DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

12420 Parklawn Drive , Room 2032 09/12/2024 - 09/20/2024

Ro ckv ille , MD 208 57 FEI NUMBER

ORAPHARMint e rnat i onal 483 r esponses@fda . hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Sub hash Patil , Unit Head

FIRM NAME STREETADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENT I NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

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 determination regarding
your compliance. If you 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.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1

Written procedures is not established and followed for investigating critical deviations or the failure of a
batch of intermediate or API to meet specifications. The investigation is not extended to other batches
that may have been associated with the specific failure or deviation.

Specifically,

Market complaint
(b,{il' l
A. On 8/12/2022, you received a market complaint CPL/22005 fo for presence
of foreign particle during the analysis of Appearance of solution test. The market complaint was
(bT(-0:
for batches (Table 1).

11
You confirmed the presence ofl (b , foreign particles by inspecting the retain samples of at least
r ,y-c41bate
(b)(4
(bT1 Through the mvestigation,
,., (-1}
•
(bT(l\i
• • you
'iof the I
\UJ\~
concluded that th~ root cause is thel f 122101. The ature of
(b) (41 and\1 (bT~4inature (of the API) caused the:I (b,{<111,of the API at
I
(b11i material looks like I
4 4
the surface otj (b)( jThis( tbH lor foreign particle in

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAME AND TITLE (Prlnl Of Type) DATE ISSUED

Digitally signed by Rajiv R.

Rajiv R. Srivastava -S
09/20/2024
SEE Srivastava -5
Date: 2024.09.20 15:35:34 Rajiv R Srivas tava , cso
+05'30'
REVERSE OF
Suzanne N. Vallez - DigitallysignedbySuzanneN,
THIS PAGE
s
Vallez-5
Date: 2024.09.20 1S:SS:42 +-05'30'
Suzanne Va llez , cso

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGE I OF 12 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

12420 Parkl awn Drive , Room 2032 09/12/2024 - 09/20/2024

Ro ckv ille , MD 208 57 FEI NUMBER

ORAPHARMint e rnat i onal 483 r esponses@fda . hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Sub hash Patil , Unit Head

FIRM NAME STREETADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENT I NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

{6}('
the l I.

CbT'lmplicated with CbT~fi .

Table 1. Batches ofl ore1gu_
CbTt<ll

You implemented CAPA No. CAPN23006 on 2/8/2023 and reworked (Corrective action) the
batches and applied! wc~(Preventive action) on the CbJC4?isurface of the' CbTc4

Your investigation is deficient for multiple reasons including but not limited to:

• Your sampling procedure for analyzing thd CbH4limpurity has no assurance that
the [ : 3 ,articles were part of the sample. The experiment suggests that you tested the API

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAME AND TITLE (Prlnl Of Type) DATE ISSUED

Digitally sig ned by Rajiv 09/20/2024

Rajiv R. R. Srivastava -S
SEE Rajiv R Srivastava , cso
REVERSE OF Srivastava -S Date:
+05'30'
2024.09.20 15:46:53

THIS PAGE Suzanne N. Vallez Vaftez.s

D,i<>lly ggned~SulanneN,
Suzanne Vallez , cso
-5 Date: 2024.1)9.20 1S56:16 • 05'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGE2OF 12PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parklawn Drive , Room 2032 09/12/2024 - 09/20/2024

Ro ckv ille , MD 208 57 FEI NUMBER

ORAPHARMint e rnat i onal 4 83 r esponses@fda . hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Sub hash Patil , Unit Head

FIRM NAME STREET ADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

c th e
1or {6}(' • • d ·1 th
-------rmpunty an not necessan y e._ __ {6}(4l •
ore1gn • 1
part1c e.

• You did not extend the investigation to other batches of AP Is that were manufactured in the
same equipment, wc4b2101 during the time period that covers the manufacturing.£lates of
the im licated batches. The im licated batches were manufactured betwee~ (bTt~and
(b)14l (b)14l (6}lil¼
Table 1 Entries You manufactured at least dditional batches
.....- - - - - - - - - - - -~1-0 {6}~ ~~ ~1-0
amounting to _ _ _ _ _ _of_______...~ PI between_ _ _ _and _ _ _ __
that were not part of your investigation.

