Research Quality Assurance

by: Konstanze Frank

Table of Contents

Abbreviations 4

1 Coursework Assignment / Section 2 Research Quality Assurance 5

2 Selection of Title / Statement of Anonymisation 5

3 Introduction 6

4 Responsibilities of Non-CRO Personnel in Key Roles 6

4.1 Independent Ethics Committee (IEC) 7
4.2 Regulatory Authorities / Agencies 7
4.3 Sponsor 7

5 Fulfilment of the Responsibilities of CRO Personnel in Key Roles and Proposal of Improvements 8

5.1 Project Manager 8
5.2 Investigator / Sub-investigator 8
5.3 Project nurse 9
5.4 Data Manager / Statistician 9
5.5 Medical Writer 10
5.6 Quality Control (QC) 10
5.7 Quality Management (QM), (optional, no GCP requirement) 10
5.8 Quality Assurance (QA) 11

6 Conclusion 11

7 References 12

Abbreviations

BfArM = Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte)
CRF = Case Report Forms
CRO = Clinical Research Organisation
ECG = Electrocardiogram
GCP = Good Clinical Practice
GLP = Good Laboratory Practice
GMP = Good Manufacturing Practice
ICH = International Conference on Harmonisation
IEC = Independent Ethics Committee
PEI = Federal Institut for Sera and Vaccines (Paul-Ehrlich-Institut)
PI = Principal Investigator
QA = Quality Assurance
QC = Quality Control
QM = Quality Management
SAP = Statistical Analysis Plan
SOP = Standard Operating Procedure

1 Coursework Assignment / Section 2 Research Quality Assurance

Choice of one from two titles

- Evaluate how the personnel in key roles in your organisation demonstrate fulfilment of their responsibilities as required by either GMP, or GCP, or GCP(v), or GLP. Propose one improvement in this respect, with a reasoned argument, for each role.

- Identify and give reasons for the documents and records essential for either GCP, or GCP(v), or GLP, or GMP. Discuss how they are controlled and managed in your organisation. Propose one major improvement to your current systems with a risk/benefit analysis for its implementation.

2 Selection of Title / Statement of Anonymisation

For a thorough consideration in the field of Good Clinical Practice (GCP) the first title was chosen:

- Evaluate how the personnel in key roles in your organisation demonstrate fulfilment of their responsibilities as required by either GMP, or GCP, or GCP(v), or GLP. Propose one improvement in this respect, with a reasoned argument, for each role.

With respect to the Standard Operating Procedures (SOPs) of my company, to my employment contract, and to my confidentiality statement I am not allowed to notify third parties of any real or assumed deficiencies within my organisation. Therefore, GCP key personnel and their key functions are identified according to applicable regulations (please refer to Section 7 References). Based on the example of a common German Clinical Research Organisation (CRO) working in the field of Phase I trials duties and fulfilment of responsibilities are discussed. Additionally, only presumed or theoretical deficiencies and their improvement are specified.
However, please let me re-emphasise that all facts below are based on regulatory requirements and my experiences but do not allow any conclusions to the operational state of my organisation and to any current or former deficiencies.

3 Introduction

Regarding ICH GCP guidelines [1, 2], European directive 2001/18/EC [3], and/or German drug law and principle [4, 5] multi-faceted key roles are identified when conducting clinical trials. The sponsor, who is defined as “an individual, company, institution, or organisation which takes responsibility for the initiation, management, and / or financing of a clinical trial” [1], can contract a CRO (Clinical Research Organisation) “to perform one or more of a sponsor’s trial-related duties and functions” [1]. There are requirements to be fulfilled by the volunteers/patients participating in clinical trials. If not performed by the CRO itself external vendors, e.g. pharmacist, archivist or monitor, can be contracted to undertake specific tasks. Additionally, regulatory agencies/ authorities and an Independent Ethics Committee are closely involved in the authorisation, approval and conduction of the trial. They supervise sponsors and of course CROs.

4 Responsibilities of Non-CRO Personnel in Key Roles

The following functions are non-CRO roles:
- Independent Ethics Committee
- Regulatory Authorities / Agencies
- Sponsor
Why can a CRO not assume these responsibilities?

Additionally, the tasks of
- Pharmacist / Qualified Person
- Monitor
- Archivist
are regarded as non-CRO herein. Although a CRO can inherit these responsibilities, they are excluded from the following evaluation.

The most important roles in clinical trials are definitely held by
- Volunteer / Patient
- Independent Witness
- Legally Acceptable Representative.
Without trial subject new substances/drugs could not be tested adequately.

4.1 Independent Ethics Committee (IEC)

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