McNeil 483 2010 FINAL Redacted

DEPARTMENT OF HEALTIl AND HUMAN SERVICES FOOD AND DRUG ADlvllNISTRATJON

DISTRIClT ADDRESS AND PHONE NUMBER

US Customhouse, Rm 900 2nd & Chestnut St Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/industry

DATE(SIOF INSPECTION

04/19/2010 - 04/30/2010 FEINUMBER

2510184

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUEO

TO: Hakan Erdemir, Vice President of Operations FIRM NAME

McNeil Consumer Healthcare, Div of McNeil-PPC, Inc.

STREET ADDRESS

7050 Camp Hill Road

CITY, GTATe,ZIP CODE, COUNTRY

Fort Washington, PA 19034 TYPE ESTABLISHMENT INSPECTED

OTC Pharmaceutical Manufacturer

This documenllists observations made by the FDA represenlative(s) during lhe inspection ofyour facility. They are inspeclional observations, and do not represent a final Agency determination regarding your compliance. Ifyou 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 representative(s) during the inspection or submit this infonmilion to FDA at the address above. Ifyou have any questions, please contact FDA at the phone number and address above.

DURING AN INSPECT/ON OF YOUR FIRM WE OBSERVED: .

Quality System

OBSERVATION 1

The responsibilities and procedures applicable to the quality control unit are not fully followed.

Specifically,

a. The Quality Control Unit (QA) authorities most responsible for overseeing daily operations at the Fort Washington facility did riot ensure that the responsibilities of the Analytical, Microbiological, Compliance, and Quality Assurance departments were enforced for rejection and withholding from approval any raw material component that contained 1I1mown". contamination of gram negative organisms. Raw material~ lots 0 ~ had lmown contamination with gram negative organisms and were approved for use to manufacture several fmished lots of Children's and Infant's Tylenol drug products, which remain wit . ., th keto Res onsible firm officials did ere to G for

• no Quality otl lea lOn was llnp emente regar mg t ere] ec IOn 0 contammated

b. QA and Compliance Department overall responsibilities per the firm's deficient as follows: It does not maintain adequate laboratory facilities or e stmg an approval (or rejection) of components and drug products; it neglects review and approval ofvalidation protocols regarding changes in product processes and equipment to determine when revalidation is or should be warranted; it is default in investigations, tracking, trending and maintenance of consumer complaint follow-up; and it lacks trending ofproducts, components (i.e., water), and complaints to demonStrate a broad perspective to assure plant conformance with CGMPs.

SEE REVERSE OF THIS PAGE

eMPLOyeEISj SIGNATURe

Anita R. Michael, Investigator Matthew R. Noonan, Investigator Sharon K. Thoma, Investigator Hala L. \'IJ:l,Qta;,tQ:AtJ. Investigator

5e1b\. 1/.:' eo /0

OATE'Bsueo

04/30/2010

FORJII FDA ~83 (89/08) rltEVIllUS EDITIOIl ODSOLETE INSPECTIONAL OBSERVATIONS PAOE I OF 17 PAGES

HTTP://www.fda.gov/oc/industry

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATION

DiSTRICT ADDRESS AND PHONE NUMBER

US Customhouse, Rrn 900 2nd & Chestnut st Philadelphia, 'PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/industry NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED


McNeil Consumer Healthcare, Div of McNeil-PPC, Inc. cm, STATE, ZIP CODE, COUNTRY,

Fort Washington, PA 19034

STREET ADDRESS

7050 Camp Hill Road

TYPE ESTABLISHMENT INSPECTED


DATEIS) OF INSPECTION

04/19/2010 - 04/30/2010 FEINUMBER

2510184

EMPLOYEEIS) SIGNATURE OATEISSUEO

Anita R. Michael, Investigator tJ1;J. Matthew R. Noonan, Investigator ~fJdSEE REVERSE Sharon K. Thoma, Investigator 04/30/2010

OFTHIS PAGE Hala L. ~nel::~ . Investigator H rJS ~(Jl.,bL '/lJ '

FORM FDA '4B3 (09/0B) PREVIOUS nOITlON ODSOUlTE • INSPECTIONAL ODSERVATIONS PAGB 2 OF 17 PAOllS

OBSERVATION 2

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

Specifically, Lacle of rocess idation for the manufacture of Infant's Dye-Free TYlen_Drops, Cherry, Formul II 80 mg/D.8 mL. The compounding and transfer of the 0 ~ ~ atch size 'suspension to the ' hold tame is not in a "state of control". The firm did not effectively evaluate the change in the manufacturin itation and tame lev time to when the batch size was increased from into a and/or when the hold tame size used for a • batch was decreased from a rmIIlhold tank.

OBSERVATION 3

Control procedures fail to include adequacy ofmixing to assure uniformity and homogeneity.

OBSERVATION 4

Control procedures are not established which monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.

