DEPARTMENT OF HEALTH AND H UMAN SERVICES

FOOD AND DRUG ADMINISTRATION

D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

Rockville, MD 20857 FEJNUMBER

3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr. Pradipta Swain, Vice President - Operations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical I ndustrie s Ltd. Halol - Baroda Highway

CITY. STATE. ZIP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat, 389350 I ndia Steri le and Non- Steri le Drug Manufacturer

This document lists observations made by the FDA representative(s) during the inspection of yom· facility. TI1ey are inspectional
observations, and do not represent a final Agency determination regarding yom compliance. If you have an objection regarding an
observation, or have implemented, or plan to implement, co1Tective action in response to an observation, you may discuss the objection or
action v.rith the FDA representative{s) dtu-ing the inspection or submit this information to FDA at the address above. If you have any
questions, please contact FDA at the phone ntunber and address above.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1
There are no written procedures for production and process controls designed to assure that the chug
products have the identity, strength, quality, and purity they pmpo1t or are represented to possess.

Specifically, your Quali!Y. Unit failed to implement adequate and validated controls for ensuring that
. 1s o f r ><4>
' 'bute d via
d1stn .'i-:n·~ ect10n
. USPtb><4> g/ L 1
l_Jll m a ways comp1y wit
. h th e qua 1ty r
they are pmpo1ted to

4>
It1>>< 1. tb)(4) Iand,tb)(4)
_.release/regulato1ys})ecification range is i
4 I
release/regulatory specification range is < > I Fi

41
A. On 25 May 2018, assay testing of~b>< >
4
J nj ection usrr >< }ig1mL; LotL
Expiration date ARril 2020 was Rerfo1med by HPLC. Out-of-specification (OOS) results were observed
for content of1
[(6)(4 ) ~. lb)l4)
,an di w·
1th average values o tb)(4) I
respectively. Your Quality Unit initiated the laborato1y investigation PR ID #5 5 524, and no laboratory
root cause was identified. Manufacturing investigation PR ID #56109 was also initiated and
documented that the source £or th e OOS results observed were not dete1mmed.
. .
Approximately,[lb)l4)1
4
. 1s o f Lo ttl(b)( ) . d.
via eJecte

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvestigat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvestigat or KeUaNtta
= K e ll iN. HICU-S
Dongping Dai, Chemist /Biologist x S9lE'O 12-1.J.al19 1829 1.0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 1 of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2 4 20 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/13 /20 1 9*

Rockville, MD 20857 FEJNUMBER

3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipta Swain, Vice President - Operations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical I ndustrie s Ltd . Halol - Baroda Highway

CITY. STATE. ZIP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat, 389350 I ndia Sterile and Non- Sterile Drug Manufacturer

B. On 24 Nov 2018 OOS and Out of trend (OOT) results were also observed for assay testing of
!bll4> (n.Jecbon
. USP tt>H4>~L · ots tbH4> E xmraiion
. . D ate,__ _
4 4
October 2020. Tlie OOS results for Lot<b>< > ere observed for content of!b>< >
4
an~tb><>4 4
'"""kith average values ofj<b>< > res]Jectively. The,_O
_ O_T- re_s_ul_t""'H >
was o tameu :.i· t·
or content o~L rlb><4> . Lo <b><4>
m Y our Q ua1.ity U mt. mibate
. . . d tlie
laboratoiy investigation PR ID1fl 70804 and documented that based on the preliminaiy QC laborato1
assessment no assignable cause could be identified for the original OOS/OOT results in Lotstt>> 141,__.._
f(b)(4)
an d

Your
. Quality (b)(4) additional assa~esting
tb)(4) Control laboratoiy perfoimed . for
. lottt>ll-4>(b)(4) Vials from
(b)l4),__ _
different were analyzed. ID,1ection USB mg/mL; Lot.
.fi . c (b)(4)
showed resu ts witIi:m speci icabons 10
(b)(4) • (b)(4) - - - - - - -r(b) (4)
respectively. The sh

