Your Research Site SOP No.

: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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Your Research Site

Your Research Address Your Research City

Standard Operating Procedure

Confidential & Proprietary nfor!ation
Department Clinical Operations !itle Correcti$e and Pre$entati$e Actions 'ffecti$e Date !herapeutic Your !herapeutic Area"s# SOP %o& SOP-CO-03 Re$ision Original

"pproving Official: Clinical (n$estigator ############################### %ame "Printed# ############################### Signature ############################## !itle ############################## Date of Appro$al

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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Your Research Site

COPYR(*+! %O!(C'

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All material presented is -ritten and o-ned .y Your Research Site& /aterial pro$ided herein is confidential property and copyright protected .y Your Research Site& %o part of said material can .e reproduced or transmitted in any form or .y any means0 electronic or mechanical0 including photocopy0 recordings0 emailing0 or any information storage and retrie$al system no- or to .e in$ented0 -ithout permission in -ritten form from Your Research Site
Your Research Address Your Research City

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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$"%&E O' CON$EN$S

1& )& 3& 1& 4& Purpose Scope 2ac3ground Procedure Re$ision !rac3ing or Reappro$al Documentation Page 1 Page 1 Page 1 Page 4 Page 5

"ttach!ent(s):
Attachment A Attachment 2 Attachment C Attachment D Attachment ' CAPA Assessment !rac3ing 6og CAPA Assessment Plan CAPA 9orm Completed ':ample of a CAPA 9orm (ssue !rac3ing 9orm

Page 7 Page 8 Page 10 Page 1) Page 11

CORREC$ *E "ND PRE*EN$"$ *E "C$ ONS

Your Research Site Page 1 of 11 SOP No.: SOP-CO-03 +. P,RPOSE Revision: Original Effective Date: !o esta.lish a Correcti$e and Pre$entati$e Actions "CAPA# Program for conducting and Confidential & Proprietary Information documenting internal acti$ities for continual assessment of compliance -ith clinical trial protocols0 esta.lished regulations0 (C+ *CP guidelines0 internal standard operating procedures0 and policies to acti$ely see3 ;uality process impro$ements& *lo.ally0 this system is esta.lished as the Correcti$e and Pre$entati$e Actions "CAPA# Program of Your Research Site& -. SCOPE !his procedure is applica.le to the Correcti$e and Pre$entati$e Actions "CAPA# Program and Clinical Operations functional areas& Applies to all clinical research team mem.ers in$ol$ed in the regulatory implementation and coordination of Clinical (n$estigations& !his procedure is applica.le to all internal continual CAPA re$ie-s and assessments managed .y the Clinical Director and under the direct super$ision of the Clinical (n$estigator& 9unctions can .e delegated to Clinic /anagers and the clinical research team mem.ers under the direction of the Clinical Director& Applies to all clinical research team mem.ers in$ol$ed in the implementation and coordination of clinical Revision $rac3ing or in$estigations&

2.

Position Signature of (n$estigators include any other indi$idual mem.er ofDate that Signed team according toDescription the )1 C9R Re$ision"s#< Date of 40&3"d# and 31)&3 definitions& Clinical Research Coordinators "CRCs# at Your Research Site Re$ision"s#< %ote if are listed as Su.-(n$estigators on the 9orm 9DA-145)0 Statement of (n$estigator& Signature"s# is for Reappro$al Only /edical Director .. %"C/0RO,ND !he Clinical (n$estigator and Clinical Research Director must maintain the CAPA Program Director of Clinical Research for continual systems e$aluations and process impro$ements for o$erall clinical operations& !he Clinical (n$estigator is responsi.le for the o$erall conduct of a research study at the clinic0 ho-e$er< delegation allo-s the clinical research team mem.ers to perform =defined> study acti$ities and procedures under the direct super$ision of the Clinical (n$estigator in the implementation and conduct of a Clinical (n$estigation& Clinical research team mem.ers can not perform medical and protocol procedures a.o$e their medical ;ualifications& $his procedure is conducted in accordance 1ith: )1 C9R Parts 11"if applica.le#0 400 410 4?0 31)0 and 311 9DA Compliance Programs 5317&7080 5317&710 and 5317&711 (C+ *uideline '? *ood Clinical Practice Office of (nspector *eneral /andates for /inimi@ing Conflict of (nterest A&S&C& !itle 17 Selected State la-s0 additional 9ederal la-s "OS+A#0 and local regulations for the protection of human research su.Bects Si: Sigma for Pharmaceutical Products