Specifically,

Control procedures used did not validate the manufacturing processes that caused variability in the ' characteristics of the drug product. For examples, the agitation speeds and time to reach~in the hold tame during processing of the Isuper potent batches that failed APAP (end of run) assays, I released batches, and the demonstration batch, The firm did not demonstrate the adequacy ofmixin assure unifo~d homoge e' , tis Dye-Free Tylenol Suspension Drops, Formula using a ~ batch in a • hold tame. Agitation and tame levels with • the amount of liquid) in a ~old tame were evaluated with one demonstration bulle batch, lot


DISTRICT ADDRESS AND PHONE NUMBER

US Customhouse, Rm 900 2nd & Chestnut St Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: wwW·:fda.gov/oc/industry

oA1E(S) OF INSPECTION

04/19/2010 - 04/30/2010 FEINUMBER

2510184

NAME AND TIllE OF INDIVIDUAL TO WHOM REPDRT ISSUED

TO: Hakan Erdemir, Vice President of Operations FIRM NAME STREE< ADDRESS


7050 Camp Hill Road

CITY, SlAlE, ZIP CODE, CCUNlRY

Fort Washington, PA 19034 TYPE ESTABLISHMENT INSPEClEo


gator Matthew R. Noonan, InvestigatorAnita R. Michael, Investi

Q

DAlE ISSUED

SEE REVERSE Sharon K, Thoma, Investigator 04/30/2010OF THIS PAGE Mala L. ~~~ InvestigatorSe.{.· NLtil:. 0 0

FORl\! r-Dt\ 463 (09/08) PItEVIDUS BDITION oDSOlElB INSPECTIONAL OBSERVATIONS PAGE 3 OF 11 PAGES

he II batches into ~ using the weight 0 for the batch

otent batches, APAP concentrated at the end of run in the tanle).

Criticl!rocess parameters established during the 01'1

~:IIhold .tank for agitation speed used 0

hold tank used Original validation fro 0 wei hts of old taille used weights from II

OBSERVATION 5

Written production and process control procedures are not followed in the execution ofproduction and process control functions. .

Specifically,

a. equires a CAPA (Corrective Action Preventive Action) to be initiated when systemic GMP issues or significant trends have been identified associated with nonconfonnance event.s, consumer complaints, manufacturing events and significant trends. The procedure defines a CAPA as a process for ensuring that identified corrective and preventive actions are verified for effectiveness. No CAPA was initiated for the following batches from May 2009 to Apri12010 where foreign material, particulate matter and/or contamination were observed: Q

o

e

1:1

o

o

o

DEPARTMENT OF FOOD AN

OISTRIOT ADDRESS AND PHONE NUMSER

US Customhouse, Rm 900 2nd & Chestnut Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

HEALTH AND HUMAN SERVICES D DRUG ADMINISTRATION

st

industry


McNeil Consumer Healthcare, Div of McNeil-PPC, Inc. OIT'/, STATE, ZIP cC{o.E, OOUNTRY


STREET ADDRESS

7050 Camp Hin Road

TYPEEETABUSHMENT NSPEOTEO


DATEIS) OF INSPEOTION

04/19/2010 - 04/30/2010 FEINUMBER

2510184

EMPLOYEE(S) SIGNATURE , DATE ISSUED

Anita R. Michael, Investigator C( ICtt Matthew R, Noonan, {L,NInvestigator~!'V\SEE REVERSE Sharon K, Thoma, Investigator , 04/30/2010

OFTHIS PAGE Hala L. \'/he~e, Investigator ,1'/.6.'2lbL I ~5 ~.o /1, 0

FORM FDA 493 (09/08) PREVIOUS COITION ODSOUITE INSPECTIONAL OBSERVATIONS PAGE 4 OF 17 PAGES

b. No CAPA was initiated for -46 consumer complaints regarding foreign materials, black or dark ~toApriI2blO. .

c. ~ectionrmmJ requires armmJmetrics review of all new CAPAs, closed CAPAs, CAPAs open for more tha • • , and CAPAs exceeding the due date for review. No

tfUIJ_Metrics for CAPAs wa , d. No CAPA was com leted for QN or OOS on' :,j

OBSERVATION 6

There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has been ah'eady distributed,

Specifically, 1. A thorough investigation' 01' any additional analytical testin~s not conducted for Infants Dye-Free

Tylenol Suspension Drops, Cherry, 80 mg/0.8'mL, FormulaWIIUII for the followinm~bl:rr.m_"", a. WJIIJIIlots that were super potent and confirmed to fail release specification ofrtDJl..

cet mino hen APAP assa. For~ofRunsamplel~s~ • :.l and~ .mtDlis the .batch manufactured

Gl

o

G

o

Q

DEPARTMENT OF HEALTH AND HUMAN SERVrCES FOOD AND DRUG ADMINISTRATlON

DATE(S)OF INSPECTIONDISTRICT ADDRESS AND PHONE NUMBER

US Customhouse, Rrn 900 2nd & Chestnut St 04/19/2010 - 04/30/2010 FEIN MBER,Philadelphia, PA 19106 2510184

Industry Information: www.fda.gov/oc/industry (215) 597-4390 Fax: (215) 597-0875

NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

TO: Hakan Erdemir, Vice President of Operations FIRM NAME STREET ADDRESS

7050 Camp Hill Road McNeil-PPC, Inc. McNeil Consumer Healthcare, Div of

TYPE ESTABLISHMENT INSPECTEDCITY, STATE, ZIP CODE, COUNTRY

OTC Pharmaceutical ManufacturerFort'Washington, PA 19034

EMPLOYEE(S) SIGNATURE DATE ISSUED

Anita R. Michael, Investigator CCI..II Matthew R. Noonan, Investigator r4JJSEE REVERSE Sharon K. Thoma, Investigator ~ 04/30/2010

