EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE OF THIS PAGE

Zacha ry Nayan J

L Stamm, Investigator Pa t e l, Investigator IX Zadlaly L Slamm

JA:"())11 3/2 4 /2017

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FORM FDA 483 (09108) PR.EVIOUS EDITION 06SOlET€ INSPECTIONAL OBSERVATIONS PAGE I OF 15 PAGES

DEPARTMENT OF HEALTH AND HUMAN SERVlCES FOOD AND DRUG ADMTNISTRATION

OISTRJCT ADDRESS ANO PHONE NUMBER

6th & Kipling S t . (P . O . Box 25087) Denver, co 80225-0087 (303)236 - 3000 Fax: (303)236- 3100

OATE{S) OF INSPECTION

2/22/2017-3/24/2017* FEI NUM6ER

3011752429

NAME mo mL.E OF INOIVIOOAl TO 'NHOM REPORT ISSUED

Will iam 0 . Richardson , CEO FIRM NAME

Isomeric Phar macy Soluti ons , LLC CITY. STATE. ZIP CODE. COUNTRY

Sal t La ke City, UT 8 4 109-1479

STREET ADDRESS

2401 Sout h Foothil l Dr, Su i t e D TYPE ESTABLISHMENT INSPECTED

Ou t sourcing Facil i t y

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

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1 Written records of investigations into Wlexplained discrepancies and the failure of a batch or any of its components to meet specifications do not always include the conclusions and follow-up.

Specifically,

A) Environmental Monitoring (EM) Excursions- Investigations are not always conducted or are incomplete for alert and action limit excursions for viable and non-viable environmental monitoring. a) There have been approximately 85 viable alert and action level personnel and environmental

excursions in your classified clean room. There has been no documented product risk assessmentand corrective and preventative actions are not identified and documented on your Monitoring Event Form (MEF). Additionally, as part of your investigations, the identification of the microorganism recovered is not included in product risk assessment, or corrective and preventative action. For example:

i) MEF No. 17009 documents positive (1 CFU) personnel monitoring results on the 4 CbH >

r (b) (4 ) ofan operator collected on 1/4/2017. MEF No. 17013 documents two positive (TNTC) r (b) (4 ) surface environmental monitoring samples collected on 1/10/2017,[ (t>J (4 ) of Triamcinolone Acetonide 40 mg/mL Preservative-Free (PN (b) (4)~, Lot 12004. The micro identification was reported for both action level events by your contract laboratory on 1/27/2017 as chaetomium sp. (fungi genus). On 1/20/2017 (seven days before the micro identification results were reported) the MEF meeting used to discuss product risk associated with MEF No. 17009 and MEF No. 17013 was held. Lot # 12004 was released on 2/6/2017 and distributed.

b) Your firm failed to document and investigate non-viable particle excursions in your ISO 5, ISO 7

DEPARTMENT OF HEALT H AND H UMAN SERVICES FOOD AND DRUG ADMJN!STRAT!ON

OATE(S) OF INSPECTIONDISTRICT AOORESS AND PHONE NUMBER

2/22/2017-3/24/2017*6th & Kipling St . {P .O . Box 25087) FEINUMBERDenver, co 80225- 0087 3011752429(303)236-3000 Fax : (303)236- 3100

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Will i am 0 . Richardson , CEO FIRM NAME

Isomeric Pharmacy Solutions, LLC CITY, STATE. ZIP CODE. COUNTRY

Salt Lake City, UT 84109- 1479

STREET ADDRESS

2401 Sout h Foothill Dr , Suite D TYPE ESTABLISHMENT INSPECTED

Outsourcing Facility

EM PlOYEE(S) SIGNATURE DATE ISSUED

l~l 7 Za c hary L Stanun, Investigator 3/24/2017SEE REVERSE Nayan J Patel, Investigato rOF THIS PAG E IX Zachaty l Stamm

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FORM FDA 483 (09/08 ) PR.EVlOUS EDITION09SotETE I NSPECTIONAL OBSERVATI ONS PAGE 2 OF IS PAGES

and ISO 8 classified areas per your SOP-607-02, Envirorunental & Personnel Monitoring. T here is no documentation to support tha(b) (4 ) logs were reviewed and since the previous inspection ( 6/20 16) the following action level particle excursions were observed without any documented investigation:

• 218 action level particle excursions in the r (b)(4) (action limit: 1(b) (4 ) \(b) (4) \

• 206 action level particle excursions in the l (b -(4) I (action limit: [(b) (4) J ~l::i) (4) ] ).

• 239 action level particle excursions in the (1:5) (4) (action limit: [ b) (4) \(b) (4) J).

• 373 action level particle excursions in the r (D) (4) (action limiqb) (4 ) ~b) (4) ] ).

• 221 action level particle excursions in the (b) (4) wh~re sterile product is produced I (b) (4 ) (action limit:Qti> (4)

• 600 action level particle excursions in the_~, (b)(4) where sterile product is produced (b) (4 ) " (action limit: ~b) (4 ) - J

*Approximately ~bl<4l batches of sterile finished products have been produced and released using at least one of the areas listed above.

