SEE ~SE Samlllltha J. Bradley, Investigator010 THIS 9/23/2015Jason D. Abel, lnvcstigatorPAGE

FORM f>DA 483 (111081 ~OUSEomoN OBSOLETE INSPECTIONAL OBSERVATIONS Page 1of7

DEPM111ENT OF HEALTH AND HUIIAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT OFFICE ADDRESS AHO Pt10fo.i:: NlMBER OATE(S) OF' INSPECTIOO

New Orleans District Office 404 BNA Drl\l'e, Bldg. 200, Sle. 500 Nashville, TN 37217 (61$) 3~7g()J

industry Int<mnatioo: wwwJdagov/oc/indu.o;uy

an412ots. 9123/20 rs•

3006014626

NAMEANO T1Ti..e Of ~t. TO 'M-IOM REPORT IS ISSUEO

TO: Marl< D. Acker, CEO F1RN NAME Sme€1" IIOI:lRESS

Medistat RX, LLC J10 East Azalea Avenue CITY, STAT!ANOzi=-:Pcooe==----··------------l-:TYc::::PE=-:OF:-cE::::S:=TABUSHM~==ENT=INSPECTE===oo,..------------1

Foley, AL 36535 OutsoUrcing Facility

1'K1S ~ USTS OSSERVATlONS MACE BY THE FDA REPRESENTATh'E{S) ~lNG THE INSPECTION OF YOUR FACIUiY. lliEY ARE INSPecnO!'W. OBSERVAtlONS; NoiD DO NOT REPRESENT AFlW.L AGENCY OETeRMINAllON REGAROING YOll~ COMf'l».NCE. tF YOU HAVE AN OS.IECTION REGARDING AN 08SERVATIOH. OR HAVE IUPLENEHraJ, OR PlAN TO IMF'l.EMENl CORRECTlVE ACTION IN ReSPONSE TO AN oese:wATION, YOU MAY DISCUSS fHE OEIJECTtON OA ACTION 'Mnl THE FDA R5PRESENTATfVE(S) OURING THE ~CnON OR SUBMIT fHIS INFORMATtON TO FDA AT THE ADDRESS AOOVE..IF YOU H.lo.VE IW'f QUESTIONS, P1..EASE COI'ITftCT FDA AT THE PHONE NUMBER ANO ADDRESS ABOVE.

OURrNG AN INSPE;CilON OF YOUR FIRM (!I ~~ 09SSMD:

OBSERVA110N l

There is a failure to thoroughly review any unexplained discrepancy and the failure ofa batch or any of its oomponents to meet any of its specifications whether or not the batch has been already distributed .

Specifically,

a) Environmental monitoring failures and trends are not adequately addressed and investigated. During the previous 10 months, numerous organisms have been identified, including gram negative bacteria, yeast, and mold, within ISO 5 hoods on both surfaces and in the air.

b) Methylprednisolone 40 mglmL, Lot 07082015@1 , Triamcinolone Acetonide 80 mglmL, Lot 0707iOJ 5@1, Tri· Mix (2.S/l0/L25), Lot 07092015@1, and Tri-Mix (2511011.25), Lot 07092015@2, were released after receiving failing sterility results from their contrad laboratory. The investigation concluded it was laboratory error. A new sample of the same size for each product was sent to an alternative laboratory, which produced aC(jeptable results. The products were released and distributed.

c) HCG 3000, Lot 12262014@5, JC (50/50/0.175/0.175), Lot 12232014@1, Triamcinolone, Lot 12232014@1, Testosterone Cypionate/Propionate 180/20 mg/mL, Lot 12232014@1 0 and @ll, were released after receiving failing sterility results from their contract laboratory . 111e investigation concludes analyst error, though there is n.o evidence to support this conclusion . A new sample ofthe same size for each product was sent to an alternative laboratory, which produced acceptable results. The products were re~d and distributed.

