DEPARTMENT OF HEATTIVAND NU NTAN SERVICES Pradesh, brug Prd This document lists observations made by the FDA representative(s) during the inspection of your f ‘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. Ifyou have any questions, please contact FDA at the phone number and address above. DURING AN INSPECTION OF YOUR FIRM WE OBSERVED: OBSERVATION 1 Equipment and utensils are not cleaned and maintained at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality or purity of the drug product, 1. Cleaning procedures do not include provisions for routine cleaning or inspection of the™™ po areas. During a facility walkthrough, layers of dark colored Ba) and black) P@) drug products residue were observed on the inside surfaces of me of multiple non-dedicated Pua) These were directly connected to the BH) a. On October 18, 2021 in Manufacturing Bloch@@W a layer of PU flack colored aw drug product residue was seen on the inside surface of 4 of 180/01 (ID # EQUIN2BI/O1). There isan integral part of the drug manufacturing system that are directly connected to BI |(ID EQUN2/814/01) ‘Your cleaning procedure SOP No. PG/012-11 Cleaning and Operation of (Effective date 9/17/2020) and preventive maintenance procedure SOP No. UG/013-07 SEE Rojie @ on fox}aX{ Rajiv Srivastava, ¢80 REVERSE OF F Dipesh shah, cso | THIS PAGEMacleods Pharmaceutica: 4 Theda, Post office hsil Badd Solan, Himachal Preventive Maintenance of P10 (Effective date 8/8/2020) do not have provision to clean the] that are contaminated and are integral part of PREI}/O1 (ID # EQUN2 (9/01). Additionally, your General Manger Engineering confirmed that these®4) are not cleaned as part of the equipment cleaning. Your @@)/01 (ID # EQUN29¢8I/01) is « non-dedicated equipment and has been used to manufacture and ship a number of drug products to US. A list of products manufactured and shipped 0 US during 2019-2021 include but not limited to; Tablets Bimgeuimg PUey tablets), and (6 Tablets 25 ot tablets. On October 18, 2021 in Manufacturing Block) a layer of black colored oe ‘drug product residue was seen on the inside surface of of 1702 (ID # EQUN2PHANTO2). TheP®) isan imtegral part of the drug manufacturing system that are directly connected to B02 (ID # EQUN2H95702), 4) Your cleaning procedure SOP No, PG/013-08 Cleaning and Operation of! (GM 30/45 HW) (Effective date 9/17/2020) and preventive maintenance procedure SOP No. UG/013-07 Preventive Maintenance of P@! (Effective date 8/8/2020) do not have provision to clean the®#4 7) that are contaminated and are integral part of ®#) {02 (ID # EQUN2@#9702). Additionally, your General Manger Engineering confirmed that these® i) are not cleaned as part of the equipment cleaning, ‘Your POO? (ID # EQUN2PNAH 02) is a non-dedicated equipment and has been used to manufacture and ship a number of drug products to US. A list of products manufactured ang, shipped to US in during 2019-2021 include but not limited to; PABNTTT|Capsutes Puig PELE tablets), ance Tabletsta) me P14 tablets) see Rogie ReGrintostave —aagiv arivastavn, oxo |" REVERSE OF / Dipesh Shah, 50 THIS PAGE, peeh Shahy 8 own ron mmonasit INSPECTIONAL OBSERVATIONS oes mrsDEPARTMENT OF APALTH AND HUMAN SERVICES lage Loahimad r: heda, 174101, c. On October 18, 2021 in Manufacturing Block a layer of black colored pe drug product residue was seen on the inside surface of of 03 (ID # EQUN2 9 03). The PU is an integral part of the drug manufacturing ystem that are directly connected to @14 03 (ID # EQUN2®H95 103). Your cleaning procedure SOP No. PG/109-07 Cleaning and Operation of ) (Effective date 9/17/2020) and preventive maintenance procedure SOP No. UG/013-07 Preventive Maintenance of B38) (affective date 8/8/2020) do not have provision to clean theBl@N that are contaminated and are integral part of PI@HO03 (ID # EQU/N2/9405 03), Additionally, your General Manger Engineering confirmed that thes@@4 are not cleaned as part of the equipment cleaning. ‘Your P14§03 (ID # EQUN2/P49%F03) is