OF THIS PAGE Hala L. Wl>etGtWie.~1 Investigator ~'Jjtelh I 'mJ'1/~(}/ID 0

FORM FDA 483 109/08) 1'llEVIOUS EDIT'DN oaSOLllTE JNSPECTIONAL OBSERVATIONS PAGE S OF 17 PAGES

ofthe atch campaign foll batch of the campaign, and Notification/Investigations rejected theseBDbatches based on release testing 0 end ofrun samples that failed assay.

b. The firmls investigations did not extend to the ther batches and the demonstration batch ofthe same drug product associated with the manufacturing change. These ~batches and demonstration batch passed release sees for APAP assa and were distriputed to the market. For exam les: Lots 0 ~

c. As of 04/23/1 0, no trending was com campaign manufactured including:'

2. The firm's i.nvestigation into~ous :ylenol products containing ~id not mclude reVIew of all lots of~rece1V contract manufacturer between the lot used in manufacture of recalled products i to the first full lot of • received. from one entire vendor lot i.e illot For exam Vendor lots,

a,

II

or Childrenls Tylenol Oral Suspension, expiration date 11/10.

Gl ~1IlII$!JI~"~or Children's Tylenol Plus Cold, expiration date 11/1 O.

Fort Washington, PA 19034 OTC Pharmaceutical Manufacturer

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADMINISTRATJON

DISTRICT ADDRESS AND PHONE NUMBER

US customhouse, RID 900 2nd & Chestnut St Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/industry NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED


McNeil ConsUmer Healthcare, Div of McNeil-PPC, Inc. CllY, STATE. ZIP CODE, COUNTRY

STREET AODRESS

7050 Camp Hill Road

TYPE ESTABUSHMENT INSPECTED


04/19/2010 - 04/30/2010 FEINUMBER

2510184

EMPLOYEE(S) SIGNATURE DATE'SSUEO

Anita R. Michael, InvestigatorClIt,{f Matthew R. Noonan, Investigator n/(NSEE REVERSE Sharon K. Thoma, Investigato.r /.Y~J 04/30/2010

OF THIS PAGE Hala L. ~ 1. Investigator rf-JOS ~ L j'l.!, J /0

FOMI FDA 4B3 109/0B) INSPECTIONAL OBSERVATIONS MGE 6 OF 17 PAGES

. .

or Children's Tylenol Oral Suspension,

x iration''date 11/10. ,

expjratioIl;,date 1,2 10., G _orChildren's Tylenol Plus Multi-Symptom Cold,

• ~ _forChildren's Tylenol Plus Cold & Cough, expiration date 12/10.CIl •

o for Infant's Tylenol Drops, expiration date 12/10. e or Children's Tylenol Oral

SuspensioJ.1" ex iration date 12110. III for Infant's Tylenol Drops, expiration date 12/10. o for Infant's Tylenol Drops, expiration date 12/10. Cl or Children's Tylenol Oral Suspension, expiration 4ate 11/10.

b.

CIl Children's Tylenol Oral Suspension, expiration date 12/10. o for Children's Tylenol Plus Cold & Cough,

~ration date 12/10. o _lIforChildrenls Tylenol Oral Suspension,

expiration date 12/10.

Gl or Children's Tylenol Plus Multi-

FIRM NAME STREET ADDRESS

7050 Camp Hill RoadMcNeil Consumer Healthcare, Div of McNeil-PPC, Inc.

TYPE ESTABLISHMENT INSPECTEDCITY, STATE, ZIP CODE, COUNTRY

OTC Pharmaceutical ManufacturerFort Washington, PA 19034

TO: Hakan Erdemir, Vice President of Operations

DEPARTMENT O.F HEALTH AND HUMAN SERVJCES FOOD AND DRUO ADMINISTRATION

DATEIS) OF INSPECTIONDISTRICT ADDRESS AND PHONE NUMBER

04/19/2010 - 04/30/2010us Customhouse, RID 900 2nd & Chestnut St FEINUMDERPhiladelphia, PA 19106 2510184

'Industry Information: www.fda.gov/oc/industry (215) 597-4390 Fax: (215) 597-0875


EMPLOYEEIS) SIGNATURE DATE ISSUED

Anita R. Michael, Investigator 4~)1 Matthew R. Noonan, Investigator /"'lr..1JSEE REVERSE Sharon K. Thoma, Investigator fft 04/30/2010OF THIS PAGE Hala L. Wlle/SCOIlil' Investigator I ~,JS

$€ b' I ZJJ 3D/lu V'

FORII1 FDA 483 (09/08) rREVIOUS EDITION OnSOLllT1l INSPECTIONAL OBSERVATIONS PAGE 7 OF 17 PAGIlS

l) for Children's Tylenol Oral Suspension, expiration date 12/1 O. II [WX$__for Children's Tylenol Oral _12/10.

II) ~orTylenol Infantls Drops, expiration date 12/10. iii ~_orChildren's Tylenol Plus Cold & Cough, expiration date 12/1 O.

WllW_

OBSERVATiON 7

GMP training is not conducted with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them.

Specifically, employees are not given training in current good manufacturing practices and written procedures required by current good manufacturing practice regulations as follows: .

a. As of 04/23/10, Compliance Specialist, an Granulation Operator, did not attend new· em 10 e cGMP classroom trainin which is con ucted • ," , :' " versionII • ~ effective 3/29/1 0, requires initial cGMP

training before departmental training. G arted working for the firm as a contract employee on 02/24/10, and started departmental

traming on 02/25/10. G alwas temporarily transferred from the company's Lancaster, PA plant

04/18/10 and started departmental training on 02/01/10. According to version ~ transfer employees must receive the same initial trai. as new employees.

b. As of 04/23/10, there was no documented training i~_for of anulation SOPs required to be reviewed b Granulation Operator, during his transfer from 02/ 1/10 to 04/18/10. The firm uses earning management system to electronically document training activities.

c. As of 04/20/1 0, s Coordinator, did not receive training on e o ~ ." ffective 04/02110. Bis responsible for cleaning and maintaining tooling in the Compression tool room.

