In this article, we will be talking about GCP Audits, also known as Good Clinical Practice Audits. You will learn everything there is to know about what a GCP audit is, starting from the preparation steps when it comes to planning a GCP audit, to the execution of the audit and what to expect once your GCP audit has been completed. Furthermore, we will explain the basics of GCP (Good clinical practice), the Global guidelines for GCP, and various Good Clinical Practices (GCP) audit types and more.
What is GCP (Good Clinical Practice)?
In order to understand all things related to a GCP audit, one must understand GCP (Good Clinical Practices). GCP refers to an international standard for designing, recording, and reporting trials involving human subjects’ participation. Complying with GCP provides you with the public assurance that human trial subjects’ rights, safety, and well-being are protected and that the clinical-trial data are credible. The protection of human clinical trial subjects should be consistent with the Declaration of Helsinki principles. The Declaration of Helsinki explains the ethical principles of medical research involving human subjects, including research on identifiable human data and materials. The World Medical Association (WMA) has developed this statement. There are requirements for conducting clinical trials in the EU, including good manufacturing practice (GMP) and inspections in accordance with GCP or GMP.
Global Guidelines for GCP
According to the principles of ICH E6 (R2): Guideline For Good Clinical Practice, there are 13 principles that set out the global guidelines for GCP, which are as follows:
- Ethical Principles
As part of clinical trials, ethical principles originated in the Declaration of Helsinki must be followed, as well as GCP and other applicable regulatory requirements.
- Trial risk vs. Trail benefit
Before initiating a trial, a trial’s foreseeable risks and inconveniences should be evaluated against the foreseen benefits for the individual trial subjects and society. A trial should be initiated and conducted only if the anticipated benefits justify the risks.
- Trail Subjects
The rights, safety, and well-being of the human trial subjects are the most vital considerations, should prevail over interests of science and society.
- Information on Medicinal Products
The available clinical and nonclinical information on the investigational product should be satisfactory to support the proposed clinical trial.
- Good Quality Trails
A clinical trial should be scientifically sound and documented in a clear, detailed protocol.
- Compliance with the protocol
The trial should comply with the protocol that has received prior approval or favorable opinion from the IRB (institutional review board) or IEC (independent ethics committee).
- Medical Decision
The medical decision that is made on behalf of a subject must be the responsibility of the qualified physician or, a qualified dentist (when appropriate).
- Trail Staff
In order to conduct a successful trial, each participant should be qualified by education, training, and experience for their respective tasks.
- Informed Consent
Before participating in a clinical trial, free and informed consent should be obtained from each subject.
- Clinical Trail Data
The recording, handling, and storage of clinical trial data should ensure that it can be reported, interpreted, and verified accurately.
The confidentiality of records that could identify trial subjects should be protected in accordance with the applicable regulatory requirements), respecting the privacy and confidentiality rules.
- Good Manufacturing Practice (GMP)
The Investigational product should be manufactured, handled, and stored under applicable good manufacturing practices (GMP). And those products should be used as per the approved protocol.
Quality System with procedures assures the quality of each aspect of the clinical trial should be implemented.
Additionally, WHO has published a handbook of GCP Guidance for implementation, which is called “Handbook for Good Clinical Research Practice (GCP).” Similarly, this guideline consists of 14 Principles.
Good Clinical Practices (GCP) – Audit types
The backbone of GCP compliance is the GCP audit. Principal investigators and site support personnel conduct GCP audits to assess compliance with regulatory requirements for clinical trial protocols and clinical quality management plans (CQMPs). GCP audits can have different purposes related to the clinical trial processes. Clinical trials can be audited for GCP compliance in many ways, including audits of sites monitoring, and operations conducted by monitors and trial management. This may be a full clinical trial audit of the trial sites, or an audit of the CRO conducting the trial on behalf of the sponsor. It is also possible to conduct a GCP audit to qualify and select a CRO.
Parts of a Comprehensive GCP Quality Audit
There are three main focuses to achieving a comprehensive GCP audit.
- Audit of the investigator sites that are participating in the clinical trial
This will accomplish two things:
- to identify site-specific problems which can be addressed on a case-by-case basis and highlight systemic issues that can damage the quality of the trial, whether issues are large and systemic, small and localized, or both issues can throw the results of a clinical trial into question.Conducting an audit of an investigator site can prompt corrective and preventative or both actions to eliminate risks, fix issues, and prevent possible problems that can reoccur before they impact the quality of your results.