a non-dedicated equipment and has been used to manufacture and ship a number of drug products to US. A ist of products manufactured and hipped to US during 2019-2021 include but not limited 10924 ‘Tablets@yy) mele) PUG tablets), ano Tablets) mg BAH tablets) On October 18, 2021 in Manufiacturi a layer off) (black colored ro) drug product residue was seen on the inside surface off of 05 (LD # EQUN2@N 05). Thee is an integral part of the drug manufacturing system that are directly connected (2224705 (ID # EQUN2#1005), oe Your cleaning procedure SOP No, PG/164-08 Cleaning and Operation of pe (Effective date 9/14/2020) and preventive maintenance procedure SOP No. UG/013-07 Preventive Maintenance of U9) (Effective date 8/8/2020) do not have provision to clean the®@0) that are contaminated and are integral part of 499 05 (ID # EQUN2#%05). Additionally, your General Manger Engineering confirmed that thes) are not cleaned as part of the equipment cleaning. SEE Royle R Givatene Rajiv Srivastavs, CSO a INSPECTIONAL OBSERVATIONS ocr nes12429 Parkli Hockville, RAE: MD 20 DEPARTMENT OF HEALTH AND AU Srmvicrs 374101, ow oe ea) ow SEE REVERSE OF THIS PAGE ‘YouiPi0) 05 (ID # EQUINE 05) is a non-dedicated equipment and has been used to manufacture and ship number of drug products to US. A Tist of products manufactured and shipped to US during 2019-2021 include but not limited to; 249 Tablets On October 18, 2021 in Manufacturing Block®™ PP) 06 (ID # EQUN200805 06), Thee isan integral part of the drug manufacturing, system that are directly connected 10 B18) 06 (ID # EQUN2®195'06). Your cleaning procedure SOP No, PG/246-04 Cleaning and Operation ofa SOP No. UG/013-07 Preventive Maintenance of PM® (Effective date 8/8/2020) do not have provision to clean the®40)99) that are contaminated and are integral part of) 106 {iD # EQUN2BM 06). Additionally, your General Manger Engineering confirmed that these “are not cleaned as part of the equipment cleaning. Your PUONO6 (ID # EQUN 2/006) is a non-dedicated equipment and has been used 10 manufacture and ship « number of drug products to US. A list of products manufactured and shipped to US during 2019-2021 include but not limited to; 4 ‘Tablets? mg On October 18, 2021 in Manufacturing Block 39 (ID # EQUN2 #1000) 09), Thee is an integral part of the drug manufacturing system that are directly conn me Your cleaning procedure SOP No, PG/246-04 Cleaning and Operation of] Tehsil Baddi Drug Product Manuf weer mg tablets). a layer off%0) black colored drug product residue was seen on the inside surface of) of (Effective date 9/17/2020) and preventive maintenance procedure tablets), ancP@ Tablets m4 mg mee tablets). a layer off) black colored {drug product residue was seen on the inside surface off of xd to 048 /09 (ID # EQUN ZEN 09). secon Roy ee najiv sivastava, 080 j Dipash Shah, C80 — INSPECTIONAL- OBSERVATIONS ce sonyonaces(Effective date 9/17/2020) and preventive maintenance procedure SOP No, UG/013-07 Preventive Maintenance of PU (Effective date 8/8/2020) do not have provision to clean that) that are contaminated and are integral part of) 09 flip # EQUN2(EN®N09). Additionally, your General Manger Engineering confirmed that these are not cleaned as part of the equipment cleaning ‘Your 944)/09 (ID # EQUN2 M09) is a non-dedicated equipment and has been used to ‘manufacture and ship @ number of drug products to US. A list of products manufactured and shipped to US during 2019-2021 include but not limited to; 2 Tablets) mg me tablets), anc@@ ‘Capsulesena)) mai tablets). (On October 18, 2021 in Manufacturing Block 00%) a layer off%0) black colored ow ‘drug product residue was seen on the inside surface off of P11 (ID # EQUN 2PM 11), Thee is an integral part of the drug manufacturing system that are directly connected te 711 (1D # EQUN2,B005/11), ‘Your cleaning procedure SOP No. PG/357-01 Cleaning and Operation of a (Effective date 1/10/2021) and preventive maintenance procedure SOP No, UG/013-07 Preventive