Joanne E. King, Investigator~~~~ ~~~-YL

DEPARTMENT OF HEALTH AND liUMAN SERVJCES
FOOD AND DRUG ADMINIS"ffi.ATION
DISTRICT .ot>ORESS AND
~liONE
NUMBER
DATE(S) OF INSPECTION
555 Winderley Place, Suite 200
Maitland, FL 32751
( 4 0 7 ) 4 7 5-4 7 0 0 Fax: ( 4 0 7 ) 4 7 5-4 7 6 8
Industry Information: www.fda.gov/oc/industry
06/09/2015 - 06/17/2015*
FEINUMSER
3003099089
NAME AND nTl.E Of' INOJVIOUAl TO WHOM REPORT ISSUED
TO:
Michell e Pease, Re g ional Area Mana ger , Southeast
FIRM NAME
smi:ET ADDRESS
Cardinal Health 414, LLC
5601 Powerline Rd Ste 108
CITY, STATE, ZIP CODE, COUNTRY
~E
Fort Lauderdale, FL
33309-2831
ESTASLISHMENT INSPECTED
Positron Emission Tomography (PET) Drug
Manufacturer
This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional
observations, and do not represent a fmal Agency detennination regarding your compliance. If you have an objection regllfding 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. If you have any
questions, please contact FDA at the phone number and address above.
DURING AN INSPECTION OF YOUR FIRM WE OBSERVED:
OBSERVATION 1
When errors occurred or a production batch failed to meet specifications, you did not determine the need for an investigation,
conduct an investigation, and take appropriate corrective actions when necessary.
Specifically, upon review of Temporary Deviation Authorization (TDA) # 01150002-T approved by the Regional Quality
Manager on 2/2/15, it was found that FDG F-18 Injection lot# 01020215-4 showed an unidentified peak at the retention time
of (b) (4) minutes when tested for residual solvents in the (b) (4) GC. The TDA was approved to re-test the product sample
in the(b) (4) as there was no time to conduct maintenance on the (b) (4) GC. The(b) (4) in the (b) (4) did not show the
extraneous peak and the batch was released and distributed; however, no investigation was conducted as per SOP NPSRAQA-0118 "Out of Specification (OOS) Investigations" Rev. 3.0 to confirm the root cause of the extraneous peak in the
(b) (4) GC test was due to lab or equipment issues and not to'product quality. In addition, since no investigation was
conducted other batches tested the same day in the same (b) (4) GC equipment (FDG lots 01020215-1, 01020215-2, and
01020215-3) were not evaluated and no corrective and preventive action was identified, implemented, and documented.
OBSERVATION 2
Laboratory records did not contain a complete record of all data obtained in the course of each test.
Specifically, upon review of the audit trail for the (b) (4) GC for 2/2/15 and 2/3115 it was found that FDG F-18lot #
01020315-4 was tested for residual solvents in this equipment at 10:09 a.m. on 2/3/15. However, upon review of the
completed and approved production batch record, it was found that laboratory data related to the initial residual solvent test
was not present or referenced in the batch record: Instead, labOratory data for a subsequent residual solvent re-test conducted
on 2/3/15 at 10:49 a.m. in the(b) (4) was included. Upon inquiry during the inspection, it was stated that the initial test
failed "standard bracketing" but there was no documentation of such determination in the production batch record. In
addition, Temporary Deviation Authorization (TDA) # 01150004-T approved three (3) weeks later on 2/26/15 was provided
as justification to re-test stating that the (b) (4) can be used as an emergency back~ up GC due to ongoing software or
maintenance issues with the (b) (4) GC which were not documented or investigated. Furthermore, there is no
documentation of a laboratory investigation for failed suitability and invalidation of data as required by SOP NPS-RAQA0118 "Out of Specification (OOS) Investigations."
EMPLOYEE(S) SIGNATURE
SEE REVERSE
OF THIS PAGE
FORM FDA 483 (09/01)
Joanne E. King, Investigator~~~~
~~~-YL
CDR Ileana Barreto - Pettit, I~~;i~~t~~~
PREVIOUS EOffiON OBSOLE'IE
INSPECfiONAL OBSERVATIONS
DATE ISSUED
vv
'1 7 /2015
PAGE I OF 4 PAGES
DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRICT AOORESS ANO PHONE NUMSER
DATE(S) OF INSPECTION
555 Winderley Place, Suite 200
Maitland, FL 32751
(407) 475-4700 Fax: (407) 475-4768
Industry Information: www.fda.gov/oc/industry
06/09/2015 - 06/17/2015*
FEINUMBER
3003099089
W\ME AND TITLE Of' INOIV10UAL TO wt-lOM REPORT ISSUED
TO:
Michelle Pease, Regional Area Manager, Southeast
FIRM NMIE
STREET AOOIIESS
Cardinal Health 414, LLC
5601 Powerline Rd Ste 108
CtTY, STATE, ZIP CODE, COUNTRY
TYPE ESTABLISHMENT INSPECTED
Fort Lauderdale, FL
33309-2831
Positron Emission Tomography (PET) Drug
Manufacturer
OBSERVATION 3
You did not follow procedures to investigate the cause(s) of the nonconforming batch(s) of a PET drug product.
