Good Clinical Practices MINISTRY OF SOCIAL PROTECTION National Institute for Food and Drug Surveillance - INVIMA Managing Director Jairo Céspedes Camacho Deputy Director of Health Records Clara Isabel Rodríguez Serrano Deputy Director of Medicines and Biological Products Martha Cecilia Rodríguez Ramírez Deputy Director of Health Supplies and Miscellaneous Products Ana Graciela Criado Aussant Deputy Director of Food and Alcoholic Beverages Laura Pasculli Henao General Secretary Perla Inés Llinás Álvarez Head of the Legal Advisory Office Aura Yineth Correa Child Head of the Planning, Informatics and Statistics Advisory Office Astreed Carolina Sierra Arias Head of Internal Control Office Norma Constanza García Ramírez Content Development Juana Tobos Otálora Paola Vitery Ortíz Adriana Vanegas Sánchez Editorial Coordination Teresa Huertas Molina Silvia Blanco Díaz Design and layout Bernardo Arias Blanco Monica Cabiativa Daza Print www.digitosydisenos.com Bogotá, D.C. 2009 © Content INVIMA 5 Presentation Introduction 7 1. What is a Good Clinical Practice? 9 2. How were Good Clinical Practices born? 9 3. What is the legal basis for implementation of Good Clinical Practices in Colombia? 10 4. Who is in charge of evaluating the protocols research with drugs in humans? 10 5. Who participates in an investigation with medications in humans? eleven 6. What authority is it to verify compliance with Good Clinical Practices? 12 7. What is the certificate in Good Clinical Practice? 13 8. What is the scope of the certificate in Good Clinical Practice? 13 9. What are the main legal requirements that must be met in Good Clinical Practice and what role Does each member of the system play? 14 10. What are the roles and responsibilities from the main researchers? 17 11. What happens if a breach occurs of any of the requirements? 18 12. How to request an evaluation visit to qualify for the Certification in Good Clinical Practices? 19 13. What other aspects should be taken into account when requesting the evaluation visit? twenty 14. Glossary 22 15. Index of tables of the standard (Resolution 2378 of 2008) 28 INVIMA Presentation The National Institute for Food and Drug Surveillance INVIMA is a public establishment of the national order, attached to the Ministry of Social Protection, which as Colombian Health Agency implements policies in the field of health surveillance and quality control. The scope of its management involves products of vital importance to society such as: medicines, biological products, natural and homeopathic products, diagnostic reagents, devices and elements medical surgical and dental, processed foods, meats, packaged beverages, alcoholic beverages, cosmetics, condoms, toiletries, among others. INVIMA's mission is to guarantee public health in Colombia, exercising inspection, surveillance and sanitary control of a scientific technical nature on matters within its competence. In accordance, INVIMA has defined the north of its management on three fundamental axes: guaranteeing the public health in Colombia, contribute to raising the country's health status so that it is recognized at the international, and be a support in competitiveness. INVIMA's Technical and Scientific Character In the execution of health policies, INVIMA interacts with four national systems: System of Public Health, Environmental Health System, System of Sanitary and Phytosanitary Measures and System of Science and Technology. The technical and scientific nature of INVIMA is supported by the Institute's interaction with agencies health organizations, organizations of the academic community, scientific associations and associations of professionals; and inside it is based on the conformation and full functioning of the six Specialized Rooms of the Review Commission (Medicines and Biological Products, Natural Products, Homeopathic Medicines, Food and Alcoholic Beverages, Medical Devices and Various Products, and In Vitro Diagnostic Reagents), in the specialization of the Missionary Subdirections and in the professional capacity of those who make up the teams of job. INVIMA's powers INVIMA develops its management as a Health Authority with the exercise of these powers fundamental: 5 • Issuance of Sanitary Registries and Sanitary Notifications • Certification visits • Inspection, Surveillance and Control Actions • Pre and post marketing surveillance, and special programs • National Reference Laboratory • Regulatory harmonization in health matters • Knowledge Management and Applied Research • Training and Technical Assistance • Sanctioning processes INVIMA in the Country INVIMA has placed eight Territorial Working Groups at the service of Colombians, which are being strengthened to consolidate the presence of the Institute in the Country, with the technical, scientific and administrative capacity to assume all your skills. The Territorial Working Groups of INVIMA and its host cities are: 1. Caribbean