Maintenance of (Effective date 8/8/2020) do not have provision to clean the PN that are contaminated and are integral part of M71] (ID # EQUN2@0N/11), Additionally, your General Manger Engineering confirmed that these?” are not cleaned as part of the equipment cleaning, ‘Your P11 (ID # EQUN2@09011) is a non-dedieated equipment and has been used to manufacture and ship @ number of drug products to US. A list of products manufuetured and shipped to US during 2019-2021 include but not limited to Capsules By moe) tablets). oR Svytslayt Rajiv seivastava, cso Bence | os ‘ipesh shah, C80 THISPAGE | QPS Paresh 4 - oe ~ onary 0889 orn eet INSPECTIONAL-ORSERY.A yc c0w naceTAD HUMAN SERVICTS _ AOMINISTRATION h. On October 18, 2021 in Manufacturing Block PI) layer ofP1 black colored ow drug product residue was seen on the inside surface of) of ey 12 (ID # EQUN2 AIM 12). Theme isan integral part of the drug manufacturing system that are directly connected to 8/12 (ID # FQUN2@ 12). Your cleaning procedure SOP No. PG/359-00 Cleaning and Operation of PMY ow (Effective date 12/8/2020) and prevemtive maintenance procedure SOP No. UG/013-07 Preventive Maintenance of PM) (liffective date 8/8/2020) do not have provision to clean the®{950H) that are contaminated and are integral part of®)'12 offP.# BQUNABUNET 12). Additionally, your General Manger Engineering confirmed that these re not cleaned as part of the equipment cleaning, Your S480 12 (ID # EQUN 284908) 12) is a non-dledicated equipment and has been used to ‘manufacture and ship @ number of drug products to US. A list of products manufactured and shipped to US during 2019-2021 include but not limited to) Capsules 9 mg PF PE) tablets), anche) Tablets mg @#) tablets). On October 18, 2021 in Manufacturing Block M9) a layer off60) black colored pe rug product residue was seen on the inside surface of) of PUA O1 (ID # EQUN2@%@H 01). The is an integral part of the drug manufacturing system that are directly connected t0 09/01 (ID # EQUINE /01). Your cleaning procedure SOP No, PG/129-14 Cleaning and Operation of (Effective date 1/2/2021) and preventive maintenance procedure SOP. x UG/146-07 Preventive Maintenance of B® (Effective date 12/4/2019) do not have provision to clean the) that are contaminated and are integral part of 8M@)/01 (D # EQVN2BH1/01), Additionally, your General Manger Engineering confirmed tha these tare not cleaned as part of the equipment cleaning Oars QD SEE Koyos RGrWelare — Raiv seivastava, C80 REVERSE OF A spesh Shah, cS THIS PAGE, Papesh Shahy CSO rons 704.49 40) eee! INSPECTIONAL ORSERVATIONS, rua 00 pssDEPARTMTNT OF RFALTH AND ATIAN SPRVICES eods Pharmaceuticals Limited colan, Himachal Pradesh, Your POV! (ID # EQUN29 01) is a non-dedicated equipment and has been used to ‘manufacture and ship a number of drug products including for US. A list of products, manufactured during 2019-2021 include but not limited t0; PNA) MENT Capsules USP PM mg) eae capsules) as potential registration pbgtches for US, Prey Capsules) ng 0 capsules) to Korea, and ng BU capsules) (0 S15) | Germany Capsules ‘On October 18, 2021 in Manufacturing Block a layer off) black colored peo drug product residue was seen on the inside surface PU of 702 (ID # EQUN2ANOH 02), TeV is an integral part of the drug manufacturing system that are directly connected tel 02 (ID # EQUN2BNE 02). Your cleaning procedure SOP No. PG/292-05 Cleaning and Operation of PU em (Effective date 2/28/2020) and preventive maintenance procedure SOP No. UG/146-07 Preventive Maintenance of 4 (Effective date 12/4/2019) do not have provision to clean the®M50 NE) that are contaminated and are integral part of BIH 02 (ID # EQUN28977 02). Additionally, General Manger Engineering confirmed that these not cleaned as part of the equipment cleaning ‘Your PH 02 (ID # EQUN2/A48§ 02) is a non-dledicated equipment and has been used to ‘manufacture and ship @ number of drug products to US, A listof produets manufactured and shipped to US in