Production Systems

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUO ADMINISTRATION

DISTRICT ADDRESS AND PHONE NUMBER DATE(S) OF INSPEOTIDN

US Customhouse, Rm 900 2nd & Chestnut St Philadelphia, PA 19106 . (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/industry

04/19/2010 - 04/30/2010 FEINUMBER

2510184




STREET ADDRESS

7050 Camp Hill Road

CITY, STATE. ZIP CODE. COUNTRY

Fort Washington, PA 19034 TYPE ESTABUsHMENT INSFECTED

OTe Pharmaceutical Manufacturer

SEE REVERSE OFTHIS PAGE

EMPLOYEE(S) SIGNATURE

Anita R; Michael, Investigator tt/t ~ Matthew R. Noonan, Investigator ~iJ Sharon K. Thoma, Investigator Hala L. W~ Investigator ':5

5::lh"' IllJj 50/1 ~

DATE'SSUED

04/30/2010

FORM FDh 4UJ (09/08) PIlEVIOUS EDITiON OUSOLl!l1l JNSPECTJONAL OBSERVATIONS PAOl! 8 OF 17 PhOBS

OBSERVATION 8

Procedures describing the handling of all written and oral complaints regarding a drug product are not followed.

Specifically, No review of the 'batch production and packaging records was. con¢hlCted for "lack of effect" regarding Infant's Dye Free Tylenol Suspension Drops, Cherry, Lot __

ualit Assurance evaluation ofcomplaints documented in Quality Notifications (QNs)[~ o ~ • '. " .' determined that no quality issues were warranted and hence, no

manufacturing or packaging investigation was co~ducted. QN DfDI!Iegardil;Ji!e~recallof Microcrystalline Cellulose and Carboxymethycellulose Sodium NF McNeil, lot# LW.IID.IIwas associated with this fmished product 10t@_ ApproX:imate1Y[~QNreports regarding lot~were forwarded froni the Corporate Benefits Risk Management group to this manufacturing site for investigation from August to November 2009.

OBSERVATION 9

Each container of component dispensed to manufacturing is not examined by a second person to assure that the weight or measure is correct as stated in the batch records.

Specifically, Infant's Tylenol Suspension Drops, Cherry, batch

Acetaminophen (APAP) Assa results for beginning, middle and end samples were OOS and sub potent as follows release spec is

eg= id =

nd=

Retest (Le., re-mea~ure) results were also OOS and confirmed the original OOS results.

Manufacturing batch records indicate thatM!mofthe active APAP was weighedas required by the fonTIu1ation. The batch record also states that the correct amount was weighed as"drums at


DATE(S) OF I SPECTIDND STRICT ADDRESS AND PHDNE NUMBER

US Customhouse, Rm 900 2nd & Chestnut St 04/19/2010 - 04/30/2010 FEl NUMBERPhiladelphia, PA 19106

(215) 597-4390 Fax: (215) 597-0875 2510184 Industry Information: www.fda.gov/oc/industry NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED


7050 Camp Hill RoadMcNeil Gonsumer Healthcare, Div of McNeil-PPC, Inc.

TYPE ESTABUSHMENT INSPECTED CITY, STATE. ZIP CODE. COUNTRY

Fort Washington, PA 19034 OTC Pharmaceutical Manufacturer

EMPLOYEE(S) SIGNATURE DATE ISSUED

Anita R. Michael, Investigator d/..JA SEE REVERSE Matthew R. Noonan, Investigator "":. ~

Sharon K. Thoma, Investigator "'<'V/. 04/30/2010OF THIS PAGE Hala L. WheJ;.s.1;GI'I.a-/.?,:>, Investigator N/:5J..5

Seth r'/[Is, 'iJil 0 V

FORM FDA ·183 (U~/08) INSPECTIONAL OBSERVATIONS PAGE 9 OF 17 PAGES

\j each) and It m ofAPAP at•.The batch record indicates that the correct amount o APAP was weighed by operator 1 and verified by operator 2. Investigation states the likely cause of sub-potency is caused by not charging in the correct amount of APAP. A mix up occurred and a partial drum weighing less than the required amount was used instead of the correct drum. Operator 1 and Operator 2 weights checks did not prevent the use of the wrong amount of APAP.

Labeling & Packaging Systems

OBSERVATION 10

Strict control is not exercised over labeling issued for use in drug product labeling operations.

Specifically, on 04/20/10, labeling was observed to be stored throughout the warehouse accessible to all warehouse operators and personnel that have access to the raw materiiH/component storage warehouse. Lab~s not stored in a locked cage with limited access. For examples: a. • ~ immediate container labels for Concentrated Motrin Infants' Drops, Oral Sus e . ,50 mg

ibuprofen per 1.25 mL, I fl. oz., Ori inal Berry Flavor, part BD label lot 8 ere stored in warehouse location ~ .

b .[(BIimmediate container 1 els or Children's Tylenol Plus Mul . Cold, Oral. Suspension, 160 mg acetaminophen per 5mL, 4 fl. oz., Grape, part labellotR)l were stored in warehouse 10cation[4jJB)_

c. Several others.