. . PR ID #170804 revealed th e m ost ]Jrobab1e root cause 1or

fuvestigabon c th . Lot tb)(4)
e OOS m
possi·b·1 · h
i ity t at"b)(4) d c "b)(4)
. (b)(4)use 1or
rmght have not completely
(b)(4)
c d fill .
trans1ene to i mg ta
nk d- .- -.- .- .- l - -d- '(bH4>
urmg imha pro uc . Lot
----
4
As conective actions
(b)(4) our Quality Unit im]Jlemented the followingjb>< >
(b)(4)
_ _ _ _ _ _ Nonetheless, the manufa ctur~§ £rocess
of<bH4> g/mL diug product was validated discai·ding<b> <>filled
. 1 (b)(4) at<bH4> L--_,-y-our Q ua1.ity u mt. re1eased tb)(4)
via s
------------
EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvestigato r 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvestigato r
Dongping Dai, Chemist/Biologist

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 2 of 16 PAGES
 DE PARTMENT OF HEALTH AND H UMAN SER VICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr. Pradip ta Swain, Vice Pre sident - Operations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical I ndustrie s Ltd. Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat, 389350 I ndia Steri le and Non- Steri le Drug Manufacturer

. USR(b)(4) mg/mL; Lo t tb)(4)

fu'~ect10n ~ven though this lot was manufactured under similar
£ . d' .
manu actunng con 1b ons as Lo b)(4)
t

OBSERVATION 2
The responsibilities and procedures applicable to the quality control unit are not in writing and fully
followed.

Specifically, your fnm failed to establish and implement controls which ensure data integrity in the use
of the environmental monitoring MODA EM PROD version 3.4 computerized system used by your
Microbiology Laboratory for all microbiology samples including all sterile environmental monitoring.

A. Your Quality Conb'ol (QC) Microbiology Laboratory failed to establish conb'ols which monitor an d
prevent all environmental monitoring data from being manipulated in the MODA-EM PROD version 3.4
computerized system, in which data from all environmental an d personnel microbiology analyses at your
facility are entered which are associated with all sterile manufacturing.

Fmt her, your fnm failed to establish and implement procedures which require the review and evaluation
of quality ti·ends of audit ti·ails in the MODA-EM PROD version 3.4 computerized system from 2016-
2019. Hence, your fnm failed to perfo1m reviews of audit trails and evaluate quality trends in this
computerized system to date, to include, QCU oversight and corrective an d preventive actions for
minimizing and decreasing the likelihood of reoccmTence of identified trends. Your microbiology
. ~b)(4)
laborato1y processes approximately d
<b><4> !samples per tt>><4 > em was

EMPLOYEE(S) SIGNATURE DATE ISSU ED

SEE REVERSE Kellia N Hicks, I nvestigat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melende z, I nvestigat or KelbNltt5
~K•naN. lb6.S
Dongping Dai, Chemist / Biologist x Dale Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL O BSE RVATIONS PAGE 3 of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2 4 20 Parklawn Drive, Room 20 3 2 1 2/ 3 /20 1 9 - 1 2/ 1 3 /20 1 9*

FEJNUMBER
Rockville, MD 20 857
3 002 8 0 9586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr. Pradipta Swain, Vice President-Operations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical Industries Ltd. Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABU SHMENT INSPECTED

Halol, Gujarat, 38935 0 India Sterile and Non-Sterile Drug Manufacturer

imQlemented in 2016 in your facility, your microbiology laborato1y has processed approximately
4
lbH > here audit trails were not reviewed, and the results trended.

For example, MODA-EM operating procedure, "QCM-153/05, Operating procedure for MODA-EM
and MODA-FDC system, Effective Date: 23/07/2019" [dd/Illilliyyyy], establishes that users, who are
not defined in the procedure, have access privileges to edit sample infonnation including the following:
sample staii date (includes time), sample end date (includes time), sampling technician, environment
(Dynainic/Static), person sampled, and personnel site (ai·ea sampled, such as, ~bH4>I . The procedure also
does not require prior authorization for such edits from management. All user roles also have the ability
4
to delete infonnation to be printed on the sample labels, such as, plate name, type rb)( ) :etc.), plate
barcode, vendor, media/Lot, and media used.

