GCP ppdf


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GCP ppdf

  1. 1. Good Clinical Practice (GCP) Compiled by-Shamon Ahmad,, M.Pharma (Q.A) Chandigarh Group of Colleges, Landra, Mohali(Punjab India)email-shmmon@gmail.com 25/12/2012 Good Clinical Practice (GCP) is an international quality standard that is provided by International Conference on Harmonisation (ICH), an international body that defines standards, which governments can transpose into regulations for clinical trials involving human subjects. Good Clinical Practice guidelines include protection of human rights as a subject in clinical trial. It also provides assurance of the safety and efficacy of the newly developed compounds. Good Clinical Practice Guidelines include standards on how clinical trials should be conducted, define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors. In the pharmaceutical industry monitors are often called Clinical Research Associates. International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use. A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected. Ethical and scientific quality standards for designing, conducting, recording and reporting trials that involve participation of human subjects to ensure that the RIGHTS, SAFETY and WELLBEING of the trial subjects are protected. Ensure the CREDIBILITY of clinical trial data. Good Clinical Practice (GCP) is the internationally- recognized standard for the design, conduct, recording and reporting of clinical trials involving human subjects. Adherence to the principles of GCP is essential in ensuring ethical standards and scientific quality, while providing public assurance that the rights, safety and well-being of trial subjects are protected. This website focuses on the practical implementation of GCP standards, with an emphasis on training and development. WHAT IS GCP? Good Clinical practice (GCP) is a standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial subjects are protected.
  2. 2. GCP ensures that subjects are properly protected in clinical studies. Such studies should be based on good science, are well designed and properly analysed and adhere to procedures that are properly undertaken and documented. Adherence to GCP is vital otherwise, subjects participating in the trials may be put at risk or the clinical trial data submitted may be rejected by health authorities and the scientific committee, if found to be unreliable. Also, the research credibility of the researcher and the research institution may be damaged. Only investigators with GCP training and certification should therefore be chosen by pharmaceutical or healthcare companies to ensure that the studies conducted conform to regulatory requirements. A series of meetings held between the regulatory authorities and representatives of the pharmaceutical industry companies in the USA, Europe and Japan, together with observers from Scandinavia, Australia, Canada and the WHO (collectively known as ICH) gave birth to a set of GCP guidelines that would be universally accepted. In May 1996, the ICH GCPs came into being and is now the standard by which all clinical trials have to be performed in order to achieve universal recognition. In 1997, the European Union accepted the ICH GCP as a legal requirement and since May 1997, the FDA expect all trials conducted outside the USA and used to support an application for marketing authorisation (NDA, new drug application) to be conducted in accordance with the ICH GCP Guidelines. Japan implemented the ICH GCP Guidelines in April 1997. In Malaysia, clinical trials conducted before 1996 were usually Phase IV trials. The last 2 years have seen an increase in Phase III and some Phase II clinical trials. In the 7th NIP, only 19% of research in the Health Sector was attributed to clinical research. This of course did not include clinical research sponsored directly by pharmaceutical companies and those performed within the operating budget. The principles of GCP recommended by the ICH Harmonized Tripartite Guidelines for GCP can be discussed under the following headings: 1. Rights and protection of Subjects 2. The Trial 3. The Protocol 4. Roles, Responsibilities, Qualifications & Experience 5. Procedures 6. The Investigational Products 1. Rights and Protection of Subjects To protect the rights of subjects, all clinical trials should be conducted in accordance with the ethical principles based on the Declaration of Helsinki and are consistent with the applicable regulatory requirements. The clinical trials taken should also weigh foreseeable risks and inconveniences against the anticipated benefits for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks. The rights, safety and well being of the trial subjects are the most important considerations and
  3. 3. should prevail over interests of science and society and any trial taken must include freelygiven consent to take part in a clinical study. In addition, trial subjects can withdraw from studies at any time without giving a reason and such withdrawal does not prejudice any future medical treatment.. The confidentiality of records that could identify subjects must be maintained, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements. 2. The Clinical Trial The proposed clinical trial should be supported by adequate(sufficient) non-clinical and clinical information on the investigational product under study. It should also be scientifically sound(fact) and described in a clear detailed protocol. 3. The Protocol The protocol is the formal record of how the trials must be conducted and must be clear and detailed. The protocol must have the prior approval of the Institutional Research Review Committee and its Ethics Committee. No modification should be made without prior consultation with the sponsor, unless it poses immediate danger to subjects under the study. All agreed protocol amendments must be documented and approved by the Ethics committee (unless purely administrative in nature) prior to implementation. The composition of the Ethics committee must fulfill the ICH-GCP requirements. The Ethics Committee should safeguard the rights, safety and well-being of all trial subjects. 4. Roles, Responsibilities, Qualifications and Experience Throughout the trial, the medical care given to and medical decisions made on behalf(ki tarfdari m/hak m) of subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist. All investigators involved in the trial should be qualified by education, training and experience to perform his/her respective tasks. The investigator must have the time and the discipline to do the study. He or she must also provide the sponsors with an up-to date, signed and dated CV as evidence of his or her qualifications. In addition, he or she must provide evidence of suitable post-graduate experience in the specialty under study, backed by relevant publications. He or she must be frilly aware of the proper use of the investigational product, be thoroughly familiar with the study protocol and, at all times, comply with his or her GCP responsibilities. A common problem is the inability to meet study recruitment targets and this issue needs to be given special consideration. 5. Procedures All trial procedures should be consistent with GCP/applicable regulatory requirements. All clinical trial information should be recorded, handled and stored in a way that allows for accurate reporting, interpretation and verification. Systems with procedures that assure the quality of every aspect of the trial should be implemented.