DEPAMMENT OF HEAL.TH AND HUMAN SER\1CCS FOOO AND DRUG ADMINISTRA'TlON

OtSTRICT OFFICE A.OORESS AHO f'HONENIMBER DA.TE(S) Of' INSP£CT!QN

New Orleans Di3trict Office 404 BNA Drive, Bid&. 200, Ste. SOO

812412015- 9/23120!5•

Nasbo.ille, TN 37217 (61S) 366-7801

3006014626

TO: Mark D. Acker, CEO A~ NAME STRC.EiADDRESS

110 East Azalea Avenue

CfTY, STAT£ AKJ ZIP CODE

Medistat RX, LLC TYPt; OF ESTABLISHMENT INSPECTED

Foley, AL 3653S Outsourcing Facil ity

SEE REVERSE OF THIS PMf:

EMPLOYEE!Sl W<ME AHO TTTlE (Prirtt or Type)

Samanlha J. Bnldley, Investigator Jason D. Abel, ln~Jg.3tor

INSPECTIONAl. OBSERVAllONS

912312015

Page 2 of7

t---·--·-·--·------ ­OBSERVATION 2

Procedures designed to prevent microbiological contamination ofdrug products purporting to be sterile are not established. written, and followed. Procedures shaH include validation ofall aseptic and sterilization processes.

SpecifKaJly,

a) Injectable drug suspen.sions are sterilized in located within the ISO 8 Prep Room. The

.

r}i::~~:::::::!.:h ::.:::.:ave not been qualified and the sterilization cycles have not been validated. There bas been no studies or b) ( 4 ) determinations. The are used to

sterihze injectable drug products b) 4 ~~~----------------~

b) On 8/3112015, during observation ofcompounding of Me.droxyprogesterone Suspension Vehicle, Lot 08312015@3, and Medroxyprogesterone Acetate 150 mglmL, Lot 0831201 5@2, the following was n.oted:

i. Opt,'1iltors were observed to handle a keyboard, mouse, scanner, phone, and cabinet handle and resume compounding activities without re-sanitizing their hand~ within the ISO 8 Pr !I'Tf" _m. .--------------_ ep R,oo'IT1

ii. An o tor poured Benzyl Alcohol into a depyrogenated 6 4

'( b) ( 4 within the ISO 8 Prep Room 5 lJ iiL During aseptic filling within the ISO 5Hood, Hood "

open via.ts prior to f:llling dlern with product. iv. During aseptic filling within the ISO 5 Hood, Hoo the oper"tor was observed to place stoppers on filled

vials with tweezers and then pu,sh them into the vials using fingers. .

c) Smoke studies have not been performed in the clean room~. including the ISO 5 critical areas, in either static or dynamic conditions.

e) There is no viable air monitoring within the ISO 5 hood during aseptic operations .

l

I

~ . .. .. .. DEPARTMENT Of HEAL.TH AHD HUIIAN SI!RVICES... ( ', ' i .. ;. FOOD AND DRUG ADMINISTRATION; ·J··· ..~. ·~t',; ' :..• . ' ~~ .. DISTRICT OFFICEHlORESS AND PHOfE I>MII~ OATt:($1 OF INSPECTION

1 ~- "t-\ . • .. ·, . ~ .. . ~"'' ~~:~~ ;!:lew Orleans.District Office 8124120ls-912312015.,. ..~,~ r!.,f.~ '-\;,..?'.1 ~· 404 BNA Drive, Bldg. 200, Ste. SOO ~ ·4-r_.. ;-.<c

Nashville, TN 37217 FaN\NBSR:,~~:(;f~:

f(615) 3~7801!'" ~ ·, 3006014626. Industry Infonnation: www.fda.gov/oo'industry

. "'AME AND llll.E Of I TO 1MiOU ~RT IS ISSUED

TO: Marie D. Acker, CEO"' ' ·~ F~MNAMeI' .. STREET ADORESS

r·~..~ " . 1 ' Medistat RX, LLC 110 East Azalea Avenue t~ .

CfTY, sT-'TE AND ZJP cooe TYPE OF ESTAEIUSHaieNT I~CTEO

Foley, At 36535 Outsourcing Facility

EMPlOYEE{S.) NAME AND llll.E (Pdnf OT 1~} OAl'E ISSUED . SEE

REVERSE

EM.PlOYEe(S) SJGNA~

Samuntha J. Bradley, InvestigatOrSj8OF THIS 91231'2015Jason D. Abel, lnvestige.twPAGE

f) Media fiUs are not ~ntative ofthe most challenging product compounded and aseptically filled. The largest media fill was[~) (2l) land the largest batch sire made is[(6r (4) l

1it· ·.,~ · ·1-A•• >

!··... . ;~•' '

g) During a media fill, Lot 10302014@20. growth was found on an operator•s ]eft and right sleeve and it was not ~vestigated or identified.

