SEE REVERSE Michel e Perr y - Williams, Inves t igator OF THIS PAGE Robert J . Ham, I nves t igator

Sara h E . Rhoades, Investigat or

£W«.Ll J .. ~-·f? - - .• ~ 0 10/27/2017 x~.tt ,;,, .. ,

FORMFDA4U (OM18) PREVIOIJS EDmON OBSOLEIE INSPECilONAL OBSERVATIONS PAGE 1OF 8 PAGES

DEPARTMENT OF Jil:ALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT ADDRESS ANO PHOM; NUMBER

805 0 Marshall Drive , Suite 205 Lenexa, KS 66214

(913) 495-51 00 Fax : (913) 495-5115

OATE\S) OF INSPECTION

1 0/1 6/2017 - 1 0/27/2017 FEl NUMeER

1 925262

NAME ANO1TTl.E Of l/IDMDIJAI.TO \MlDM REPCRT ISSllEO

Carole A . Johnson, Site Leader

Hospira Inc. A Pfizer Company CllY, STAlC,ZIP CCOE. COUNTRY

McPherson, KS 67460

STREET ADDRESS

1776 Centennial Dr. TYPE ESTABLISHMENT INa:'ECTEO

Human Sterile Drug Manufac turer

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

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1 There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been already distributed.

Specifically,

A. You have received approximately 50, 43 and 46 lack ofeffect complaints for Bupivacaine HCI with Dextrose (Marcaine) lots 550503A, 641003A and 641403A, respectively. These complaints were received from approximately 02/09/2016 to 10/26/2017. A trend notification and a Supplemental Medical Review were conducted, but no action or additional testing was performed. To date, there bas not been any additional testing or adequate trend analysis performed for these lots.

B. During retain examination ofHydromorphone HCl lot 510053 (ANDA 078591), 15 of n•

vials exhibited particulate matter, which was identified on 07/15/2016 as silicone based. This investigation began on 07/12/2016 and was not completed until 07/27/2017, \\rith a recall initiated on 07/3 11201 7.

C. The complaint investigation for a vial of Vanocmycin HCl for Injection lot 632153A (ANDA 062912), is inadequate in that it did not address potential inadequacies of the visual inspection process. A complaint vial was returned vvith a hair partially embedded in the stopper section that is inside of the vial. During the complaint investigation, the visual

DEPARTMENT OF HEALTH ANU JllJMAN SERVICES FOOD AND DRUG AD.MJNlSTRATION

OISTPJCT ADORES& " NO PHONE l'AJMSER

8050 Marshall Dri ve, Suite 205 Le nexa, KS 6621 4 {913) 495-5100 Fax: (913 ) 495- 5115

O"TE(3) OF INSPECTION

10/1 6/2017 - 10/27/2017 FEI l'l.JMBER

1925262

N>J.tE J..'10 TIll.E ~ l~OMOIJAI. lO W/i(l,'A Ri;PQRT ISSUED

Carole A. Johnson , Site Leader FWJ~E

Hospira Inc. A Pfizer C-Ompany STR!:El AW.JHtl>5

1776 Cenlennial Dr. Cll'I, STAIt. ~IP COtlE. COUNTRY

McPhe rson, KS 6i460 TYPE ES1"AOU6HMEITT IN&f'eCr ED

Human Ste r i l e Drug Manufacturer

inspection process was not identified as a contributing factor for the distribution of the returned product.

D. During the'.(D} (4)] requali:fication run the I (o) (4) asset no.~o) (4J depyrogenation tunnel located on Line till' , two of the(o) ( 4 )J endotoxin challenge samples failed to meet the acceptance criteria of a 3-log reduction ofendotoxin indicators. During this Validation No. 0062.00-1 7-0028 "Depyrogenation Endotoxin Indicator Study" performed 1II0117, two of theL (t:>) (4) l samples had results that achieved a log reduction o~(bTl4] and the second sample yielded a result of 4

l>fl As a part of this investigation, you reported complaints were evaluated. You did not look at adverse events reported during the time you had acceptable qualification results reported until the time when lbe failing endotoxin indicator results were reported during the {l)J <'1 Tunnel Validation.