Coast 1 with headquarters in Barranquilla and coverage in Atlántico, Guajira, Magdalena and Cesar 2. Costa Caribe 2 with headquarters in Montería and coverage in Córdoba, Sucre, Bolívar and San Andrés, Providencia and Santa Katherine 3. Centro Oriente 1 with headquarters in Bucaramanga and coverage in Santander and Norte de Santander 4. Centro Oriente 2 with headquarters in Bogotá and coverage in Boyacá, Cundinamarca and Amazonas 5. Centro Oriente 3 based in Neiva and coverage in Tolima, Huila and Caquetá 6. Occidente 1 with headquarters in Medellín and coverage in Antioquia, Chocó, Caldas, Quindío and Risaralda 7. Occidente 2 with headquarters in Cali and coverage in Valle del Cauca, Cauca, Nariño and Putumayo 8. Orinoquía based in Villavicencio and coverage in Meta, Casanare, Arauca, Guaviare, Guainía, Vichada and Vaupés INVIMA carries out its management, always seeking the health and well-being of all Colombians. 6 Introduction Scientific and technological advances in health represent a challenge in terms of health surveillance, especially when research for the development of new drugs They directly involve for their studies the participation of human beings, healthy and / or sick. As the National Health Agency, INVIMA is responsible for evaluating the protocols of the clinical investigations to be carried out in Colombia, follow up on the approved research course and issue the Certificate in Good Clinical Practices to the Healthcare Institutions that carry out or plan to start clinical investigations with medications in Colombia, all this with the fundamental objective of guaranteeing the protection of the rights, safety and well-being of the participating colombians in clinical research, and that the parameters for the development of the research keep the ethical and scientific guidelines that allow obtaining final reports of total quality and reliability. This ABC publication of Good Clinical Practices, aimed at those interested in developing research with medicines in humans, has been carried out by INVIMA in order to disclose in a language clear and simple, fundamental aspects such as the concept and historical context of Good Clinical Practice, steps to follow for the certification process and the main components involved in the process of evaluation of institutions. We hope that the content of this publication will become a valuable source of consultation and an instrument to advance in the proper implementation and certification of Good Clinical Practices, for the benefit of health and quality of life of Colombians. Jairo Céspedes Camacho Managing Director 7 What is a Good Clinical Practice? It is an international standard of ethical and scientific quality for the design, conduct, realization, monitoring, auditing, recording, analysis and reporting of clinical studies that involve the development of participation of human beings. This model ensures that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of the study subjects are protected. How were the Good Clinical Practices born? In 1995 the World Health Organization, based on regulations established in some countries, developed the “Guide to Good Clinical Practice for research of pharmaceutical products in human beings human ”, in order to establish standards applicable worldwide. In 2004, the World Health Organization formed a working group dedicated to studying in depth of the regulatory issue in Good Clinical Practice and Ethics. This working group formulated a series of recommendations, among which are: • The adoption of Good Clinical Practice guidelines for all clinical studies • The requirement of informed consent documents: those in which patients voluntarily accept their participation in medical studies (especially in vulnerable populations) and to obtaining biological samples in genetic studies. In the Americas, under the leadership of the Pan American Health Organization, work has been ongoing since 1999 with the initial formation of a regional working group charged with promoting Good Clinical Practices and provide nations with the respective implementation guides. 9 Regional diagnostics have been carried out for a subsequent harmonization of regulations and The countries have accepted the recommendations of the working group, especially in relation to the Ethics Committees and informed consent. In 2005, the Technical Working Groups delegated by the countries that make up the Pan American Harmonization Network of the Pharmaceutical Regulation, REDPARF, prepared the document Good Clinical Practices: document of the Americas. This was sent to Colombia in March of the same year. What is the legal basis for the implementation of Good Clinical Practice in Colombia? The Ministry of Social Protection issued Resolution 2378 of June 27, 2008, through which were officially adopted and with mandatory character the Good Clinical Practices for institutions that conduct research with medicines in human beings in Colombia. Who is responsible for evaluating drug research protocols in humans? The group of experts that make up the Specialized Chamber of Medicines and Biological Products of The INVIMA Review Commission is in charge of evaluating the scientific, methodological and ethical aspects of research protocols with drugs in humans and give a "favorable" or "not favorable" concept of the themselves. Once the concept of the Specialized Room has been issued, which is published through the Act on the website www.invima.gov.co, the INVIMA Subdirectorate for Medicines and Biological Products welcomes the concept and "Approves" or "denies" the development of the research protocol. 