International Clinical Harmonisation Proper Systems in Place

International Clinical Harmonisation

PROPER SYSTEMS IN PLACE

The International Congress Harmonisation

WHO Principles of Good Clinical Practice

Clinical research is conducted to insure the safety and efficacy of health and medical products and practices (WHO 2002). In the past, randomized controlled trials gave most of the information about the safety and efficacy of these products and treatments. Randomized clinical trials were considered the foundation of evidence-based medicine but reliably only when conducted according to principles and standards. These principles and standards comprise good clinical research or GCP. The guidelines were created to help national regulatory authorities, sponsors, investigators and ethics committees to implement GCP for overall clinical research. These were based on the guidelines provided by major international organizations, such as the International Conference on Harmonization or ICH GCP, and used as reference (WHO).

GCP incorporates accepted and established ethical and scientific quality standards complied with for the design, conduct, recording and reporting of clinical research with the participation of human subjects (WHO 2002). This compliance is a public guarantee of the rights, safety, and well-being of the subjects, as required by the Declaration of Helsinki and other relevant and internationally recognized ethical guidelines. It insures the reliability of the data that evolve from the research. The process is complex and made more complex by the involvement of a diverse group o experts who all need to perform skillfully and efficiently. These players are all responsible for GCP. They include sponsors, investigators and site staff, contract research organizations, ethics committees, regulatory authorities and respondents to research (WHO).

The 14 guiding principles of GCP surround human subjects of research (WHO 2002). It should be scientifically sound and conducted according to basic ethical principles emanating from the Declaration of Helsinki. The three basic ethical principles permeating all other GCP principles are respect for persons, beneficence, and justice. It should be justified and described clearly. Before it is started, foreseeable risks and discomfort and anticipated benefits should be identified. The anticipated benefits should outweigh the risks as they relate to the respondents' rights, safety and well-being. It should be approved by an independent ethics committee or institutional review board beforehand. It should comply with approved protocol. Participating respondents should first provide informed consent according to their respective cultures and requirements. It should proceed only if the benefit is favorable as compared with the risks. Qualified and duly licensed medical personnel are responsible for their care and medical decisions for them. The medical staff should possess the appropriate education, training and experience for the task. All information proceeding from the research should be recorded, managed and kept safely for accurate retrieval, reporting, interpretation and verification. The records of participants should be kept private and confidential. Products ensuing from the research should be handled according to Good Manufacturing Practice and approved protocol. And systems and procedures, which assure the quality of each aspect of the trial, should be implemented (WHO).

International Congress on Harmonization

This was launched in 1990 for the purpose of connecting drug regulatory authorities and the pharmaceutical industry of Europe, Japan and the United States (ICH 2011). Regulatory harmonization will directly benefit these sectors in protecting public health. Benefits include the prevention of the duplication of clinical trials involving human subjects; the reduction of animal testing; streamlining the process for new drug applications; and reducing time and resources needed for developing. These are the advantages of harmonizing trials worldwide. Harmonization is in turn achieved by observing ICH Tripartite guidelines. The guidelines were drawn from the scientific consensus of regulatory and industry experts who work together. Commitment of these regulators to implementing the final guidelines is paramount to the success of the process itself (ICH, Gajic 2004).

Four Clinical Aspects

These are quality, efficacy, safety, and multidisciplinary (ICH 2011). Quality pervades the conduct of stability studies; establishes limits of impurities testing and adapts pharmaceutical quality to GMP risk management standards. Efficacy relates to the design, conduct, safety and reporting of clinical trials. It also covers new medicines developed through bio-technological processes and pharmacogenetic or genomic techniques used to produce target medicines. Safety guards against potential risks, such as carcinogenicity, genotoxicity, and reprotoxicity. Recently, safety guidelines proved helpful for assessing the QT interval prolongation liability as the most important cause of drug withdrawal. And multidisciplinary guidelines cover topics other than those covered by these first three aspects. Examples are ICH medical terminology, the Common Technical Document, and the Electronic Standards for the Transfr of Regulatory Information (ICH).

FDA Role

Many countries have adopted and observe GCP principles and guidelines as laws or governing regulations (FDA 2011). These are universally recognized requirement to the conduct of clinical trials involving human subjects. FDA regulations for such clinical trials have been in effect since the 1970s and cover both GCPs and human subject protection. The agency's bioresearch monitoring program conducts on-site inspections of clinical and non-clinical studies, supporting research and marketing applications (FDA).

The Harmonization Process