REPEAT OBSERVATION from 6/8/2016

OBSERVATION 2 Employees engaged in the manufacture and processing of a drng product lack the training required to perform thei.r assigned functions.

S pecificalJ y,

Employees performing your incoming quality visual inspection process associated with your glass components are not adequately trained. Your employees do not utilize physical glass components nor do you obj ectively measure this training process. Thls incoming quality inspection is critical to the prevention ofcontainer/closure integrity defects which affect critical attributes such as sterility and potency. Th.e glass components are used as the primary container in all your sterile products including but not Limited to VancomycinHCl Injectable (numerous ANDAINDAs), Marcaine HCI/Bupivicaine

SEE REVERSE Miche l e Perr y-Williams, Inves t iga tor _.A1J 10/ 27 / 2017 OF THIS PAGE Robert J . Ham, Investigator /!~~

Sarah E. Rhoades, Investigator

fOR!\I FDA 4113 (0~/08) PRl!VIOUS EDrrlO.'f OSSOLElE INSPECTIONAL OBSERVATIONS PA0!!20f8i'AG£S

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUGADMJNISTRATION

OISTRICT "DORESS ANO PHONE NUM8ER DATE(S) OF 1NSPEC"TION

8050 Ma r shall Drive, Suite 205 10/16/2017 - 10/27/2017 Lene xa, KS 66214 FEl Nl/MaER

(913 ) 495 - 510 0 Fa x: (913)4 95- 51 15 1925262

KAME. ~onneOF IN)IViOUAL ro WHOM FU;.PORT ISSUED

Carol e A. J ohnson , Site Leader f !RMN•ME STREET ADO><as

Hospira Inc. A Pfizer Company 1776 Centennial Dr. CllY, STATE. ZIP COOE. COUNTRY 1YPE ES1'A8l.15HMENT UISPECTED

Mc Pherson , KS 674 60 Huma n Steri l e Drug Manufacturer

HCI Injectable (numerous ANDA/l\1DAs), Levophed/Norepinepbrine Bitartrate Injectable (AL"'\TDAJNDA 0075 13), Diltiazem HCl Injection (ANDA 074941, 075853), etc.

OBSERVATION 3 Equipment used in the manufacture, processing, packing or. holding ofdrug products is not of appropriate design to facilitate operations for its intended use.

Specifi.call y,

You have not appropriately qualified your automated visual inspection labeling process used as your in-process control for lot and expiry label defects.

A. Your qualification required the successful rejection of approximately defective units and it did not provide any detail surrounding the magnitude of the lot or expiry defects presented to your visual inspection equipment. Additionally, your equipment is designed to reject defective units whenl (b) (4) Iof the surface area of the lot or expiry is missing.

B. You manually inspect approximately 16><~ finished units for defects including but not limited to lot and expiry critical text. Batch sizes for these products and packaging configurations routinely approach[(t:>) (4)] units. 1b.erefore, your sampling size is inadequate to provide statistical assurance for lot and expiry defects. Additionally, these types of defects are classified as general appearance and assigned an AQL of!bl14! .

This process affects products to include but not limited to your ADD-Vantage configurations such as Diltiazem 500mg, Vancomycin 500mg/750mg/lg, Erythromycin lOOmg, and Azithromycin 500mg.

SEE REVERSE Michele Per r y- Wi l l iams, I nvestiga tor ff~n- 10/27 /2017

OF THIS PAGE Robert J. Ham, I nvestigator Sarah E . Rhoades, I nves t igator

F ORM FDA 43;1 (O'JiW) PREVIOUSromor< OBOOt.ETE JNSPECTrONAL OBSERVATIONS PAGE l OF 8 P"GES

DEPARTMENT OFHEALTII AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATlON

DISTRICT ADDRESS NO PHONE NUMBER DATI:($) OF INSPECTION

8 0 50 Marsha ll Driv e , Suite 205 10/16/2017 - 10/27/2 017 Lenexa , KS 66214

(913)495-5100 Fax: (913 ) 4 9 5 -5115

FB~MBER

1925262

NAMEA~O lfl\£0f INl)IVVUAL TQ\\t!OM l<EPORTISSUS)