during 2019-2021 include but not limited tos Capsules Rl mg PAY tablets) and R20) Capsule mg USP oo capsules, yet to be shipped), 2. Layers of colored PM) drug product residues were observed on the inside surfaces off ‘of naultiple table | machines. ‘These®4 were directly connected to the table 9] Your cleaning procedures do not include provisions SEE Rajiv Srivastava, C80 REVERSE OF THIS PAGE Dipesh shah, CSO ony 1B 83.0 reaeneenooer INSPECTIONAL OBSERVATIONS sce ror notsDEPARTMENT OF Klawn Drive, Room 2 MD 20857 rnat ional 49 3zeaponsest Hara Prasad Rath, Vice President - Macleo for routine cleaning or inspection of the®4 areas a, On October 21, 2021 layers of colored PMO drug product residues were seen on the inside surface of ofall (01 (ID # EQUN2/4901). The pu is an integral part of the drug manufacturing system that is directly connected to MENTO! (ID # EQUNZUNNHO!), Your SOP No, PG/029-08 Cleaning and Operation of M4 (Effective date 8/12/2020) and preventive maintenance procedure SOP No. UG/020-06 Preventive Maintenance off fective date 8/2/2020) do not have provisions to clean the™ that are contaminated and are integral part of 701 (1D # EQUN2@@F01), Additionally, General Manger Engineering confirmed that these®I@)) are not cleaned as part of the equipment cleaning. Your®Us0iF01 (ID # EQUN2N8901) is a non-dedicated equipment and has been used! to manufacture and ship a number of drug products to India and ROW (excluding US). A list of products manufactured and shipped to India Market (vig we during 2019-2021 include but not limited to; oo) mg Tablets (4) tablets), and 4) img Tablets 1 M0 tablets. During the inspection of the@@ 01), Lobserved that theme) were connected via a PUM Talso verified this for PIVOT on p procedure SOP No, PG/129-14 Cleaning and Operation of 4) (Effective date 1/2/2021). On October 25, 2021, your General Manager, Engineer schematic diagrams for 11/01, 03, and fENHO4 that confirmed that thee were connected with a) Tnoted that the@e further inereases potential eross 16 of the cleaning shared 1 jou/202h sce Roy RDittighar — najiv srivastava, 80 REVERSE OF THIS PAGE ‘ Dipesh shah, cso hora DLs evan ISPECTIONAL OBSERVATIONS agence 1 acesDEPARTMINT OF HEALTH ANDIN STAN SPRVICES rklawn Mr. Hare Pras i Rath, 14101, India contamination and compromises the safety and efficacy of the drug products that are manufactured on pe ‘Your GM Engineering also shared a CAPA 58909. I noted that the CAPA. was initiated on 2/13/2021 against observation trigger by USFDA as per C1F/21/0001 On October 21, your Executive Vice President Corporate QA stated that the firm was aware about the Ageney’s concems with the similar issues and shared a document, Risk Assessment for Installation of | " Cleaning System in PM|(EQUN2@4NH 12), Document No. MPL/RAS/PR#62370, Effective date 4/20/2021. I noted that the document was mainly around installing 20 sysiem for one of the PMN 12 (ID # EQUNZMENF12). The outcome of the risk assessment (Summary) stated that, “***Available cleaning procedures are sufficient to clean the P44) in order to mitigate the risk of contamination and cross contamination.***" However, | noted the current cleaning procedures has provisions to clean the S24 only until the ON Mciosest to the and does not extend to the) PO extend beyond the" The report did not extend to the potential cross contamination from the layers of dark colored and black) PI) drug products residue were observed on the inside surfaces off of multiple non-dedicated we On October 25, 2021, the firm management shared Report No, MPL/N2/RMIS/PR#93773/01 that contain testing results for the samples collected from the inside of thet fc This report confirmed the presence of at least previous three drug substances on the inside of thet ‘As of October 25, 2021. the firm continues with the manufaeture of the drug products in the contaminated®20 [ivoureses SEE fa QGifpsiat apse seivastare, cso | REVERSE OF ce a THIS PAGE| fe Dipesh shah, 0 