DEP ARTM ENT OF HEALTH AND HU:MA.i"' SERVIC ES FOOD AND DRUG ADMINISTRATION

DISTRICT ADDRESS AND PHONE NUMBER

One Mont vale Avenue Stoneham, MA 02180 (781)587 - 7500 Fax : (781)587 - 7556

OATE(S) OF INSPECTION

12/1/2015- 1/29/2016* FEI NUMBER

3010015551

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Carole V . Dupont , Director of Pharmacy F IRM NAME

Central Admixt ure Pharmacy Services, Inc .

STREET ADDRESS

27 Village Ln

CITY. STATE. ZIP CODE. COUNTRY

Wallingford, CT 06492 - 2426

TYPE ESTASLISH MENT INSPECTED

Producer of S t erile Drug

This document lists obse1vations made by the FDA representative{ s) during the inspection ofyour facility. They are inspectional obse1vations, and do not represent a final Agency determination regarding your compliance. Ifyou have an objection regarding an obse1vation, or have in1plemented, or plan to implement, con·ective action in response to an observation, you may discuss the objection or action with the FDA representative(s) dw-ing the inspection or submit this information to FDA at the address above. Ifyou have any questions, please contact FDA at the phone munber and address above.

DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:

OBSERVATION 1 Aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions.

Sp ecifically,

A. The firm has not cei1.ified the clean rooms (ISO 5, ISO 7 and ISO 8) under dynamic conditions since •B. Two HEPA filters within the ISO 5 area (HEPA - ) appeared to have black splotchy patches with inegular boundaries. Additionally, all HEPA ~ening were observed to have a "1ust" color on the outside within the ISO 5 and ISO 7 areas.

D. The facility is not adequately designed an d controlled to prevent influx of contamination from lesser contro lled areas. The ceiling light fixtures within "Compounding Room # 1" (ISO 7) directly outside the - baniers were observed to be lifted up (approximately 112 inch space between the light and the Ceiiiiigj"'alld not flush with the ceiling.

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Mary- Jeanet Mcgarry, Investigator 1/29/2016 John P Mist ler , Investigat orOF THIS PAGE X Mary·Jeanet Mcgany

Juanit a P Versace, Microbiologist (CTNH) Philip F Ist afanos, Microbiologist

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlETE INSPECTIONAL OBSER VATIONS PAGE I OF6 PAGES

DEPARTMENT OF HEALTH AND HU:MA.i"' SERVICES FOOD AND DRUG ADMINISTRATION

D ISTRICT ADDRESS AND PHONE NUMBER OATE(S) OF INSPECTION

One Montval e Avenue 12/1 /201 5 - 1/29/201 6 * FEI NUMBERS t one h am, MA 02180 301 001 5551(7 8 1 )587-7500 Fax: (7 8 1 )587-7556

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Carole V. Dupont , Direc t o r o f Ph armac y F IRM NAME STREET ADDRESS

Ce n tral Admixtu re Pharmac y Servic e s , 27 Village Ln I n c. CITY. STATE. ZIP CODE. COUNTRY TYPE EST ASLISHMENT INSPECTED

Wall i ngf o rd, CT 06 492 - 2 4 26 Pro d ucer o f Steri l e Dr ug

OBSERVATION 2 Procedmes designed to prevent microbiological contamination of dmg products purpotiing to be sterile are not written and followed .

Specifically,

room (ISO 7)­. to entering the ISO 5

The vials ar~ any Th~

not assme that the vials are fully cleaned any potentia contaminant prior to and producing sterile product for adult and pediatric patients. The fum's written documentation does not require staff to perfonn this step.

OBSERVATION 3 The building lacks adequate space for the orderly placement of equipment and materials to prevent mix­ups between in-process materials and to prevent contamination.

Specifically,

A. On December 8, 2015, an operator was observed beneath the baniers, potentially blocking first air with an exposed face (forehead and eyes), engaging in mam·pula · ofsterile injectable dmg products within the ISO 5 areas.

B. Differential pressme is not adequately monitored and controlled between the controlled manufactming areas and non-contt·olled areas. Specifically; there is no continuous monitoring of the pressme differential between the ISO 8 (Prep Room) and warehouse.