Carole A. Johnson , Site Leader

Hospira lnc. A Pfizer Company 1776 Centennial Dr. CITY, STAT!:. ZIP cooe.COUM'RY

McPherson , KS 67 4 60 Human Ste ri l e Dru g Manufacturer

10/ 27/2017 SEE REVERSE Mi c hele Perry-Wil l iams, I n vest i g a tor OF THIS PAGE Robert J . Ham, Investigator

Sarah E . Rhoades , Inves t igato r

FORM J1DA 48:1 (09/0S) PlU\VIOUS wmON OBSCIEC:E JNSPECJ'lONAL OBSERVATlONS l'AGE 40FBPAGES

OBSERVATION 4 Reserve samples from representative sample lots or batches of drug products selected by acceptable statistical procedures are not examined visually at least once a year for evidence of deterioration.

Specifically>

Your SOP does not appropriately classify deterioration to your critical text, namely lot number and expiry. You classify faded print to the critical text fields of lot number and expiry as minor with AQLs for this defect type of 4

• A randomly selected retain review of Vancomycin HCl Injectable Lot 67230DD identified approximately units with faded lot numbers.

REPEAT OBSERVATION from 6/8/2016

OBSERVATION 5 Cleaning procedures designed to prevent microbiological contamination of drug p roduct<; purporting to be sterile are not followed.

Specifically,

A. 'The .mop used to clean the walls of the filling room with( (41] was stored upright on a cart that

also contained a b_ox of sterile 6IT4 wipes used for cleaning. The mop was observed to be

dripping onto the floor, and had the potential to drip into the container of sterile 4 !bl < wipes when

the lid was removed to obtain a clean wipe. This storage configuration has the potential to spread

contamination cleaned from a wall to areas that are cleaned with the sterile 6J r4J wipes, such as

windows and plexiglass in the filling room.

B. (D 4) cleaning ofwindows and plexiglass with (b) (4) in the ~ filling room is not documented in the Sanitation Log Book, only the walls and ceilings being cleaned with[

~~

(t>) (4~

1is

DEPARTMENT OF HEALTH AND HUMAJ SERVICES FOOD AN'D DRUG ADMINISTRATION

DISTRICT ADDi1 ESS ANOPflONE NUMBER DATE{S) OF INSPECTION

8050 Ma rshall Drive, Suite 205 10/16/2017 - 10/27/2017 ~~I NVMOERLenexa, KS 66214 1925262

(913 ) 495-5100 Fax: (913) 495-5115

Caro l e A. Johnson , Si t e Leader flRJ.INllME STReET ADDRESS

Hospira Inc. A Pfizer Company 1776 Centennial Dr. CI TY. STATE, ZI' CDOF., COUNTRY TYPE ESTABLISHMENT INSPECTED

McPherson, KS 67460 Human Sterile Drug Manufacture r

SEEREVERSE Michele Perr y-Wil l iams, Inves tigator 10/27/2017 OF THIS PAGE Robert J . Ham, Investigator

Sarah E . Rhoades, I nvest igator

FORM IDA 4U (07!01) PiCEVIOVS El>ITIOH 08SCl.67E INSPECTIONAL OBSERVATIONS PAGES Of SPAGES

docwnented. While two different sporicidal agents are used in this room, they are not rotated so tha.t each surface type is cleaned v.-1.th two different sporicida1 agents.

C. On 10/21117, during the aseptic cleaning of rn filling room, we observed employee, User ID no.

(6 , perform cleaning and sanitization operations which included the following inadequate cleaning practices.

1. Overlapping strokes were not always used when cleaning the walls.

2. Missed cleaning different areas in the room, including but not limited to the reject bin and sample port.

3. The employee was observed stepping back onto the cleaned floor area where he had mopped and did not re-mop that area.

D. During the aseptic simulation (media fill) of Line 4 >lT you do not record or simulate all

activities/interventions which occur during routine sterile processing operations. For example, the frequency for the activities you classify as "Inherent Interventions" such as loading stoppers,

fill volume checks, traying vials, etc. are not accounted for during your aseptic fill operations.