ONSERVATIONS, jrscesDEPARTMTNT OF NPAT AD AT MIAN TRICE 12420 Parklawn Dz. @ Theda, Post Office ajra, Tehsil Baddi District Solan, Himachal Manufactu “174101, Indi, OBSERVATION 2 ***REPEAT OBSERVATION*** ‘Your Quality Unit invalidated several OOS investigations through deficient investigative procedures. ‘The root cause for a number of OOS investigations were obtained without scientific rationale. Examples include, but are not limited to, the following OOS investigations, (008/19/016: On 10/20/2021, your Quality Assurance Manager reviewed OOS/19/016 that was initiated to probe an OOS result for 24 stage) fo! ‘Tablet USP img Batch No. The OOS results were obtained for ME (@NE%) and 2%RSD PHMN%) With the mean value 9% (Specification %RSD NMT@% and individual values within =B\% of the mean, mean NLT®™% and NM1®@09}%). Even though, your Phase | and Phase IIA investigation did not reveal any discrepancies, yet you retested the sample and invalidated the initial 00S resulis. This batch was used in the manufactaring of) Tablet USP gy mati Batch No. 14 Manufacturing date 1/5/2019, Expiry date P16) On the firm shipped®® units (5) tablets) to the US. According to your CAPA (CAPA/19/072), the root cause for the OOS results reads as, “**#there might be a chance of error during withdrawing of sample or holding of sample which resulted into abrupt value of Bij sample.***" ‘The respective CAPA/19/072 appears to be irrelevant to the OOS results, This CAPA initiated a change request CCD/19/616 to update the procedure for sampling, The changes included in the sampling procedure include, “***@0) po It is not clear how this revised sampling procedure would have changed the outcome of the assay result. 008/19/134: On 10/20/2021, your Quality Assurance Manager reviewed OOS/19/134 that was initiated to probe an OOS result for SU stage) for! Tablets see Rags RDiya Javi —-Radiv Srivastava, CSO REVERSE OF Dipesh shah, C80 Ww : THISPAGE | l oan FOAL ae nat eu INSPECTIONAL OBSERVATIONS ra 00"DIPARTMHNT OF HFALTIT AND NUMAN SPRVTCTS 12420 Parklawa Drive, Room 2032 Rockville, ORAPRARNINter: Mr. Hara Pra. Macleods Phar! District UsHf}imgil mg Batch No. P24 ‘The OOS results were obtained for the sample mean (1% (Specification mean NLTPH® % and NMIPHHI% of the label claim), Even though, your Phase | and Phase IIA investigation did not reveal any discrepancies, yet you retested the sample and invalidated the initial OOS results. Tis batch was used in the manufacturing o! Tablet USI mg) Batch No, 2) Manufacturing date 3/22/2019, Expiry date , On Or the firm shipped SUS units tablets) to the US. 00S/19/136: On 10/20/2021, your Quality Assurance Manager reviewed OOS/19/136 that was initiated topprobe an OOS result for stage) Foie Tablets USPi)ma”"img Batch No. 4) ‘The OOS results were obtained for the sample mear®N)% (Specification mean NLTON® % and NMT PHSIHI% of the label claim), Even though, your Phase | and Phase IIA investigation did not reveal any discrepancies, yet you retested the sample and invalidated the initial OOS results. This batch was used in the manufacturing ofP14 fgble USHER ma) Batch Nome Manufacturing date 3/28/2019, Expiry date Ong the firm shippec®® 9] units PNET tablets) to the US, (00S # 54646: On 10/21/2021, your Quality Assurance Manager reviewed OOS # 54646 that was initiated to probe an OOS result for M4) stage) foe) Tablets USHa} mg Batch No. 4) ‘The OOS results were obtained for the sample ™® PHB %4) that is not within =P4.