(b1
• You reworked (not reprocessed) the above implicated batches and at least c«eworked
41
batches _ _ _ ___, -----------------. (bT< failed
41
USP specifications for ~ own impurity (Specification NMT (bH o). You retested
these batches under (b)C4),specification and shipped to the local market and at least one of the
(bTTi! .
batches (Batch No _ _ _ _ _ _ _was shipped to Export market (Morocco). Your
procedure Reprocessing and Rework oflntermediate and Finished Product SOP No. 1049
Rev 7 (Effective date 1/29/2023) does not allow shipping of reworked batch to Export
market.

00S results
(b)14l (b) (4}
B. On 1/26/2022 you recorded 00S result OOS~ 2/02 for __ ~ llfor_ --=--.-=-=--i

Appearance of solution test. This OOS result was recorded for Batch No (bH4lYour
investigation concluded that the probable root cause was due to improper7 (b)<4l
<6><"~during the1 wc~operation. You implemented CAPA~APN2200"7 ana
_r_o_c_e-ss-e""'d,..the batch and mcluded a1oot note in the batch record,"***
""r-ep (b)C4l
41
wc **".Your ~ __Head (bH ·ould not
explain how the operator will determine that (bH4l Review of the batch
manufacturing record suggested that you (bH4lthe failed batch U>><")o
----
EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAME AND TITLE (Prlnl Of Type) DATE ISSVED

Digitally signed by Rajiv R.

Rajiv R. Srivastava -S 09/20/2024
SEE Date, 2024.09.20 15:4a;04 Rajiv R Srivas tava , CSO
Srivastava -5 +05'30'
REVERSE OF
THIS PAGE Suza nne N. Digitally signed by Suzanne N.
Vallez-S Suzanne Va llez , CSO
Vallez-$ Date: 2024.09.20 15:56:4 1 +05'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGE 3 OF 12PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parklawn Drive , Room 2 03 2 09/12/2024 - 09/20/2024

Rockvi lle, MD 208 57 FEI NUMBER

ORAPHARMint ernat i onal 4 83 responses@fda .hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Subhas h Patil , Unit Head

FIRM NAME STREET ADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

~ e API, which is not part of the original manufacturing process. This confirmed that it was
a Rework and NOT Reprocess. The failed batch was reworked to manufacture Batch No.
I Cb)W~ ou wrongly designated this batch as a reprocess bath by including "RP" in
1li"e batch number.

C. On 6/19/2022 you recorded OOS result OOS...:,J22/07 for

(b)14J h
J Or Assay by
.
(b}(4>'tc

HPLC method. 1p-e_QOS esult 4

was reported for Batch No. Cb><
4
f(Mfg. date June
2022 Expiry dateL Cb>< rfhis batch was analyzed along with two other batches in the same
sequence for Related Substances (RS) and Assay by HPLC method. All the three batches passed
the RS test and only one batch, Bat~h No.,I4 (lif()ailed for the Assay. The tested
assay result for the failed batch was. Cb>< >ro against the Specification[ CbT<}o -~ lo. Phase Ia
investigation did not reveal any obvious error. The hypothesis test in Phase lb further confirmed
the OOS results. Based on the passing RS test by HPLC method, you concluded that the sample
preparation was the issue and made sample preparation as the Assig_I1able root cause. You then
retested a single sample and based on the passing Assay values
4
Cb>14'/fo and C Tc fo), I
invalidated the initial OOS result.

You did not follow your procedure for OOS results investigation, SOP No. 1094 Rev 7
(Effective date 3/19/2024) that has a provision for retesting byr (6)T"\malysts inl (b)(1Your
assignable root cause (Sample Preparation-Human Error) is ba~ on your assumptions and not
proven/confirmed by any experiment.