Additionally, the, MODA-EM operating procedure, "QCM-153/05, Operating procedure for MODA-
EM and MODA-FDC system, Effective Date: 23/07/2019" [dd/Illilliyyyy], establishes in section
7.2.3. 7.1, "Sample info1mation that has not yet been approved may be edited to conect enors or add
info1mation that was not collected eai·lier in the sample life cycle. The edit sample info1mation for the
cmTently selected sample, the user selects the Edit option on the Operation ribbon menu. Fmiher, global
program operating procedure, "Fo1m027545, Computerized Systems Administration Protocol for Lonza
MODA, Version 1.0, Effective Date: 24 Dec 2018" establishes in Attachement-3, List of pai·ameters for
different authorization level for Lonza MODA, that the Administrator [IT], Functional Admin [QA], and
the Supervisor have user access privileges to un-approve samples. Samples can be edited in an
unapproved status.

Fmiher, the MODA-EM PROD version 3.4 computerized softwai·e system used to manage
microbiological environmental monitoring data, establishes via assigned user roles within the program

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, Investigato r 1 2 /13/ 2 01 9

OF THIS PAGE J o se E Melendez, Investigato r Kelb Nltt5
~K•naN. lb6-S
Do ngp ing Dai, Chemist / Bio l o gist x Dale Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 4 of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICE S
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

12 4 20 Parklawn Drive, Room 2032 12/3/2019- 12/13/2019*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipt a Swain, Vice President-Operat ions

F IRM NAME STREET ADDRESS

Sun Pharmaceut ical I ndust ries Lt d . Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat , 389350 I ndia St erile and Non- St erile Drug Manu fact u rer

and procedure, "Fo1m027545, Computerized Systems Administration Protocol for Lonza MODA,
Version 1.0, Effective Date : 24 Dec 2018", that all user roles including: Administrator, Lab Approver,
and the Site Supervisor, have access privileges to edit all Inicrobiological test results in MODA without
prior authorization from management, including, but not limited to, the following names:

• "TestResultEdit"
• "TestResultincubation"
• "T estResultOrganism"
• "T estResul tProduct"
• "TestResultResults"
• "T estResultSampling"
• "T estResul tTesting"
There is no oversight of this data to include trending and CAPAs.

B. Trend reports procedure, "QCM-147 /03, Trend reports in Quality Control Microbiology, Effective
Date: 30/03/2018" [dd/mm/yyyy], fa ils to establish that all identified Inicrobiological findings must be
trended and coITective actions identified and implemented to Ininimize or coITect quality trends in
MODA. CmTently, your fnm trends results data only. For example, your procedure, failed to require the
trending of sample edits and edited test results. There is no evaluation with regards to dete1mining the
root cause or coITective and preventive actions were taken to control editing, and to address miniinizing
and decreasing the likelihood of reoccmTence of identified trends.

41
C. The control Qrocedure SOP-ANA-017/10 entitled. "Cleaning and operation od bH I)
~bH4l .J; 4
effective date 19 Apr 2021 establishes, "if maximum cycle time andFH >
1141
value is ooserveo more tlian established liinit forj Jnjection (Non-USA-

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvest igat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvest igat or KelbNltt5
~K•na N. lb6-S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1~2019182910

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 5 of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2 4 20 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJ NUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr. Pradip ta Swai n , Vice Pre s iden t - Ope rations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical I n dus trie s Ltd. Halol - Baro da Hi ghway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol , Gu jarat, 389350 I n dia Steri le and Non- Steri le Drug Manufacturer

product), then fmiher data is to be evaluated/investigated, an d based on finished product results, batches
will be released for commercial pmpose."