Reapproval Personnel responsi.le Clinical (n$estigator and0 when delegated by the Investigator: All Docu!entation clinical research team members collectively referred to as Sub-Investigators & Su.-

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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"ttach!ent " E4a!ple Only C"P" "ssess!ent $rac3ing &og

Sponsor Protocol Nu!5er &ist and Descri5e Docu!ent6 Syste!6 or 'acility nspection Perfor!ed Clinical Research $ea! 7e!5er Perfor!ing Revie1 Date(s) of Revie1

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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"ttach!ent % E4a!ple Only C"P" "ssess!ent Plan

Protocol %um.er ,,,,,,,,,,,,,, Assessment Plan (ssued Date ,,,,,,,,,, Sponsor ,,,,,,,,,,,,,,,,,,,,, (ssuer>s (nitials ,,,,,,,,,,,, Date"s# of Re$ie- ,,,,,,,,,,,,,,,, Re$ie-er"s# ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, O$erall Purpose of the Assessment

Descri.e the System0 Documents0 andDor 9acility to 2e Assessed

6ist Clinic Research !eam /em.ers to .e (n$ol$ed 6ead Re$ie-er

Additional Comments

':pected (nitial Preliminary !imeline (nitial Apdate ':pected Completion

,,,,,,,,,,,,,,,,,,,,,,,,, Clinic Director Signature ,,,,,,,,,,,,,,,,,,,,,,,,, Clinical (n$estigator Signature

,,,,,,,,,,,,,,,,, Date of Signature ,,,,,,,,,,,,,,,,, Date of Signature

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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"ttach!ent C E4a!ple Only

CORREC$ *E and PRE*EN$"$ *E "C$ ONS (C"P") 'OR7

Section

dentified ssue:

Section

Casual "nalysis:

Section

Proposed Resolution(s):

Section *

'inal Root Causal "nalysis

ssued Resolved On: #################### Continuing to 5e Revie1ed: ##############

Ne4t Planned "ssess!ent: ###################

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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CORREC$ *E and PRE*EN$"$ *E "C$ ONS (C"P") 'OR7

Section * /em.ers Re;uired to Attend Retraining Attach Attendance Sheet -ith /inutes Section *

Docu!entation of Staff Retraining:

Section *

Continual Process !prove!ent:

'$ent Reoccurrence Address reoccurrences and further pre$entati$e measures and retraining and process impro$ements& Section *

nvestigator8s Revie1 or Corrective "ction Plan and "c3no1ledge!ent of Continual !prove!ent:

######################################## Corrective "ction Plan Preparer8s Signature ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Clinical nvestigator8s Signature

######################### Date of Signature ,,,,,,,,,,,,,,,,,,,,,,,,, Date of Revie1 and "pproval

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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"ttach!ent D 'or! E4a!ple 9 Co!pleted C"P"

C& N C"& N*ES$ 0"$OR8S CORREC$ *E "C$ ON RESO&,$ ON 'OR7

Protocol A2C 158 CRC R& Eac3son Section (n$estigator A& Eohnson Date of Report /ay 30 )004

dentified ssue:
Su.Bect %S/ F 001 is a su.Bect of child .earing potential and .egan study participation on Decem.er 130 )001& During an A2C sponsor audit0 Dr& Eohnson -as made a-are that su.Bect 001 did not ha$e a screening pregnancy test completed& Section