Specifically, your firm did not follow procedures NPS-RAQA-0118 Outof Specification (OOS) Investigations, Version (b) (4)
Section
and NPS-LC-0035 Bacterial Endotoxin Test (BET) by the (b) (4)
, Versfons (b) (4)
(b) (4)
for test suitability requirements. These procedures require that you develop and document a re-measurement test plan and
that re-test procedures are followed in the event of spike sample recovery failures, spike reaction time coefficient of variation
(CV) failures, sample reaction time CV failures, and no sample detected error~. The following batches with bacterial
endotoxin test suitability failures and error messages were not re-tested in accordance.with these procedures in that dilutions
were not conducted as specified, but the re-tests were approved and released by the quality unit:
A. Sodium Fluoride F-18 Injection lot# 01042715-5 with OOS # 01150035-0, dated 4/27/15 had an initial spike
sample recovery result (b) (4) (sp~c (b) (4) ,) and a spike reaction time CV of(b) (4) spec (b) (4) ,) that resulted in a
test suitability failure. The duplicate re-test samples were not dilut~d accordance with written re-test procedures
·' ·
.· ·, · .· · · ·
·
to determine if there was product inhibition.·
m.
B. Fludeoxyglucose Fl8 Injection lot numbers 01021115-4 (OOS# 01150008-0 dated 2/11/2015), 01021915-4 (OOS#
01150013-0 dated 2/19/2015), .0103231?-.l(OOS# 01150023-0 dated 3/23/15),, and 01050.615-1 (OOS# 01150039O dated 3/6/15) all had initial spike recovery result failures with passing spike reaction time CV results and
suitability failures. The re-test samples were not diluted in accordance with written re-test procedures to determine
if there was product inhibition.
C.
Fludeoxyglucose FIS Injection lot# 01041315-2 with OOS# 01150028-0 dated 4/13/2015 had initial spike reaction
time CV failures and test suitability failure. The re~test samples were not diluted in accordance with the written retest procedures.
D. Fludeoxyglucose Fl8 InjectionJot numbers 01071614-1 (OOS # QI 140.06~-0 dated 7/.1.6/2014) and 01030515-4
(OOS # 01150017-0 dateci 3/5/2015) had sample reaction time CV failures and test suitability failures. The re-test
samples were not diluted in acc.o:r;1ance with the written re-test proceg.ures.
E.
Fludeoxyglucose Fl8 Injection lot numbers 01062014-3 (OOS# 01140055-0'dated6/20/2014) and 01020515-4
(OOS# 01150006-0 dated 2/5/2015) had spike reaction time CV, spike recovery, and test suitability failures. The
re-test samples wen; not diluted iri accordance with the· written re-test procedures. ;
F.
Fludeoxyglucose Fl8 Injection lot 01010715-l(OOS # 01150001-0 dated 1/7/2015) had an initial test error message
of"sample not seen". The restest
samples
were not diluted in accqrdance
with the. written re-test procedures.
,.·.,
.·, '
.·
'
'
G. Florbetapir Fl 8 Injection lot# AV4501030415-l with OOS# 01150015-0 dated 3/4/2015 had an initial spike sample
DATE ISSUED
EMPLOYEE(S) STGNATURE
SEE REVERSE
OF THIS PAGE
FORM FDA 483 (09/08)
9t"/C
Joanne E. King, Investigator
CDR Ileana Barreto-Pettit, Investigator
~~
INSPECTIONAL OBSERVATIONS
06/17/2015
PAGE 2 OF 4 PAGES
DEPARTMENT OF HEALm AND HUMAN SERVICES
FOOD AND DRUG ADMINISTRATION
DISTRJOT ADDRESS ,&,l'IO !'HONE NUMBER
DATE(S) OF INSPECTION
555 Winderley Place, Suite 200
Maitland, FL 32751
(407) 475-4700 Fax: (407) 475-4768
Industry Information: www.fda.gov/oc/industry
06 /09/20 15 - 06/17 /2 015*
FEINUMBER
3003099089
NAME AN.O TITLE Of INOlVIDUAL TO WHOM REPORT ISSUED
TO:
Michelle Pease, Re gi onal Area Manage r, Southeast
FlflM NAME
STREET ADDRESS
Cardinal Health 414, LLC
5601 Powerline Rd Ste 108
CITY, STATE. ZIP CODE, COUNTRY
TYPE ESTABUSHMENT INSPECTED
Fort Lauderdale, FL
33309-2831
Positron Emission Tomography (PET) Drug
Manufacturer
recovery result of(b) (4) (spec (b) (4) ) and a spike reaction time CV (b) (4) (spec (b) (4) ) that resulted in a test
suitability failure. We found that there were no re-test sample dilution procedures established to determine if there
was product inhibition.