[(ljf{4) f(b)(4) :b)(4)}v

On 17 Aug 2018, one (1) of~ !AN-026 located at Bloc~ as found
(bH4>mg[Cb><4 >
4
,cgut-of-limit (OOL) durin{ >< > ol 0H 41 pags; Lots
(b)(4) (b)(4) (b)(4) . . .
The j showed a value ofa C (acceptance range lllllit IS
]'"'
0
""~' 0 1
to j " " . 1n a dd'Ib·on, the exposure time
· wasf"'"' ,,ct he acceptan ce rllllit
· ·
IS •
!4>
Cb><4> . Your Quality Unit initiated the investigation PR ID #103640 which documented a damaged
CbH4> was th e most prob a bl e root cause o f t h IS
. mcI
. .dent.

WW WW l
Although the.___;cycle for Lots 1was found out-of-validated rangei the lots were
sam12.led by the Q,A unit and released to QC laboratoiy for an alyses. The failure of the{b>< >
tb)(4)
I
cycle was not repoiied to the QC Laboratoiy. On 5 Sep 2018 and 17 Sep 2018, out-
of-trend (OOT) (PR ID # 115388) and out-of-specification (OOS) (PR ID #123172) results were
observed for Related Substance (~~ testm~ .
.Lot till (4) ~.
showed OOT result - o and Lot LI
~b><
1
4
> ~owe d OOS 1 [(6><
resu t ~
4
> Y< £
• o or
6 4
>< > J 1: •
Impurity. Th e acceptance l"imit
.
4
is NMT[ >< >(/o. After completion of Phase-1and2 investigations w here no laboratory assignable cause
was identified ~(b >
114 4
'1ng F>< > lmjection (Non-US marketed product); Lots
(bf{4) .
1were rejected.

p . Your fnm failed to ensure data integrity in raw material dispensing. During a walkthrough of the
~b>< > Block<b><4~Dn 03 Dec 2019, we observed that the material dispensed date on the container label for
4

4 4
dispensed raw m aterials of productf:>< > ._j ablets USP,m_mg, batch n0 J b>< > iwas missing on 3
4
(three):b>< >j of the sam e material. Fmifier tfie "Material D ispensed By'' was typewritten and

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hi cks, I nvestigat o r 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvestigat o r KelbNltt5
~K•naN. lb6.S
Dongpi ng Dai, Chemi s t / Biologi s t x Dale Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 6 of 16 PAGES
 DE PARTMENT OF HEALTH AND H UMAN SER VICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2 4 20 Parkl awn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9 *

FEJNUMBER
Rockvi lle, MD 2085 7
3002809 5 86

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSU ED

Mr. Pradip ta Swain , Vic e Pre s iden t - Operations

F IRM NAME STREET ADDRESS

Su n Pharma c eutic a l I n dus trie s Ltd. Ha lol - Baro da Hi g h way

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABU SHM ENT INSPECTED

Ha lol , Gujarat, 389350 I n dia Steri l e a n d Non- Steri l e Drug Man ufac turer

completed by an employee ahead of time but was not completed contemporaneously. The Employee
documented as the dispenser did not dispense the raw material but was the 2nd person verification.

OBSERVATION 3
Laboratory controls do not include the establishment of scientifically sound and appropriate test
procedures designed to assure that drng products confo1m to appropriate standards of identity, strength,
quality and purity.

Your Quality Control Unit (QCU) failed to establish scientifically sound and aQQroQ11ate analytical test
4
procedures designed to assure that representative sample vials of FH > ;Injection USP
LJng/mL filling process are taken for analysis and confo1m to expected quality attrioutes.