10 Who is involved in a drug research in humans? When a study is undertaken in which the safety and efficacy of a drug will be evaluated and involves human beings as part of it, various actors with specific responsibilities are integrated within the process: • The Institutional Ethics Committee: It is an independent body, made up of a professional group multidisciplinary with critical capacity that watches over the integrity of the participating subjects. • Health Services Provider Institution: This is where the research process takes place. This institution must have the certificate of the “Unique Enabling System”. • The principal investigator: He is the expert doctor in the matters related to the investigation matter, and is who conducts the study. • The clinical laboratory: It is in charge of taking, processing and packaging the samples related to the study. • The sponsor: It is the institution or organization that makes the contributions to finance the study. • The impartial witness: Person (s) who attend the procedure of declaration of informed consent and with Your signature attests that sufficient and clear information has been given about the study's risks and benefits. The witness impartial cannot have any link with the other actors in the investigation. • Participating subjects: People who voluntarily and informedly participate in the process of investigation. eleven SPONSOR Investigator Financer RESEARCH PRODUCT Pharmaceutical form CLINICAL STUDY CENTER WHERE THE STUDY IS CARRIED OUT - IPS Ethics Committee Institutional Independent Principal investigator Research team Clinical laboratory Participating Subjects Impartial witness Which authority is responsible for verifying compliance with Good Clinical Practices? Resolution 2378 of 2008 establishes that it is INVIMA's responsibility to verify that the institutions that develop or intend to carry out research in Colombia with drugs in human beings, comply with Good Clinical Practices and in such a case, it is INVIMA who issues the corresponding certificate. 12 What is the certi fi cate in Good Clinical Practice? It is the certificate that INVIMA grants, for a period of five (5) years, to the Institutions Providers of Health Services that advance or wish to initiate research with medications in human beings human, legally authorizing them for this purpose. This document is issued once verification of compliance with the contemplated requirements is verified on inspection visits. in Resolution 2378 of 2008. What is the scope of the certificate in Good Clinical Practice? Taking into account that the Certificate in Good Clinical Practices issued by INVIMA authorizes a whole research process covered under a system, which includes the design, conduct, realization, monitoring, audit, registration, analysis and reporting of clinical studies, will specifically certify the Institutions Providers of Health Services where the studies are carried out. About the other actors (Ethics Committee, clinical laboratory and sponsor), who are fundamental in the process certification, INVIMA evaluators verify compliance with the requirements specifically for each one in Resolution 2378 of 2008. IMPORTANT: Institutions that do not have a clinical laboratory and / or Research Ethics Committee within their facilities, may have the external support of these components. 13 What are the main legal requirements that must be met in Good Clinical Practice and what role does it play? each of the members of the system? In the first instance, INVIMA verifies that the Institution that Provides Health Services where will carry out the study, is certified in the Unique Habilitation System defined by the Ministry of Social Protection and verified by the Secretaries of Health. This Unique System of Habilitation is the set of rules, requirements and procedures by which it is established, registered, verifies and controls compliance with the basic conditions of technological and scientific capacity, patrimonial and financial sufficiency and technical-administrative capacity of health service providers. INVIMA also verifies that the actors involved in the study are clearly defined. clinical. IMPORTANT: The evaluation visits for certification in Good Clinical