  4. 4. The case report form (CRF) is usually prepared by the sponsor of the study. The investigator should ensure that the pages in the CRF are completed, frilly and legibly, at every visit and that all data recorded in the CRF must be properly done to allow verification during the process of source data verification. There are strict rules for amending data in CRFs. Recording of data, done in accordance with GCP requirements, can be very tedious but necessary to ensure integrity of data. The investigator must cooperate frilly with the study monitor in this somewhat demanding exercise. ICH GCP requires the study monitor to have direct access to all subject files to ensure that all data that have been recorded is correct. An important part of GCP is the collection and maintenance of documents in the trial that demonstrate adherence to all the GCP requirements. All adverse events must be properly recorded. The investigator must obtain information from the subjects about any adverse events that may have occurred as this information may not be readily offered by the subject unless specifically asked for. An adverse event is any untoward medical occurrence in a trial subject who has been administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. So all adverse events need to be recorded. Of course serious adverse events (as defined by study protocol) must be reported immediately to the sponsor. The Ethics committee must also be informed of serious, unexpected adverse events that are product related. 6. The Investigational Product Investigational products should be manufactured, handled and stored in accordance with applicable Good Manufacturing Practice (GMP) and used in accordance with the approved protocol. CONCLUSION The responsibilities of the sponsor, the monitor and the investigator must be frilly understood by all parties involved in the study. The cost of individual clinical trials has escalated substantially since the implementation of GCP. Clinicians who undertake clinical trials must be frilly aware of the importance of conducting the study efficiently and in the shortest time possible. Therefore before agreeing to do the study, the investigator must read the protocol carefully and decide whether he or she is able to recruit subjects based on the inclusion and exclusion criteria and whether the study procedures fit into his or her usual clinical practice. He or she must regularly check the performance against the agreed recruitment rate and identify problems as they occur and not hibernate then until it is too late. For successful implementation of the study, the investigator will need a good team including a good research assistant and efficient co-investigators, all of whom are very familiar with GCP and the study protocol. Enough time must be devoted for the study with regular meetings being held to discuss progress and problems pertaining to the study. Proper and accurate documentation is crucial.