OBSERVATION 3

Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.

SpecificaJJy, on 8131/2015, after the p~uction ofMedroxyprogesterone Acetate I50 mg/mL, lot 08312015@2, an operator was observed to sanitize hands prior to finger plating.

OBSERVATION 4

Acceptance criteria for the sampling and testing conducted by the quality control unit is not adequate to assure that batches ofdrug products meet appropriate statistkal quality contTol criteria as a condition for their approval and release.

Specifically,

a) Visual inspection ofuyectable products is limited to the presenre ofparticulate matter (PM) for rejection. For example, apparent product residue was observed around and in the closures of8 vials ofMethylprednisolone Acetate 80 mglmL, Lot 080520 J5@2, and 2 vials ofUpostat, Lot 070120 I5@1. This is not considered significant and vials arc a«epted.

b) There is no established limit for PM and excessi~ rejections were noted for the following:

. i. MJC 25/50/50/0.175/0.175 mgfmL, Lot 07272015@1, resulted in Kb) (4 l vials. Two hundred and

FORM FOA.ata (9103) PReVIOUS eDmON 9SSOLETE INSPECTIONAL OBSERVATIONS Page3of7

DEII'ARTMENT OF HEALTH AND HUMAN seRVICES FOOD AND DRUG ADMINISTRATION

O!STRICT OFFICE ADOOESS AND PHONE N1.M9SR DA'ltl(S) OF INS?ECTION New Orleans District Office 8/24/20l:S. 9/23/2015• 404 BNA Drive, Bldg. 200, St.e. 500 Nashville, TN 37217 (61 S) 366-7801

3006014626Industry lnfonnatioo: www.fda.gov/QC/indusuy ~ TO~~O~~~NFo~~--------------------~--------------

,~~~~11 0 East Azalea A venue

• STATEANOZIPCOOE

foley , AL 36:535

llol.....l~""'-----'

EMPLOYEE($) NAME AND TnlE (PI#t: or Type> DAlEISSUED

SEE REVERse Samantha J. Bradley, lnvmti&:~torSjEOF THIS 91231Wl5PAGE Jason 0. Abe~ Investigator

FORM FDA 483 (9108) AA£\'IOUS · .ON.OSSOI..ETE ~SPECTIONALOBSERVAnONS Page 4 of 7

·-----·-·--···-·-·--···~ ..

twenty nine (229) vials, or approximately %, v.-ere rejected for PM.

ii. Triamcino1o Acetate 80 mg/mL, Lot 05192015@ I, resulted in vials. Seventy four (74) viafs, 1 1

or approximately %, were rejected for PM.

iii. Tri-Mix 30/1 0/ J mg/mL, Lot 080320 15@3, resulted in vials. Twenty seven (27) vials, or approximateiYL)'o, were_ rejected for PM.

OBSERVATION 5

Aseptic processing areas are defic-ient regarding systems for maintaining any equipment used to control the aseptic conditions.

Specifically, the design ofthe clean room is deficient in that:

a) Pressure differentials between rooms are not monitored during production.

b) There are no gauges between the ISO 8 Prep Room and uncontrolled rooms, and, therefore, no pressure monitoring between the rooms.

c) There are openings between the ISO 7 Large Buffer Room and the ISO 8 Prep Room, but there is no pressure differential monitoring between these two rooms to identify which directi<m air is moving. The ISO 8 Prep Room does not receive HEPA filtered air.

d) The hand-washing sink and hand dryer are located directly in front ofan air return in the ISO 7 AnteRoom.

is used for all sanitizing activities within the ISO 8 Prep Room.