Practices will be informed by the INVIMA with a maximum of 10 days in advance. The requirements that each of the actors involved in the clinical study must specifically meet are defined in the technical annex of Resolution 2378 of 2008. The Chapters and Reference Tables of these requirements are listed below: 14 ETHICS COMMITTEE IN INVESTIGATION AND DELEGATION Compliance with responsibilities Chapter II, Table 1 Correct composition of the committee Chapter II, Table 2 Compliance with procedures Chapter II, Table 3 Existence of required documentation Chapter II, Table 4 Manuals, operating guides, procedures, minutes, correspondence, others PRINCIPAL RESEARCHERS Investigator skills Chapter II, Table 5 Compliance with the duties and responsibilities of the principal investigator Chapter II, Table 6 - 16 Existence of required documentation Chapter II, Table 17 Manuals, operating guides, procedures, minutes, correspondence, others fifteen SPONSOR OF THE INVESTIGATIONS Compliance with responsibilities Chapter II, Table 18 Functions of the sponsor Chapter II, Table 18 Relations with the financing entity Chapter II, Table 20 Project files, INVIMA approval document, product delivery and return letters, manuals, budget, monitoring reports, others Existence of required documentation Chapter II, Table 18 - 20 SPONSOR OF THE INVESTIGATIONS Application of operating procedures Chapter IV, Table 9 Certificate of registration to the special registry of health service providers Chapter IV, Table 9 Use of necessary equipment and technology Chapter IV, Table 8 Certificate of compliance with enabling conditions Chapter IV, Table 8 Compliance with Compliance with laboratory personnel responsibilities procedures for the sample handling Chapter IV, Table 7 Laboratory director Chapter IV, Table 2 Compliance with your internal audit program Chapter IV, Table 6 Professional in charge of the clinical laboratory study Chapter IV, Table 3 Personnel involved in the collection, processing, conservation and transport of biological specimens Chapter IV, Table 4 Compliance with your quality system Chapter IV, Table 5 16 What are the roles and responsibilities of principal investigators? FUNCTIONS AND RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATORS Disclosure of research results Chapter II, Table 16 Standardization of procedures Chapter II, Table 6 Collection and processing of biological samples and specimens Chapter II, Table 15 Management of the product under investigation Chapter II, Table 14 Request for informed consent Chapter II, Table 13 Study staff Chapter II, Table 7 Compliance with ethical regulations Chapter II, Table 8 Adherence to the project while conducting the study Chapter II, Table 9 Information management Chapter II, Table 10 Inclusion and monitoring of participants in the study Chapter II, Table 12 Adverse events presented in participating subjects Chapter II, Table 11 17 What happens if there is a breach of any of the requirements? Institutions that carry out clinical studies with medications must meet ALL the requirements stipulated in Chapter II of Resolution 2378 of 2008, in order to guarantee the suitability of the process of research, the protection and safety of the participating subjects and the validity of the results. Taking into account that some of these aspects are more relevant than others, the following is they present the requirements classified into two categories, (high importance and medium importance) defined in accordance with the relationship that each aspect evaluated has with the safety and rights of the subjects study participants. Highly important aspects Failure to comply with critical aspects has a high impact on the quality of the investigation and may jeopardize the safety of the participants. Aspects of medium importance Failure to comply with this section has a medium impact on the quality of the investigation and does not jeopardize the safety of the participants. 1. Number of members (men and women) 2. Minutes of the Committee. 3. Approval of the project by INVIMA or the delegated Health Entity. 4. Files. 5. Regarding the evaluation of researchers. 6. Resumes of the researchers. 7. Records and training certificates for all personnel. 8. Conflict statements signed by the investigator. 9. Manuals of procedures. 10. Handling and procedure of the amendments. 11. Formats of case reports. 12. Written procedures and records. 13. Selection of participants. 14. Controls and monitoring of each and every participants selected for the study. 15. Reports of adverse effects. 16. Handling of biological samples. 17. Instructions for handling the product to be investigated. 18. Informed consent. 19. Registration of the project in a public or private testing network. 1. Manual or operational guide of the Committee. 2. Manual and / or format for preparing reports. 3. Specification in the manual of the number of members required to comply with a quorum. 