustries Ltd .

CITY. STATE, ZIP COOE. COUNTRY
Halol - Baroda Highway
TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat, 389350 India Manufacturer

...,,
- Removal of the'<b><4> ' t he asept1ca
,to . . steri· 1e I~b><4>
. II y sea Ied tan k contammg ,media.

- Maintenance Activity to repair/reset the )<bJ<4 > of the filling station and
.. bevel gear due to reversal of~bH4> imovement resulting in intake of air instead of delivery of
..
•i
•I
media.

- Quality Assurance Impact Evaluation as part of the 'Breakdown Maintenance Report' regarding
·. the filling station reversal (Sr. No.[<b><
4
> )·

-
Laboratory

OBSERVATION 2
Established laboratory control mechanisms are not documented at the time of performance.

The assurance of the data from the all analytical testing data is not provided

Specifically,

Environmental monitori.ng of plates on June 5, 20 19 included review of more than ·::: sample sets. ln my review
of the data in support of the EM review, it was noted that in selected examples, the primary reviewer performed
the plate analysis almost 2 hours prior to the witness review. As explained by your EM QC staff and detailed in
wrinen procedure SOP QCM-042, the witness is to perform the witness review of the reading of the EM plates at
the same ti me as the pri mary review.

AM ENDMENT 1

SEE REVERSE
f.lriWlOY'f.f:(llil SfUMAfllf¥.

F'arhana Kha n, Investigator

1
-PVG>Dt~ e_ · 0.TE 1$$.JEO

6/ 11 /201 9
OF THIS PAGE Mo ni c a C Burg ~ s Garcia , I nvestigato r
Kejun Cheroq , E'DA Ce n ter l!:mµl o yee or
Employee o f Other Federal Agenc ies
)(
--
·---
r~M-21
~-z!~ 1:',;7i'..,. a u

Rebe cca E Don~ r ow ski , F'DA Center Empl o yee

o r f:J111.d o y.;;e of Ot 11.;,c fed.;.1 d l Ay .c:rh; l .:S
tOk M IOA .a.t •""\ii• t""l'\•·••• ••11> 1.u 11"-'""'""°'"'' '• l '\:Sl't:t "I'll>'\: \l Oll.'SUt\ .\ 110."S P."-GE : ol S PAGES
.
..~ DEPARTMENT OF llEALTll AND m;~L\l'\ SER\lCES
FOOD AND DRli G ADMINISTRATIOS
DISTRICT AOORESS ANO Pl<ONE NUMBER OATEfS) QF INSPE,_, "'"

1 2420 Parklawn Drive, Room 2032 6/3/20 19- 6/ 11 /2019 *

i Roc kvi l le , MD 2 08 57 FEl >IUMBEA
·.1
30 028 09 586

fri(AME AHO TlnE Ct: INONl'.>lW. TO WWOM REPOA:T ISSUEO

Pradipt a K. Swain, Vic e Pr esident of Ope rat ions

FIRM NAME STREET ADDRESS

Sun Pha r ma ceutical Indus t rie s Ltd. Halo ! - Ba roda Hi ghway

CITY, STATE. ZIPCOOE.CO~ TYPE ESTABLISHMENT IHSPECTEO

Halol , Guj a rat , 389350 Indi a Manu f acturer

For example, and as noted in the MODA system for EM data:

tt>l14l
a) sample plate l initial read/results entry: I 0:09:05, review: 12:05: 17
b) sample plate
t6){4) -.initial read/results entry: I0:09:05, review: I 2:05: 17

Device Observations

OBSERVATION 3
Design plans that describe or reference the des ign and development activities and define responsibility
for implementation have not been adequately established.

Specifically, your de~ign plan for ~b)( )

L 4
associated to <b>< > ·
4
__ (Injection, E_J <> pcg/mL, tbH4> mL & tbH4> mL
4

was approvea on M ay 20 t 9 . H owever, your hnn

- began the d es1gn
·
es
activities associated to this product on August 2012. Additionally, your firm did not have an established
device history file that demonstrated conformance to an established design plan.

OBSERVATION 4
A process whose results cannot be fully verified by subsequent inspection and test has not been
adequately validated according to established procedures.
[b){4)
Specifically, the requal ification of your (ma·? 41)) conduct.ed on 6.!:29 0 01 7_
under Protocol No.: QUA-S/0253 Requal ification Protocol/Report for1
<b><4> I(equipment ID:240) does not demonstrate tha·t the air supply, assemo1y air, and~