B) Out of Specification COOS) Results- Investigations are not always conducted when products fai l to meet your internal specification for potency, sterility, or bacterial endotoxin. Additionally there has been no assessment of how these failures affect any previous or future production. The following are examples of commercial and stabi lity batches that had OOS results associated with them: a) Commercial Batches

i) Testosterone Cypionate/Testosterone Propionate 200/20mg/mL Injectable Solution[(b) (4)l [ .J Lot 11042 (PN ~b) (4W, fai led steri lity release testing.

ii) Triamcinolone Acetonide 40 mg/mL Preservative-Free Injection (PN (b) (4 ) , Lot 04035, failed endotoxin release testing.

b) Stability Batches i) Triamcinolone Acetonide 40 mg/mL Preservative-Free Intrathecal Injection - Labeled BUD

OEPARTMEI\T OF HEALTH ANO HUMAN SERVICES FOOD AND DRUG ADMTNISTRATION

DISTRICT ADORES$ AND PHONE NUMBER

6th & Ki pling St . ( P. O . Bo x 25087) Denver , co 80225-0087 (303 ) 236 - 3000 Fa x: (303 ) 2 36- 3100

NAME AND Tn L.E OF INOIVI.OUAl TO 'w\IHOM REPORT ISSUED

Wi lliam 0 . Richa rdson , CEO

OATE(S) OF INSPECTIOH

2/22/20 17- 3/24/2017* FEII'fUMtiER

3011752429

FIRM NAME

Isome r ic Pharmacy Solutions , LLC CITY, STATE, ZIP CODE, COUNTRY

Salt La ke City, UT 84109-1479

STREET AOORfSS

2401 Sout h Foothill Dr, Suite D TYPE ESTABLISHMENT INSPECl'EO

Ou t sourcing Facil it y

EMPI.OYEE(S) SIGNATURE DATE ISSUEO

SEE REVERSE Zachary L S t amm, Invest i gator )/'l<4(ltl1 3/24/2017 OF THIS PAGE Nayan J Patel, Inves tigator IX Zachary L Slamm

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FOR\1 FDA 483 (09/08) PREVIOUS EOITIOtl OBSOLET! INSPECTIONAL O BSERVATIONS PAGE 3 OF 15 PAGES

180 days- Failed endotoxin at t-1 -(15f 4) (1) Lot 03041 -Compounded Date: 04-22-2016; Test Completion Date: 04-29-2016-59.28

EU/mL against a specification of(b) (4 ) I 1

(2) Lot 02052- Compounded Date: 03-22-201 6; Test Completion Date: 04-05-2016-39.22 EU/mL against a specification oft(b) (4)

ii) Testosterone Cypionate 200 mg/mL, Testosterone Propionate 10 mg/mL, Vitamin D3 200 IU/mL- Labeled BUD 90 days - Failed Vitamin D3 potency at t={ (b) (4) r (b)(4) (1) Lot 08027- Compounded Date: 09-23-20 16 Original Test Completion Date: 01-3-2017­

172% against a specification ~15 ) (4 ) . ,, (2) (4

4Re-Tests Completion Date: 01-19-2017- 116% and 119% against a specification ofj(ll) ( )j ~b) n

iii) Methylpred nisolone Acetate/Lidocaine HC140/1 Omg/mL- Labeled B UD 180 days- Fai ledpreservative content (antimicrobial effectiveness) at t=, (b) (4 } f t Specification oft(b) (4 ) (I) Lot 06252015@19 Compounded Date: 06/25/2015; Test Completion Date: 01108/2016

70.6%. (2) Lot 080520 15@14 Compounded Date: 08/05/2015; Test Completion Date: 02/03/2016

69.1%.

C) Visual Inspection Rejects- Your firm does not conduct investigations into vials rejected during your[(ll) (4) 1visuaJ inspection process. Additionally, you have not established a reject limit for the number of vials that can be rejected for a given batch size. For example, your batch record for TriamcinoloneAcetonide 40 mg/mL Preservative-Free Injection, Lot #07021, compounded on 8112/2016, documents 488 vials were visually rejected out of(DJ (4)]1led vials. No investigation was conducted and the batch was released 9/13/20 16.

D) Production Process Change- When changes in production are made as a corrective action to identified production process issues, investigations are not always extended to determine the impact on already distributed product. For example, in September 2016 your firm changed th6, (b)(4)

DEPARTMENT Of HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT AOORESS AND PHOI'IE NUMBER DATE(S) OF INSPECTION

6th & Kipling St . (P.O. Box 25087) 2/22/2017 - 3/24/2017* FEI NUMBER Denve r , co 80225- 0087 3 0 11752429(303 )236-3000 Fax : (30 3 )236- 3 100

NAME AND m tE OF INDIVIDUAL TOWHOM REPORT ISSUED

William 0 . Ri char dson , CEO FJRMNAME

Isomer i c Pha rmacy Solu tions , LLC CITY, STATE. ZJP CODE, COUNTRY

Salt Lake City, UT 84 1 09 - 1479

STREET AODRESS

24 0 1 South Foothill Dr , Sui te D TYPE ESTABLISHMENT INSP€CTEO

Out sourcing Facility

EMPlOYEE(S) SIGNATURE DATE ISSUED

)Jl4f»17Zachary L Sta mm, I nvestigator 3/24/201 7 SEE REVERSE INayan J Pa tel, Invest i gatorOF THIS PAGE X Zachary LSt!mm _.. ~·-~~lll(iwrty i.,$C.I! ... •.$ I

FORJ\1 FDA 4SJ (09/08) PREVIOUS EDmON OBSOLETE fNSPECTIONAL OBSERVATIONS PAGE 4 OF 15PAGES

~~b) (4)1 for Testosterone Cypionateffestosterone Propionate 200/20mg/mL Injectable Solution from 1(b) (4) tas a result of consumer complaints associated with stopper brittling and coring. Your firm performed aj (b) (4) Jtitled "~D) (4) I' to demonstrate that the r (b) (4) :did not result in the same container closure integrity issues that were identified with f (b) (4) However, your firm failed to extend the scope of this investigation to detem1ine the impact of the closure system issues into the approximatel)(b) (4} lots of (6}(4 !distributed product on the market at that time.