DeflARTliiENT OF HEA~TH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

OISTRlCT Of1'1CE IIDDRESS AND PHONE NI.INBER

New Orleans District Office 404 BNA Drive, Bldg. 200, Stc. 500 Nashville, TN 37217 (615).366-780 I i ndustry lnfonnarion: www.fda.gov/ociiruiustry

DATE(S) Of' IN$PECTTON

8/24/2015. 91231201 5 •

FEINUMBER

30060J-#26

NAMe AND mil:: Of~-· ·--TOWiCIM REPOfiT IS ISSUED

TO: Mark f), A c ker, CEO FIRM NAME

Medlstat RX, LLC

STREET ADDRESS

1 10 East Azalea Avenue

CITY. STATE AND ZIP COOE

Foley. AL 36535

TYPE OF t:'STASUSHMENT INSPECTED

Outsourcing Facili ty

··­SEE

REVE."fSE o;: TH1S PAGE

EMPlOYEE(SI SIGMA~

Sj'fs EMP\..OYEE(SI NAME AHCJ TITLE (Print or T)tlej

~.mha J. Bn41ey, ln"'t:$(igator ]IJSQn 0 . Abel, lnvestig11tor

CATE ISSUED

9/23/2015

FORM FDA 413 {1108) PREVIOUS EOmON.OBSOJ.ETE INSPECTIONAL OBSERVAnoNS Page 5 of 7

OBSERVATION 6

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment

I

to produce aseptic conditions.

Specifically,

a) Nonwsterile, non-shedding wipes are used in the clean rooms, including the ISO 5 areas.

b) 4 on-sterile cleaners are used on aKI:5) (.1:1.) ,within the clean room. OnlyOC b) (~) cleaners acts as a sporicide, which appears to be ineffective or ineffectively used based on the identification ofspore-forming bacteria during environmental monitoring.

OBSERVATION 7

The written stability testing program is oot followed.

Specifically, the procedure for extending expiration dates with stability data, SOP 3.17, is not fo11owed. Stability data is insufficient to support the expiration dates assl gtled to injectable drug p.roducts, which include ex,piration datesofupto570days. Only ( b)(4) 1 ~0 . (4) "l withnotestingbetween Kb (4) (5H 4J, For example Lipostat, Lipostat Plus, and Sulfa-Free Lipostat are assigned expirations of 570 days and Cyanocobalamin is assigned an expiration of450 days.

OBSERVATION 8

Drug product containers and closures were no1 sterilized and processed to remove pyrogen ic properties to assure that they ate suitable for their intended use using a validated process.

Specifically, vials and glassware used for injectable drug products are sterilized and depyrogenated in-house using

FQley, At.. 3653S Out!Ourcing facility

DEPARTMENT OF HEAL.TH AND HUJIIAN SERVICE$ FOOO ANtl DRUG ADMINISTRATION

OISlRICT OFHCE AtCRESS ANC PHONE NUMBe:'R

New Orleans District Office 404 8NA Drive, Bldg. 200, Ste. 500 N11Shville, TN 37217 (615) 366-7801 Industry l.nfonnation: www.fdB..govloclindusuy

NAME AND Ttll..E'OF INOMWAL TO~REPORT lS tssvro

TO: Made D. Acker, CEO·

-·~·----

FIRM NAME

Medistat RX, lLC

CITY, STATE AND 2lP CODE

OA~S) OFI~SPECnON

8124/2015. 9123/201 5*

FEINUMaeR

3006014626

STREET ADDRESS

110 East Azalea Avenue '!YPE OF ESTABLISHMENT INSPECTED

Kb) (4) i(b) (2J) l(b)(4)

(15) (4) (5)(4) IJ b) (4j I

(5) ( 4)

EMPLOYEE.(S) NAill£ AND TITlE (PMt or1)poe) OAlt: ISSUED

SEE

EMPlOYEE(S) SIGNI\n.JRE

REVER~ Samantha J. Bradley, lnvcsti&atorSjBOFTHJS 912312015PAGE Jason 0 . Abel, lnvcsti~ator

FORM FDA 4.3 {Me PREVIOUS EOmOH ~Ol.EI'E INSPECTlONAl. OBSERVATIONS Page6of7

- - · . ..

a non-validated process. Within dle ISO 8 Prep Room. vials are lin the ISO 7 Ante Room prior l b) (4) ~

~

? They are[(6) (2J)

j b) (4) IJocated in uncontrolled rooms, and are[ b) (4) Therebasbeen no0C b) (4) studiesforthe~ b) 4)

detennined. l b) ( 4) •are used approximately IThere is no assurance the vials and glassware are adequately sterilized and depyrogenated.