Laboratory incidence

D. On 6/15/2023, you recorded laboratory incidence Al-06-23-002 for sequence that did not start
due to power failure during the analysis o t"JT1 for Related Substances (RS) and Assay
by HPLC method. The root cause of power failure was due to UPS-I failure. In the Impact
Evaluation, you recorded "No any impact". As per your procedure, Preventive Maintenance of
UN-Interrupted Power Supply SOP No. 6437 Rev 1 (Effective date 8/28/2023), the UPS-I is

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAME AND TITLE (Prlnl Of Type) DATE ISSVED

Digitally signed by Rajlv R.

Rajiv R. Srivastava -S 09/20/2024
Date: 2024.09.20 1S:48:38 Rajiv R Srivastava , CSO
SEE Srivastava -S +05'30'
REVERSE OF Digitally signed by
THIS PAGE
Suzanne N. Suzanne N. Vallez -S
Date: 2024.09.20 15:57:03 Suzanne Vallez , CSO
Vallez-$ +o5'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGE4OF 12PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPECTION

12420 Parkl awn Drive , Room 203 2 09/12/2024 - 09/20/2024

Rockvi lle, MD 208 57 FEI NUMBER

ORAPHARMint ernat i onal 483 responses@fda .hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Subhas h Patil , Unit Head

FIRM NAME STREETADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

attached/connected to at leas{(b>1"1equipment in the Quality Control and Production area including

but not limited to; Stability Chambers, Incubators, Plant o;)>LC & HMI, and SCADA.

OBSERVATION 2

Test procedures is not scientifically sound and appropriate to ensure that raw materials, intermediates,
and APis, conform to established standards of quality and/or purity.

Specifically,

A. You use inhouse test method for the analysis of Related Substances o (bTC1
I (bT<1by HPLC. A review of the corresponding Analytical Method Validation Report No.
MVR/Rsr -(lirc"p 1 (Effective date 12/25/2012) confirmed that the method is not validated for
impurities; {"JT1 You use this inhouse test method to release the
(b)1-0 (bTOO
I or the manufacturing o~ I.

B. You use inhouse test method for Assay o (b)14lby

HPLC. The test method was validated at a contract laboratoryJ (b)(.;,,F d th en trans fierred to
your laboratory. The method validation report AMVR-009 (Effective date 7/18/2018) confirmed
(bTC-0 '(1>)(41
use of three batches o~ (bT1 Batch No's. andl owever, your
method verification/transfer Report No. AMVR/Assay( (bH 1 (Effective date 8/6/2018)
confirmed use of two different batches of! (b)14Y a c o ' s. I
t h N (b}I(, y our
procedure, Transfer of Analytical Method SOP No. 1067 Rev 02 (Effective date 1/29/2023)
requires testing of the same sample for both the sites, contract lab and the (receiving) firm.

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAME AND TITLE (Prlnl Of Type) DATE ISSUED
Digitally signed by Rajiv R.
Rajiv R. Srivastava -S 09/20/2024
SEE Srivastava -5 Date: 2024.09.20 1 S,49:13
+o5'30'
Rajiv R Srivastava , cso
REVERSE OF Digitally signed by Suzanne N.
Suzanne N. Vallez-S
THIS PAGE
Vallez -S Date: 2024.09.2015:57: 35 Suzanne Vallez , cso
+o5'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGES OF 12PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parkl awn Drive , Room 2 03 2 09/12/2024 - 09/20/2024

Rockvi lle, MD 208 57 FEI NUMBER

ORAPHARMint ernat i onal 4 83 responses@fda .hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Subhas h Patil , Unit Head

FIRM NAME STREET ADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

C. You use inhouse test method for Assay ofj <6Jc1 usp by HPLC. The test method was validated
1 (b11-0 .
at a contract laboratory I ias per the Report No. 14113/05112016/7 (Effective date
11/5/2016). You did not perform a method transfer as per your procedure, SOP 1067 Rev 02
,ili[f~;!ive date 1/29/2023). You use the above method to routinely test and release the API,
L....:JUSP.

