HANDBOOK OF

SOPS FOR GOOD

CLINICAL PRACTICE
SECOND EDITION
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 HANDBOOK OF
SOPS FOR GOOD
CLINICAL PRACTICE
SECOND EDITION

Celine M. Clive

0
* Taylor & Francis
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Version Date: 20150505

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 Dedication

The author gratefully dedicates this book to Patrick and Josephine Meehan for their
continuous support and encouragement, and for providing an example to follow in life.

Celine M. Clive
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 Introduction

This handbook is divided into three sections containing Standard Operating Procedures (SOPs)
applicable to the activities of the three major groups involved in the clinical development
process:

The SponsorIContract Research Organization (CRO)

The study site
The Institutional Review Board (IRB)

A fourth section, called Forms, contains all of the attachments that are referred to in the SOP
sections. Some of the forms may apply to more than one group affected by the SOPs. For
example, the "Subject Information and Consent Form Checklist" may be used by Study
Coordinators, when they are developing the document, and IRB members, when they are
reviewing it.

The advantage of this handbook is that by using the disk that accompanies it, each SOP and all of
the forms can be customized to the needs of the specific institution. To do this, the user should
open the document and make a global change replacing the word "Company" with the
company's actual name. Be aware that the length of the company's name may affect line and
page spacing and that some minor formatting may be needed after this global change is
implemented. If the institution's logo is added to the header of the first page, the formatting may
also need to be checked. Finally, the effective date should be added to the header of the second
page. From there, it will automatically be captured on all subsequent pages.

These templates should serve as a starting point for the development of SOPs. The user should
ensure that the specific processes at hislher institution are reflected in the final, approved SOP.

The language in these SOPs may appear to be limited to drug development; however, with a few
alterations, they may be adapted to medical devices and biologics as well.
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 About PoPolbnk Clinical Research Consultants, Inc.

Polaris Clinical Research Consultants, Inc. is a training and auditing company specializing in
clinical research topics and processes. Our mission is to enhance the productivity and
efficiency of clinical research teams by providing training, auditing, and Standard Operating
Procedure (SOP) development to our clients.

Polaris offers consulting services to pharmaceutical companies, Contract Research

Organizations (CRO), investigative sites, and Institutional Review Boards (IRBs). The
company offers several off-the-shelf training programs for Monitors, Investigators, Study
Coordinators, and IRB Members. Because we are interested in establishing collaborative
relationships with our clients, more often our training programs are customized to the specific
needs of our clients. We recognize the demand for experienced professionals exceeds the
supply and we believe that through training we can help bridge that gap.

Some of the advantages of using Polaris include:

Active participation of the learners. Polaris' training programs are delivered through
exercises, case studies, role-playing, and worksheets. This active involvement by the
participant ensures that the lessons become more intrinsic and the learning becomes more
effective.
Experienced personnel. Polaris' training programs are developed and delivered by
experts in various areas of the pharmaceutical industry. This provides students with high
quality training that is realistic and practical.
Program flexibility. Polaris3 training is delivered so that the point-of-view and needs of
both the CRO and Sponsor company are discussed. Programs to investigative sites include
discussions on what site personnel are required to do by regulation and which tasks are
driven by Sponsor-specific requirements.

Celine M. Clive
Pohris Clinical Research Consultants, Inc.
130 Iowa Lane; Suite 103
Cary, NC 275 11
Telephone: 9 19-463-0003
Fax: 919-463-0004
E-mail:
Programs Available through Pohris

Overview of Drug Development

Overview of Clinical Research
History of the Regulations
FDA Structure and Processes
Regulations that Affect Clinical Research (FDA and ICH)
The Responsibilities of Sponsors, Monitors, and Site Personnel
The Responsibilities of Contract Research Organizations
The Role of the Institutional Review Board
Preparing Documents for Study lnitiation
Selecting Investigators and Study Sites
Developing Protocols and Case Report Forms
Conducting the Study Initiation Visit
Developing and Obtaining Informed Consent
Conducting the Interim Visit
Adverse Experiences and Serious Adverse Experiences
Editing Case Report Forms
Interacting with the Study Coordinator
Reviewing Regulatory Documents
Case Report Form Tracking and Management
Managing Clinical Trial MaterialIDrug Accountability
Writing Trip Reports and Follow-up Letters
Role of Data Management in the Clinical Research Process
Safety When Traveling
Writing Protocols
Designing Case Report Forms
FDA Audits
Detecting Fraud in Clinical Research
 Table of Contents

