Instruction

Effective Date: 28-Nov-2008 Electronic copy - not controlled if printed Page 1 of 9

Quality Control in Clinical Trials

Scope
To describe specific procedures for quality control in clinical trials performed within
International Operations (IO) region.

Applies to
This procedure applies to both clinical trials included in a Clinical Development Plan (CDP)
with trial sites in IO, and local clinical trials conducted in IO.
Trial Manager (TM), including Regional Trial Manager (RTM), Business Area Trial Manager
(BA TM), and Local Trial Manager (LTM), could perform Trial Site Visit for CDP trials and
local trials as described in section 1.2.
Both the CDP trials conducted in one country or in multiple countries, and local trials, may
be subject to Clinical Quality Support Visit (CQSV) as described in section 1.3.

Table of Contents
Scope........................................................................................................... 1
Applies to ...................................................................................................... 1
Table of Contents ........................................................................................... 1
1 Process Description.................................................................................. 2
1.1 Review of Site Visit Report................................................. 2
1.2 Trial Site Visit by Trial Manager .......................................... 2
1.3 Clinical Quality Support Visit (CQSV)................................... 2
1.4 Documentation................................................................. 3
2 References.............................................................................................. 4
Appendix 1: Abbreviations and Definitions ......................................................... 5
Appendix 2: TM Trial Site Visit Report ............................................................... 6
Appendix 3: Clinical Quality Support Visit (CQSV) Report..................................... 7
Change Log ................................................................................................... 8
Signatures ..................................................................................................... 9

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
Quality Control in Clinical Trials Page 2 of 9

1 Process Description

1.1 Review of Site Visit Report

This section applies regardless of whether IMPACT Portable is used for documenting
site visits. All site visit reports (except contact report forms) must be finalised and
signed by both LTM and Monitor within two weeks after the report available.
Note: If the LTM is also the Monitor within a country, site visit reports must be
reviewed by the second person with appropriate experience according to the local and
project specific situation. If necessary, the RTM may review site visit reports.

1.2 Trial Site Visit by Trial Manager

Trial Site Visits are performed by TM in order to assess trial progress and monitoring
at sites across IO. Not all sites need to be co-monitored, and it’s highly recommended
to set up the Trial Site Visit plan at the early phase of clinical trial. The frequency of
such visits will be determined on a project basis by the TM. The visit report must be
finalised and signed off within one month after the site visit.

Responsibility Action

1. Perform visit to trial site with monitor.

2. Document visit (Appendix 3.2).
TM 3. Forward a copy of the signed final visit report to LTM / monitor.
4. File the signed final visit report centrally rather than in the
individual TMF.
LTM / Monitor 5. Follow-up issues identified at the visit, if any.

1.3 Clinical Quality Support Visit (CQSV)

CQSVs are conducted as IO quality control initiative, which are not pre-audit visits and
should be planned independently from Novo Nordisk CQA audit schedule.
CQSVs are performed at selected trial sites to assess compliance to Protocol, ICH GCP,
Novo Nordisk Clinical Trial SOPs, any relevant HQ / local Novo Nordisk procedures, and
local regulatory regulations in place. The visits will be performed by CQSV Team,
which is composed of IO-CQTM Committee and additional assigned trial mangers with
rich experience and appropriate expertise.
Not all clinical trials need to have a CQSV. Below factors might be taken into
considerations: CRA competency, project priority, site performance, etc. The decision
will be made by CQTM in collaboration and input from TM responsible for the project.
A CQSV will comprise of In-house Review and On-site Visit. The CQSV report
(Appendix 3.2) must be finalised and signed off by all parties within one month after
the visit. The report should be centrally filed at the home city of the person who
conducts the CQSV.

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
Quality Control in Clinical Trials Page 3 of 9

Note: Signatures to CQSV reports are accepted in other formats than the original signature, i.e.
by faxed signature or signature in a PDF-file.

Responsibility Action

CQTM 1. Plan CQSV schedule including assignment of staff to perform

specified CQSV.
2. Review and update CQSV schedule at six-monthly intervals.

CQSV Team 3. Co-ordinate with LTM / Monitor (for selected trial site) for the
visit.
4. Perform the CQSV with the support by the LTM/Monitor.
5. Document visit in a CQSV report (Appendix 3.3).
6. Forward report to LTM / Monitor for documentation of response
and action plan.

LTM/ Monitor 7. Complete response and action plan.

8. Sign report and forward to CQTM.

CQSV Team 9. Review action plan and sign off the finalised report.

CQTM 10. Ensure central filing of all CQSV Reports.

1.4 Documentation

There are two report templates (Appendix 3.2 and Appendix 3.3) used for the Trial
Site Visit and CQSV. The format and structure can be modified and additional
components can be included as long as the form contains the required minimum
components. The report could be customised to satisfy the protocol specific
requirements.
Note: Narratives may be inserted within the form at any point if required.

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
Quality Control in Clinical Trials Page 4 of 9

2 References

Ref. No. Document No. - Title

[1] Document 110073: Monitoring During the Trial, Current Edition
[2] Document 110087: Trial Files, Current Edition

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
 Quality Control in Clinical Trials Page 5 of 9

Appendix 1: Abbreviations and Definitions

Term Definition
CQTM Clinical Quality & Training Manager
CQSV Clinical Quality Support Visit
IO-CQTM Committee CQTMs located in IO region. It includes the International
Operations Clinical Development Center (IOCDC) CQTM and
Business Area CQTMs. The chairperson is the IOCDC CQTM.
Site Visit Report Documentation for a visit to trial site. This includes all types of
visits to a trial site:
• Site Selection
• Site Initiation
• Site Monitoring
• Site Closure
Very brief visits which would not be considered a full
monitoring visit (such as those to drop off equipment, collect
queries etc) must be recorded using a contact report form.