OBSERVATION 6 An NDA-Field Alert Report was not submitted within three working days ofreceipt of information concerning a failure of one or more distributed batches of a drug to meet the speci fications established for it in the application. Specifically,

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

t>Ar E(S) O!' IHSPIOCllONDISTRICT ADDRESS AND PHONE tiUl.WER

10/1 6/2017 - 10/27/20178050 Ma rshall Drive, Suite 205 FEI NUMSERLenexa, KS 66214 1 925262

(913) 4 95-5100 Fax: (913) 4 95-5115 NAME ANO TITtE OF JNOIVIOUAL TO V!MOM REPORT fSSUEO

Ca role A. Joh nson , Site Leader flRM NAME STl!EIITADD~SGS

Hospira Inc. A Pfizer Company 1776 Centennial Dr. Cm'. STAIE. ZIP CODE, COUNIRY

McPherson , KS 67460

T'lf'E E.SiABLISHMENr INSPECr Et>

Human Sterile Drug Manufacturer

;i)Mi c he l e Perry-Williams , Investi gator 10/27/2017SEE REVERSE Robe rt J. Ham, Inve s t igatorOF THIS PAGE x~ Sarah E. Rhoades, Investigator

FORM FDA 433 (09/08) PIUMOUS £l>IDOM OllSCLETB INSPECTIONAL OBSERVATlONS PAGE 6 01' 8 PAGES

A. On 01/10/2017, an Out of Specification (OOS) result was obtained for Vancomycin HCL for Injection lot 620203A (ANDA 065455), during potency assay testing at the (6f(<t:Lmonth stability timepoint. The initial result was not invalidated, and you had inadequate docwnentation to attribute the assignable cause to analyst error. ll"l: additional samples completed testing on 01127/2017, and were within specification. The time elapsed between these two events was 13 wor!<lng days, and a Field Alert Report (FAR) was not filed for the original OOS result.

B. On 2/1/201 7, you received a complaint for defect type missing label associated with V ancomycin HCl lot 610403A. A Field Alert Report was not filed until 3/1/2017.

C. Demerol Injectable Lot no. 490903A reported in PR ID 1539131 which was created July 11, 2016. This report docwnents the reserve sample for this product had been reviewed on 71116 by

employee UID I (b) (6) I and found a CriticaJ A crack/dam.aged unit on 6)14'/49003A, which was con.finned by MQ Supervisor UID, -(t:> (6) I· The Initial FAR was not filed until July 18, 2016 for this event.

D. Labetalol Hydrochloride lnj . USP 5 mg/mL, 4 mL in 5 mL Carpuject Luer Lock, lot no. 55595LL reported in PR ID: 1539291 created on July 11, 2016, reported reserve samples were evaluated on 7/5/15 by employee ~o found a Critical A crack/damaged unit on 6f(4'/55595LL which was confirmed by MQ Supervisor UIDI (b) (6) I The Initial FAR was not reported until July 18, 2016.

REPEAT OBSERVATION from 8/16/2013 and 6/8/2016

OBSERVATION 7 Written records of investigations into the failure of a batch or any of its components to meet

specifications do not always included the conclusions and follow-up.

Specifically,

In your Annual Product Reviews for the following products you identify trends but fail to initiate appropriate corrective and preventive actions to address and correct these failures.

A. Marcaine HCl 0.75% w/Dextrose 8.25% Injection, for the review period of 4/2/2016 to 4/1/20 17 you identified a trend with 367 complaints classified as Lack ofEffect, which caused this complaint type to exceed your trend limit.

B. Hydromorphone HCI Injection USP, lOmg/mLNial, for the review period 6/11/2016 to 6/10/2017 you identified your visual inspection process a<> a root cause and you failed to incorporate corrective and preventive action.

