Global Regulations and Inspections –
Research Quality Assurance

by: Konstanze Frank

Table of Contents

Abbreviations 4

1 Coursework Assignment / Section 4 Global Regulations and Inspections 5

2 Selection of Title 5

3 Introduction 6

4 Purpose of government inspections for GCP 6

5 Preparation programme for inspections 7

5.1 Permanent preparation programme for inspections 7
5.2 Specifics for preparation prior to an announced inspection 7
5.3 Specifics to immediate preparation for an ‘for cause’ inspection 8

6 Improvements 9

7 Summary 10

8 References 11

Abbreviations

BfArM = Bundesinstitut für Arzneimittel und Medizinprodukte (German Regulatory Authority)
CRO = Clinical Research Organisation
EMEA = European Medicines Agency
EU = European Union
FDA = Food and Drug Administration
GCP = Good Clinical Practice
GXP = Good Clinical/Manufacturing/Laboratory Practice
ICH = International Conference on Harmonisation
MHRA = The Medicines and Healthcare products Regulatory Agency
QA = Quality Assurance
QC = Quality Control
QM = Quality Management
SOP = Standard Operating Procedure
UK = United Kingdom

1 Coursework Assignment / Section 4 Global Regulations and Inspections

Choice of one from two titles

- Discuss the purpose of government inspection for one of the GXPs. Describe your/an organisation’s preparation programme for such inspection and propose improvements in line with current expectations.
- Has global harmonisation of Regulations contributed to efficient management of the audit process in your particular organisation? Discuss.

2 Selection of Title

The first title was chosen:

- Discuss the purpose of government inspection for one of the GXPs. Describe your/an organisation’s preparation programme for such inspection and propose improvements in line with current expectations.

The issue was discussed on the basis of Good Clinical Practice (GCP) with special focus on a Clinical Research Organisation (CRO).

3 Introduction

In 2001, when the Clinical Trial Directive 2001/20/EG [2] was released in the European Union, Article 15 stated the regulations and legislation for government inspections of trial sites to be implemented by the Member States. The competent authorities of the Member States shall verify protection of the rights and welfare of trial subjects, compliance with the provisions of good clinical practice and the quality of data generated in clinical trials by appointing inspectors to inspect the sites concerned with any clinical trial [3, 4]. The European Medicines Agency (EMEA), which needs to be informed about the inspections, shall coordinate them [4, 10]. The inspections are performed on behalf of the European Union; the results should be accepted by all Member States [4, 6]. In Germany, authorisation of inspections is detailed in the German Drug Law [5] and the corresponding GCP ordinance [6]. The BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte) is the responsible German regulatory authority. The UK competent authority is The Medicines and Healthcare products Regulatory Agency (MHRA) [9].
In the US inspections are regulated by the Food and Drug Administration (FDA). The specific instructions for inspecting Clinical Research Organisations (CROs) are given in the Bioresearch Monitoring Compliance Program No. 7348.810 [8].

What is an ‘inspection’? The definitions given in the different regulations are very similar. The ICH GCP Guidelines §1.29 [1] state:
‘Inspection’: the act by a regulatory authority(ies) of conducting an official review of documents, facilities, records, and any other resources that are deemed by the authority(ies) to be related to the clinical trial and that may be located at the site of the trial, at the sponsor’s and/or contract research organisation’s (CRO’s) facilities, or at other establishment deemed appropriate by the regulatory authority(ies).

4 Purpose of government inspections for GCP

Inspections by competent/regulatory authorities are performed in order to verify:
- Protection of the personal rights, health, and welfare of trial subjects;
- Compliance with the provisions of applicable laws, GCP, protocol, contract, and Standard Operating Procedures (SOPs);
- Quality of data generated in clinical trials, and validity and traceability of reported data to finally demonstrate the safety and efficacy of regulated products in support of a marketing application [4].
Additionally, inspections might serve
- Determination of fraud (‘for cause’ inspections).
Inspections can take place periodically during or after the conduct of clinical trials, and/or as part of the verification of applications for marketing approval (or follow-up of these) [4]. Inspections by national and local authorities are the most frequent ones. However, the European Agency EMEA or the US FDA, e.g., might also inspect trial sites in different countries for the above reasons.

For cause inspections are conducted in response to information that raised concerns or suspicions within a clinical trial with regard to the integrity of the study data or the ethical treatment and protection of the research subjects.

As clinical trials in humans, i.e. the investigation and development of drugs, are very sensitive issues; government authorities must gain their responsibilities in terms of assuring the marketing of safe drugs to the greatest possible extent, e.g., by performing independent regulatory inspections. Additionally the efficacy of new drugs must be proved. With regard to the financial situation of national health systems within the EU it is mandatory to give marketing authorisation only to safe and effective drugs. In my opinion it is very important to check as much trial sites as possible.

5 Preparation programme for inspections

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