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
 Quality Control in Clinical Trials Page 6 of 9

Appendix 2: TM Trial Site Visit Report

Trial ID: Site ID: Investigator:
Local Trial Manager: Monitor:
Date of In-house Review: Date of On-site Visit:
Participants at Meeting: (Investigator, Trial Site Staff, or NN staff present)
Recruitment/ Subject Status at Trial Site

TMF Review and Summary if any

(Please refer to SOP 110087 Appendix 1 and Appendix 2)

Overall Assessment of Trial Site in Terms of Recruitment & Conduct:

Overall Assessment of Monitoring of Trial Site & Identified Areas for Improvement

Comments on items Reviewed:

1. On-going Trial Site and Trial Site Staff Assessment
2. Subject Status and Recruitment Tate
3. Adverse Event Review
4. Previous Adverse Events Followed-up
5. Protocol / Amendments Adherence (including Inclusion / Exclusion Criteria)
6. Informed Consent Procedure
7. Source Data Verification (SDV)
8. CRF Completion / Collection
9. DCF Review, Correction and Handling
10. Trial Supplies and Storage Conditions
11. Drug Accountability
12. Laboratory Procedures
13. Investigator Trial File (Pleaser refer to SOP 110087 Appendix 3)

TM Name:
Signature Date

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
 Quality Control in Clinical Trials Page 7 of 9

Appendix 3: Clinical Quality Support Visit (CQSV) Report

Trial ID: Site ID: Investigator:
Local Trial Manager: Monitor:
Date of In-house Review: Date of On-site Visit:
Summary

In-house Review:
1. General TMF Review (please refer to SOP 110087 Appendix 1):
2. Site Specific TMF Review (please refer to SOP 110087 Appendix 2) :
3. Conclusion Meeting with LTM / Monitor

On-site Visit:
1. Opening Meeting with Investigator and Site Staff
2. ITF Review (please refer to SOP 110087 Appendix 3)
3. Availability of Source Data and CRF for all subjects
4. Full Check on Signed ICF
5. Full Check on SAE if any
6. Selected Subjects Review
• Source Document Review:
¾ Medical History
¾ Concomitant Medication History
¾ Statement of Involvement into the Clinical Trial
¾ Description of Informed Consent Process
¾ Comments on the Lab Values outside Normal Range
¾ Completeness of Source Data
¾ Correct Action to the Data Change on Source Data
• CRF Review
• SDV Performed: please state if 100% SDV conducted
• Patient Completed Document: Diary Card
7. Drug Accountability
8. Site Facility Review
• Calibration / maintenance records of equipments used for the project
• Storage of trial supplies review with strict temperature control and limited access
• Storage of non-drug trial supplies review with limited access
• Others
9. Closing / Conclusion Meeting with Monitor & Investigators

Highlight Points
Note: Highlight Points refer to the better practice that could be leveraged.

Comments & Action Plan

Note:
• Comments refer to the points that need to be improved.
• Action Plan refers to what the LTM / Monitor should do next to correct the inappropriate action.

Name of Person
Conducting CQSV:
LTM Name:
Monitor Name:
Signature Date

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
 Quality Control in Clinical Trials Page 8 of 9

Change Log

Edition No. Effective date Replaced document(s)

1.0 28-Nov-2008 104088 (IOCDC/COD/02)
CR number: IOCDC/08011

Description of 1. Implementation of 3-in-1 Template required by HQ;

changes to 2. IOCDC moving from Singapore to China;
operational 3. Expanded stakeholders for Trial Site Visit and Clinical
document: Quality Support Visit;
4. Removal of Appendix 3, 4, and 5 to avoid unnecessary
change of document as the result of the reference update;
5. Updating the report format to satisfy the needs.

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524
 Quality Control in Clinical Trials Page 9 of 9

Signatures

Reviewers
[Yeo Jing Ping] / [YJP] [Clinical Operations Director, IOCDC]
[Debbie Ostani] / [MDOS] [Clinical Project Manager, IOCDC]
[Huimei Feng] / [HUF] [Clinical Project Manager, IOCDC]
[Bhaskar Pramanik] / [BHAP] [CQTM, ROFE]
[Lijun Han] / [LJHN] [CQTM, CRO]
[Ninella Starkova] / [NSTA] [CQTM, ROM]
[HyunAh Yang] / [HYY] [COM, KR]
[Itani Mashau] / [IMAS] [COM, ROAG]
[Ana Laura Romeo] / [AROO] [COM, LARO]

Author(s)

Date Maggie Zhao Hua / MAZH Clinical Quality &

Training Manager

Approvers

Date [Ole Molskov Bech] / [OMB] [Vice President, IOCDC]

Date [Erik Kirkegaard] / [EKGA] [Corporate Vice President, Quality R&D]

Date [Maggie Zhao Hua] / [MAZH] [Clinical Quality & Training Manager,
IOCDC]

Process: Clinical Safety and Efficacy Edition: Internal number: Document number:
Evaluation 1.0 IOCDC/TM/02 121524