DEPART1"!ENT OF HEALTH AND HUMAN SERVIC ES FOOD AND DRUO ADMIN ISTRATION

OISl T AOORESS ANO PHOr-E MJMBER

8050 Ma rsha ll Dr ive, Suite 205 Lenexa , KS 66214 (913) 495-5100 f'ax : (91 3) 495 - 5115

www. fda.gov/oc/industry

0A1E(S) C* INSPE~l'ION

05/ :2/20 15 - 05/22/201 5*

30037 18003

0

TO: Justin M. Kohll, Vice Pr esident FIRM NAM€

Essential Pharmacy Com ounding STREET ACORESS

62 0 N 114 th St CITY STATE, Z:P COOE. COUNTRY

Omaha, NE 68154-1571 TV E ESTASUSHMEH'T INSPECT£.0

Producer of sterile drug products

This document lists observations made by the fDA represemative(s) during the inspection of your faciliry. They l\J'e 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 reprcsentat ive{s) during the inspection or submit t.his information to FDA at the address above. If' you have any questions, please contael FDA at the phone number and address above.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

The observations below pertain to your production of human and veterinary sterile drug products.

OBSERVA TlON 1

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile do not include adequate validation ofthe sterilization process.

Specifically,

a) Smoke studies showing static ai rflow patterns in sterile production areas do not have a documented evaluation by management. Smoke studies conducted under dynamic conditions are not documented.

b) An operator was observed on 5/12115 producing sterile drugs (in your ISO 5 classified hood) not following procedures requiring' In addition, the same operator was observed with arms resting on surfaces ofthe flow hoods (JSO 5) whi le producin g sterile drugs.

c) Media fills performed by the technicians for srerile injectable human and animal drugs have not been performed under representative worst case aseptic processin conditions to assure the steri lity of drug products. Your procedure for media fill is to prepare with media for incubation . This is in contrast to the higher vol ume batching of at most of sterile injectable human (b) (4)

d) (b) (4) utilized as the primary sterilization step in producing steri le injectable human and an imal drugs have not been challenged to establish upper bio-burden limits. The bio-burden of incoming

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F'ORM FDA <!.) ( 09/01)

t.OYEE(Si SICNATURE

Z: ;::i c M. Mue ller , Investigator~ Joseph R. Lambert, Investigator Jenny A. Agila Sefen, Investigator

PREV".OU'S EDITION 0Bsol£i E INS P ECTIONAL OBSERVATIONS

OAlE ISSUCO

05/22/2015

PAGE I OF 1 PAGES

DEPARTMENT OF HEALTH AND HUMAN SERVJCES FOOD AND DRUG ADMINISTRA T!ON

E.SS i'J'IO PHONE >~U~<eEf\

Suite 205 05/12/201 5 - 05 /22/20 15+ J!EI ~MBER

300 3718003

J ustin M. Kohl l , Vice President Sl REET ADORESS

Omaha, NE 681 5 4-1571 Produc er of steri l e d r u products

non-sterile active pharmaceutical components is not evaluated and limits have not been established for non-sterile active pharmaceutical fonnulated product ensuring sterilization steps are adequate to remove microbiological load.

OBSERVATION 2

Clothing of personnel engaged in the processing of drug products is not appropriate for the duties they per form.

Specifically,

a) Your employees have exposed eyes and forehead area in the clean room ("Buffer room" ISO 5 area) where sterile drug products are produced.

While cleaning, an employee was observed on 5/12/15 placing exposed forehead/eyes, and upper body, inside of the ISO 5 laminar airflow hood where sterile drug products are produced.

b) Sterile gowns, known as "bunny suits" covering the body, legs, head and arms of employees can be reused if exiting and reh1rning to sterile drug production areas.