D. You use inhouse test methods for Related Substance (RS) and Assay for I
11
(b 1usP.
These methods were validated at a contract laboratory (bTC-Oand documented in Validation
Report No's. 22289/280215/08, Effective date 2/28/2015 (Assay) and 10698/300315/21 ,
Effective date 3/30/2015 (RS). On 9/ 19/2024, you stated that the firm has conducted the method
transfer and the corresponding report was documented in Method Transfer Report and Protocol
ofl {l,H" ccording to your binder, the document was stored in Rack -(G4/5) under
File No. 8/13. On 9/19/2023, you were unable to locate the document in your document
repository location and were unable to share the report during the curse of inspection.

E. There is no method validation established for growth promotion test of microbiological media.
There are no critical steps and parameters identifieqfor this process such as the time limits
parameter during sterilization and1 (bT<41of the (b)C-O There is no assurance of the sterility of the
r (b1 <~without establishment and validation of the timefrarnes. The SOP 2004 titled "For Procure,
R eceipt and Maintenance Microbial Culture" also failed to provide any defined timefrarnes
during these critical steps.

OBSERVATION 3

You assign the storage conditions and retest or expiry dates of the APis using test procedures that are
not stability indicating.

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAME AND TITLE (Prlnl Of Type) DATE ISSUED

Digitally signed by Rajiv R.

Rajiv R. Srivastava -S 09/20/2024
Date: 2024.09.20 15:49:4 2 Rajiv R Srivastava , CSO
SEE Srivastava -S +05'30'
REVERSE OF Digitally signed by Suzanne
THIS PAGE Suzanne N. N.Vall ez-S
Date: 2024.09.20 15:57:58 Suzanne Vallez , CSO
Va llez-$ +05'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGE6OF 12PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parklawn Drive , Room 2032 09/12/2024 - 09/20/2024

Ro ckv ille , MD 208 57 FEI NUMBER

ORAPHARMint e rnat i onal 4 83 r esponses@fda . hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Sub hash Patil , Unit Head

FIRM NAME STREET ADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

Specifically,
A. Your protocol for forced degradation study ofl l."JT1DocWl!ent No. AD/FDP/2020/005-09
4
Effective date 12/ 16/2020, stated degradation limit to be (b)1 ~o-'~ . However, the
corresponding report, Document No. AD/FDR/2020/005-00 Effective date 2/8/2021 confirmed
no degradation such that the subjected API (under all the forced conditions) met the API release
specifications.
. •I (b)14J
B. Your protocol for forced degradation study of1_ ________Document No. FDSP-
1,1,rc<11_004/2023 Version 00 Effective date 5/ 10/2023 has no degradation limit stablished and the
1141
corresponding report, Document No. FDSR- (b 004/2023 Version 00 Effective date 6/7/2023
confirmed no degradation such that the subjected API (under all the forced conditions) met the
API release specifications.
. (b>1ili (b>14J .
C. Your protocol for forced deiadat10n study ofl_ _ _JDocument No. 1 1 f DS/001 Effective
1
date 10/5/2006, stated1 (b 1must show some degradation. However, the corresponding report,
Report of Forced Degradation Study of1 (b11, Effective date 11/9/2006 confirmed no
degradation such that the subjected API (under all the forced conditions) met the API release
specifications. You concluded the report with a statement, "method followed for forced
degradation study is stability indication".
. ~w
D. Your orotocol for forced degradation study o iUSP, Document No.
I (bJOO 302 Effective date 2/3/2015, stated degradation limit to be ~}/4 - ~1/o.
However, the corresponding report, Document No. 22290/040315/11 Effective date 3/4/2015
confirmed no degradation such that the subjected API (under all the forced conditions) met the
API release specifications.

Your Quality Control department head 1 <6>1\tated that the purpose of the forced degradation
study is to evaluate the inherent stabilim e API under the forced conditions. He further

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAME AND TITLE (Prlnl Of Type) DATE ISSUED

Digitally signed by Rajiv R.

Rajiv R. Srivastava -S
09/20/2024
SEE Date: 2024.09.20 15:S0:14 Rajiv R Srivas tava , CSO
REVERSE OF
Srivastava -S +05'30'
Digitally signed by Suuinne N.
THIS PAGE Suzan ne N. Vallez-S
Date: 2024,09.20 l S:58:23
Suzanne Va llez , CSO
Va llez-$ +0S'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGE 7 OF 12PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parklawn Drive , Room 2 03 2 09/12/2024 - 09/20/2024

Rockvi lle, MD 208 57 FEI NUMBER

ORAPHARMint ernat i onal 4 83 responses@fda .hhs . gov 3006418686

NAME AND TlnE OF INDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Subhas h Patil , Unit Head

FIRM NAME STREETADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

stated that all the above forced degradation study confirmed that the corresponding APis are
stable under the forced degradation conditions.