Laboratory Operations

OBSERVATiON 11

There is no written testing program designed to assess the stability characteristics of drug products.

Specifically, a. Lack of stability data to support the rmDexpiration date assigned to lots produced following the

of the packaging run. Stability samples are not representative samples from the beginning, middle and end of the fill run specifically for the three batches with super potent end sample fills. For example,[WD»JJl_'l\l_

DISTRICT ADDRESS liND PHON5 NUMBER

DEPARTMENT OF HEALTH AND HUMAN SERVICES FOOD AND DRUG ADM!NISTRA T!ON

DIIT5{S) OF INSPECTION

US Customhouse, Rm 900 2nd & Chestnut St Philadelphia, PA 19106

04/19/2010 - 04/30/2010 FEINUMBER

· (215) 597-4390 Fax:(215) 597-0875 2510184 Industry Information: www.fda.gov/oc/industry

· NIIM511ND 11T~5 OF INDIVIDUAL TO WHOM R5PORT ISSU50

TO: Hakan Erdemir, Vice President of Operations FIRM NIIM5 STREET IIDDR5SS

McNeil Consumer Healthcare, Div of McNeil-FPC, Inc. CITY, STATE, ZIP CODE, COUNTRY

Fort washington, PA 19034

7050 Camp Hill Road

TYPE ESTABLISHM5NT INSPECTED



FORM FDA 4H~ (09/08)

EMP~OVEE(S) SIGNATURE

Anita R. Michael, Investigator . 0: /. h[ Matthew R. Noonan, Investigator ~:.1 Sharon K. Thoma, Investigator . Hala L. ~&e~, Investigator • ~~/C

S?-fh· lfl:JJ <//.suit.. D-'

rRili'IOUS UDITICIN ODSOL!ITE INSPECTJONAL OBSERVATIONS

DATE ISSUED

04/30/2010

PAOE lOOF 17 PAOllS

b.

stability samples are pulled from the beginning

OBSERVATION 12

Laboratory controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that components and drug products confonn to appropriate standards of identity, strength, quality and purity.

Specifically,

Scientific justification does not the reason(s) why the finn does not .test TSA, a non-selective general microbial growth medium, lot · growth promotion tests for microorganisms to include for example, molds, yeasts known environmental contaminants found in the manufacturing facility and/or raw materials. This media was used for test~!fvraw materials and finished products testing from· 03/01/09 to 08/03/09; ~~~~ as isolated from raw

~--however, TSA was with not isolated from raw material lot #s

OBSERVATION 13

Adequate lab facilities for testing and approval or rejection of components and drug products are not available to the quality control unit.


DISTRIOT ADDRESS AND PHONE NUMBER DATEIS) OF INSPEOTIDN

US Customhouse, Rm 900 2nd & Chestnut Bt Philadelphia, PA 19106 (215) 597-4390 Fax:(215) 597-0875 Industry Information: www.fda.gov/oc/industry NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED


McNeil Consumer Healthcare, D~V of McNeil-PPC, Inc. CITY, STATE, ZIP CODE, COUNTRY


STREET ADDRESS

7050 Camp Hill Road


OTC Pharmaceutical ~anufacturer

04/19/2010 - 04/30/2010 FEINUMBER

2510184

EMPLDYEEIS) SIGNATURE DATE ISSUED

Anita R. Michael, Investigator tll. fA Matthew R. Noonan, Investigator ~",(l/llSEE REVERSE Sharon K. Thoma, Investigator .L:\ 04/30/2010OF THIS PAGE Hala L. ~e, Investigator ,~

S::'I/0. rQ)s I /3bl 0

FORM FDJl4B3 (09/08) rnnVlllU~ nDmDN DDSDLnTn INSPECTIONAL OBSERVATJONS PAGE II GF 17 PAGES

1. Lack of investigation, review and follow-up of as follows: a. Calibration on 0310911 0 per Test Report N emonstrates that certification of th~wasoutside the e criteria and the leak test for the~ filter failed the specification of enetration of the upstream concentration in two areas on the [lll]fil in ad ition to eakage at the frame.

b. Test Report No. 0 monstrates airflow into the~ack room where microbiological testing of finished products and raw materials is conducted in Hoods _in relation to tIle general microbiological room outside of the airflow is not positive to the general microbiological room (i.e., Walle-In Chambers, re Igerator and freezer room).

c. The aerosol challenge installation leak test and air velocity results Test Report No.rmm1 as not evaluated by the microbiological laboratory until requested during~

current Inspection. ,This report is typically sent fi::om the contract service to the maintenance department and filed with no evaluation or follow-up by the microbiological laboratory personnel concerning failing results.

d. No procedure regarding the allowable percentage of leakage across the ~lter ~nd no specifications conceming the width and height areas for total allowable repairs.

2. Lack of investigation, review and follow-up of s follows: a, Calibration on 03/0911 0 per Test RepOlt No. emonstrates that certification of

the ~velocity was outside the ce criteria and the leak test for the~ 'filter failed the specification ofpenetration of the upstream concentration in two areas on themlJfilter at~"inadditiOn t? leaka e at the frame.

b. Car . on 09/16/09 per Test Report No. 0 ~ 'i emonstrates that certification of the air velocity was outside the olerance criteria.

c. , c1)allenge installation leak,test and air velocity results per Test Report No. as not evaluated by the microbiological laboratory. This report is typically sent

from the contract service to the maintenance department and filed with no evaluation or follow-

pe:

WII

up on failing results. d. No procedure regarding the allowable percentage of leakage across the~filter and no

specifications conceming the width and height areas for total allowable repairs.