E) Deviations - Your fim1 failed to perform investigations and determine the impact ofdeviation events on previous or future production. Additionally, your fiffi1 has not been able to provide documentation to support that the corrective actions stated in deviation documents occurred. For example, the following deviations are related to _(bJ (4) excursions fOI{{I::i} (4} j a) On three consecutive days from July 13th to July 15th 2016, the [ (b)(4) (D) ('l) I

l(l::i} (4} (b) (4) (b) (4) l Each deviation stated that the corrective action taken was that~l::i} (4 ) l"was red-tagged and removed from service until a calibration and system check is perfom1ed and the unit is cleared to return to service." However, batch records indicate the equipment was still used on the two days which followed the initial deviation event on 07/13/2016. The following three deviations occurred in July 2016 for lots of released product: i) DVN-16186 initiated on 07/13/2016 for lot 06002 for Methylprednisolone Acetate/Lidocaine

HCl 80/1 Omg/mL.

ii) DVN-16182 initiated on 07/14/2016 for lot 05045 for Methylprednisolone Acetate/LidocaineHCl 40/1 Omg/mL.

iii) DVN-16180 initiated on 07/15/2016 for lot 05052 for Methylprednisolone Acetate/Lidocaine HCl 40/1 Omg/mL.

b) Deviation document DVN-16197 initiated on 09/08/2016, for released lots 07023 and 07032 of Methylprednisolone Acetate/Lidocaine HC140/l Omg/mL, states that equipment~IJ) (4}1 [ (b) (4) the (b) (4) There was no investigation into this (b) (4) JAdditionally, DVN-16197 states that[(b} (4} I"is scheduled to be recalibrated during the week of 15 Sept 20 16." However, the Equipment Log for(6} (4Jldoes not indicate that recalibration occurred during the week of 15 Sept 2016 and

DEPARTM ENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT AODRESS AND PHONE NUIIBCR DATE(S) OF INSPECTION

6th & Kipling St . (P . O . Box 25 08 7) 2/22/201 7- 3/24/2017 * F EI NUMBERDenver, co 80225 -0087 3011752429(303) 236- 3000 Fax: (303) 236- 3100

NAME ANO TITlE OF lNOtV!OUAL TO \M-IOM REPORT ISSUED

William 0 . Richardson , CEO FU:tMNAME STREET ADORESS

Isomeric Phar macy Solut ion s, LLC 2401 Sou t h Fo o t h i ll Dr, Suite D CITY. STATE. ZIP CODE. COUNTRY TYPE ESTABLISHMENT INSPECTED

Salt Lake City , UT 84109- 1479 Outsourcing Facil ity

I EMP!.OYEE(SJ SIGNATURE DATE ISSUED

SEE REVERSE Zachary L Stamm, Investiga t or

lx lachiwy lSlamm

l/l4,/N11 3/24/2017 OF THIS PAGE Naya n J Patel , Investigator

bCMIJ L"-'-rn.e._.,t« SlgMIII,.,: f.KWI"fL S\1-·S

··oRM FDA 43J (09108) PREVIOUS EDITION OBSOLEI"E INSPlCflONAL OBSlRVATIONS PAGES OF IS PAGES

servicing records show that the equipment was never serviced between 11/23/2015 and 10/03/2016.

F) Media Fill Failures- Microbial growth observed during media fiBs lack investigations to include the potential impact to other commercial product produced during the same time period. During the media fills for Prednisolone Acetate Ophthalmic Suspension USP, 1%, (b) (4) media fills were documented as sterility failures. No investigations were conducted to determine the source of the repeated failures and no corrective and preventative actions were implemented wh ich would determine the impact on future production for· the following media fi lls: (b)(4) r

This is a r e(!eat observation from the (!revious FDA ins(!ection conducted June 20th-29th2

2016.

OBSERVATION 2 Procedures describing the handling ofall written and oral comQlai nts regarding a drug Qroduct are not followed .

Specifically,

Since the previous inspection, your firm has documented 33 customer complaints and none have been investigated. Although you have not fully evaluated these complaints as they may apply to past or future production of these products, your quality control unit continues to approve batches for distrib ution. Since the previous inspection (6/2016) your firm has released approximately(b) (4)batches of finished sterile drug product. Of these complaints there were:

I

A) Eleven unique complaints related to infection, pain, swelling or knotting at injection site fo r Testosterone Cypionate/Testosterone Propionate 200/20mg/mL (PN (b) (4 )). These lots were produced via[(o} (4} I

B) Six unique complaints related clumping in finished product, Methylprednisolone Acetate/Lidocaine

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMJNJSTRATION

DISTRICT ADORES$ AND PHONE NUMBER DATE($) OF INSPECTION

6th & Kipling St . (P.O . Box 25087 ) 2 / 22/2017- 3/24/2017* FEI KUMBER . Denver, co 80225- 0087 3011752429(303)236-3000 Fax: ( 303 )236- 3100

NAME AND TITLE OF INDIVIDUAL TOV<MOM REPORT ISSUED

William 0 . Richardson , CEO FIRM NAME STREET AOORESS

Isomeric Pharmacy Solut ions , LLC 2 401 South Foothill Dr , Suite D CITY. STATE. ZIP CODE. COUNTRY TYPE EST ASLISHMENT INSFECTEO

Salt Lake City , OT 84109- 1479 Outsourcing facility

EMPLOYEE(S) SIGNATURE OATEISSUED

SEE REVERSE Zachary L Stamm, Investigator )f2~t1 3/24/2017 OF THIS PAGE Nayan J Patel , Invest igator IX Zachary L Stamm

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FORM FDA 43J (09108) PRNIOUS EOtnON OBSOL<TE rNSPECT IONALOBSERVATIONS PAGE 6 OF I S PAGES

HCl40/1 Omg/mL (PN (b) (4J). Four of these six complaints involved lot 05052.