AMENDMENT 1

EMPLOVEEtl ) SIGNATORli
cp~_)[U!.' ()ATE """-EO

6 / 11 /2 019
SEE REVERSE Farhana Khan , Investigat o r
._ .....
OF THIS PAGE Moni c a C Burgos Garc ia , Investigator
Kejun Ch e ng , E'UA Center Empl o ye e or x
--·
~~~~·.~1a1u::o

Emp l o yee of Other f'ederal A<:Jenc ies Er"?:.1\..--y

Re becca E Dombrows ki , f'UA Cen t er Employee
o c E:1t.1; l ovee o f 01. r1er FaL!eral A..:i;:;n,~ 1 es
l."\Sl' H 'TIO.S \l llll:O.t It\'.\ no~s PACf 3ol5PAGCS
fO llM l'DA ~l.l 1l"" 01 1 a•,;1 \ l, 14 ~·· o V II k 14\1\ ...l.W <I I t 1.
 DEPARTMENT Of ll EAL Tll AND lll'M,\N SERVICES
FOOD AND DRUG ADMIN15TR1\TION
DISTRICT ADDRESS A>ID Pl<ONE NUM<IER DATE!SI OF INSPECTION
12420 Parklawn Drive, Room 2032 6/3/2019-6/1 1/ 201 9*
Rockvill e , MD 20857 l'=EI NUM8£A

3002809586

NAME AND Tm.E Of INOMOUAL TO WHOM REPORT ISSUED

Pradipta K. Swain, Vice President of Opera tions

STREET ADOAESS

..
FIRMN.f.M£

Sun Pharmaceutical Industries Ltd. Halol - Baroda Highway

~
I CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENT IHSPECTEO

Halol, Gujarat, 389350 Indi a Manufacturer

clamp air pressures required per your reference document, were challenged to determine optimal
. parameters. Accord.mg to your re tierence document,~Kbf(4 )
prod uct1on I
4
lb>< > Instruction approved on 12/07/2019, the pneumatic assembly machine requires an air supply of
1:'.,~)si, assembly air cylinders requireKbH4 > ± "b><4> si and clamp air cylinders require bH4 > ± '<b><4> si. During~
the review of Protocol No.: QUA-S/0253, it was noted that the air supply pressure was recorded as~bH >
4

(approximately ~b>< > )Si). However, no other data was documented for the assembly air cylinders, the
4

clamp air cylinders, and for the tolerances provided by your supplier.
Moreover, the pneumatic assemhlv macbjne 00:240) :was used to assemble exhibit lots associated to
'( b)(4) _ J ib)(4)
(b)(4)
j
*DATES OF INSPECTION
6/03/2019(Mon), 6/04/2019(Tue), 6/05/2019(Wed), 6/06/2019(Thu), 6/07/20 l 9(Fri), 6110120 l 9(Mon),
6/ 11 /20 l 9(Tue)

AMENDMENT 1

SEE REVERSE
F.MPl0YEE(6) 81GHATUAf

F'arhana Khan, Investigator C1)k)J)_';J °"TE ISSUEO

6 /1 1/ 2019
OF THIS PAGE Monica C Burgos Garcia , Investigator ..........
··~'4Mt
~~~·,;:
Kejun Cheng, F'DA Centec Emp l.oyee oc x
... ,U:Jl

Employee of Othec Federal Aqenc ies

Rebecca E Dombrowski, FDA Center Empl oyee )i~Acr·
or: Employee of Orher. Federet l Aqen..:ias

l'OICM fOA 41..1 1119/0li i~I. 1.' 11•I •) ti4l ~· .t~ lkll'M al j , 11 li\ Sl'~:t ' 1'10!\.\l. 06Sf.R\'.\l'lll:\S PAGE ~ ,:/ ~ PAGES
 .. ... ...... - .. ~ · - ... • • - • . r ' .._ •

DF.PARTME;<.I OF ll EALTll A:'\D llUl.\~ SERVICES

FOOD A:><D DRUG AOMINlSTilATION
OA TEiS\ CW INSPECTlON

12420 Parklawn Drive , Room 2032 6/3/2019- 6/11/2019•

Rockvil l e, MD 20857 FEINUM&ER
3002809586

- ~ rnu OF INDIVllUN. TO WHOM REPORT ISSUED

Pradipta K. Swain, Vice President of Operations
f RM- STREET AOORESS

Sun Pharmaceutical Industri es Ltd. Halol - Baroda Highway

CITV. STATE. ZIP CODE. COUNTRY

Halol, Gujarat, 389350 India Manu fact urer

Annotations to Observations
., Observation I: "1/A
•.
.1

.I
·I
Observation 2: IJ /,A

Observation 3: Promised -Iv Corre.cl

Observation 4: Pro.')\ lscd It; corrf-c.:I

AMENDMENT 1

.
MfEISSVEI>
EMPl.OYEE(B}SIGHo\TUAE
6 / 11 / 2019
SEE REVERSE
OF THIS PAGE
Farhana Khan , I nvestigator
Monica C Burgos Garcia, I nve stigator
Kejun Cheng , F'DA Cen ter Emp l oyee or
Employee of Other federal Agenc ies
--
,.,...._
x Sy_.._, ! .WI , . .
O.~l» \•..aDIHl'ltU

~r-c./~/
Rebecca E Dombrowski , E'DA Center Employee
or Emol o vee of Other Federa l Aq en..:: ie s
PAGE 5 .)( S PAGES
FORM FDA 41.J flfJilll1 ·~Sl't:CTIO~.\l. OBSt:tff.\ no~s