4. Coincidence in the number of patients recruited and the sample size specified in the project. 4.a. Verification that the patient has a copy of the informed consent. 4.b. Copy of the certificate or certification where INVIMA approved the use of the product for research. NOTE: INVIMA will choose different corrective measures, which will vary according to the number of breaches of these requirements, taking into account this classification. 18 How to request an evaluation visit to opt for the Certi fi cation in Good Clinical Practice? Institution requests visit by official letter INVIMA notifies the start of the evaluation process and delivers the technical document Institution appoints delegate to INVIMA Evaluation visit begins Delegate coordinates visit, contacts participants and lists information Resolution 2378 of 2008 contemplated transitory measures for entities that, as of the date of promulgation of the The norm will carry out studies with medicines in human beings, giving them a 6-month term (which expired passed December 26, 2008) for the presentation of a Gradual Compliance Plan. In this Plan the process of implementation, development and application of the Good Clinical Practices in the entities where the investigations are carried out. Institutions that did not manage to benefit from this gradual implementation process can send (of extemporaneously) its schedule for the implementation, development and application of Good Clinical Practice, which will enter the visit scheduling process. 19 Those who to date have not conducted research with drugs in humans, must be certified in Good Clinical Practices before starting the development of research protocols. The legal representative of the Institution in which the study will be carried out, must request the visit of certification by official letter addressed to the INVIMA Subdirectorate for Medicines and Biological Products in Carrera 68D 17-11 in the city of Bogotá, attaching: • The receipt of payment of the certification fee • The Unique Habilitation System Certificate specifying the services in which it will conduct research • The self-assessment format for compliance with requirements, based on the technical annex to Resolution 2378 from 2008 • The list of protocols that are currently underway or have ended in the last twelve (12) months • The name of the sponsor or sponsors with whom they have developed these activities • The contact details of the institution's directors, the main researchers, the Chairman of the Research Ethics Committee and the director of the entity's clinical laboratory. What other aspects should be taken into account when requesting the evaluation visit? 13.1 It is important to note that the evaluation process is divided into two phases: • In the first, a selection visit of projects under evaluation is carried out. • The second may consist of one or more visits where the compliance with the requirements demanded in the standard: twenty PHASE 1 1. START OF THE OPENING MEETING Between evaluator and delegate by the Institution 2. REVIEW AND REGISTRATION OF PROJECTS Last 12 months 3. RANDOM SELECTION OF PROJECTS 10% of projects or at least 2 projects PHASE 2 1. Evaluation to the Ethics Committee 4. Evaluation to Clinical Laboratory INVIMA evaluation visit 2. Evaluation to Researchers 3. Evaluation to Sponsor 13.2 Final report of results: At the end of each evaluation process with visits to stakeholders participants, the evaluation group generates a "visit record": document describing the findings of the evaluation. The analysis of this information determines the concept of compliance with requirements and the consequent granting of the Certificate in Good Clinical Practice. twenty-one Glossary Direct access: Authorization to examine, analyze, verify and reproduce any record and report that is important to the evaluation of a clinical study. Either party (for example, authorities and auditors of the sponsor) who has direct access, must take all reasonable precautions, within the provisions of the applicable regulatory requirements, to maintain the confidentiality of the identity of the subjects and of the information owned by the sponsor. Quality assurance: All the planned and systematic actions that are established to ensure that the study is being conducted and that data is generated, documented (recorded), and reported in compliance with Good Clinical Practice (PCB) and the regulations that apply to them. Random assignment: It is the process of assigning study subjects to treatment or control groups, using chance to determine subjects in order to reduce bias. Audit: It is a systematic and independent examination of the activities and documents related to the study, to determine if the activities were evaluated and the data was recorded, analyzed and Accurately reported according to the project, to the Sponsor's Standard Operating Procedures (Poes), to Good Clinical Practices and