OBSERVATION 9

Protective apparel is not worn as necessary to protect drug products from contamination.

Specifically, on 8131 /2015,

a) During the compounding ofMedrox.yprogesterone Acetate Suspension Vehicle, Lot 083120 15@ 3, in the ISO 8 Prep Room, I observed personnel to be wearing all non·sterile garb, with the exception of ~ilc gloves. The gloves are not donned io a sterile manner and are sanitized using non....~terile [b) (4) 1, '

b) During the compounding of Medroxyprogesterone Acetate 150 mglml., Lot 083120 15@2, l observed personnel to be wearing no protective covering over their eyes, cheeks, or forehead, leaving their skin exposed -within the ISO 5 critical work zone.

OBSERVATION 10

Batch production and control records do not include complete information relating to the production and control of each batch.

SpeciiicaJiy, records are sometimes or always lacking the following infonnation :

D&NmiENT Of' HEAI.llt AND HUIIIIAH SEIMCU FOOD AND DRUG AOt.IINISTRATION

OISTRfCT OFFlCE AOORESS Nm PHONE NlMBER

New Orleans DisU'ict Office 404 BNA Drive,. Bldg. 200, Ste. 500 Nashville, TN 31217 (615) 366-7801

Industry lnfonnatioo: v.ww.fdagov/oclindustry INANE AND llT'...E OF INDMtlUAl.. TO 'M10M REPORT IS ISSUED

TQ; Mark 0. Acker, C.'EO FIRMNAAIE

Medistat RX, LLC em', STAT£ AHD2JP COOE

Foley, AL 36535

OATE~)OF INSPeCTION

8/24/2015. 91'23/2ots•

3006014626

STRaiT ADDRESS

11 0 East At.alea Avenue

OutsOurcing Facility

a) Actual and theoretical yield b) Label samples and reronciliation c) Dates for signatures d) Veriflcation of shortage status prior to production e) The number ofvials produced,. sent for sampling, and kept f) Verification of calculations g) References to investigations h) Final batch disposition i) Batch release signature and date

OBSERVATION 11

The labels and containers ofyour outsourcing facility's drug products do not .include information required by section 503B(a){10).

Specifically,

The following information is not found on some ofyour drug product labels: 1. The statement •'Not for resale ."

Examples ofdrug product Ia~Is that do not contain this information include: a) Testosterone Cypionatelfestosterone Propionate f80mgl20mg!ml b) Triamcinolone Acctonide USP 80mglml tOml Vial c) Trimix (Papaverine 30mg/Alprostadill0mcg/Phentolarnine lmg!ml) 5ml Vial

•Dates of inspection: 8/24-28/2015,8131-9/3/2015,9/17/2015,9/2312015

EMPlO'teE{S) NAME AND TTllE (Print Ql' Type) OATE!SS\JeO

Stm«ntha J. Bradley, Investigetor 912.3/2015Jason D. Abtl. Investigator

~CnONALOBSeRVAnONS Page7of7

. i

--------··· ·-·------

The observations of objectionable conditions and practices listed on the front of this form are reported:

1. Pursuant to Section 704(b) of the Federal Food, Drug and Cosmetic Act, or

2. To assist firms inspected in complying with the Acts and regulations enforced by the Food and Drug Administration

Section 704(b) of the Federal Food, Drug, and Cosmetic Act (21 USC 374(b)) provides

"Upon completion of any such inspection of a factory,warehouse, consulting laboratory, or other establishment, andprior to leaving the premises, the officer or employee making theinspection shall give to the owner, operator, or agent in charge areport in writing setting forth any conditions or practicesobserved by him which, in his judgement, indicate that any food,drug, device, or cosmetic in such establishment (1) consists inwhole or in part of any filthy, putrid, or decomposed substance,or (2) has been prepared, packed. or held under insanitaryconditions whereby it may have become contaminated with filth,or whereby it may have been rendered injurious to health. Acopy of such report shall be sent promptly to the Secretary."