The principles and processes for the validation of computerized systems are well-known and understood within the Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) sectors of the life science industry, and the GAMP® Guide, now in its fifth revision, is well-established as a recognized industry guideline for these processes. The origin of the GAMP® 5 Guide is based upon concepts developed over 20+ years within the pharmaceutical manufacturing sector, but during this time the fundamental principles of the risk-based life cycle approach have been expanded to be equally applicable across all GxP regulated industry areas. However, the guideline does not cover those requirements specifically applicable to the field of Good Clinical Practice (GCP). The need to validate computerized systems used in the context of a clinical trial has increasingly become the focus of regulatory oversight as industry has changed from mainly paper-based processes to electronically supported processes, particularly in the last decade.
The fundamental principles and concepts are identical whether computerized systems are operated in GMP and GCP environments, however there is a need to identify the relevant similarities and differences and to define some best practices for applying GAMP® 5 principles in the context of GCP systems. In this concept paper, we will demonstrate how the GAMP® 5 principles can be applied to the validation of a key system used in clinical trials, an Electronic Data Capture (EDC) system, and explore particular aspects to be considered when implementing these systems.
Figure 1.1 highlights that Clinical Development of a medicinal product is an essential part of the whole product life cycle, and one that has to be conducted in compliance with GCP. The diagram shows the phases of development, manufacturing, and distribution of medicinal products related to their GxP areas, and that there is Guidance gap between GMP and GLP.
Figure 1.1: Development, manufacturing, and distribution of medicinal products related to their GxP areas.
2 Similarities and Differences between GMP and GCP Systems
2.1 Product Quality vs. Data Integrity
The GAMP® 5 Guide states that “patient safety is affected by the integrity of critical records, data, and decisions, as well as those aspects affecting physical attributes of the product” and product quality in the GMP environment is defined as the quality of a manufactured physical product that is directly consumed by or used on patients. Product quality is therefore of paramount importance as people might be harmed by products of poor quality. Companies manufacturing medicinal products are very aware of the quality requirements and the regulatory controls. They address these requirements through the implementation of a Quality Management System – an organizational structure and implementation of formally documented procedures, processes, and activities (e.g., extensive training) often supported by processes for the thorough testing and validation of computerized systems.
Ensuring the integrity of data managed by a computerized system is essential to support the evaluation of product quality and ultimately protect patient safety. The result of a clinical trial is not a physical product but rather data relating to the safety and efficacy of an Investigational Medicinal Product (IMP); always assuming that the IMP is of sufficient product quality. The quality parameters that can be evaluated for a clinical trial are correctness of the data and the constantly maintained integrity of data throughout the complete clinical trial. As data are collected, analyzed, processed, and corrected continuously, data integrity is at risk throughout the entire lifetime of the study. Since all data collected originate from study subjects, the protection of personal data and patient confidentially provide additional challenges that are more predominant than in most GMP environments.
2.2 Project Character of Trials
Every clinical trial is conducted and managed as an independent project even if they use the same IMP. Each clinical trial may be different as each addresses different parts of the development cycle (Phase I to IV or Non-Interventional Studies [NIS]) or varying product indications or endpoints. Trial projects, especially across the various phases, vary greatly in terms of duration, number of patients to be recruited, the pace of enrollment, and the spread of geographic location(s) involved.
The life cycle of a GCP system configuration, or in some cases the system itself, is primarily limited to the duration of the trial, while GMP systems are often in place for the lifetime of the manufactured product. While few trials run longer than three years, marketed products often exist for decades. Even though GCP systems are often used for multiple studies (e.g., Electronic Data Capture (EDC) system platforms), these systems must be adapted, configured, and sometimes deployed for each study separately to meet the trial specific requirements.
There are time pressures in the project/trial setup phase because the more time required for the development of a product, the less time that product can be marketed exclusively under a patent. Moreover, each trial investigates a different product or product aspect with a unique set of data to be collected and processed.
Read more by downloading Application of GAMP® 5: Implementation and Operation of a GxP Compliant Clinical System (Published: September 2013).