3. On 04/19/10, during the walle through of the Microbiological Laboratory, the following deviations were observed:


DIBTRICl ADDRESB AND PHONE NUMBER

US Customhouse, RID 900 2nd & Chestnut st Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fdp.gov/oc/industry NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISS EO

TO: HaJcan Erdemir, Vice President of Operations

DATE(S) OF INSPECTION

04/19/2010 - 04/30/2010 FEINUMBER

2510184

FIRM A E

McNeil Consumer Healthcare, Div of McNeil-'ppC, Inc. OITY, STATE, ZIP ODDE, COUNTRY

Fort Washington, PA' 19034.

STREET ADDRESS

7050 Camp Hill Road



EMPLOYEE(S) SIGNATURE OATE'SSUEO

Anita R. 11ichael, Investigator a~ILiIJ Matthew R. Noonan, Investigator (\1'SEE REVERSE Sharon K. Thoma, Investigator 04/30/2010

OF THIS PAGE Hala L, W:Rel;steae, Investigator1 -:5 =t: b.. i .' S LIl~i:lll (;I

FORlII FDA 4UJ (P9/08) rREVIOUS OOJ1leN ODSOLETO INSPECTIONAL OBSERVATIONS PAGE 12 OF 11 PAGES

a. No cleaning/use log for the I raw material weighing. b, Thick dust covering the grill inside the filtered cabinet.. c. No identification of the temperature probes in • d. Duct Tape wrapping the copper piping insulation inside thetmB»llfillllwhere the firm stores

water samples and refrigerated media. e, Incubatorijhad a large amount of visible grey aJ;ld brown dust/debri observed on the bottom of

the chamber under the shelves where media filled containers and media hold time studies were located,

f. There was a large exposed hole (gap) in the ceiling above incubator and next to the air vent in the ceiling.. .

I g. No inventory of~ontaining ~organisms.. h. Various microbiological rooms containing laboratory equipment "not in-use" that contained

dust/debri. "Out of Service" equipment cluttered laboratory areas, For examples, equipment "out of service" dates are as follows: Ii) water sample refrigerator dated 07/2007); e pH meter (09/30/09); III Shaker incubator (12/16/08); o Culture incubator (May 2007); Etc.

4. On 04/22/10, the following deviations were observed durin microbio_esting of Children's Zyrtec 'Sugar Free Syrup, 10tDilJlllllfonnula n the 11 • aclc Testing Room in Hood~ a. Hoodll had about a 6 inch silicon lu located on the right side upper filter. b. The·left side oftbe 1'1 :or had a very large spider-like crack on the left side

of the hood plexiglass where the gas vacuum hose was located. This vacuum hose is not used, c. The microbiologist was observed to pour media into the negative contro .

placed in front ofthe larger 250 mL bottle, which blocked/disrupted the Ii air flow.

d. The microbiologist was obsel-velbJlGien media (i.e. close to the outside of the hood rather than inside the hood with' > filtered horizontal airflow. .

e. The microbiologist was observed to spray hands and items in the hood withtmmoisinfectantScented Spray directed into the [~ filter.

f. The microbiologist was observed to spray the outside wrapped items placed in the hood, which


DISTRICT IIOORESS AND PHONE NUMBER

US Customhouse, Rm 900 2nd & Chestnut St Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/industry NAME liND TITLE OF INDIVIDUIIL TO WHOM REPORT ISSUED


McNeil Consumer Healthcare, Div of McNeil-PPC, Inc. CITY. STATE, ZIP CODE, COUNTRY


OATE(S) OF INSPECTION

04/19/2010 - 04/30/2010 FEINUMBER

2510184

STREeT /\DORESS

7050 Camp Hill Road

TYPE ESTABLiSHMENT INSPECTED

OTe Pharmaceutical Manufacturer

EMPLOYEEIS) SIGNATURE OIlTEISSUEO

Anita R. Michael, Investigator Matthew R. Noonan, InvestigatorSEE REVERSE Sharon K. Thoma, Investigator 04/30/2010

OF THIS PAGE 'Hala L. ~, Investigator i -.s L!I:bllt:.

INSPECTlONAL OBSERVATIONS PAOE i3 OF )7 MOllSFORM FDA 4B3 (0910B)

were opened outside of the hood rather than inside the hood. For example, pipettes used to transfer product with ~o the plates.

g. Grills in front ofthe entire face oftheatJtilters in Hood # ~ were plastic with ~one inch diameter squares and not easily sanitized/cleaned. Hood '11 was dirty with grime in each square and missed pieces ofplastfc in several locations on the plastic grill.

OBSERVATION 14

Laboratory records do not include complete records of the periodic calibration of laboratory instruments, gauges, and recording devices.

Specifically,

Laboratory refrigerators (i.e., OIl_werenot calibrated adequately in that they were not calibrated to the probes inside the units- or to Ii national standard until 04/22/10.

OBSERVATION 15

Written specifications for laboratory controls do not include a description of the sampling procedures used.