OBSERVATION 4
Written procedures are not established for cleaning of equipment and its subsequent release for use in
the manufacture of intermediates and APis.

Specifically,
Your firm has not established adequate cleaning validation for your equipment located in PlanLJnd
Plant ~ed in the production of the APis for the U.S. market. There is no sufficient documentation to
support your cleaning method and choice of reagents for your API products. There is also no procedure
on how to determine the location of vour swabbing and justification for your hard to clean areas
_ r ·-<6n"'
selected. For example, yoW:l1
(ti) (4);
cl-; _____,__. D # 1 ~2101 has only a single swabbjmdocation at
4
ther T( 11.nd your I
4 4
(b <11D# (b)(~2 l 01 have only a single swabbing location at theT (b)( lbut no
rationale to support these decisions. In addition, there is also no dirty hold time (DHT) and clean hold
time (CHT) studies established for your equipment.

OBSERVATION 5
Responsibilities and procedures for quality units are not in writing and/or followed to ensure the API
and intermediates manufactured at your facility are in compliance with CGMP.

Specifically,

A. Your firm failed to provide a comprehensive assessment and remediation plan for your deviation
reports DEV-24004, DEV24001 and DEV-24002 to ensure effectiveness. There was no
corrective action plan established for DEV-24001 and DEV-200 and the corrective action plan

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAMEAND TITLE (Prlnl Of Type) DATE ISSVED

Digitally signed by Rajiv R.

Rajiv R. Srivastava ·S 09/20/2024
Date: 2024.09.20 1S:S0:41 Rajiv R Srivastava , CSO
SEE Srivastava -S +05'30'
REVERSE OF Digitally signed by Suzanne
THIS PAGE
Suzanne N. N. Vallez -S
Date: 2024.09.20 15:58:51 Suzanne Vallez , CSO
Vallez -S +-05'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGES OF 12PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parkl awn Drive , Room 2032 09/12/2024 - 09/20/2024

Ro ckv ille , MD 208 57 FEI NUMBER

ORAPHARMint e rnat i onal 4 83 r esponses@fda . hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Sub hash Patil , Unit Head

FIRM NAME STREET ADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

established for DEV-24004 did not adequate to address the deficiencies.

{6)(41 _ J (b,{il~
B. Your firm changed from predominantly! 1plates to now exclusively1
plates. There is no documentation of a change control conducted to show adequate -------I
implementation and risk assessment of this change. The firm' s current SOP 2025 titled
"Cleaning of Glassware in Microbiology Laboratory" is the only documentation that has any
reference to the use ofi Cbn"}plates in the context of how to clean the plate.

C. Your firm fails to have an adequate tracking system in place to ensure sample traceability in each
of the laboratory. There is an initial registration completed upon receival into QC sample storage
room. However, after the initial registration there is no sample logbooks maintained by any of
the laboratories to provide traceability of the samples and their quantities received or removed
from the laboratories.

D. Your firm does schedule and monitor training throughout! Cbm~however, the training
provided to your firm is insufficient. There are several incidents where activities at the facility
are inadequately completed despite training given. For example, your firm has had to retrain
several personnel on the same topic due to inadequate completion of an activity, even though all
personnel had recently received their required training on the topic. E.g., On 7/29/2023, you
recorded laboratory incidence LE-07-23-020 when your employee[ :CbT<jrrom Intermediate
Manufacturing failed to follow procedure to correctly use Electroruc Laboratory Notebook
(ELN). On 8/9/2023 you recorded another laboratqry incidence, LE-09-23-004 for the same issue
~ (b1(6l; ,-
when your employee from HPLC department,_L _ __.jlailed to follow the procedure to correctly
use ELN. This confirms that your training is not effective.