Sponsor/Monitor/CRO SOPs Page

MON-00 1.O Preparation, Issue, and Revision of Standard Operating 1
Procedures (SOPs)
MON-002.0 Training Clinical Research Staff 5
MON-003.0 Selecting Investigators and Study Sites 9
MON-004.0 Developing Informed Consent Forms 13
MON-005.0 Conducting Site Evaluation Visits 17
MON-006.0 Conducting Study Initiation Visits 21
MON-007.0 Conducting Periodic Site Visits 27
MON-008.0 Reviewing Case Report Forms at the Study Site 33
MON-009.0 Reviewing Regulatory Documents 39
MON-0 10.0 Adverse Experiences (AEs), Serious Adverse Experiences 51
(SAEs), and IND Safety Reports
MON-0 11.O Managing Study-Specific Clinical Supplies 57
MON-0 12.0 Conducting Study Termination Visits 61
MON-0 13.0 Telephone Contact Reports 67

Investigational Site SOPs

SITE-001.O Preparation, Issue, and Revision of Standard Operating 69
Procedures (SOPs)
SITE-002.0 Training Study Site Clinical Research Staff 73
SITE-003.0 Assessing Protocol Feasibility 77
SITE-004.0 Investigator Agreements with Sponsors or Contract Research 79
Organizations
SITE-005.0 Organizational Chart for the Study Site 81
SITE-006.0 Interactions with the Institutional Review Board 83
SITE-007.0 Recruiting Study Patients 87
SITE-008.0 Study Initiation and Implementation 91
SITE-009.0 Reviewing and Obtaining Informed Consent 95
SITE-0 10.0 Adverse Experiences (AEs), Serious Adverse Experiences (SAEs) 101
and IND Safety Reports
SITE-011.0 Drug Storage and Accountability 105
SITE-012.0 Managing Biological Samples 109
SITE-013.0 Interactions with the Sponsor or Contract Research Organization 111
(CRO)
SITE-014.0 Study Files and Record Retention 117

Institutional Review Board SOPS

IRB-00 1.o Institutional Review Board Responsibilities 121
IRB-002.0 IRB Membership and Training 125
IRB-003.0 Institutional Review Board Meetings 131
IRB-004.0 IRB Record Keeping 137
IRB-005.0 IRB Review of Research 141
IRB-006.0 IRB Review of Informed Consent 147
IRB-007.0 IRB Review of Advertisements 153
IRB-008.0 IRB Review of Unscheduled Mandatory Reports 157
IRB-009.0 Criteria for Exempt and Expedited Review 161

Forms - Alphabetical by File Name

File Name (.dot) Form Name &
Ad Review Advertisement Review Checklist 167
Amendment Protocol Amendment Form 169
Bio Sample Biological Samples Inventory 171
CRF Review CRF Review Form 173
DCF Form Data Clarification Form 175
Dispense Drug Dispensing Log 177
Dispense by Pt Study Subject Investigational Product Dispensing Record 179
Drug Disposition Clinical Trial Materials Disposition Form 181
Drug Order Investigational Drug Shipping Order 183
Drug Receipt Investigational Product Receipt Form 185
Drug Return Drug Return Form 187
Enrollment Screening and Enrollment Log 189
Expedited Expedited Review Form 191
ICF Review Subject Information and Consent Form Checklist 193
Init Doc Track Study Initiation Document Tracking Worksheet 197
Initial Sub Initial Submission Form 199
IRE3 Member IRl3 Membership Roster 207
Minutes Template IRE3 Meeting Minutes Template 209
Monitor Log Monitoring Log 213
Patient Master Master Subject Log 215
Phone Rpt Telephone Contact Report 217
Progress Rpt IRE3 Progress Report Form 219
Responsibilities Study Responsibilities Form 22 1
Review Cklist Reviewer’s Checklist 223
Review Results IRl3 Review Results Form 225
SAE Serious Adverse Experiences 227
Safety Rpt Safety Information Form 233
Sig Sheet Study Site Personnel Signature Sheet 23 5
St Term Ack IRB Study Termination Acknowledgement 237
St Term Notice IRE3 Notification of Study Termination Form 239
Training Plan Training Plan Form 24 1
Training Record Training Record Form 243
Training Request Staff Training Request Form 247
Training Verification Staff Training Verification Form 249
Trip Rpt Evaluation Site Evaluation Visit Trip Report 25 1
Trip Rpt Init Study Initiation Visit Trip Report 255
Trip Rpt Interim Periodic Site Visit Trip Report 259
Trip Rpt Termination Study Termination Visit Trip Report 263

Index of Forms - In Alphabetical Order By Form Name 269

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 Company

Standard Operating Procedure: MON-00 1.0 Effective Date: DDIMMMNY

Title: Preparation, Issue, and Revision of SOPs Supersedes: N/A

AUTHOR

Name:

Title:

Department:

Signature and Date:

APPROVED BY DEPARTMENT HEAD QUALITY ASSURANCE

Name:

Title:

Department:

Signature and Date:

REVISIONS

No. Section Pages InitialsJDate

I. Purpose
To describe the procedures by which Standard Operating Procedures (SOPs) for
Company are prepared, issued, and revised.