.. · DEPARTl\1ENT OF HEALTH AND HUMAN SERVJCES

FOOD AND DRUG ADMJNISTRAT!ON DISTRICT ADDRESS AND PHONE NUMBER

US Customhouse, Rm 900 2nd & Chestnut St Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: WVlW. fda. gov/oc/industry NAME AND liTLE OF INDIVIDUAL 10 WHOM REPORT ISSUED


01\ lE(S) OF INSPECTION

04/19/2010 - 04/30/2010 FEINUMBER

2510184

HcNeil Consumer Healthcare, Div of :McNeil-PPC, Inc.

7050 Camp Hill Road

CITY, STAlE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Fort Nashington, PA 19034 OTC Pha~~aceutical Manufacturer

l\1ateria1 System

OBSERVATION 16

Samples taken ofiu-process materials for determination of conformance to specifications are not representative.

Specifically,

gait) samples pulled by the .J.UU.J..J.LLJ'GI."'" finn for tmJ!IJIII not a statistically significant =the number of

representative san.lple oftbe total The sample includes only ~ag from each ofi!l!lballets orUamples.

OBSERVATION 17

Each lot of components .was not appropriately identified as to its status in terms of being quarantined, approved or rejected.

Specifically,

Separate or defined areas to prevent contamination or mix-ups are deficient re$arding operations related to the storage of released components and labeling. 211.42(e]f.B pt~\~11'\ \11 ·~\~~l'b ''\f,J*t> 0.~~11\1'"

a. On 4/20/10, drug components and labeling in unrestricted status were observed stored in the open inco:oiing inspection area in the warehouse, along -with materials in quarantined and blocked status.

stored in tlvo lanes of pallets on the floor, and included: container labels for Children's Non-Drowsy Reactine~etirizine

Symp, 5 mg/5 mL, 118 mL, Dye Free Grape, part tmJIJli label lot U1Jl:eSII1GleU in tmmml

o Artificial Bubble gum Flavor, part 111 component lot~ oucirBJ'ltl!led in ~but lacldng a status sticker. ·

"' of Com Starch NF, part component lot[Q)IB, blocked in bearing a status sticker, lealdng powder from one bag

tmmm,


FORM FDA 483 (09/08)

EMPLOYEE{S) SIGNATURE

Anita R. 11ichael, Investigator Cf.tl.IA Matthev1 R. Noonan, Investigator f'l~~ Sharon !<. Thoma, Investigator .(~~

Hala L. Whetsteme, Investigator~ !:"e{•bL ff,; S L 2£' /0 '

PI!EVIDVS EDmON ODSDL!ITll INSPECTIONAL OBSERVATIONS

DATE ISSUED

04/30/2010

!'AGE J 4 OF J7 PAGES


DISTRICT ADDRESS AND PHONE NUMBER .

US Customhouse, Rm 900 2nd & Chestnut St Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/industry


04/19/2010 - 04/30/2010 FEINUMBER

2510184


TO: HaJcan Erdemir, Vice President of Operations FIRM NAME

McNeil Consumer Healthcare, Div of MCNeil-PPC, Inc.

STREET ADDRESS

7050 Camp Hill Road

CITY, STATE, ZIP CODE, COUNTRY

Fort Washington, PA 19034 TYPE ESTABLISHMENT INSPECTED


.


EMPLOYEEIS) SIGNATURE

Anita R. Michael, Investigator ?[l~tl Matthew R. Noonan, Investigator $iI\..N Sharon K, Thoma, Investigator , Hala L. Whotstone, Investigator . ~~

5=!l' f3; 'I/:ro) (U '{j

DATE ISSUED

04/30/2010

roORM FDA 483 (U~I08) PIUlVIDUH nDITION DDSDLp.Tn INSPECTIONAL OBSERVATIONS PAGE IS OF 17 PAGES

The status of the materials could not be determined via visual examination, with the exception of the Corn Staroh NF.

b. On 04/20110, ~artons for Concentrated Tylenol Infanis:l2:ws, 80 mg acetaminophen per.8 mL, 1 fl. oz., Dye Free Cherry, part abellota~, were observed stored in cardboard boxes on a pallet in the incommg inspection area. "Bad cartons" had been handwritten in black ink on the oardboard boxes. The cartons were in unrestricted status in SAP.

c. Stock Roorrj!iiRestricted Storage Room located in the microbiological laboratory had excess media in boxes and special projects stored in the room with no designated areas of storage for approved, quarantine, OT rejected status. The room was cluttered with boxes of media, special projects that had bins with various containers of chemicals, special projects with boxed finished OTC products, boxes of computer items, out of service equipment, etc. Until 04/23/10, the firm had no inventory of the room contents.

OBSERVATION 18

Components are not microscopically examined when appropriate.