4 41
Your fam validated analytical J)rocedure entitled 'i<b>< > _jinjection USPtt>>< lng[ml ,,
f.i~L" sp?ufication number~'"' effective on 28 Aug 2019, for tlie Oetennination otf" " '
tt>>i4> ontent in~bll4> jl njection USP[(bll4)F g/mL diug product. Per test procedure
(b)(4)
the assay sample reqmres tfie transfer of
f(b)(4)' tb)(4)
g ~) of finished product i
1·
Oil
'Vo umetn c flask. Per 4your Deputy General Manager QC, the laborato1y receives sample vials
representative from tbH > 1of the filling process. Nonetheless, your fum only uses
4
"bH > Chug product vials for prepanng tlie sample. In addition, there is no documented evidence to
show at which tbH4> f the filling process (i.e ~!bll4 > I the vials analyzed. This practice
also impacts the analytical testing of the following US marketed products:

tb)(4)
• ~~
<4> Injection USP, ~)(· /vial;
(b)(4)
• !Injection, (4) g/vial;

EMPLOYEE(S) SIGNATURE DATE ISSU ED

SEE REVERSE Ke ll ia N Hi c k s , I nve s tig ato r 1 2/13/20 1 9

OF THIS PAGE J ose E Me l e n dez, I nve s tig ato r Kelb N ltt5
~K•naN. lb6 -S
Dongpi ng Dai, Che mi s t / Biologi s t x Dale Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL O BSERVATIONS PAGE 7 of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICE S
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

Rockville, MD 20857 FEJNUMBER

3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipt a Swain, Vice President-Operat ions

F IRM NAME STREET A DDRESS

Sun Pharmaceut ical I ndust ries Lt d . Halol - Baroda Highway

CITY. STATE. ZIP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat , 389350 India St erile and Non- St erile Drug Manufact urer

{b)(4)
• tb)(4)
• {b)(4)
•
• [{b)(4 )

•
• lb)(4)
• (b)(4)
•

OBSERVATION 4
Procedures designed to prevent microbiological contamination of diug products purpo1i ing to be sterile
are not established, written and followed.

**REPEAT OBSERVATION**
There are no written control procedures that describe2 in sufficient detail, the instm ctions a microbiology
ana1 st must £o 11ow dunng . tne h samp1.mg process £or tD)(4) 1ocated m. th e fill.
I mg mach. me/tbH
__
4
> _
{b)(4) . - ){6>14 ) - - - - , .

----- loadmg.i1 room manufacturmg ar

. . . . 1 . 1 c.. lb)l4) h . .
Per Semor Executive QA-M1crob10 ogy, a swab sample IS col ected 1iom the t at IS used m
critical operations such as; handling interventions near opened vials or near pro uc exposure zone at the
end of the filling R,rocess.
"b)(4)
However, there is no mechanism in place which defmes .
the sampling
procedure and the areas that should be sampled at the end of the filhng process. Therefore,
there is no assuran rent surface monitoring (i.e. swab sampling) is sufficiently robust and can

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvest igat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvest igat or KelbNltt5
~K•naN. lb6.S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1~2019182910

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 8 of 16 PAGES
 DEPARTMENT OF HEALTH AND H UMAN SERVICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr. Pradipta Swain, Vice President - Operations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical I ndustrie s Ltd. Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat, 389350 I ndia Steri le and Non- Steri le Drug Manufacturer

be used to detect potential microbiological contaminants. This discrepancy impacts the filling lines
.
located m Blocks i
(bll4> I

OBSERVATION 5
Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.
4
Specifically, The Online Paiticle C~unt Sampling Location Risk analysis of Roomlb>< > .Jsvp
Filling Room; Document No. SPIL~bH ~PC-RA01 ; approved on 06 Sep 2016 was founa to be
41

inadequate in that:

• There is no documented evidence in the repo1t that describes the conditions in which the study
was can1ed out (i.e. dynamic/static conditions);
• There is no documented evidence in the report that describes how the critical operations (e.g.
operator's interventions~ 4set-uo activities and exposition time of open containers) were evaluated
to cons1·der th e cunent~lb>< > · as sam rmg cntlca
l1ocat10ns · · 11ocahons;
·
• The ong~na. . 1n.sk ana1( ns1.dere l>mJ samprmg 1ocatlons
. (between f(b)(4) L
t~i'(~a..andJbH J
4
area) durin ll the assej sment. No evaluation was carried out near t e ~bH J
4

i even though several operators interventions/process

activities (e.g. stopper movements, stopper jams and pick and place movements) are canied out
within this critical zone.
There is no documented empirical data which demonstrates that the selected sampling locations in filling
Line~bH41 roduces meaningful results and represents the all critical zones of the Grade~~: illing