applicable regulatory requirements. Auditing Study Data: A Comparison of the Source Data and Records Associated with the Report intermediate or final, to determine if said data were accurately reported, establish whether the studies were carried out according to the project and the applicable PCBs, obtaining additional information not provided in the report and establish whether procedures were used to obtain the data that could invalidate them. Biosecurity in the clinical laboratory: It is the set of rules and procedures that guarantee the control of factors of physical, chemical, biological and ergonomic risk that may affect the personnel linked to the clinical laboratory or to community members. Good Clinical Practice (PCB): Standard for design, conduct, conduct, monitor, audit, registration, analysis and reporting of clinical studies that provides a guarantee that data and reported results are credible and accurate, and 22 that the rights, integrity and confidentiality of the study subjects are protected. Well-being (of the study subjects): Corresponds to the physical and mental integrity of the subjects participating in a clinical study. Blinding: Procedure in which one or more parts of the study are unaware of aspects of the treatment. The Simple blinding generally refers to participants being unaware of the assignment, while double means that the participants, researchers, monitor and, in some cases, the analyst, the allocation to the research product is unknown. Center where the study is carried out: Places where the activities related to the study. Audit certificate: It is the minutes signed by the parties that participated in the audit, where the auditor confirms its completion. Participant subject identification code: Unique identifier that the researcher assigns to each subject of the study to protect the identity of the latter and that is used instead of the name of the subject when the investigator reports adverse events and / or some other data related to the study. Coordinating Committee: A committee that may be organized by the sponsor to coordinate the conduct of a study multicenter. Institutional Ethics Committee (CEI): Independent organization made up of medical, scientific members and non-scientists, whose responsibility is to guarantee the protection of the rights, safety and well-being of humans involved in a study through, among other things, constant review, approval and review of the study project and amendments to the documentation and the informed consent of the subjects of the study. Independent Ethics Committee: Independent organization (a review board or institutional, regional committee, national or supranational), made up of medical / scientific professionals and non-medical / non-scientific members, whose responsibility is to ensure the protection of the rights, safety and well-being of human beings involved in a study and provide a public guarantee of that protection of the rights to through, among other aspects, the review and approval / favorable opinion of the study project, the capacity of researchers and the adequacy of the facilities, methods and material to be used when Obtain and document the informed consent of the study subjects. Confidential: Corresponds to information, reports or communications, property of the sponsor or the identity of a subject, which can only be disclosed to others who are authorized or to the health entity correspondent. 2. 3 Comparator: A research or marketed product (eg, active control) or placebo (substance that, by itself lacking therapeutic action, produces some curative effect in the ill, if he receives it convinced that he really has such an action) often used in a study clinical. Informed consent: A process by which a subject voluntarily confirms their desire to participate in a particular study, after being informed about all aspects of it relevant and may affect your decision to participate. Informed consent is documented through the informed consent form, which must be signed and dated by the participant, two witnesses and the medical researcher. Quality Control (CC): The techniques and operational activities carried out within the insurance system of quality to verify that the quality requirements of related activities have been met with the study. Essential documents: Documents that individually and collectively allow an evaluation of the driving of a study and the quality of the general data. Source documents: Original documents, data and records (for example, hospital records, clinical sheets, notes laboratory reports, memoranda, subject diaries or evaluation checklists, records of delivery of the pharmacy, recorded data from automated instruments, certified copies or transcripts after verify that they are exact copies, microfiche, photographic negatives, magnetic media or microfilm, x-rays, subjects' records and records kept at the pharmacy in the laboratories and in the departments medical technicians involved in the clinical study). Project amendment: Written description of changes or formal clarification of a project. Funding entity: Individual, company, institution or organization responsible for financing a clinical study. Biological specimen / sample: Tissues, liquids, or substances derived from the human body for the purpose of being analyzed and thus provide information for the diagnosis, prevention or treatment of any disease or for the evaluation of the health of a person. 