Specifically,

orts written for the microbial water test results per for G ince on or before 05/01/09. Pages 18 and 19 of25 reads in part: "9.0 DOCUMENTATION 9.1 The monthly/weekly samples are automatically logged into the computerized data system [GjBD***9.2 Results are documented in the assigned laboratory logbook and are entered into the computerized data system~ *** 9.3 A monthly report ofmicrobial water testing results shall be performed and documented. 9.3.1 The monthly trending of the purified and potable water systems is done *** throughout the facility. *** 9.3.2 The report will consist ofthe current month and at least the summarized data from the previous month. 9.3.3 The following must be part of the full report: *** Sanitization dates of the system ***Quantity of samples *** Quantity of samples within limits *"'* Action/Alert levels *** Investigations ***9.3.4 The report will be initiated by a Team Leader or designee and will be signed by the Microbiology MaDijer ***The Team Leader will have the responsibility of collecting and compiling the information fron&IBr the testing logbooks and verify its accuracy. The Microbiology Manager will review the report for completion and determination of any abnonnal trends ofthe water system. *** 9.3.5 The report will be completed

DEPARTMENT OF HEALTH AND HUMAN SERVICES rOOD AND DRUG ADMINISTRATION

DATE(SI OF INSPEOTlDNDISTRI(;f ADDRESS AND PHONe NUMBeR

US Customhouse, Rm 900 2nd & Chestnut st 04/19/2010 - 04/30/2010 FEINUMBeRPhiladelphia, PA 19106 2510184

Industry Information: www.fda.gov/oc/industry . (215) 597-4390 Fax: (215) 597-0875

NAMe AND TITLe OF INDIVIDUAL TO WHOM RepORT IssueD

TO: Hakan Erdemir, Vice President of operations STREeT ADDRESS

McNeil Consumer Healthcare, Div of 7050 Camp Hill Road McN!3il-PPC, Inc. CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPEOTED

Fort washington, PA 19034 OTC Pharmaceutical Manufacturer

EMPLOYEEIS) SIGNATURE DATE ISSUED

Anita R. Michael, Investigator ttA~i. J

Matthew R. Noonan, Investigator fArlvSEE REVERSE Sharon K. Thoma, Investigator ~ 04/30/2010OF THIS PAGE Hala L.. ~-eFle, Investigator't-p,:')s

.-;O.l .S 41i!Oll 0 'CJ .

FORM FDA 483 (09108) rnOVIOUR ODITION ODRDurrO INSPECTIONAL OBSERVATIONS PAGE \1, OF 17 PAGES

., and

within sixty days from the end of~he month. ***". No _data was entered from 02/09/10 to 04/24/10, No trend reports of microbial water testing results was conducted and documented since on or after 05/01/09.

Facilities & Equipment

OBSERVATION 19

Records are not kept for the maintenance and inspection of eqiIipment.

Specifically,

a. On 04/20110, hoses on the 0 were said to not be dedicated to products processed on these two fluid bed dryers.by an operator and team leader. Cleaning validation of the equipment did not evaluat!=l cleaning ofthe 2.5 foot hose on~ ~eca?se the Cleanin~110Wed~ Cleaning of equipment lacks documentatlOll that ~was followed and/or a statement that the 2.5 foot hose wa reIIlov~d and replaced. aft.er.th~. campaign was completed for each drug product processed in th_I For example, cleaning on 04/17/10 by ope verified by operator TE. .In addition, the person verifying that cleaning was performed • 04/17/10 was a temporary person from a different McNeil site and lacked training on ~ . ~~ .

b. Seals on the III ere observed to be in disrepair and not maintained with several cracks.

c. Inlet air insulation was wrapped with peeling masking-like tape. d. No documentation on cleaning and maintenance of the Microbiolo ical Laborato ~

~ol1denser filter and gasket as required. On 04119/10, the 0

to contam a large amount of visible grey and brown material on the filter behind the grill. Review of the manufactures' maintenance manual indicates to clean the condenser at least every mJmJllor more often if the laboratory. area is dust prone. The filter should be removed, fan checks perfonned, filters replaced, and condenser vacuumed,

as 0 served


DISTR CT ACDRESS AND PHONE NUMBER DATE(S) OF INSPEOTION

US Customhouse, RID 900 2nd & Chestnut St Philadelphia, PA 19106 (215) 597-4390 Fax: (215) 597-0875 Industry Information: www.fda.gov/oc/industry NAME AND TITLE OF INDIVIDUAL TO WHOM REPORT ISSUED

TO: Hakan Erdemir, Vice President of Operations

04/19/4010 - 04/30/2010 FEINUMBER

2510184

FIRM NAME STREET ADDRESS

McNeil Consumer Healthcare, Div of 7050 Camp Hill Road McNeil-PPC, Inc.., CITY, STATE, ZIP CODE, COUNTRY TYPE ESTABLISHMENT INSPECTED

Fort Washington, PA 19034 OTe Pharmaceutical Manufacturer

.',

OBSERVATION 20

The persons double-cbecldng the cleaning and maintenance a~e not dating and signing or initialing the equipment cleaning and use log,

Specifically,

No second signature verifying that maintenance was completed. The second signature in the system is a sign off that the maintenance was entered into th~ system alld notyerification of the adequacy of maintenance conducted. For examples, Maintenance CJ ated 12/11/09; Maintenance ~417/10; etc.


EMPLOYEE(S) SIGNATURE

Anita R. Michael, Investigator (1~1..1..b ...-{/I(j-;::;../, _, . Matthew R. Noonan, Investigator t1 ./~~ Sharon K. Thoma, Investig~tor f/J/P:IlJ.-r /{' -1/Lr.7it-r.-J fkF'fYl<.D Hala L. WheEstea,e, InvestJ.gator N·5i."I~u.u Lldl ~l];..JJOl1vt.!:"J..,;ia.i:>f

.::el b<-\ tI$l::' lll8C'lio U - erJ '. 't:I

DATE ISSUED

04/30/2010

FORIII FDA 483 (09/08) rnevlOus EDIllON ODSriLETE INSPECTIONAL OBSERVATIONS PAGIl17 OF 17 PAGIlS

. .

Documents

McNeil 483 2010 FINAL Redacted