C) Five unique complaints related to black particles, fragments, or coring in Methylprednisolone Acetate/Lidocaine HC140/1 Omg/mL (PN (b) (4J) and Testosterone Cypionate/Testosterone Propionate 200/20mg/mL Injectable Solution (PN (b) (4J). These lots were produced via !0) (4Jj

0Cb} (4} and (o} (4} 1

OBSERVATION 3 An adeguate number of batches ofeach drug Qroduct are not tested to determine an am:1ronriate expiration date.

Specifically,

A) Product beyond use dates (BUD) are not adequately supported by stability studies. Your firm did not follow stability protocols in regards to the (3) minimum number of batches on stability, testing intervals, and statistical analysis. These BUD stability failures are reflective of the production process used to support current finished product production and distribution. Additionally, the data results collected as part ofyour real-time stability studies do not support your shelf-life conclusions. For example: a. Per MS-1920, revision date 11129/2016, Triamcinolone Acetonide 40 mg/mL Preservative-Free

has a BUD of 180 days. Your endotoxin specification for this intrathecal injectable product is no OCo} (4} I however, the stability lots 02052 and 0304 1 had out ofspecification t=O days endotoxin levels of 39.22 and 59.28 EU/mL, respectively. Additionally, the stability studies were not performed in the same container-closure system in which this product is marketed. During the stability study,Ro} (4Jl,ials were used for stability study lots while the product is marketed in a 2 mL vial.

b. Per MS-PN1200, revision date of05/12/2016, Testosterone Cypionate/Testosterone Propionate 200/20mg/mL has a BUD of 180 days[. (b) (4) of this product( (b) (4) , was included in your stability study. Additionally, for lot (b) (4) there was no sterility testing performed after the last passing sterility result of (b) (4 ) in support of a 180 day BUD.

DEPARTMENT OF H EALTH AND HUMAN SERVICES FOOD AND DRUG ADMiNISTRATION

DISTRI CT ADORESS AND PHONE NUMBeR DA Tl:(S) OF INSPECTION

6 t h & Kipl ing St . ( P. O . Box 2 5 087 ) 2/22 / 2 0 17- 3 / 24/2 0 1 7* FEI NUMB<.RDe n ver , co 80225-0087 30117 5 2 4 2 9 ( 303) 2 3 6-3000 Fa x: (303 ) 236- 3100

NMdE AND TITLI! Of' INOIV!OUAl TO WHOM REPORT ISSUED

William 0 . Richardson , CEO FIRM NAME STREET ADDRESS

I someric Pharma c y Solut i o n s , LLC 2401 South Foothil l Dr, S u ite D CITY, STAn;, liPCOOE. COUNTRY TYPE ESTABUSHMENT INSPECTED

Sa lt La ke City, UT 8 4 1 09- 1 4 79 Outsou r cing Facility

EMPI.OYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE OF THIS PAGE

Zacha ry L S t a mm, I n ve s t i gato r Na y an J Pa t el, I nvestiga t or IX Zachary l Sli>mm

""""" 3/24 / 2017

Z~LSb.rm

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FORM FDA 483 (09108) PREVIOUS EDI00:-1 oesot.ETE JNSPECTIONAL OBSERVATIONS PAGE 7 OF 15 PAGES

B) Additionally, seven of the ten BUD stability protocols reviewed do not appropriately specify container storage conditions to ensure that drug product comes in contact with the closure system. These protocols state vials should be stored upright or do not state the storage position of vials.

This is a reueat observation from the urevious FDA insuection conducted June 20th-29th~ 2016.

OBSERVATION 4 Deviations from written production and process control procedures are not recorded and justified.

Specifically,

There is not adequate written justification for re-work process deviation from your master batch records (MBR). Deviation No. DVN-16269, documents the planned re-work procedure of lots 09021 and 09029,ofTestosterone Cypionate 200 mg/mL/Testosterone Propionate 10 mg/mLNitamin D3 200 IU/mL (PN(b) (4) that failed finished product assay for Vitamin D3 (lot 09021=41.62% and 09029=47.32%). In the "Justification" section ofDeviation Form, FRM-850-02-02, you did not address potential quality risk's associated with process deviations from your val idated procedures listed in your Master Batch Record.

This is a reueat observation from the urevious FDA insuection conducted June 20th-29th~ 2016.

OBSERVATION 5 Procedures designed to prevent microbiological contamination of drug nroducts purnorting to be sterile do not include adeguate validation of the sterilization process.

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD A.N1) DRUG ADMINJSTRAT JON

Ot$TRICT ADDRESS AND PHONE NUMBER OATE(S) OF INSPECTION

6 t h & Kiplin g St . (P. O. Bo x 25087) 2 / 22/201 7- 3/24/2017 * FEI NUMBERDen ver, co 8022 5 - 0 0 87 30 11752 42 9( 303)236- 3 00 0 Fax: (303)236 - 3 1 0 0

NAME AND TITlE OF INDIVIDUAL TO WHOM REPORT ISSUED

Wi lliam 0 . Richardson , CEO FIRM NAME STREET ADDRESS

Isomeri c Pha rmacy Solu t ions, LLC 240 1 South Fo othil l Dr, Suite D CITY, STATE, ZIP COOE,COUNTRY TYp-E ESTABLISHMEN T INSPECTED

Salt Lake City, UT 8 41 0 9-14 79 Outsourc ing Fa c i lit y

EMPl OYEE($ ) SIGNATURE OATEISSUED

SEE REVERSE OF THIS PAGE

Zac ha ry L Stamm, I nvestig a t o r Naya n J Patel , I nve stiga t o r lX Zachary l ~mm

IIWlO" 3/24/2017

Z.W..IlL~

lmot~~otii:W

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FORM fDA 4U (09/ 03) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 8 O F 15 PAGES

Specifically,

A) Written procedures and cleaning practices for your ISO 5 hoods in the ISO 7 ~o) (4) IRoom could lead to contamination of the aseptic production area. For example: a. Grates were removed from the ISO 5 hoods by operators, set on the floor and leaned against

walls of the ISO 7 suite for cleaning. There was no recertification of the ISO 5 hoods after cleaning. Your cleaning SOP, SOP-302-01, does not include details on HEPA recertification after cleaning and approved cleaning agents to use during cleaning.