REPEAT OBSERVATION from 4/23/2014 and 6/8/2016

DEPARTMENT OF HEALTH AND llUMAN SERVICES FOOD AND DRUGADMINISTRATION

Ul~l'I RJC I A!Jll~S AND Pl'iONE NUMOER IJAT1'(S) OF INSO'\oCTION

8050 Marshall Dri ve, Suite 205 10 /16/2017 - 10/27/2017 Lenexa, KS 66214 1'1'!N\JM.,..,..

{913) 495-5100 Fa x: (913) 495- 51 15 1925262

NAN.E A~!l muOf' f~OMDUN.TO 1M10N REPORT ISSUED

Carole A. Johnson, Site Leader FR.o.IM'~ 5TRE..~ l\llllRESS

Hospira Inc. A Pfizer Company 1776 Centennial Dr. ClTY. STA~. ZJ• COil€. COUNTRY lWE ESTAUUSHMENT INSPECTED

Mc Pherson, KS 67460 Human Sterile Drug Manufac t u r e r

OBSERVATION 8 Procedures describing the handling of ~'Iitten and oral complaints related to drug products are

deficiently written.

Specifically,

Your complaint handling procedure does not require you to procure the lot number from your customer

in the event it is not provided at initial intake. You have received approximately 285 complaints without a lot .nmnber ofapproximately 1510 total complaints received. This represents approximately 20% of all

complaints. Products which represent this process include but are not limited to Glatopa/Glatiramer

Acetate Injection , I (5) (4) I Injection, Mak.ena/HydroxyProgesterone Injection, Epinephrine Injection,

etc.

SEE REVERSE Mi che l e Perry-Wi lliams, Invest igator _AJJ 10 /27 /2017 OF THIS PAGE Robert J. Ham, Investigator x~

Sarah E . Rhoades, I nvestigator

FORM FDA U.1 (0~108) J'R.i;V10U$ EOrtx:>t< OBSOLETI': INSPECTIONAL OBSERVATIONS PAGE 7 OF 8 PAGES

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG- ADMIN'ISTRATION

DC3TRJCT ADORESS ANO PHONE NU~IBER

8050 Marshall Dri ve , Suite 205 Lenexa , KS 66214 (913) 495-5100 Fax : (913) 495-5115

NAME AND Tiil.£Of~ liUC~l.l<JAI.TO v.tiOM RS'Ql{T ISSUEV

Car ole A. Johnson, Site Leader FIRM NM1E

Hospira lnc. A Pfizer Compruty CITY, STA~ ZlP CODE, COIJNTRY

.McPherson , KS 67460

DAl l:(S) Cl' INSPECTION

10/16/2017 - 10/27/201 7 Fe.JNUMOl!R

1925262

STREET A!lCRfSS

1776 Centennial Dr. TYl'E ESTAllLISte.16'< f lliSl'ECTEC

Human Sterile Dr ug Manufacture r

~· J) ._\ !...

~~' ~(,~

FORM FD/\ 483 (09/08) 11UMl>U$ EOrtlON 08SOl..£TE JNSPECTIONAL OilSERVATJONS PAGE 8 OF 8 PAGES

'

OBSERVATION 9 Deviations from written test procedures are not recorded and/or justified.

Specifically, dwing sterility testing on 10119/2017, dynamic monitoring of the isolator conditions during testing was not observed. SOP QC0695.40, Environmental Monitoring Inside thei i tl) (4) I I IIsolator, requires that contact plates are taken I (t>) (4) anda viabJe air sample is taken (o) (4) '. (b) (4) I

OBSERVATION 10 Drug products are not stored under appropriate conditions of temperature so that their identity, strength, quality, and purity are not affected.

Specifical ly,

A. You currently store raw materials and equipment which list temperature storage requirements on their labels in your In-coming Warehouse which is not temperature and hwnidity

controlled. For example, Mannitol lot no. 1 (t>) (4) Jwas observed in the warehouse which is used to manufacture over 9 sterile injectable products. The label on this product had temperature storage requirement of 14 R• !11> > degree Celsius.

B. There is a temperature recorder located in the In-coming warehouse which is not always

monitored and reviewed in accordance to your SOP no. QC0877.00 "Monitoring of Recorders". In addition, you have not performed a temperature mapping study of this area

SEE REVERSE OF TH IS PAGE

Michele Per ry-Williams , I nve s t i gator Rober t J. Ham , Investigator Sarah E. Rhoades , I nvestigat or

10/27/2017