24 Clinical Study: Also called a clinical trial. It is any investigation that is made in beings humans with the intention of discovering or verifying the clinical, pharmacological and / or any other effects pharmacodynamic effect of investigational products, any adverse reaction and / or to study the absorption, distribution, metabolism and excretion of products under investigation, in order to check their safety and / or efficacy. Non-clinical study: Biomedical studies not performed in humans. Multicenter study: Clinical study conducted according to a single project but in more than one place and, therefore, performed by more than one researcher. Evaluator: Person designated by INVIMA or another entity in charge of executing the evaluation process, to carry out said procedure in one or more institutions. Adverse Event (AE): Any adverse medical occurrence in a patient or subject of a clinical investigation a who was administered a pharmaceutical product and who does not necessarily have a causal relationship with this treatment. Therefore, an adverse event (EA) can be any unfavorable sign and not intentional (including abnormal laboratory finding), symptom or disease temporarily associated with the use of a medicinal (research) product, whether or not related to it. Serious Adverse Event (EAS): Any adverse medical occurrence in a patient or subject of a clinical investigation a who was administered a pharmaceutical product and who does not necessarily have a causal relationship with this treatment. Therefore, an adverse event (EA) can be any unfavorable and unintended sign (including abnormal laboratory finding) symptom or disease temporarily associated with the use of a product medicinal (research), whether or not related to it, that at any dose: a) Results in death. b) Threatens life. c) Requires hospitalization of the patient or prolongation of the existing hospitalization. d) Results in persistent or significant disability / invalidity. Case Report Form (FRC): It is a printed, optical or electronic document designed to record all the information required in the project to be reported to the sponsor about each subject of the study. Committee Operational Guides (GOC): Detailed and written instructions to achieve uniformity in the execution of a specific function. Equivalent to the Standardized Operating Procedures Manual (MPOE). 25 Inspection: The action of the health authorities or the Ministry of Social Protection to carry out an official review of documents, facilities, records and any other resources that the authorities consider that they are related to the clinical study and that they can be located at the site where the study, at the facilities of the sponsor, the Contract Research Organization (OIC), or other sites that the authorities consider appropriate. Health Services Provider Institution (IPS): For the purposes of this resolution, they are considered as such health service providers and professional practice groups that have infrastructure physical to provide health services. Researcher: Person responsible for conducting a clinical study at the institution. If a study is led by a group of individuals, the investigator is the responsible leader of the group and will be called an investigator principal. Investigator's Manual: Compilation of clinical and non-clinical data on the products of research that is relevant to the study of research products in humans. Standard Operating Procedures Manual (MPOE): Detailed written instructions to achieve uniformity in the execution of a specific function. Equivalent to the Written Operational Guides (GOC). Monitoring: It is the act of monitoring the process of a clinical study and ensuring that it is conducted, recorded and reported in accordance with the project, Standard Operating Procedures Manual (MPOE), Good Clinical Practice (PCB) and the applicable regulatory requirements. Contract research organization: Person or organization (commercial, academic or otherwise) hired by the sponsor to perform one or more of the sponsor's duties and functions related to the study. Study participant / participating subject: Individual participating in a clinical study, either as a recipient of the products under investigation or as a control subject. Sponsor: Individual, company, institution or organization responsible for initiating, managing, control and / or finance a clinical study. This function may be