EMPLOYEE(S) SIGNATURE DATE ISSU ED

SEE REVERSE Kellia N Hicks, I nvestigat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvestigat or KelbNltt5
~K•naN. lb6.S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1~2019182910

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 9 of 16 PAGES
 DEPARTMENT OF HEALTH AND H UMAN SERVICE S
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipt a Swain, Vice President-Operat ions

F IRM NAME STREET ADDRESS

Sun Pharmaceut ical I ndust ries Lt d . Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat , 389350 I ndia St erile and Non- St erile Drug Manufact urer
~b)(4)

area. This fa ilure also impacts the following plastic bottle and vial filling lines: Bloc
{b)(4)
IBlock~b><4> iBlockFll4 > I

OBSERVATION 6
Control procedures are not established which monitor the output of those manufacturing processes that
may be responsible for causing variability in the characteristics of in-process material and the drng
product.
~b)(4)

Specifically, your fnm 's cmTent procedures fo i ,an d sterile current manual visual inspection
qualification:

•
"SUN/NS-SP/623/02, Protocol for Qualification of Visual Inspector for Inspection of
Tablets/Capsules, Effective Date : 06/06/2019 [dd/nnn/yyyy]
4
• "SUN/S-SP/083/01, Protocol for Qualification of Visual Inspector for r H >
Effective Date: 0610612019" [dd/nnn/yyyy] I
used for qualifying/ re-qualifying personnel perfo1ming the visual inspection of finished drng products
manufactured of the following types of diug products, including but not limited to:

• Tablets
tb)(4)
• Capsules I
• r )(4)
I
• Liquid Ampoules
• r )(4)
p ials

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvest igat or 12/13/2019

OF THIS PAGE Jose E Melendez, I nvest igat or KelbNltt5
~K•naN. lb6.S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 10 of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICE S
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipt a Swain, Vice President - Operat ions

F IRM NAME STREET ADDRESS

Sun Pharmaceut ical I ndust ries Lt d . Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat , 389350 India St erile and Non- St erile Drug Manufact urer

• Plastic Bottles

• Suspension Vials

• Liquid Vials
. r)(4)
I
• rb)(4)
I
• Colored Liquid Vials

Bags
does not require the use of a visual inspection kit, which includes physical samples of all critical defect
in different ampoule/bottle sizes or variations of types and sizes of paii iculates and different types of
product fo1mation defects that may be found in batches the hlspectors would be required to inspect in
real-time for visual inspector training or qualification, including, but not limited to the following critical
defects:
• Tab lets not in unifo1m size

• Missing de-bossing

• Abno1mal discoloration of product

• Removal of stopper from the bag

• Stopper quality

The ~b
1141
and sterile hlspectors ability (illspector Fatigue) to identify the above-mentioned defects at the
beginning of a~b>< ~ ersus the~bJ< >
4 4
Jias not been evaluated during the qualification of the
hlspectors. None of the hlspectors were originally qualified on all critical defects.

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvest igat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvest igat or KelbNltt5
~K•naN. lb6.S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 11of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICE S
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS AND PHONE NUMBER OATE(S) OF INSPECTION

1 2 4 20 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

Rockville, MD 20857 FEJNUMBER

3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipt a Swain, Vice President-Operat ions

F IRM NAME STREET ADDRESS

Sun Pharmaceut ical I ndust ries Lt d . Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat , 389350 I ndia St erile and Non- St erile Drug Manufact urer

Additionally,

{b)(41~f th el{b) <4>---i.llnspectors mt . h qua l'11cahons

. he coh 01t wit fi . dated 20 Apr 2018- 20 Apr 2020 are sh·11
cmTent y employed as Inspectors by your fum have been trained on additional defects with pictures, but
the ti·aining was not verified for critical defects with qualification to ensure their ability to identify the
additional three (3) defects added to the Defect Albums since they were updated in October 2018
(Change Conti·ol - PR ID#l39557 dated 10 Oct 2018) and December 2018 (Change Control- PR
ID#188252 dated 18 Dec 2018), which is 14 months and 12 months respectively to date.