- Auditing third-party service providers
When conducting an audit of third-party service providers, company is ultimately responsible for the quality of the conducted clinical trial. Ensuring the service providers’ network is adhering to rigorous standards is crucial. A routine audit of a service provider by an independent team ensure that you rely on and meet regulatory requirements in order to remain compliant.
- Auditing specific systems
A system audit can evaluate whether a particular activity is compliant. Sometimes, even though a specific system meets all requirements, an audit can observe improvements to streamline processes and all written procedures. A comprehensive system audit analyzes SOPs currently in use, gathers information from those procedures, and samples the collected data to make sure the system is compliant.
GCP Audit Readiness
Being prepared and ready for a GCP audit is a very critical process. The Clinical Research Site must always remain audit-ready at all times. To ensure such preparedness, procedures should be in place. For example, applicable staff should possess a thorough knowledge of the study,local regulations and good documentation practices to support the study and comply with all relevantrequirements. In addition, the site should maintain a GCP Audit Preparation standard operating procedure (SOP) in place. This may be an institutional or site-specific SOP and must be reviewed and approved for use by the Office of Clinical Site Oversight (OCSO) or Program Officer (PO). In addition to having an SOP in place, the CRS leadership must ensure that GCP audit readiness is incorporated into daily operations and procedures. This can be accomplished by implementing routine meetings with the study team to identify and address issues when they arise. Careful review of monitoring reports, audit reports, and CRS quality management activities can also help identify areas of concern.
In conclusion, to implement GCP Audit readiness, ensure personnel understands the protocol and the scientific details of the trial. Identify which team members are responsible for specific aspects of the study. Ensure that all trial documents are well organized and updated. Finally, prior to an actual audit visit, educate staff on how to communicate with the auditor!
What Happens Following a GCP Quality Audit?
When the audit is completed, a comprehensive report is compiled detailing all observations collected during the audit. Then the auditor puts together a corrective and preventive action (CAPA) plan that clearly outlines a timeline for actions and those responsible who will carry them out. At this time, an Audit Response should be prepared, including the details of the below items.
- Provide information regarding taken actions that are directly addressed to the finding and recommendations (if any).
- Provide specific actions that are committed by the management to fixthe finding
- Make your response clear and concise
- Identify specific positions, if applicable, responsible for the implementation
- Provide a specific and realistic timetable for implementation
Benefits of a GCP Certification
Investigators and all staff involved in conducting, overseeing, or managing clinical trials should complete training in Good Clinical Practice (GCP). The GCP training should be repeated every three years to be consistent with the principles of the ICH (International Conference on Harmonization). In addition, an individual who holds the Good Clinical Practice Certification has a basic understanding of regulations and requirements governing research using investigational drugs or devices that are not FDA-approved. Therefore, having personnel with a GCP certification ensures all team members have the proper knowledge and will assist with maintaining compliance with GCP guidelines.
An understanding of GCP guidelines and how a GCP audit is conducted, will allow a CRO (Clinical Research Organization) to have a heightened level of audit readiness which in turn will allow for a successful audit and a proper audit response from the organization.
Clinical Quality Assurance (QA) Auditors analyze elements of clinical research and development (CR&D) trial activities. They may also participate in site selection, vendor qualification, GCP training for monitors, and SOP management.
The basic ethical principles are of equal importance, namely respect for persons, beneficence, and justice, and permeate all other GCP principles. Research that involves human subjects should be scientifically justified and described in a clear, detailed protocol.
GCP (Good Clinical Practices) is an ethical and scientific quality standard to design, conduct, perform, monitor, audit, record, analyze, and report on clinical trials. It also serves to protect the rights, integrity, and confidentiality of trial subjects.
A clinical trial audit’s purpose is to ensure; the protection of subjects enrolled in clinical trials and to increase confidence that the data collected and subsequently submitted is valid. In addition, verify compliance with regulations including the principles of Good Clinical Practices (GCP).
GCP in Quality Assurance means that all the planned and systematic actions are established to ensure that the clinical trials are performed, and the data is generated, documented, and reported in compliance with GCP and applicable regulations.