E. Your procedure, Reprocessing and Rework of Intermediate and Finished Product SOP No. 1049
Rev 7 (Effective date 1/29/2023) has provision for shipping the reworked batches only after
obtaining the stability data for I wc1 You shipped multiple batches of reworked APis before

EMPI.OYEE(SJ SIGNATURE EMPI.OYEE(S) NAMEAND TITLE (Prlnl Of Type) DATE ISSUED

Digitally signed by Rajiv R
Rajiv R. Srivastava -S 09/20/2024
Date: 2024.09.20 15:51:09 Rajiv R Srivas tava , CSO
SEE Srivastava -5 +05'30'
REVERSE OF Digitally signed by Suzanne N.
Suzanne N. Vallez-$
THIS PAGE Date: 2024.09.20 15:59:18 Suzanne Va llez , CSO
Vallez-$ +o5'30'

FORM FDA 433 (09/08) PREVIOUS EI>mON OOSOLETE lNSPECTIONAL OBSERVATIONS PAGE90F 12 PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parkl awn Drive , Room 2 03 2 09/12/2024 - 09/20/2024

Rockvi lle, MD 208 57 FEI NUMBER

ORAPHARMint ernat i onal 4 83 responses@fda .hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Subhas h Patil , Unit Head

FIRM NAME STREET ADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

completing the CbT~of stability data. Batches of reworked APis that were released/shipped
without ><4lof accelerated and/or long-term stability data including but not limited to;
(b) ~ . ff4 '
!API Batch N (b <JMfg. date December 2023, Shipped on
CbTOO . I CbH4l
_ _ _ _ _ _ _ _ _ _ _ fg. date December 2023, shipped oni_ _ _ _Both batches
were manufactured from reworked parent batches.

F. Your procedure, Reprocessing and Rework of Intermediate and Finished Product SOP No. 1049
Rev 7 (Effective date 1/29/2023) hasp . rovision for not shipping the reworked batches to Ex; ort
market. You shipped multiple batches of reworked APis to Export market. E.gj CbTt<ll
i=::¾PI Batch No' s! CbT<j (shipped to; (ljJ(1Barcelona) and CbH
4
I
(shipped to Morocco).

G. Your procedure, Investigation and CAPA SOP No. 1037 Rev 15 (Effective date 6/29/2022) lacks
procedure for the Impact Assessment such that you failed to investigate at least rT'patches,
amounting tol t"JT1 o Cb~I. These batches were manufactured
along with (b)1..''other batches o~ Cb><1API that were implicated with l (b11~foreign
particles as per Market Complaint, CPL/22005.

OBSERVATION 6
Your internal audit is not effective to verify compliance with the principles of CGMP for APis.

Specifically,

A. Your firm's internal audit is not robust and are all preannounced audits based on a predefined
checklist that is included in SOP 1017 titled "For Internal Quality Audit" The selected auditors
do not have any defined qualification to be selected as an auditor besides the completion of a

EMPLOYEE/SJ SIGNATURE EMPf.OYEE(S/ NAME AND TTTLE (Pl1rll Of Typo) DATE ISSUED

Digitally signed by Rajiv R.

Rajiv R. Srivastava -S 09/20/2024
Date: 2024.09.20 15:Sl:38 Rajiv R Srivastava, CSO
SEE Srivastava -5 +05'30'
REVERSE OF Suzanne N. Digitally signed by Suzanne
N. Vaiiez-S
THIS PAGE Date:2024.09.20 15:59:48 Suzanne Vallez , CSO
Vallez -5 +05'30'

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOLETE INSPECTIONAL OBSERVATIONS PAGE I0OFl2
PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parklawn Drive , Room 2032 09/12/2024 - 09/20/2024

Rockville, MD 20857 FEI NUMBER

[email protected] 3006418686
NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Subhash Patil , Unit Head

FIRM NAME STREETADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

general internal audit training course. There is no assurance that the auditor selected are adequate
to conduct the assessment and that the internal audits produce effective results.