B) Your firm has not performed process validation or media fills for the aseptic production of Phenylephrine HCl/Tropicamide 2.5%11% ophthalmic solution since a process change occurred in approximately [ 115)~(4) . For example, the following critical steps were added to MBR-1300-01, Rev D, without validation : a. Step(~) I b. Steps (o) (4) c. Steps (b) (4)

1 I

C) Your in situ air pattern analysis (smoke studies) were not conducted under dynamic conditions simulating routi ne production processes (i.e. aseptic operations conducted by processing employees).For example:

a. Smoke studies did not evaluate operators introducing processing equipment or components into the ISO 5 areas or normal aseptic vial/dropper fil ling operations conducted by processing employees.

b. Smoke studies did not evaluate whether operators or activities in the ISO 7 suite affect the unidirectional airflow from the HEPA filters in the ISO 5 hoods where sterile drug products are produced. On 2/23/2017, during production of Triamcinolone Diacetate 40 mg/mL, Lot 13026, operators were observed walking behind operators working in the ISO 5 hood.

D) Currently there are no procedures to ensure the aseptic conditions are appropriate for sterile producti on after l (b)_(4) the HEPA air handling system. As part ofyour ~o) (4) cleaning, you

DEPARTMENT OF HEA LTH AND H UMAN SERVI CES FOOD AND DRUG ADMIN1STRATION

D ISTRICT ADDRESS AND PHONE NUI.'JlER

6th & Ki pl i ng St . (P.O. Box 25087) Denver , co 80225 - 0087 (303)236 - 3000 Fax : (303)236- 3100

NAME AND T ITLE OF !NOIVIOUAL T O WHOM REPORT ISSVE.O

Wi ll i am o. Ri chardson , CEO F IRM NAME STREET ADDRESS

OATE(S) OF INSPECTION

2/22/2017- 3/24 /201 7* FEI MJMB;ER

301 1 7 52429

Isome r i c Pharmacy Solut ions, LLC 2401 Sout h Foothil l Dr, Suite D C ITY, STA TE. ZIP COOE. COUNTRY TYPE ESTABLISHMENT IN SPECTED

Salt Lake City , UT 84109- 1479 Outsourcing Faci lity

EMPLOYEE(S) SIG NATVRE DATE ISSVEO

SEE REVERSE OF THIS PAGE

Zac h a ry Nayan J

L S t amm, I nves t igator Pa t e l, I nvestigator IX lacllary L Stlmm

lll<Vll011 3/24/2017

Ui(!Wry LSUt~~tn ............ ~~l.Jdllry L SU111'!1·S

FORl\1 FDA 483 (09/08) PREVIOUS EDITION OBSOLETIO INSPECI'IONAL O BSERVATIONS PAGE 9 OF 15 PAGES

are(b) (4) JHEP A air filtration system without re-certifi cation to conduct (b) (4) ~;er your cleaning SOP-302-01. For the (b) (4)

(b) (4) heHEPA filtratiOn system ls!(b) (4) p essure differentials are not mai ntained between your ISO 5, ISO 7, and ISO 8 classified areas.

This is a re~eat observation from the Qrevious FDA insQection conducted June 20th-29th2 2016.

OBSERVAT ION 6 EguiQment used in the manufacture, Qrocessing, Qacking or holding of drug Qroducts is not of appropriate design to faci litate operations for its intended use and cleaning and maintenance.

Specifically,

Since approximately 6/2016, your firm has used an un-calibrated and un-qualified in-house built (b) <4.n ( · · ..(b)(4) to evaluate th6 (~). (4) I to render injectable finished drug roducts free of objectionable microorganisms. There have been approximately

(b) <4)lots of(b) (4) product produced and released using this piece of equipment.

OBSERVATION 7 There are no written procedures for Qroduction and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are reQresented to possess.

Specifically,

Your firm has failed to validate your ~D) (4) ~process used during the processing of bulk/,(oH4> ]suspension products (e.g. all Methylprednisolone Acetate and Triamcinolone products). Additionally, your firm has not qualified your ,(b) (4) Iunits.