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Mary-Jeanet Mcgarry, I nves tigato r 1 /29/201 6 OF THIS PAGE J ohn P Mi s t l er, I nves tigato r X Mary·Jeanet Mcgany

Juan ita P Vers a c e, Mi c r obi ologi s t (CTNH) Ph i l i p F I s tafanos , Mi c r obi ologi s t

FORMFDA 483 (09/08) PREVIOUS EDmON OBSOlETE INSPECTIONAL OBSERVATIONS PAGE 2 0F6PAGES

DEPARTMENT OF HEALTH AND HU:MA.i"' SERVICES FOOD AND DRUG ADMINISTRATION

D ISTRICT ADDRESS AND PHONE NUMBER OATE(S) OF INSPECTION

One Montvale Avenue 12/1/2015-1 /29/2016* FEI NUMBERS t oneham, MA 02180 3010015551(781)587-7500 Fax: (781)587-7556

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Car ole V. Dupont , Direc t or of Pharmacy F IRM NAME STREET ADDRESS

Central Admixture Pharmacy Services, 27 Village Ln I nc . CITY. STATE. ZIP CODE. COUNTRY TYPE EST ASLISHMENT INSPECTED

Wallingford, CT 06 492 - 2 4 26 Producer of Steri le Dr ug

C. Numerous batches of TPN products are Dr<)atlcea Room # 1 ". This ,.....,.,,..,.,r,

v uu..,•uvu room. For example, , as obse1ved on room

was au pattern study) under dynamic conditions for- in •. Yom fum does not maintain an air flow~ysis (smoke study) for "Compmmding Room #1" lmder dynamic conditions for greater tha~

D. The facility is not adequately designed and controlled (e.g. lack of in~ors) to prevent influx of contamination from less controlled areas. Doors accessing the- from Room (ISO 8) and "C

Room · Room # 1" (ISO 7) were obsezved to have a

Room #1" (ISO 7) are Access to the

. Materials

u..u.......~~· •.u....... areas # 1 "(ISO 7) lmder the ISO 5 workbenches.

OBSERVATION 4 Aseptic processing areas are deficient regarding the system for monitoring environmental conditions.

Specifically,

A. Production of sterile dmg products is perfo1med within ISO 5 laminar flow workbenches; however, the fum conducts momtormg with the following frequencies:

1. Pruticulate matter air samples are taken on

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Mary-Jeanet Mcgarry, I nvest igat o r 1/29/2016 John P Mi s t ler, InvestigatorOF THIS PAGE X Mary·Jeanet Mcgany

Juanita P Versace, Microbiologist (CTNH) Philip F I s tafanos , Microbiologist

FORMFDA 483 (09/08) PREVIOUS EDmON OBSOlETE INSPECTIONAL OBSERVATIONS PAGE30F6PAGES

DEPARTM ENT OF HEALTH AND HU:MAi"' SERVICES FOOD AND DRUG ADMINISTRATION

D ISTRICT ADDRESS AND P HONE NUMBE R OATE(S) OF INSPECTION

One Mont vale Avenue 12/1/2015- 1/29/2016* FEI NUMBERSt oneham, MA 02180 3010015551(781)587- 7500 Fax : (781)587- 7556

NAME AND TITLE OF INDIVIDUAL TO W HOM RE PORT ISSUED

Car ole V. Dupont , Direct or of Phar macy F IRM NAME STREET ADDRES S

Cent ral Admixt u r e Phar macy Services, 27 Village Ln I nc . CITY. STATE. ZIP CODE. COUNTRY TYPE ESTABLI SHMENT INSPECTED

Wallingford, CT 06492- 2 4 26 Producer of St erile Dr ug

3. Persotmel glove fingertips sampling is taken­ in the production of sterile dmg products.

4. Personnel sterile sleeve cover sampling is taken­- in the production of sterile dm g products. Moreover, ~-face sampling on the operators' face mask, forehead and chest.

B. The procedure "CAPS-SOP-Sys Environ Control-Infection Control-ENVIRONMENTAL MONITORING": SOP- CAPS- 4000172 is not followed during personnel monitoring (fmge1tips) after

in the of sterile Fingertips were observed being , in contrast with the procedure, as they

D. The procedure "CAPS-SOP-Sys Environ Control-Infection Control-ENVIRONMENTAL MONITORING": SOP- CAPS- 4000172 is not followed during surface bioburden monitoring after

in the of sterile Surface samples were observed being in contrast with the prt>ce,Lun

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Mar y- Jeanet Mcgarry, Invest igat o r 1/29/2016 John P Mist ler , Invest igat o r OF THIS PAGE X Mary·Jeanet Mcgany

Juanit a P Versace, Micr obiologist (CTNH) Philip F I s t afanos , Microbiologist

FORM FDA 483 (09/08) PREVIOUS EDmON OBSOlETE INSPECTIONAL OBSERVATIONS PAGE40F6PAGES

DEPARTMENT OF HEALTH AND HU:MA.i"' SERVICES FOOD AND DRUG ADMINISTRATION

D ISTRICT ADDRESS AND PHONE NUMBER OATE(S) OF INSPECTION

One Montvale Avenue 12/1/2015-1 /29/2016* FEI NUMBERS t oneham, MA 02180 3010015551(781)587-7500 Fax: (781)587-7556

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Car ole V. Dupont , Direc t or of Pharmacy F IRM NAME STREET ADDRESS

Central Admixture Pharmacy Services, 27 Village Ln I nc . CITY. STATE. ZIP CODE. COUNTRY TYPE EST ASLISHMENT INSPECTED

Wallingford, CT 06492 - 2 4 26 Producer of Steri le Dr ug

E. The finn's environmental monitoring plan is inadequate due to the fact that no surface samples are taken in the Prep Room (ISO 8), .Ante Room (ISO 8) and the Gowning Room (ISO sampling in "Compounding Room # 1" (ISO 7) does not include cart handles, walls, floors, computer printer or crui wheels.