B. The Quali!)' Unit conducts a "QA (b)1<1 Vigilance Round Observation" activity of the facility
(b)1il) ese (b)(4) reports are rev1ewe
• d and trepdedby the Qual'1ty Umt• fior
I
internal assessment. Neither of these quality activities; th; r (bn ~vigilance reports, or the
I (bT<"h rending, have an establish written procedures on how Quality is to properly conduct
and evaluate their findings.

OBSERVATION 7

Records associated with the API distribution were not readily available for inspection. You submitted
list of APis that were manufactured and shipped during the years 2022, 2023 and 2024. During the
course of inspection and document reviews, it was discovered that multiple API batches were missing
from the submitted list.

Specifically,

A. On 9/15/2024 you submitted a list of Reprocess and Reworked AP Is that suggested no

(b)14l .
I atches were Reworked and/or Reprocessed m 2022 and 2023. Howeyer,
4
your Market Complain # CPL/22005 suggested that multiple batches ofl (bH ;were
returned (Table 1). These batches were then reworked and distributed to the local as well as
Export market. Your Site Head (b)C6lacknowledged the missing data from the shared API list and
promised to provide updated list.

B. On 9/19/2024, during the review of OOS result OOS/ OOS (b>1ilh2/07 for! (b114}ror
(b)(4l
Assay by HPLC method, I noted that the corresponding Batch No. I (Mfg. date

EMPLOYEE/SJ SIGNATURE EMPf.OYEE(S/ NAMEAND TTTLE (Pl1rll Of Typo) DATE ISSUED

Dig itally signed by Rajiv R

Rajiv R. Srivastava -S 09/20/2024
SEE Srivastava -5 Date: 2024.09.20 15:52:09 Rajiv R Srivastava, cso
+o5'30'
REVERSE OF Suzanne N. Digitally signed by Suzanne N.
THIS PAGE Vallez -S
Suzanne Vallez , cso
Vallez -S Date: 2024.09.20 16:00:1 s <-05'30'

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOLETE INSPECTIONAL OBSERVATIONS PAGE II OF 12
PAGES
 DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF I NSPECTION

12420 Parkl awn Drive , Room 2 03 2 09/12/2024 - 09/20/2024

Rockvi lle, MD 208 57 FEI NUMBER

ORAPHARMint ernat i onal 4 83 responses@fda .hhs . gov 3006418686

NAME AND TlnE OF I NDIVIDUAL TO 'MiOM REPORT ISSUED

Mr. Subhas h Patil , Unit Head

FIRM NAME STREET ADDRESS

Aarti Drugs Limited Plot No. E22, M.I.D.C. Tarapur

CITY, STATE, ZIP COOE, COUNTRY TYPE ESTABLISHMENTI NSPECTED

Tarapur, Palghar, Maharashtra 401506 India API Manufacturer

11
June 2022 Expiry datel (b 1 was missing from the initial list submitted by the firm and

from the updated list "Dispatched Detail of Reprocess Batches" shared by the firm on 9/ 16/2024.
Upon review of the Logbook Issuance Register for 2022, I noted the Batch No.I (b)C1
6
was r.ecordeld on Page 023 and the bath was shipped to Export marke.t. I also found at leastr<
(b)(4l
n"~
·L....J
bathes with ·isuffix were recorded in the Logbook Issuance Register. Your QA Executive
1161
(b
tated that bateh no. w1tIL__Jsu
• , , C6Tc~ ffi1x m
• d.1cates th~J.I
...-----•C6><~Bathes. Onee agam
• you
4
stated that the during the list compilation, the (b)< 1batches were missed out.

EMPLOYEE/SJ SIGNATURE EMPf.OYEE(S/ NAME AND TTTLE (Pl1rll Of Typo) DATE ISSUED

Digitally signed by Rajiv R.

Rajiv R. Srivastava -S 09/20/2024
SEE Date: 2024.09.2015:52:39 Rajiv R Srivastava, CSO
Srivastava -S +05'30'
REVERSE OF Digitally signed by Suzanne N.
THIS PAGE Suzanne N. Vallez-S
Date: 2024.09.20 16:00:42 Suzanne Vallez , CSO
Vallez-$ +05'30'

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 12 0Fl2
PAGES