What is GCP
GCP stands for Good Clinical Practice, a set of standards for designing, recording, and reporting trials that involve the participation of human subjects.
Compliance with these standards guarantees that the rights, safety, and wellbeing of trial subjects are protected and that clinical trial data are credible (1).
Regulation VS Directive
The European Union relies on two main legislative instruments to govern GCP – regulations, and directives. There is a fundamental difference between these tools – while regulations are immediately enforceable, directives must be converted into national law by each Member State.
What is a directive?
A directive is a “legislative act that sets out a goal that all EU countries must achieve” (2). However, it is up to the Member States to arrange their own laws on how to reach these goals.
What is a regulation?
Regulation is a binding legislative act, which must be applied in its entirety across the EU (3). Usually, Member states issue national legislation that defines the corresponding national authorities and sanctions on the regulation matter.
EU GCP benchmarks
We can divide the whole history of the GCP harmonisation process in the EU into three main periods:
- Before May 2004:
- In this period, each Member State had different processes and requirements for Clinical Trial Applications. This situation was detrimental to the effective conduct of clinical trials in the EU.
- After May 2004:
- Directive 2001/20/EC. This Directive is the first step to harmonise processes and requirements for CTAs. It is currently governing clinical trials in Europe.
- May 2014:
- Regulation 536/2014. It will repeal Directive 2001/20/EC once it comes into application.
Newest legislation: Regulation EU 536/2014
Despite the fact that Regulation EU 536/2014 entered into force on 16 June 2014, it isn’t planned to go into full effect until this year. This is due to the fact that its application depends on the development of a fully functional EU clinical trials portal and database, which in turn will be confirmed by an independent audit (4).
Right now the clinical trials portal is entering an audit preparation phase. The Regulation will become applicable six months after the European Commission publishes a notice of the audit.
Although the EU Directive 2001/20 has brought some degree of uniformity in GCP rules across the Union, it was still converted into national laws by each Member State differently. Thus, the Regulation was planned as a tool that will further increase the uniformity of rules.
Regulation EU 536/2014 is designed to:
- Ensure that the procedures for authorisation are efficient and rapid;
- Simplify specific sponsor obligations;
- Guarantee public access to information regarding clinical trials.
Regulation EU 536/2014 applies to:
- Interventional clinical trials with medicinal products for human use
- The new category of low-intervention clinical trials with adapted requirements
Regulation EU 536/2014 does not cover:
- Non-interventional trials;
- Trials without medicinal products (e.g. devices, surgery, etc.).
The Directive will still apply three years from the date of application of the Regulation to:
- Clinical trials applications submitted before the entry into the application;
- Clinical trial applications submitted within one year after the entry into application if the sponsor opted for the old system (5).
Key changes
Change #1
The regulation focuses on the difference between a study without intervention, clinical trial, clinical trial with limited intervention, and a clinical study.
- Clinical Studies:
- To discover or verify the clinical, pharmacological, or other pharmacodynamic effects of one or more medicinal products;
- To identify any adverse reactions to one or more medicinal products;
- To study the absorption, distribution, metabolism, and excretion of one or more medicinal products;
- With the objective of ascertaining the safety and/or efficacy of those medicinal products.
- Clinical Trials (interventional studies):
- The assignment of the subject to a particular therapeutic strategy is decided in advance and does not fall within the normal clinical practice of the Member State concerned;
- The decision to prescribe the investigational medicinal products is taken together with the decision to include the subject in the clinical study;
- Diagnostic or monitoring procedures in addition to normal clinical practice are applied to the subjects.
Change #2
The EMA is building a new EU portal and database for clinical trials with medicines that will replace EudraCT.
The Clinical Trials Information System will serve as the single entry point for submitting clinical trial information in the EU. The information stored in this system is subject to transparency rules.
All the information will be accessible to the public, with the exception of:
- Personal data;
- Confidential commercial information ;
- Confidential communications ;
- Information disclosure of which would jeopardise effective supervision of the conduct of a trial by the Member States;
Change #3
The Regulation prescribes a precise and detailed procedure for the submission, assessment, and evaluation of requests for authorisation of clinical trials.
In the application dossier, the Sponsor will be required to propose one of the Concerned Member States (CMS) as the Reporting Member State (RMS) who will coordinate the validation and evaluation of the application.
Change #4
The Regulation defines new concepts absent from the earlier legislations:
- Co-sponsor:
- The sponsor is the health center/person responsible for a clinical trial.
- Co-Sponsors – health center/person who shares the same responsibilities unless a different arrangement is set out in a written contract.
- Low-intervention clinical trials – non-interventional study by design, which includes some form of additional diagnostic or monitoring procedures that carry minimal risk or impact on patients (e.g. study-specific blood draw).
- Auxiliary medicinal products – products included in the protocol of a clinical trial but not as investigational products.
Conclusion
The harmonisation of GCP rules in the EU is going at full speed. For Life Sciences companies, GCP compliance works in two ways.
First, it ensures the safety and efficiency of the medical products that they supply on the market.
Second, it allows avoiding punitive actions by the European Medicines Agency that will follow in case of non-compliance.
How can seQure, the business unit of Arithmos, support your QA team?
Getting support from a third party with extensive experience in GCP consulting is a way to ensure the compliance and safety of medicinal products.
seQure, the business unit of Arithmos, is able to support its clients with the whole range of the GCP activities: from an assessment of compliance status, gaps, and needs to preparation and management of inspections.
Useful links:
- Text of Directive 2001/20/EC
- Text of Regulation EU 536/2014
- Functional specifications of the EU portal and EU database to be audited
Want to know more about compliance?
- Mock Inspections: 3 tips to proceed in the right direction
- The impact of GDPR on Scientific Research
- New guidelines on Good Manufacturing Practices (GMP): what are the updates?
References
- European Medicines Agency, Good Clinical Practices. Retrieved online.
- European Union, Regulations, Directives and Other Acts. Retrieved online.
- European Union, Regulations, Directives and Other Acts. Retrieved online.
- European Commission, Clinical trials – Regulation EU No 536/2014. Retrieved online.
- European Commission, Clinical trials – Directive 2001/20/EC. Retrieved online.