OBSERVATION 7
Written procedures are not established and followed that describe the examinations to be conducted on
appropriate samples of in-process materials of each batch.

Specifically,

A. Your fnm lacks written Qrocedures describing, in sufficient detail, the visual examination of sterile
16114) 1, .
and[ rm1shed products, such as, tablets and capsules.

lb)l4)
For alli finished products, the amount of tablets and capsules, the time spent examining the tablets
and capsules, as well as, the different steps the operator must follow are not established in the BMR or
in tablet and capsule visual inspection procedure, "TAB-063/20, fuspection of Tablet and Capsule
Dosage Fo1m, Effective Date: 28 Jlm 201 9" [dd/mm/yyyy].

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, Invest igat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, Invest igat or KelbNltt5
~K•naN. lb6-S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1~2019182910

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 12 of 16 PAGES
 DEPARTMENT OF HEALTH AND H UMAN SERVICE S
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S)OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

Rockville, MD 20857 FEJNUMBER

3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipt a Swain, Vice President-Operat ions

F IRM NAME STREET ADDRESS

Sun Pharmaceut ical I ndust ries Lt d . Halol - Baroda Highway

CITY. STATE. ZIP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat , 389350 I ndia St erile and Non- St erile Drug Manufact urer

.For
(b) (4)
example, I, Investi~tor
~g Batch numberi
lb) 4)
Hicks, observed uctf
tb)(4)
isual inspection ofL. ,Capsules
l(non-US proauct on 11Dec2018. Dunng my observa~1on one (1)
(b)(4)
.
~. i(b){4)
I
114
Inspector perfo1med manual visual inspection in the following way 1) Take a handful o£ b < >
capsu1es fi·om a p1·1e o~b)( > c your v·ice Pres1·dent o perat10ns, rl
4 4
caQsu1es on a tabl ~ m · whih · b)( ><bH

repo1ted were approxrmate.

. 1 (b)(4) capsules peri{b) ----,The operator examme . d, approximate
. 1y, "
41
4
capsules, in approximatelylbH > before discarding, rejects, if any, and placing the inspected
capsules in a plastic bag. !nE4
1
me (1) operator inspects ~:' g of capsules which is approximately
~capsules. None of the tablets were carefully examined during the manual visual inspection
4
(6J< >
process that I observed.

4
B. The amount of time spent by Inspectors examining all sterile finished liquid and tbJ< > !products
is not consistent. Means of tracking time are not provided to each Inspector to ensure tlie consistency of
the manual visual inspection amongst all visual inspectors.

For examp1e, I, Investigator

. Hie . o rlb)(4l
. ks, observed sten·1e v1.sua1 mspect10n
. (b)
<4> ~
~
4 1141
Solution tb> < >Injection batch numberr tus product) on 11 Dec. 2018. I observed Inso,;ctors to
b :£ . l . l .
tbJ~per mmT g manua v1sua mspect10n ·om
. fi JCbH-4> I h h
,eac on t e
4> d h
n t e
rH

Visual inspection for parenteral products procedure, "PAR-013/25, Visual Inspection of Parenteral
Products, Effective Date: 27/06/201 9" [dd/mm/ y:m] section 7 .11.1 establishes, "Each container shall
b b d . :£ . f . . (b)(4l
lbJ~>o seuze m r e e r e n ce.J nne o m m1mum I
~o enhance the detection of pa1ticulate

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvest igat or 12/13/2019

OF THIS PAGE Jose E Melendez, I nvest igat or KelbNltt5
~K•naN. lb6.S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 13 of 16 PAGES
 DEPARTMENT OF HEALTH AND H UMAN SERVICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr. Pradipta Swain, Vice President - Operations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical I ndustrie s Ltd. Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat, 389350 I ndia Steri le and Non- Steri le Drug Manufacturer

OBSERVATION 8
There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been
aheady distributed.