A) During production, there is no in-process check for particles size to ensure product is (o) (4) I

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINJSTRATION

OISTRW::T ADORESS AND PHONE NUMBER OATE(S) OF INSPECTION

6th & Kipling St. ( P . O . Box 25087) 2/2 2 / 2017 - 3/24/2017 * FEINUMBER Denver, co 80225-0087 30 11752429(303)236 - 3000 Fax : (303)236-3 1 0 0

NAME AND TITLE OF IN OtVIOUAl. TO WHOM REPORT ISSUED

Will i am 0 . Richardson , CEO FIRM NAME

I someri c Pharmacy Solu t ions , LLC CfTY, Sl ATE, ZIP CO DE. COUNTRY

Salt Lake City , UT 84109-1479

STREET ADDRESS

2401 South Foothil l Dr , Su i te D TYPE E ST A8LISHMEN T INSPECTED

Outsourcing Facil i t y

EMP.OYEE(S) SIGNATURE OATEISSUEO

l~l?Zachar y L St amm , Investiga t orSEE REVERSE 3/24 /20 1 7 Nayan J Pa t el , I n vestigatorOF THIS PAGE I X ZliCI\aty L Stamm

z...No') \.SWMfl.._ St;l:>Mir)': l.cil.fi'I' L S:UII"'n ·~

FORM fDA 483 (09/0S) PR£ vtOUS EDrriON OBSOLETE INSPECTIONAL OBSERVATIONS PAGe IOOF IS

PAGES

B) NCR-16 160 for lot 09007 (P (b) (4)), documents on 10/10/2016, "After visual inspection, majority of vial contained clumps of drug_Qroduct, varying in size and quantity, which could not be [ .i~li4) J f j " Your (I>} (4} lrrocess was identified as the root cause. The batch was "reprocessed" on al(o}(4} ~ re-visually inspected, and released by your QA unit on 10/ 17/2016.

C) On 2/28/2017, during visual inspection of lot 13027 (PN;(I:>} (4 ) finished product visual inspectors were observed removing vials with apparent "clumps" even after~o} (4} )the vial. The visual rejectvials observed with " clumps" were set aside for use as fini shed product samples and were not identified nor documented as visual inspection rejects on the batch record.

D) Since June 2016, there have been six customer complaints (covering lots 04031, 05052, 06002, 06021, and 06034) related to clumping and unable to draw product up in syringe.

OBSERVATION 8 The guality control unit lacks authority to review groduction records to assure that no errors have occurred and fully investigate errors that have occurred.

Specifically,

Your quality control unit fails to review and approve records without completely investigating these records for errors. For example:

A) None of the eight drug product stability protocols which your firm uses to support BUD for conunercial product on the market have been reviewed and approved by your yuality control unit. For example, the Document Post-Approval for Methylprednisolone Acetate/Lidocaine HCl 8011 Omg/mL states " By review and acceptance of this complete protocol, an appropriate stability period for Methylprednisolone Acetate/Lidocaine HCl 80/lOmg/mL has been determined." The D ocument Post-Approval has not been reviewed and approved by your quality control unit but your

DEPARTMENT OF HEALTH AND HUMAN SERVICES fOOD AND DR UG ADMINISTRATION

DISTRICT AOORESS AND PHONE NUMBER OATE(S) OF INSPEC1"10N

6th & Ki pl ing St. (P .O. Box 25087) 2/22/2017- 3/24/2017 * Denver , co 80225- 0087 (303) 236- 3000 Fax: (303) 236-3100

FEINUM8E~

30117524 29

NAME AND TITLE OF INDIVIDUA L TO WHOM REPORT ISSUED

Wi ll iam 0 . Richardson , CEO FIRM NAME

I some r ic Pharmacy Solutions , LLC CITY, STATE, ZIP CODE, COUNTRY

Salt Lake City, UT 84109- 1479

STREE1" ADDRESS

2401 South Foothill Dr , Suite D TYPE ESTABLISHMENT INSPECTED

Outsourci ng Facility

EMPlOYEE($) SIGNATURE OATE ISSUEO

SEE REVERSE OF THIS PAGE

Zacha ry L Stanun, I nvest i gator Naya n J Pa t el , Investigator IX Zachary l Slllmm

IIW>I>J 3/24/2017

bctY.ty l su­......... SIGMdi:PJ: bd'oNyL St~rn~~.S

FORM FDA 483 (09108) PREVIOUS EDITlON OBSOLETE JNSPECTlONAL OBS ERVA TJONS PAGE II OFI5 PAGES

firm uses the data obtained from this stability protocol to support the 180 BUD for Methylprednisolone Acetate/Lidocaine HCl 80/1 Omg/mL.

B) The performance qualification of[(o} (4 } (VPQ-015), page 1 documents the quality assurance review and approval on 0 1/20/2017. Pages 5 and 6 of this approved document (VPQ-0 15) contained required tables which were not completed: a. All personnel participating in the execution ofthe protocol. b. Equipment and materials used in the execution of the protocol.

C) Document Change Order, DC000079, documents the quality assurance review and approval of the master batch record for Triamcinolone Acetonide 40 mg/mL Preservative-Free which was signed offby quality assurance on 03/15/2016. Pagel ofthe master batch record states the fonnulation number is(b} (4 } which corresponds to Triamcinolone Acetonide/Lidocaine HC140/l0mg/mL.

OBSERVATION 9 The senarate or defined areas and control sxstems necessary: to 12revent contamination or mix-u12s are deficient.

Specifically,

Steps are not taken to prevent contamination ofdrug product and defined classified areas of your facility. For example:

A) Operators, including those who weigh potent raw ingredients, are permitted to reuse non-sterile gowning increasing the likelihood ofdrug product cross-contamination. Operators are permitted to reuse foot covers, hair nets, and lab coats at their discretion and use the same gowning day after day.