% of the sample mean PMT %. According to your Phase 1A laboratory investigation, weight of the) empty vial was the root cause for higher assay for POT However, the investigation failed to rule out OM) vial cap as the source O/H According to the test procedure, the #M®/sample containing vials are (2 The investigation did not include™™ cap as the source off) empty vial. This batch (Batch No. 24) ‘was used in the manufacturing of Exhibit Batch PMs) SEE Royin R. Geladave Rajiv Srivastava, CSO REVERSE OF : THIS PAGE ies Dipesh Shah, C50 sony 54008 vewtoanavses INSPECTIONAL OBSERVATIONS. accu 72021DEPARTMENT OF HEALTH AND IU NAN SERVICES DOD AND DRL ADSINISTRATION himajra, Tehsil 8. e. OOS # 53444: On 10/20/2021, your Quality Assurance Manager reviewed OOS # 53444 that was initiated to probe an OOS result for assay for UM ‘Tablets USP@ mg Batch No. PUT at 0) stage, The OOS results were obtained for the assay Py (Specification NLT) % and NMT P48% of the label claim) for the [| sample. Phase | and Phase [JA investigation did not reveal any discrepancies. In Phase IIB, you hypothesized 26% sample during sample weighing as the probable root cause of the OOS. This hypothesis was developed by@ and testing®™®) me ‘You used this hypothesis to retest the sample and invalidated the initial OOS result. This batch (Batch No. @4 was used in the manufacturing of a pe ‘Tablets USF®®, mg2IM Batch No. P1@ Manufacturing date 11/30/2020, Expiry date (0%) Onna the firm shipped PHS units 4H tablets) to the US. 00S # 76396: On 10/21/2021, your Quality Assurance Manager reviewed OOS # 76396 that was tiated to probe an OOS result (for assay) for the stability sample of) pe ‘Tablet mg USP having batch numbers and results as in Table 1. see Raya B. Bividere —rasav xtvastae, om REVERSE OF THIS PAGE, Dipesh shah, C50 Fortra on saxon INSPECTIONAL OBSERVATIONS, enerTALI ANDNUMAN SERVICES Solan, Himachal Pradesh Table 1, Assay test results for the s 3 Batch No. Failed at Expiry date | Date shipped to us 8 12 month* 3/31/2023 (annual batch) pe 6 monh* (commercial validation batch) *Condition at 25 °C/60% RH. 9)%, NMT HE% ‘The Phase I hypothesis study did not identify root cause for initial OOS results. ‘There is no explanation why refill vial analysis is @iN% lower than the assay results for the same vial. Instead, you coneluced laboratory error as the root cause based on the passing results obtained by re-diluting, and extended sonification, You did not conduct Phase ITA manufacturing investigation and invalidated the initial OOS result by retesting (in triplicate in Phase 11) both the batches. These batches of drug products were shipped to the US (Table 1), 008 # 63305: On 16/21/2021, your Quality Assurance Manager reviewed OOS # 63305 that was initiated on March 15, 2021 to probe an OOS result observed in assay test for BM) { ancy Tablets S40) mg Batch No. Py at 12 month for 30 °C/65% RH. The batch failed foe part with OOS assay result:@)Y% (Specificatior®™) % 9) %). Phase IA laboratory investigation did not reveal any anomalies. In Liso1s2023 REVERSE OF THIS PAGE Dipesh Shah, c50 SEE Raga ANdyPaU Rady Setvastava, 650 roan 7o4 e800 INSPECTIONAL OBSERVATIONS, ce 8088DEPARTMENT OPAL TIO ND AU MINSPRVIONS 12420 Parklawn Drive, Room Rockvi] 7 ORAPEARMInterna® ional48. Ur. Hara Prasad Rath, Vic District Solan, 74101, In Phase IB hypothesis, the OOS result was reproduced from the same vial (re-injection) but assay data from Re-filled vial, re-dilution vial (from same stock solution) gave higher assay value. Based on the passing results from the Re-filled vial, you concluded that the root cause for OOS result was ‘s##* Analyst not shake final dilution properly at the time of vial filling***”. You did not verify the hypothesis experimentally and invalidated the OOS result by retesting the sample. The investigation guid not extend to Phase IIA manufacturing processes. This batch is part of the registration batch for and located in P& h. OOS# 13455: On 10/22/2021, your Quality Assurance Manazer reviewed OOS # 13455 that was initiated to probe an OOS result for dissolution test fo Tablets USP 8} mg Batch No. ay 21 stage. The OOS results include: D1 %, DRM %, DEY, Dé®_%, DSB_D6 BI % (Specification NL-TBNI% (Q) of the lubeled amount), No assignable ause \was identified in Phase I, In Phase Il investigation you identified root cause that reads, “***it is infer that analyst skip to attached that paddle with shaft in disso-O1 & disso-05 sample***". You invalidated the OOS results by retesting