OBSERVATION 3

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

For Example:

a) Environmental mon itoring (viab le, non-v iable, personnel) is not conducted daily during ~n areas where sterile drug products are produced. ~conduct fingertip sampling~per employee, surface microbiological sampl ing~, and air sampling (viables and non-viables) . Steri le drug production occurs II% of workdays throughout the year at your site, as management stated on 5/ 14/ 15.

b) Pressure differentials are not recorded in between rooms where sterile products are produced. Specifically not recorded are room pressure differentials from the "Buffer room" to "Ante Room". The

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FORM fOA 43l (0911)8)

Er i c M. Mue l l e r, Investigator J o seph R. Lambert, Investigator Jenn y A. Agila Sefen, Inv estiga t or

INSPECTIONAI.. O.BStQVA TIONS

05/22/20 15

PAGE ~ Of 1 PAGES

OEPART MfNI OF HEALTH AND HlJMAN SERVICES FOOD AND DR UG AOMI NISTRATIOl-1

OISTAICT AOORESSAA'()PHO+IE NUMBER OATf{$) Of INSPECTIO+I

8050 Marshall Drive, Sui t e 205 OS/1 2 / 2 C1 5 - 05/22/201 5* Lenexa, KS 662 14 J:'E! NVMBE.R

(9 13) 4 95 - ~100 f ax: ( 913 ) 495 - 5 115 3003718003 Ind ustry In forma t ion: www.fda . gov/o c/indus t ry HAMEAtN nTlE <J> INDIVIDUAL TOWHOM~EI'QR ISSUED

TO: J ustin M. Kohll, Vice Presiden t f;IR,r.t NAME. STREET ADDRESS

Essent i al Pharmacy Compounding 62 0 N 11 4Lh St Cl1'. STATE. zoo CODe. COUNTRY TYPE ESJABUShME.'T I>.SPECTED

Omaha, NE 6815 4-157 1 Pr oducer o f s t eri l e dr ug products

"Buffer Room" is where you r site has llll ISO 5 hoods where sterile products are produced. There is no assurance that positive pressure is maintained in the buffer room during sterile drug operations.

OBSERVATION 4

There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been al ready dist ributed.

Specifically,

Your investigation, into positive growth found on surface contact plates dated 4117/lS, does not identify a root cause or corrective action. Positive contact plate results were obtained during routine environmental monitoring in steri le production areas.

Furthermore, this investigation does not evaluate potential trends of other positive microbial contact plates documented in the sterile production areas of your site.

OBSERVATION 5

Buildings used in the manufacture, processing, packing or holding of drug products are nol mai ntained in a clean and sanitary condition.

Specifically,

a) Floors in areas where sterile drug prod ucts are produced appear to have build-up that is difficult to clean and visually eviden t. Additionally, there are black marks on the floor which appear to be from the ti res of movable carts used in sterile production areas.

b) There is the presence of a tall chair located in the "buffer area" of the facility. Th is chair, which appears to be difficult to clean due to construction design and mat,eria l, is located directly in front of a laminar airflow hood where sterile drug products are produced.

EAAP\.OY'fE($) SGNAIVRE. OAlE I :iS\! ED

Er i c M. Muelle r , Investiga t or ~ ~ SEE REVERSE Joseph R. Lamber t , I nvest i ga t or OF THIS PAGE Jenny A . Agi la Sefen, Investigator C)A 05/22/20 15

fO~~~ f'DA •SJ (09/0S) PR& VIOUS W IT ION OOSOl€1< INSJ>ECTJONAL OBSERVATIONS PAGE j Of1 PAGES

DEPARTMENT OF IlEAL Til AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

OATE(S) Of INSPECTION

8050 Marshall Drive, Suite 205 Lenexa, KS 662 14

05/ 12/2015 - 05 /2 2/ 2015* F N\JtA8ER

(913 ) 495-5 100 Fax : (913) 495-5115 30037!80 03 Industry Information: www.fda . gov/oc/industry

TO : Justin M. Koh li, Vice President

620 N ll4th St f'tPE ESTASUSMMENT INSP ClEO

Omaha, N8 681 54- 1571 Producer of sterile drug roducts

OBSERVATION 6

Each component is not tested for conformity wi th all appropriate wrinen specifications for puri ty, strength, and quality.