B) On 02/23/20 17, a steril e room operator was observed continuously crossing over the line of demarcation defining the ISO 7 and ISO 8 designated areas of the ISO 7/8 Ante Room while

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DISTRICT AOORESS AND PHONE NUMBER OATE(S) OF INSPECTION

6th & Kipling St . ( p . 0 . Box 25087) 2/22/2017 - 3/24/2017* FE INUMBCR Denve r , co 80225- 0087 3011752429(303 )236-3000 Fax : (303) 236-3100

NAME A ND Tl f L.E OF IN OIVIOUAL TO WH0.'-4 REPORT ISSUED

William 0 . Richa r dson , CEO FIRM NAME

Isomeric Pharmacy Solutions, LLC CITY, STATE. ZIP CODE. COUNTRY

Salt Lake Ci ty , UT 84109 -1 479

STREET ADDRESS

2401 South Foothill Dr , Suite D TYPE ESTABLISHMENT INSPECTED

Outsourcing Facilit y

EMPI.OYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE OF THIS PAGE

Zachary L St amm, I nvestigator Nayan J Patel , I nvest i gator

~

lX Zad1aty L Stamm

3/24/20 17

bctlarrLStu rn ,_b;olll,)l

$~1Jr: %Mr...<yLSlflmi·S

FORM FDA 433 (09/08) PREVIOUS EDI110N OBSOLETE JNSPECTIONAL OBSERVATlONS PAGE 12 OF IS PAGES

conducting sporicidal cleaning. The operator did not change gowning during this process and was observed crawling on the floor between ISO 7 and ISO 8 classified areas.

C) During a cleaning on 02/23/2017, we observed an operator rolling a cart over the demarcation linebetween the ISO 7 and ISO 8 classified areas. This cart, wh ich holds your ,(b) (4} I isnot monitored as part of your finn ' s environmental monitoring program per SOP-607-01.

This is a reneat observation from the nrevious FDA insnection conducted June 20th-29th2 2016.

OBSERVATION 10 Emgloyees are not given training in the garticular ogerations thex 12erfonn as gart of their function, cunent good manufacturing 12ractices and written 12rocedures reguired bx cunent good manufacturing gractice regulations.

Specifically,

A) Employees conducting visual inspections of finished sterile injectable drug products for critical defects (including particulates) are not adequately trained and qualified. For example: a. On 2/2112017, a batch of Triamcinolone Acetonide 40 mg/mL Preservati ve-Free Injection, lot

13023, was(o) (4))isually inspected by your visual inspectors and 18 vials were rejected. On or about 2/22/2017, your phannacist observed (15} (4) additional vials with un-identified b lack particles during (b) (4) J. This batch has not received final disposition by QA.

b. T he two employees were not qualified per your firm's SOP-913-01 , Visual Inspection of Finished Sterile Products, REV B. Additionally, employees were observed not following xour SOP by conducting inspection ofsolutions f (b) (4 ) (b) (':l) -~[(I>) (4)

I

B) Employees who produce drug products are not properly trained on written procedures relating to their job functions. Employees who conduct operations in the ISO 5 and ISO 7 classified suites were observed not gowning in accordance to clean room garb SOP-303-01 Rev B, with a revision date of

DEPARTMENT OF HEALTH AND HUMAN SERV ICES FOOD AND DRUG ADMINISTRATION

OISTRJCT A.OORESS ANO PHONE N UMBER OATE(S) OF INSPECTION

6th & Kip l ing St . (P . O . Bo x 25087) 2/22 / 20 17- 3 / 2 4 /20 17* Denver , co 80225-0 087 FEI NUMBER

(303)23 6-300 0 fax : (303 ) 236-3 100 3011 752429

NAME: AND T ITLE OF INOtVI OVAL TO WHOM REPORT ISSUE.O

Wi lliam 0. Richa rdson , CEO FIRM NAME STREET AOORESS

Isomeri c Pharmac y So l u t i ons , LLC 240 1 South Foothill Dr , Suite 0 CITY. ST 1\TE. ZIP CODE. COI.JNT RY TYPE ESTABtiSHMENT IN SPEC TED

Sa lt La ke Ci t y, UT 84 10 9-1 47 9 Outsou r cing Facilit y

EMPI.OYEE( S) SIGNATURE OATEISSVEO

SEE REVERSE Zacha r y 1 Stamm, I n vestigator ''"'".!! 3/24/2017 OF THIS PAGE Naya n J Pa t el , Investigato r IX zadlaoy t Stamm

lJid'wlf'l~~-.,..e.1ot S91cdbf: ~IVL. SU..•S

FORM FDA 48J (09108) PREVIOUS EDITION OBSOLETE INSPECTIONAL OBSERVATIONS PAGE 13 OF IS !'AGES

12119/2016. We observed the following examples of employees violating clean room gowning procedures while dolUling sterile garb for clean room access: a. On 02/27/2017, an operator wearing sterile coveralls, was observed leaning against the western

ISO 7/8 Ante Room door as she attempted to don sterile boot covers prior to conducting operations in the ISO 7 suite.

b. On 02/22/2017, a sterile room operator was observed first donning sterile boot covers and then eye-wear prior to entering the ISO 7 suite to (15) (4) J Cyanocobalamin/Methionine/Inositol/Choline Cl 1/25/50/50 mg/mL, lot 13025. Per section 8.4.10 through 8.4.11, operators must f (b ) (4) ..

c. On 2/22/2017, an operator was observed dolUling a new pair of sterile gloves directly over an older pair of gloves. Section 8.4.11.3 states "Aseptically don a new pair of sterile gloves. Remove current pair of sterile gloves from hand. Apply 1(15) (4 ) to hands and allow to ((6)(4) "1 ,

T his is a r eneat ob servation from the n revious FDA insn ection conducted J une 20th-29th 2 2016.

OBSER VATION 11 Testing and release of drug Qroduct for distribution do not include armroQriate laboratory determination of satisfactory conformance to the final specifications prior to release.

Specifically,

Your firm is not currently conducting any finished product testing for particulate matter in your sterile drug products. You have no scientific justification to support not testing all finished sterile drug products for paniculate matter. Furthermore, your Material Specification sheet for Testosterone Cypionate 200 mg/mL, Testosterone Propionate 10 mg/mL, and Vitamin 03 200 IU/rnL (PN (b) (4), effective 2/ 17/2017, requires testing per USP <788> Particulate Matter in Injections.