Specifically, Your Quality Control Unit (QCU) did not conduct a thorough evaluation and implement
appropriate and effective con ective actions in a timely manner for theFigh
4
nlllllber of critical alaims
(i.e. compressor failure and PLC and PC/coilllllunication) observed in >< > IM570 and
M578 located in Block ~~l area .

Specifically, control procedure SOP-PAR-237/04 entitled, "Recording and evaluation of ala1ms

generated during batch manufacturing", effective date 14 March 2019, defines critical alaims as
"Ala1ms that have significant impact on the product (strength, identity, safety, purity and
Quality". During~b><4>jtrending of ala1m evaluation[Cb><4 > '] your production
0000 woo .
department repo1ied 64 M570) and 43 M578 ompressor failure and
PLC/PC/coilllllunication during manufacturing. Nonetheless, your fnm has not caiTied out a
comprehensive assessment to identify the source for the ala1med events (e.g. cmTent equipment
preventative maintenance) and established actions for minimizing reoccurrence.

*DATES OF INSPECTION
12/03/2019(Tue), 12/04/2019(Wed), 12/05/2019(Thu), 12/06/2019(Fri), 12/09/2019(Mon),
12/1 0/2019(Tue), 12/11/2019(Wed), 12/12/2019(Thu), 12/ 13/2019(Fri)

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvestigat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvestigat or KelbNltt5
~K•naN. lb6-S
Dongping Dai, Chemist /Biologist x Dale Sll}'leO 1 2-1~2019182910

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 14 of 16 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2 4 20 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr. Pradip ta Swain, Vice Pre sident - Operations

F IRM NAME STREET ADDRESS

Sun Pharmaceutical I ndustrie s Ltd. Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat, 389350 I ndia Steri le and Non- Steri le Drug Manufacturer

Jose E Melendez
Investigator
x 5~M'ds:x~~.i3-~~~rN~54

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Kellia N Hicks, I nvestigat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvestigat or KelbNltt5
~K•naN. lb6-S
Dongping Dai, Chemist / Biologist x Ol* Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 15 of 16 PAGES
 DEPARTMENT OF HEALTH AND H UMAN SERVICE S
FOOD AND DRUG ADMINISTRATION
D ISTRICT ADDRESS ANO PHONE NUMBER OATE(S) OF INSPECTION

1 2420 Parklawn Drive, Room 2032 1 2/3/20 1 9 - 1 2/ 1 3/201 9*

FEJNUMBER
Rockville, MD 20857
3002809586

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Mr . Pradipt a Swain, Vice President-Operat ions

F IRM NAME STREET ADDRESS

Sun Pharmaceut ical I ndust ries Lt d . Halol - Baroda Highway

C ITY. STATE. Z IP CODE. COUITTRY TYPE ESTABUSHMENT INSPECTED

Halol, Gujarat , 389350 I ndia St erile and Non- St erile Drug Manufact urer

Annotations to Observations

Observation 1: Not annotated

Observation 2: Not annotated

Observation 3: Not annotated

Observation 4: Not annotated

Observation 5: Not annotated

Observation 6: Not annotated

Observation 7: Not annotated

Observation 8: Not annotated

EMPLOYEE(S) SIGNATURE DATE ISSU ED

SEE REVERSE Kellia N Hicks, I nvest igat or 1 2/13/20 1 9

OF THIS PAGE Jose E Melendez, I nvest igat or KelbNltt5
~K•naN. lb6-S
Dongping Dai, Chemist /Biologist x Ol* Sll}'leO 1 2-1 ~201 9 1 829 1 0

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlEJE INSPECTIONAL OBSERVATIONS PAGE 16 of 16 PAGES