OBSERVATION 5 Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the ro om and equipment to produce aseptic conditions.

Specifically,

Cleaning records fail to include cleaning solutions used during the-cleaning of the ISO 5 hoods where sterile TPN products ru·e produced for pediatric and adult patients.

OBSERVATION 6 Written records are not made of investigations into unexplained discrepancies .

Specifically,

A. The fum' s cettification reports document that HEPA Filter variable filter sizes in For the ~ square feet, on as ~ru·e feet and on n<>·dA.rn1o<>rl no illVesflgatiOn illtO the size variations.

B. The fnmperf01ms- identification of microbial CFUs found during routine monitoring. The finn identified one (1) CFU fiom the touchplate in the- on December 18,2014 and sent the plate to the CAPS Laborat01y located in Califomia for ~on. The laborat01y rep01i sent back

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Mary-Jeanet Mcgarry, Investigator 1/29/2016 OF THIS PAGE John P Mist ler , Investigator X Mary·Jeanet Mcgany

Juanita P Versace, Microbiologist (CTNH) Philip F Istafanos, Microbiologist

FORMFDA 483 (09/08) PREVIOUS EDmON OBSOlETE INSPECTIONAL OBSERVATIONS PAGE50F6PAGES

DEPARTMENT OF HEALTH AND HU:MA.i"' SERVICES FOOD AND DRUG ADMINISTRATION

D ISTRICT ADDRESS AND PHONE NUMBER OATE(S) OF INSPECTION

One Montval e Avenue 12/1 /201 5 - 1/29/201 6 * S t one h am, MA 02180 (7 8 1 ) 5 8 7 - 7 500 Fax : (7 8 1 ) 5 8 7-7556

FEI NUMBER

301 0015551

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

Carole V. Dupont , Direc t o r o f Ph armac y F IRM NAME STREET ADDRESS

Ce n tral Admixtu re Pharmac y Servic e s , 27 Village Ln I n c. CITY. STATE. ZIP CODE. COUNTRY TYPE EST ASLISHMENT INSPECTED

Wall i ngf o rd, CT 06 492 - 2 4 26 Pro d ucer o f Steri l e Dr ug

the identification offour ( 4) isolates from th~ate. Additiona onll

lly, on August 31, 2014 teclmicianlll had one (1) cfh identified by the pharmacist fro~ fmgers right hand. The labs repotis identified two (2) isolates gram-positive rods and gram- positive cocci. No investigation was done to explain the discrepancy.

OBSERVATION 7 Batch production and control records do not include the specific identification ofeach batch of in­process material used for each batch ofdmg product produced.

Specifically,

The batch records state that the fum is utilizing the which is intetpreted . It was observed and mspection that the fum is

co1moon•ent td.e~ntlllle:d. in their batch records and is instead using a component labeled 'to produce Total Parenteral Nutrition (TPN) for adults

*DATES OF INSPECTION 12/0112015(Tue),12/02/2015(Wed), 12/03/2015(Thu),12/04/2015(Fri),12/08/2015(Tue),12/09/2015(Wed ) , 12/ 10/2015(Thu), 12/ 1112015(Fri), 1108/20 16(Fri), 1109/20 16(Sat), 1112/20 16(Tue ), 1129/20 16(Fri)

I/2'3/1!J16

X John P Mistler

EMPLOYEE(S) SIGNATURE DATE ISSUED

SEE REVERSE Mary-Jeanet Mcgarry, I nves tigato r 1 /29/201 6 J ohn P Mi s t l er, I nves tigato r OF THIS PAGE X Mary·Jeanet Mcgany

Juan ita P Vers a c e, Mi c r obi ologi s t (CTNH) Ph i l i p F I s tafanos , Mi c r obi ologi s t

FORMFDA 483 (09/08) PREVIOUS EDmON OBSOlETE INSPECTIONAL OBSER VATIONS PAGE6 0F6PAGES

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, and prior to leaving the premises, the officer or employee making the inspection shall give to the owner, operator, or agent in charge a report in writing setting forth any conditions or practices observed by him which, in his judgment, indicate that any food, drug, device, or cosmetic in such establishment (1) consists in whole or in part of any filthy, putrid, or decomposed substance, or (2) has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. A copy of such report shall be sent promptly to the Secretary."