OBSERVATION 12

OE.PARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMfNISTRATION

DISTRICT ADDRESS AND PHONE NUM8ER

6th & Kipling St . (P . O . Box 25087 ) Denv e r, co 80225- 0087 ( 303} 236- 300 0 Fax: ( 303 ) 236 - 3100

NAME AND liTLE OF INOtVIOUAL TO WHOM REPORT ISSUED

William 0 . Richardson I CEO FIRM NAME STREET ADDReSS

I someri c Ph armacy Solutions , LLC 2 4 01 South Footh i ll Dr , Sui te D CITY, STATE. ZIP CODE, COUNTRY

Sa lt La ke City , lJT 8 41 09- 1 47 9

OATE(S) OF INSPECTION

2 / 22/201 7-3/24/2017 * FEI NUMBER

3011752429

TYPE ESTAB LISHMENT INSPECTED

Outsourci ng Facili t y

SEE REVERSE OF THIS PAGE

EMPLOYEE(S)SIGNATURf DATE ISSUED

Zachary L Stamm, Invest igator

IX ZacN<y L Sl3mm

""""" 3/24/2017 Na y an J Patel, I n vest i gator

h•"'-"1 ~ Q.o,...., I!me~

Sq:\otd 111: Z..:Nty I..~lim·$

FORM Fl>A 483 (09/03) PAGES

PR£\~Ol!S EDmON OBSOlETE INSPECTIONAL OBSERVATIONS PACE 14 OF IS

Test grocedures relative to aggroQriate laboratory testing for sterility and gyrogens are not written and followed.

Specifically,

The suitability of the sterility method, USP <71>, Steri lity Tests, used by your contract laboratory to conducted sterility testing on all your finished products was not completed prior to conducting sterility testing. The method suitability for Triamcinolone Diacetate 40 mg/mL (sterile intramuscular injection), P'N(b) (4)], and Triamcinolone Acetonide 40 mg/mL Preservative-Free Injection (sterile intrathecal/epidural injection), PN (o)(4) , were both completed 2/2112017. From 6/2016 to 2/21/2017, you have produced and released(bll"10t$ ((6) (4) vials) ofTriamcinolone Diacetate 40 mg/mL and<bH4>ots ((o) (4~ vials) of Triamcinolone Acetonide 40 mg/mL Preservative-Free Injection.

OBSERVATION 13 Routine calibration ofautomatic and electronic eguiQment is not gerformed according to a written grogram designed to assure gro12er gerformance.

Specifically,

Since installation in 1/2015 to the beginning of this inspection 2/22/2017, your firm has never re­calibrated your l(l5) (4 ) ~~s part of your ISO 5, 7 and 8 1(b) (4) . During this inspection, your (o) (4) 1

f6) (4) jwere re-calibrated and the, (b) (4) in(b) (4)[S0 5 hoods ((b) (4) Iwere found to be out oftolerance.

1

OBSERVATION 14 Written grocedures are not established and followed for the cleaning and maintenance of eguiQment, including utensils. used in the manufacture. processing. packing or holding of a drug product.

Specifically,

DEPARTMENT OF HEALTH AND HUMAN SERVlCES FOOD AND DRUG ADMINISTRATION

DISTRICT AOORESS ANO PHONE NUMSER

6th & Kipling St . (P.O . Box 25087) Denver , co 802 25-0087 (303)236-3000 Fax : (303)236- 3 1 00

NAME ANO TITLE OF INOIVIOOAL TO WHOM REPORT ISSUED

William 0 . Ric ha r dson , CEO fiRMNAMf STREET ADORESS

Isomeric Pharmacy Solut i ons , LLC 2401 South Foothill Dr , Suite D C ITY, STATE. ZIP COOE. COONTRY

Salt Lake City , UT 84109- 1 479

OATE(S) OF INSPECTION

2/22/2017-3/24/20 1 7 * FEI I'AJMBER

3011 752429

TYPE ESTABLISHMENT INSPECTED

Ou t sourcing Facility

FORM FDA ~SJ (091"08) PREVIOUS EDmON OOSOLETE I NSPECTI ONAL OBSERVATIONS PAGE 15 OF 15

PAGES

Your firm lacks adequate written procedures for the use of the (o} (4} _jagent in your ll(b} (4} to ensure cleaning of sterile suites prevents contamination. For example:

A) Your ~b) (4} ~agent is r (b) (4 ) Jper the manufacturer's direction for use.

B) The l(ll} (4} lis stored uncovered in the un-classified laboratory area and not cleaned prior to use in the ISO classified suites.

*DATES OF INSPECTION 2/22/2017(Wed),2/23/2017(Thu),2/24/2017(Fri),2/27/2017(Mon),2/28/2017(Tue),3/0l/2017(Wed),3/0220 17(Thu),3/03/20 17(Fri),3/13/20 17(Mon),3/14/20 17(T ue),3/15/2017(Wed),3/16/20 17(Thu),3/17 /20 17Fri),3/23/20 17(Thu),3/24/2017(Fri)

/ (

Jn•no11

X Nayan J Patel Nayan J ~tel

lnvest9at0f Signed by : Nayan J . Patel ·S

SEE REVERSE OF THIS PAGE

I

EMPI.OYEE(S) SIGNATURE

Zachary L Stamm, Inves t iga torNaya n J Patel, I nvestigator

,_,

IX lad>afV LStamm tlod\lt'1l$l.lll'm llo¥atf;6\0I ~by:l:.CI\Wy i.. St•MW• $

DATE ISSU EO

3/24/2017