Speci tical I y,

Incoming non-sterile active pharmaceutical ingred ients (API) utilized in producing steri le in · ble human and animal dru are not tested for endotoxin or microbial growth. Instead,

prior to the API use in sterile injectable drugs. This is important you received Acetyl lucosamine from your supplier and utilized this API in sterile animal

fin ished batch Acetyi-0-Giucosarnioe 100 mg/mL, 100 mL, lot 040l2015@40which resu lted in an out­of-specification value for endotoxin. You concluded the root cause of the out-of-specification to be the Acetyi-D-Glucosamine API. The process utilized by the sterile operat ions at your firm was not capable of preventing endotoxin from contaminating the final dosage unit. Additional ly, your supplier of this API did not include endotoxin testing results on their certificate of analysis.

OBSERVATION 7

Written procedures are not established for the cleaning and maintenance of equipment, incl udi ng utensils, used in the manufacture, processing, packing or holding of a drug product

Specifically,

The contact dwell time for (b) (4) , which is util ized as your sporicidal agent in your clean room, has not been established with support of scientific data. A techn ician was observed on 5/14/15 cleanin the ISO 5 hood in your firm's anteroom. The •• · , • \U) \q) J\UJ \q)

\U)\q) j \U) \'+) ISO 5 hood (b) (4) (b) (4) (b) ( 4)

OBSERVATION 8

Written procedures are not followed for the receipt, identification, storage, handling, sampling, testing, approval, and rejection of components, drug product containers, and closures.

Specifically,

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FORM FDA 483 (Oll108)

EMPLOYEE($) S!CW.lVR,f

Eric M. Muell er, Investigator Joseph R. Lambert, I nvestigator Jenny A. Agila Sefen, Invest igator

PlllMOUS lil'l!TICN OO"'li.ETE INS I'ECTIONAL OBS£RVA TIONS

OATE ISSUE:O

05 / 22/201 5

PAGE • OF? P.-\GES

DEPARTMENT OF HEALTH AND HUMAN SER YIC£S FOOD AND DRU<i ADMINISTRATION

OtST RICT AOORESS ANO PltONE NUMBER OATE{S) OF INSPECTION

8050 Marsha l l Drive, Suite 205 05112/2015 - 05/22/201 5* Lenexa, KS 662 14 FEI N!Jt.40ER

(91 3) 495-510 0 rax: {913) 495 - 5115 30037180 03 Industry Information: www .fda.gov/oc/ind~srry NAME ANU TnlE OF INOIViUUAI. TO V"moid REPORT ISSUtO

TO: Justin M. Kohll, Vice Presiden t fiiiM"""'E STREET AOOf<ESS

Essentia l Pharmacy Compoundi ng 620 N 114 th St CAT'<, STATE. :UP COOE. C:>Uifl'RV riPE EST>a.IS""'ENT INSPECTEO

Omaha, NE 68 154-1571 Producer of steri l e drug products

Sterile vials of all sjzes utilized in the production of sterile injectable human and animal drugs cannot be traced after removal from the suppl ier's case packaging. On 5114/15, mul tip le unma rked trays of vials with no lot identificat ion were observed in the anteroom which could nor be traced to a specific lot of sterile vials.

OBSERVATION 9

There is no \VI'itten testing program designed to assess the stability characteristics of drug products.

Speci ff ca II y,

Assurance of sterility at theli day time point for your bu lk sterile components of Papaverine, Phentolamine, and Alprostadil (which are labeled to be "BUD" otil days) are not supported by actual microbial testing resu lts. These three components are ut il ized in the fina l human sterile injectable product Papaverine/Phentolamine/ A lprostadil 30mg/ I mg/20mcglm L.

OBSERVATION 10

Laboratory controls do not incl ude a determination of conformance lO appropriate specifications for drug products.