Causal "nalysis:
!his incident is .eing reported on /ay 30 )004 -hich is fi$e "4# months after the pregnancy testing -ith no correcti$e action regarding the lac3 of a pregnancy test .eing documented& !he issue has .een noted in a monitoring follo--up letter dated /arch 150 )004& !here -as no documentation on file that the (R2 -as informed of the de$iation& Records -ere re$ie-ed and end of the study pregnancy results indicated the su.Bect -as not pregnancy .y urine testing& !here -as no documentation to indicate the employees in$ol$ed -ere retrained or corrected on pre$entati$e measures& Re$ie- of this incident indicates that the la. re;uisition -as not mar3ed as child.earing potentialDthat a pregnancy test -as re;uested& Section

Proposed Resolution(s):
/onitoring letters -ill .e re$ie-ed for all protocol de$iations upon receipt to address correcti$e and pre$entati$e issues& Retraining of employees in$ol$ed -ill .e completed& CRCs -ill .e responsi.le for issuing orders for all la.s& All protocol de$iations -ill .e reported in a timely manner to the (R2& Su.Bects -ill .e as3ed to return to the site for testing -hen critical testing is missed& !rac3ing of de$iations -ill .e instituted on a Protocol !rac3ing 6og and maintained .y the Clinical Research Director per study& Section *

'inal Root Causal "nalysis:

!he la. re;uisition -as not completed properly that led to su.Bect 001 not ha$e a screening serum pregnancy result&

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information Continuing to 5e Revie1ed: /ay 30 )004 /ay140 )004

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Ne4t Planned "ssess!ent: Section *

Docu!entation of Staff Retraining:

All clinical research team mem.ers -ere retrained on la. re;uisition procedures for completing la. test re;uest0 monitoring $isit procedures0 and reporting protocol de$iations& !he training -as documented in each employee file& Signature sheet for attendees are attached& /em.ers Re;uired to Attend Retraining Attach Attendance Sheet -ith /inutes Section *

Continual Process !prove!ent:

Continual re$ie- -ill .e completed to re$ie- each incoming monitoring letter for protocol de$iation and significant performance study issue& Su.Bect safety -ill continue to .e reinforced at -ee3ly staff meetings& 6a. tests -ill only .e scheduled as designed .y the protocol .y CRCs& Protocol de$iations -ill .e re$ie-ed and trac3ed .y the Clinical Research Director for root causal analysis for compliance concerns&

'$ent Reoccurrence Address reoccurrences and further pre$entati$e measures and retraining and process impro$ements& Section *

Clinical nvestigator8s Revie1 or Corrective "ction Plan and "c3no1ledge!ent of Continual !prove!ent:
(0 Dr& Eohnson0 ha$e read and agree -ith the CAPA plan and ac3no-ledge my agreement to super$ise and implement immediate correcti$e action to secure compliance& /y staff -as retrained on /ay 100 )004 and ( -as in attendance to participate and recei$e retraining& Ge -ill again measures ho- -e are progressing on /ay 140 )004 and ( -ill recei$e continue to re$ie- monitoring letters and compliance issues since this last occurrence to measure our compliance outcomes& ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Clinical nvestigator8s Signature ######################################## Corrective "ction Plan Preparer8s Signature ,,,,,,,,,,,,, Date of Revie1 ############### Date of Signature

Your Research Site SOP No.: SOP-CO-03 Revision: Original Effective Date: Confidential & Proprietary Information

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"ttach!ent E E4a!ple Only ssue Co!pletion $rac3ing &og

Assessment Date
(n$estigator ,,,,,,,,,,,,,,,,,,

Re$ie-er"s# ,,,,,,,,,,,,,,,
Prepared 2y ,,,,,,,,,,, Date ,, ,,,,,,,,,,

Protocol %um.er"s# ,,,,,,,,,,,,,,,, Corrective "ction Revie1: Clinical Research Director ,,,,,,,,,,,,,,,,,, Clinical (n$estigator ,,,,,,,,,,,,,,,,,,,,,,, Date ,,,,,,,, Date ,,,,,,,,

O.ser$ation"s#

Recommendation

Correcti$e Action

Completion !arget Date

Responsi.le Person"s#

Completion Date