OBSERVATION 4
Your facilities are not adequate to ensure the prevention of contamination of equipment and product by environmental
conditions that could reasonably be expected to have an adverse effect on product quality.
Specifically,
A. SOP NPS-FE-0050 "Environmental Monitoring-Equipment Surfaces" Rev. 6.0 effective 5/24/15 is not adequate in that
surface samples in the hot cell are only collected (b) (4)
(sections 7.1.7.1 and 7.2.1) instead
of (b) (4)
to clean.ing/disinfection to demonstrate controlled and adequate
environmental conditions during drug vial manipulation/processing in the bot cell.
B. During bulk vial assembly conducted oii 6/15/15, 'it was obsenied that the. operator failed to follow section 7.3.4 of SOP
NPS-FE-0051 "Environmental Monitoring-Airborne Bioburden by Settle Plate" Version (b) (4) effective 5/24/15 in that the two
settle plates placed in the Laminar Air Flow Workbench (LAFW) were partially covered with the lid resting against the
media plate instead of placing the lid next to the plate to allow full exposure of the. media during vial assembly operations.
C. During inspection of the LAFW clean room on 6/15/15, the following deficiencies were observed:
1. Rust on the locks and hinges of both doors of the pass-thru window.
2. Partially disintegrated/worn out seal around the interior door of the pass-thru window which can generate
particulates.
3. Rust observed on the foot rest ofthe stainless steel stool and on the legs of a side table.
4. Unsealed gap about 12" long between wall and floor next to the LAFW.
OBSERVATION 5
You did not document your activities in accordance with,your procedures for Cleaning all of your. equipment.
to
Specifically, your production operators failed follow section 7.1A ofSOP NPS-FE-0028 "Hot Cell Cleaning and
Disinfection" Version(b) (4) effective 10/19/14 in that cleaning/disinfectants agents ((b) (4)
were not rotated on a (b) (4) basis as specified in this SOP. A review of the (b) (4) Hot Cell Cleaning
and Disinfection Forms# NPS-FE-F-0004, version (b) (4) from 1111114 thru 6/9/15 .showed that cleaning agent rotation varied
from every (b) (4)days to every (b) (4)days on several occasions.
SEE REVERSE
OF THIS PAGE
FORM FDA 483 (09/08)
EMPLOYEE(S) SiGNATUllE
DATE ISSUED
Joanne E. King, Investigator ~
CDR Ileana Barreto-Pettit, Investigat o r~
06/17/2015
PREVIOUS EDmON 09SDLE1E
INSPECTIONAL OBSERVATIONS
PAGEJ OF4 PAOES
DEPARTMENT OF HEALTH AND HUMAN SERVICES
FOOD AND DRUG ADMINISIRATION
DISTRICT AOORESS ANO PHOHE NUMIIER
DATE(S) OF INSPECTION
555 Winderley Place, Suite 200
Maitland, FL 32751
(407) 475-4700 Fax: (407) 475-4768
Industry Information: www.fda.gov/oc/industry
06/09/2015 - 06/17/2015*
FEINUMBER
3003099089
NAME ANO TITLE Of INDMDUAL TO WHOM REPORT ISSUED
TO:
Michelle Pease, Regional Area Manager, Southeast
FIRM NAME
STREET ADDRESS
Cardinal Health 414, LLC
5601 Powerline Rd Ste 108
CITY, STATE, ZlP COO£, -NTRY
TYPE ESTABLISHMENT INSPECTED
Fort Lauderdale, FL
33309-2831
Positron Emission Tomography (PET) Drug
Manufacturer
* DATES OF INSPECTION:
06/09/2015(Tue), 06/10/2015(Wed), 06/l l/2015(Thu), 06/15/2015(Mon), 06/l 7/2015(Wed)
EMPLOYEE(SJ SIGNATURE
,
1
SEE REVERSE
OF THIS PAGE
FORM FDA 483 (09/08)
Joanne E. King, I n v e s t i g a t o r ~ ~ ~ ~ - _ ·
CDR Ileana Barreto-Pettit, I n v e s t i r a t o ~ ~ ~ - ~
-..,.-;
PREVIOUS EDIDON OBSOLE1E
INSPECTIONAL OBSERVATIONS
OATE ISSUED
~~
06/17/2015
PAGE 4 OF 4 PAGES