  5. 5. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) 1. Responsibilities 1. An IRB/IEC should safeguard the rights, safety, and well being of all trial subjects. Special well-being attention should be paid to trials that may include vulnerable subject subjects. 1.2 The IRB/IEC should obtain the following documents: trial protocol(s)/amendment(s), written informed consent form(s) and consent form updates that the investigator proposes for use in the trial, subject recruitment procedures (e.g. advertisements), written information to be provided to subjects, Investigator’s Brochure (IB), ritten available safety information, information about payments and compensation available to subjects, the investigator’s current curriculum vitae and/or other documentation evidencing qualifications, and any other documents that the IRB/IEC may need to fulfil its responsibilities. The IRB/IEC should review a proposed clinical trial within a reasonable time and document its views in writing, clearly identifying the trial, the documents reviewed and the dates for the reviewed following: - approval/favourable opinion; - modifications required prior to its approval/favourable opinion; - disapproval / negative opinion; and - termination/suspension of any prior approval/favourable opinion. 1.3 The IRB/IEC should consider the qualifications of the investigator for the proposed trial, IEC as documented by a current curriculum vitae and/or by any other relevant documentation the IRB/IEC requests. 1.4 The IRB/IEC should conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human subjects, but at least once per year. 1.5 The IRB/IEC may request more information than is outlined in paragraph 4.8.10 be given to subjects when, in the judgement of the IRB/IEC, the additional information would add additional meaningfully to the protection of the rights, safety and/or well being of the subjects. well-being 3.1.6 When a non-therapeutic trial is to be carried out with the consent of the subject’s legally therapeutic acceptable representative (see 4.8.12, 4.8.14), the IRB/IEC should determine that the 4.8.14), proposed protocol and/or other document(s) adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials. 1.7 Where the protocol indicates that prior consent of the trial subject or the subject’s legally acceptable representative is not possible (see 4.8.15), the IRB/IEC should determine that the proposed protocol and/or other document(s) adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials (i.e. in emergency situations). requirements
  6. 6. 1.8 The IRB/IEC should review both the amount and method of payment to subjects to assure that neither presents problems of coercion or undue influence on the trial subjects. Payments to a subject should be prorated and not wholly contingent on completion of the trial by the subject. 1.9 The IRB/IEC should ensure that information regarding payment to subjects, including the methods, amounts, and schedule of payment to trial subjects, is set forth in the written informed consent form and any other written information to be provided to subjects. The way payment will be prorated should be specified. 2 Composition, Functions and Operations 2.1 The IRB/IEC should consist of a reasonable number of members, who collectively have members, the qualifications and experience to review and evaluate the science, medical aspects, and ethics of the proposed trial. It is recommended that the IRB/IEC should include: (a) At least five members. (b) At least one member whose primary area of interest is in a nonscientific area. primary (c) At least one member who is independent of the institution/trial site. Only those IRB/IEC members who are independent of the investigator and the sponsor of the trial should vote/provide opinion on a tr trial-related matter. A list of IRB/IEC members and their qualifications should be maintained. 2.2 The IRB/IEC should perform its functions according to written operating procedures, should maintain written records of its activities and minutes of its meetings, and should meetings, comply with GCP and with the applicable regulatory requirement(s). 2.3 An IRB/IEC should make its decisions at announced meetings at which at least a quorum, as stipulated in its written operating procedures, is present. 2.4 Only members who participate in the IRB/IEC review and discussion should vote/provide their opinion and/or advise. 2.5 The investigator may provide information on any aspect of the trial, but should not participate in the deliberations of the IRB/IEC or in the vote/opinion of the IRB/IEC. vote/opinion 2.6 An IRB/IEC may invite nonmembers with expertise in special areas for assistance. 3 Procedures The IRB/IEC should establish, document in writing, and follow its procedures, which should include: 3.1 Determining its composition (names and qualifications of the members) and the authority under which it is established. 3.2 Scheduling, notifying its members of, and conducting its meetings.
  7. 7. 3.3 Conducting initial and continuing review of trials. 3.4 Determining the frequency of continuing review, as appropriate. 3.5 Providing, according to the applicable regulatory requirements, expedited review and approval/favourable opinion of minor change(s) in ongoing trials that have the approval/favourable opinion of the IRB/IEC. 3.6 Specifying that no subject should be admitted to a trial before the IRB/IEC issues its written approval/favourable opinion of the trial. 3.7 Specifying that no deviations from, or changes of, the protocol should be initiated without prior written IRB/IEC approval/favourable opinion of an appropriate amendment, except approval/favourable when necessary to eliminate immediate hazards to the subjects or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change of monitor(s), telephone number(s)) (see 4.5.2) 4.5.2). 3.8 Specifying that the investigator should promptly report to the IRB/IEC: (a) Deviations from, or changes of, the protocol to eliminate immediate hazards to the trial subjects (see 3.3.7, 4.5.2, 4.5.4). (b) Changes increasing the risk to subjects and/or affecting significantly the conduct of the and/or trial (see 4.10.2). (c) All adverse drug reactions (ADRs) that are both serious and unexpected. (d) New information that may affect adversely the safety of the subjects or the conduct of the trial. 3.9 Ensuring that the IRB/IEC promptly notify in writing the investigator/institution concerning: (a) Its trial-related decisions/opinions. related (b) The reasons for its decisions/opinions. (c) Procedures for appeal of its decisions/opinions. 4 Records The IRB/IEC should retain all relevant records (e.g., written procedures, membership lists, etain lists of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for a period of at least 3 years after completion of the trial and make them available upon request from the regulatory authority(ies). The IRB/IEC may be asked by investigators, sponsors or regulatory authorities to provide its written procedures and membership lists.