the sample, | inspected the dissolution equipment, EQUQC/DRT/10 Model No. EDT-14Lx that was used in the study and noted the equipment uses dA rod with one end shaped as paddle and the second end is hooked to the equipment also observed imknown peak at -B00) min in the initial (OOS) assay chromatograms that was not included in the investigation. ‘This peak was not present in the retest samples. Rajiv Srivastava, cso SEE REVERSE OF THIS PAGE Dipesh shah, cso rows Dx wo newnserronercae INSPECTIONAL-OBSERVATIONS rac ieorDiPARTMENT OF HEAT TH AND HUMAN SERVICES District Solan, Himachal Prad 274101, Indi OBSERVATION 3 Written procedures are not established for the cleaning and maintenance of equipment used in the manufacture, processing, packing, or holding of « drug product. Specifically, ‘You have not validated the cleaning process for a number of manufacturing equipment that have been used to manufacture and ship a number of drug produets to US such as 1. You have not validated the cleaning process for your®@§02 (ID # EQU/N2@4902). This is a non-dedicated equipment and has been used to manufacture and ship a number of drug products to US. A list of products manufactured and shipped to US in between 2019-2021 inglude but not limited to; ‘Capsule USPRE me PLM capsules), om Capsule USP mg 24 capsules, to be shipped), You have not validated the cleaning process for you@@§j03 (ID # EQUN2(499103), This is a non-dedicated equipment and has been used to manufacture and ship a number of drug products to US. A list of products manufactured and shipped to US in between 2019-202 include but not limited to: (Capsule USFE) mg capsules), oo Capsule USP Bing BO! capsules, to be shipped). . ‘You have not validated the cleaning process for your PII 04 (ID # EQUN2BFO4). This is a non-dedicated equipment and has been used to manufacture and ship a number of drug products to US. A list of products manufactured and shipped to US in between 2019-2021 include but not limited to Capsule USPRG mg M4 capsules). 1/01/202 SEE Rajiv Srivastava, C50 REVERSE OF THIS PAGE Dipesh Shah, cso oan 74.380 INSPECTIONAL OBSERVATIONS ro s0816DEPARTMENT OF HEALTH AND HUSIAN SERVICES OBSERVATION 4 Investigations of any unexplained discrepancy, a failure of a batch or any of its components to meet any of its specifications did not extend to other drug products that may have been associated with the specific failure or discrepancy Specifically, your firm's assessments for risk for the manufacturing of 14? usp, jo ow mg PO mg ance = jand Puy tablets products: A- Does not evaluate suppliers other than Macleods Pharmaceuticals Limited API facility located in Sarigam, Vapi, India, However, your firm sources API for the above products from other manufactures such af) For example, I- According to page 12 of Assessment Report fot ‘Tablets USP) meng anc) mg, document number CQA/RAR/2020/353-00 states, that Macleods Pharmaceuticals Ltd, is the approved vendor foil drug substance and was evaluated for potential PN impurities. On page 19 states, PI) impurities PH and @@ are monitored at API stage, further monitoring at Drug product stage is not required”. Additionally, the document states “it is concluded that @4) ‘Tablets USP manufactured by Macleods is free from PE impurities.” On page 54 states that “No source of PU) is used in the manufacturing process of key starting material, reagents, and drug substance ~ P10 from Macleods Pharmaceuticals Ltd.'s AP! facility located in Sarigam, Valsad District, Gujarat, India. The | aayo1/2021 SEE Raj R-Dyfaglave —aajav srivaseava, cs0 REVERSE OF / THIS PAGE Dipesh shah, C30 roms 994s san sore INSPECTION OBSERVATIONS ge worDEPARTMENT OF HEALTH ANDI Saw SERUTCTS Mach Solan, Himachal Pradesh, assessment does not evaluate PU@) API fron 19) suppliers. 