To provide a tool for training new personnel in the procedures by which specific
activities will be performed at Company.

11. Scope
This SOP will apply to all SOPs for Company.

MON-0Ol.O.doc Page l
 Company
Effective Date: DDIMMM/YY

111. Procedures

A. The Department Head for each Department will determine which activities require
SOPs and will assign the responsibility for writing the initial version.

B. All SOPs should include:

l. Brief, informative title.
2. The SOP number on every page.
3. Effective date of the SOP on every page.
4. Dated approval signatures for the SOP'S Author, Department Head, and Quality
Assurance (QA) representative.
5. Revision history.
6. Scope of the SOP (i.e., a statement that describes the personnel, projects, and
situations to which the SOP applies).
7. Description of the procedure (i.e., a detailed description of all procedures to be
conducted under the SOP, including when they are to be accomplished, where,
and by whom). Each step in the procedure should be numbered. All new or
unusual terms should be defined. If an abbreviation is associated with a term, it
should be placed in parentheses following the word. If specific forms or
equipment are to be used, they should be specified. Copies of the applicable
forms should be attached to the SOP in the Attachments section.
8. References (i.e., citations of any applicable regulations, guidelines, publications,
or other SOPs). Copies of the references do not need to be attached to the SOP.
9. Attachments (i.e., copies of any forms, checklists, charts, andlor tables that will be
used in executing the SOP). The Attachments section should begin with a list of
all the attachments that are included in the SOP. Attachments should be identified
by letter.

C. Review and Approval of SOPs

l. The Author will circulate the draft SOP to the Author's department members for
review and comment.
2. The Department Head will perform the final review and edit of the SOP and will
submit the final versions to QA for review.
3. After completing its final review, QA will reconcile all questions andlor
suggested revisions with the Author prior to issue.
4. The final version of each SOP must be approved by the Department Head and a
designated member of the QA Department before issuance. QA will obtain
original signatures on the SOP cover sheet before releasing the final versions of
an SOP.

MON-0Ol.O.doc Page 2
 Company
Effective Date: DDIMMM/YY

D. Distribution of SOPs
1. Each department will maintain an active SOP manual containing authorized
copies of all current approved SOPs.
2. QA will retrieve or discard all distributed versions of the SOPs (i.e., not the
archive copy) as new versions are implemented.

E. Maintaining original, signed SOPs

1. QA will maintain a complete collection of current Company SOPs and will retain
all obsolete, discontinued, or otherwise superseded SOPs in an SOP archive.

F. Revision of SOPs
1. SOPs requiring permanent modifications will be revised by the Author or
individual designated by the Department Head. Revised SOPs will be circulated
for review and approval as described in Section II1.C.
2. QA will update the cover page of the revised SOP to show subsequent revisions
of the SOP.

G. Periodic Review of SOPs

1. All SOPs will be reviewed on an annual basis to determine whether modifications
are needed or if the SOP remains in use. Annual review of SOPs will be initiated
by QA. QA will issue a reminder that SOPs are due for review.
2. If a procedure is no longer in use, the SOP will be considered inactive and stored
by QA in the SOP archives.
3. Changes to the SOP will be made according to procedures described in
Section II1.C.
4. Documentation of annual SOP review will be maintained in the SOP archives.

IV. References

ICH Guidelines for Good Clinical Practice (E6) 5.1 - Quality Assurance/Quality Control

V. Attachments

None

MON-0Ol.O.doc Page 3
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References

MON-010.0: Adverse Experiences (AEs),

Serious Adverse Experiences (SAEs), and
IND Safety Reports

Attachments Attachment A - SAE Reporting Form Attachment

B - Telephone Contact Report This page intentionally left
blank
SITE-011.0: Drug Storage and
Accountability

ICH Guidelines for Good Clinical Practice (E6) section 4.6

- Investigational Products

Attachments

Attachment A - Investigational Product Receipt Form

Attachment B - Drug Dispensing Log

Attachment C - Drug RetudDestruction Form

Attachment D - Study Subject Investigational Product

Dispensing Record
IRB-001.0: Institutional Review Board
Responsibilities

21 CFR 56.108 - IRB Function and Operations

IRE3 and Clinical Investigator Information Sheets

ICH E6 3.1 - Responsibilities

Attachments

None This page intentionally left blank

IRB-008.0: IRB Review of Unscheduled
Mandatory Reports

ICH Guidelines for Good Clinical Practice (E6) section 3.3

- Procedures

ICH Guidelines for Good Clinical Practice (E6) section 4.1

1 - Safety Reporting

Attachments

Attachment A - Safety Information Form

Attachment B - Protocol Amendment Form

Attachment C - IRE3 Review Results Form This page

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