Speci tically,

Potency testing is not perfonned on any sterile injectable human and animal drugs produced at your firm. For example, there have been approximately I

II batches equaling. via ls of human Chorionic

Gonadotropin 4,000 unit, batches of human Testosterone sterile pellet I 00 mg injectable, I batches of animal Yohimbine I 0 mg!mL, and II batches of animal Caco-Iron-Copper 6.4 rng!mL injection produced from 1/1/15 to 5/14/15 without confirmation of potency label claims.

EMPI.OYEE(S) SlONAT'UAE OATetSSUED

Er i c M. Mue l ler, Investigator

I tV SEE REVERSE Joseph R. Lambert, I nvestigator 05/22 /2015

OF THIS PAGE Jenny A. Agila Sefen, Invest i gator

F0~\-1 f'OA •83 (0910Si PRf,VIOVS EM!ONOOSOLFTE INSPtCTlONAL OBSERVATIONS PACES Of 7 PAGES

- 05/22/2015*

3 ".i03718003 v/oc/industr

Omaha NE 68154-1571 Produce of ster i le dru ts

OBSERVATION 11

The number of quali fied personnel is inadequate to perfonn and supervise the processing. packing, and holding of each drug product.

Specifically,

There is a lack of trained personnel on site to conduct the steri.le drug production operations required. This was verified by management on 5/13/15, and evident by deficient training records for operators producing sterile drug products.

Add itionally, your training records are deficient:

a) Training records for operators producing all of your steri le drug products are deficient. Specifically, 2 ofl operators have deficient or absent sterile annual train ing records for the year 2014, as required. Defic iencies were observed for years 20 13 and 2014. These training deficiencies are attributed by management to a lack of time to conduct training adequately.

b) Training records do not exist for conducting environmental sampling in your sterile processing areas. Lastly, there are no training records of how to read, document andl interpretWJJIJ) environmental mon itoring results.

OBSERVATION 12

Written complaint records do not include, where known, the name and strength of the drug product, lot number, name of complainant, nature of complaint, and reply to complai nan!.

Specifically,

You do not record information regarding consumer complaints. including the name of the product, lot number, and investigations.

There is no consumer complaint records on site. Management stated on 5/14/t5, that

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Eric M. Muel l er , I nvestigator Joseph R. Lamber t, Investigator Jenny A. Agila Sefen, I nvestigato r

lNSP

fORM POA <Sl (09108) PREVIOI.IS EOITIONOBSOl.E'i'S INSPECTIONACOBSERVATIONS PAGE 7 OF 7 PAGES

O:STRIC T AOOAESS AHO ~""""' NlJM8EK

DEPARTMENT OF AEA.LTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

01\Je(S) OF TNSP<CTION

8050 Marshall Dr ive, Suite 205 Lenexa, KS 66214

05/1 2 /2015 - 05/22/2015* FEIN"JM8£R

(9 13) 495-5 100 Fax: (913) 49 5-5115 30 03718003 Industry Information: www.fda.gov/oc/ industry IIAME AH:) m lf OF IN()jVIOUAL TO WHOM REPORT lSSVEO

TO: Justin M. Kohl l, Vic e President FIRM NAME STRICT ADDRESS

Essential Pharmacy Compounding 62 0 N ll 4 th St CITY, STATE. ~p CODE. CO UN mY TYPE ES1A8LJSHMEtiJ INSOf.CTCD

Omaha, NE 68154 -1 571 Produce r of sterile dr~ products

and no investigation into the problem is documented. Management stated that complaints veto your firm approximately one or two times per month. Th is information was not documented .

• DATES OF INSPECTION: 051!2/20 I S(Tue), 05/13/20 I S(Wed), 05/ 14120l5(Tilu), 051 15120 l5(fri), 05/1912015(Tue). 05/20/201 5(Wed), 05/22120 15(Fri)

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EMPlOVEE(S)SIGAATURE

Eric M. Mue ller, InvestigaJoseph R. Lambert, Investigator Jenny A. Agila Sefen, Investigator

~- 1 /I /I/'? tor~ ~~A'~'~JJ1~-~c~~~~ i---­n. ; _ ~

/)' ~

UAtl; ISSUED

05/22/2015