2. According to page 17 of Assessment Report for 0 Impurities of 0 and, a be Tablets Pua) mg ng, document number CQA/RAR/2020/376-00 states, that based on the assessment “it is concluded than and) Tablets manufactured by Macleods is free from impurities.” The assessment does not evaluate) APL from ow vendors are used to manufacture products on nondedicated manufacturing equipment. B- According to Executive Vice President, Corporate Quality Assurance and Vice President of Operations the firm does not test for PA impurities. The evaluation of impurities of incoming (9) APL’s are dependent on the suppliers COAS, The firm transeribes the results from the suppliers supplied COA on to the firm’s ‘Active Pharmaceutical Ingredient Specification. For example, page 6 of Active Pharmaceutical Ingredient Specification, C/SPC/RM002505C/06, with effective date November 16, 2019 for a state content are by LCMS, microgram/gram, “Results to be reproduced from vendors Certificate of Analysis.” ‘According to Executive Vice President, Corporate Quality Assurance also stated that the firm does not test for” impurities in S24 tablet products. ‘The firm is currently validating their methods in their Research and Development Department. - . py202% see Ragin KR. Sristajet — nagsv srivastava, 60 REVERSE OF THIS PAGE Dipesh Shah, C30 org Fo ow INSPECTIONAL ORSERV ATIONS. nce pore‘DEPARTMENT OF HEALTH AND HUMAN SERVICES District Solan, 174101, India OBSERVATION 5 Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. **AREPEAT OBSERVATION*** Specifically, manufacturing process performance qualification Report No MPL/N2/PPQR/19/046/02 for tablets USP B} mg, with approved Quality Assurance date July 7, 2021, failed for J) during the? stage of manufacturing. The? wastitON§% with a specification limit of PH )%. Your firm has manufactured and shipped batches (total of pe tablets) of 12 tablets USPQ mg to the United States of America since August 2021 OBSERVATION 6 Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Specifically, on October 25, 2021, while in tele area it was observed that individual passwords are not being used foi ‘machine (equipment # EQUN2@9)/18). In reviewing the list of equipment and access control for manufacturing equipment, it was found that approximately 44 equipment had employees sharing operator, supervisor and / or manager passwords, For example, cquipment such as PUA (equipment # EQUN21899/01 and EQUN2@UANOS) nayoi/202 Ydoysi Rajiv srivastava, c50 REVERSE OF THIS PAGE see Boyes & ¢ bipesh ehh, 80 Fo roa wuss arts toonecooi INSPECTIONAL OBSERVATIONS. ae 98 8DEPARTMHAT OF HEALTIVANDIN SIAN SERVICES Macleods Pharma olan, Himachal oy 0 machines (equipment # EQUN2@@19)21 and EQUN2@IAN 18), machines (equipment # EQUN2PIF08 and EQUN2PH | 0), PUA (equipment # EQUN2@HaF02 and EQUN2/@§04) and capsule filling machine (equipment # EQVN2/CF/01 and EQUN2/CF/04) ‘employees? are sharing passwords and user names. Additionally, 44 out of] manufacturing equipment used to manufacture product do not have data storage capability, The data that is created while product is manufactured from the equipment are not stored and cannot be recovered. Examples of these equipment are Py (equipment # EQUN2] 02 and EQUN2@@H08) (equipment # EQUN2@9O6 and EQINVZNEET OS), machine (equipment # BQUN2@UAINTIOS) and (equipment # EQUNB2@NP/OL and EQUN 2 08). OBSERVATION 7 Building used in the manufacturing, processing, and packing of a drug product are not maintained ina good state of repait Specifically, on October 16, 2021 during walkthrough of Manufacturing Block®M) | observed water spillage on the floor in the primary packing corridor in front of blister packing PM and blister packing® observed water leaking from the HEPA box on the ceiling. I noted you were packing?) mg Batch No) in blister packing ance mg Capsule Batch No. 4) in blister packing ®14% These drug products were for ROW (Chile) The firm management stated that a water spillage on the service floor caused the leakage in the packing area through the HEPA filter box. | a1/on/2022 SEE Rajiv Srivastava, C50 REVERSE OF THIS PAGE Dipesh Shah, ¢80 ous amy a3 surest INSPECTIONAL OBSERVATIONS oe i90r