performed by a corporation or agency external to the institution or by the investigator or hospital institution. Research Sponsor: Individual who initiates and conducts, alone or with others, a clinical trial and under whose immediate direction the product under investigation is 26 administered, delivered or used by the subject. The obligations of a sponsor-researcher include both the from a sponsor like a researcher. Standard Operating Procedures (SOPs): Detailed and written instructions to achieve uniformity in the execution of a specific function. Investigational product / medicine: Pharmaceutical form of an active ingredient or placebo that is being testing or using as a reference in a clinical study, including a product with an authorization from marketing when used or conditioned (formulated or packaged) in a manner different from that approved, or when used to obtain more information about a previously approved use. Project: Document that describes the objective or objectives, design, methodology, considerations statistics and organization of a study. Generally also provides background and rationale for the study, but these could be provided in other documents referenced in the project. East term includes its amendments. Audit Report: The sponsor's auditor's written evaluation of the results of the audit. Study subject: The individual participating in a clinical study, either as a recipient of the products under investigation or as a control. Quality system: It is defined as the group of actions and processes that aim to guarantee the quality of the results over time, immediately detect changes in the results due to failures in any of the components of the processes and monitor the different factors that can alter the precision of the results. Impartial Witness: Independent study person, who cannot be influenced in bad faith by staff involved in the investigation, who is present in the process of obtaining informed consent, if the subject or the representative of the subject legally accepted does not know how to read, and who is responsible for reading informed consent and any other written information provided to the subject or by the subject. 27 Index of tables of the standard (Resolution 2378 of 2008) Chapter II Chapter III Chapter IV 28 TABLE 1 TABLE 2 TABLE 3 TABLE 4 Table 1 Table 2 TABLE 5 TABLE 6 TABLE 7 TABLE 8 TABLE 9 TABLE 10 TABLE 11 TABLE 12 TABLE 13 TABLE 14 TABLE 15 TABLE 16 TABLE 17 TABLE 18 TABLE 19 TABLE 20 I II TABLE 1 TABLE 2 TABLE 3 TABLE 4 TABLE 5 TABLE 6 TABLE 7 TABLE 8 TABLE 9 RESPONSIBILITIES OF THE INVESTIGATION ETHICS COMMITTEE (CEI) COMPOSITION OF THE INVESTIGATION ETHICS COMMITTEE (CEI) PROCEDURES OF THE INVESTIGATION ETHICS COMMITTEE (CEI) DOCUMENTATION AND RECORD FILE OF THE INVESTIGATION COMMITTEE (CEI) Number of files of participating subjects to be evaluated for each selected study Number of files to select to assess informed consent INVESTIGATOR'S COMPETENCE FUNCTIONS OF THE PRINCIPAL INVESTIGATOR REGARDING THE STANDARDIZATION OF PROCEDURES DUTIES OF THE PRINCIPAL INVESTIGATOR WITH RESPECT TO THE STUDY STAFF FUNCTIONS OF THE PRINCIPAL INVESTIGATOR REGARDING COMPLIANCE WITH ETHICAL REGULATIONS FUNCTIONS OF THE PRINCIPAL INVESTIGATOR REGARDING ADHERENCE TO THE PROJECT DURING THE CONDUCT OF THE STUDY FUNCTIONS OF THE PRINCIPAL INVESTIGATOR REGARDING INFORMATION MANAGEMENT RESPONSIBILITIES AND FUNCTIONS OF THE PRINCIPAL INVESTIGATOR REGARDING ADVERSE EVENTS PRESENTED IN SUBJECTS PARTICIPANTS FUNCTIONS OF THE PRINCIPAL INVESTIGATOR REGARDING THE INCLUSION AND MONITORING OF PARTICIPANTS IN THE STUDY ROLES / RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR WITH RESPECT TO THE REQUEST FOR INFORMED CONSENT RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR WITH RESPECT TO THE MANAGEMENT OF THE PRODUCT (MEDICINAL PRODUCT) IN INVESTIGATION RESPONSIBILITIES OF THE PRINCIPAL INVESTIGATOR WITH RESPECT TO THE COLLECTION AND PROCESSING OF SAMPLES AND BIOLOGICAL SPECIMENS RESPONSIBILITIES AND FUNCTIONS OF THE PRINCIPAL INVESTIGATOR WITH RESPECT TO THE DISCLOSURE OF RESULTS OF THE INVESTIGATION DOCUMENTS AND RECORDS THAT THE PRINCIPAL INVESTIGATOR MUST HAVE IN THE FILES RESPONSIBILITIES OF THE STUDIO SPONSOR FUNCTIONS OF THE SPONSOR RELATIONS WITH THE FINANCING ENTITY APPLICATION INSTRUCTION TECHNICAL SHEET FOR THE INSTITUTIONAL EVALUATION OF ENTITIES THAT ADVANCE CLINICAL INVESTIGATION WITH HUMAN BEINGS MANDATORY REQUIREMENTS TO BE FULFILLED BY ALL CLINICAL LABORATORY REQUIREMENTS FOR THE LABORATORY DIRECTOR REQUIREMENTS OF THE PROFESSIONAL IN CHARGE OF THE STUDY IN THE CLINICAL LABORATORY REQUIREMENTS TO BE FULFILLED BY THE PERSONNEL INVOLVED IN THE COLLECTION, PROCESSING, STORAGE AND TRANSPORT OF THE BIOLOGICAL SPECIMENS OF SUBJECTS PARTICIPATING IN THE INVESTIGATION QUALITY SYSTEM INTERNAL AUDIT PROGRAM MANAGEMENT OF SAMPLES OF PARTICIPANTS IN THE INVESTIGATION EQUIPMENT, MATERIALS AND REAGENTS STANDARDIZED OPERATING PROCEDURES