HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 1 of 11 1. OBJECTIVE: Publicize the guidelines for evaluation, monitoring and completion of the protocols for research with medicines that are carried out in Colombia. 2. REACH: This guide is applicable to Sponsors or whoever does their time, Research Organizations for Contract (OIC) or CRO in its acronym in English, Ethics Committees (IEC), Research Centers, Researchers and their Research team involved in the development of a Research Protocol with Medicines in humans. 3. DEFINITIONS Observational study: Study in which medications are prescribed in the usual way, according to the conditions established in the authorization. The assignment of a patient to a therapeutic strategy concrete will not be decided in advance by the protocol of an essay, but will be determined by practice usual of medicine, and the decision to prescribe a certain medication will be clearly dissociated from the decision to include the patient in the study. No intervention, whether diagnostic, will be applied to patients or follow-up, which is not the usual clinical practice, and epidemiological methods will be used for analysis of the data collected.1 Phases of clinical research: 2 Phase I: These are initial safety studies of a new medication, usually conducted in healthy volunteers. • Various dose ranges can be evaluated. • They can be done in patients with disease when the mechanism of action of the medication or ethical aspects so require (HIV or cancer). • Pharmacokinetic studies are usually considered phase I Phase II to: • Clinical trials (pilots) to evaluate efficacy and safety in selected patient population with the disease or condition to be treated, diagnosed or prevented. • The objectives may be: Dose-response, patient type, dose frequency, or questions of safety and efficacy. Phase II b: • Well-controlled trials to evaluate efficacy and safety in patients suffering from the condition or disease. • These are clinical studies that usually represent the most rigorous demonstration of the efficacy of a drug. They are called pivot studies. Phase III to: • Trials performed after the effectiveness of the drug was demonstrated, but before the regulatory submission of sanitary authorization. • Studies in patients where the drug is directed. • Efficacy and safety data + number of patients. • Controlled and uncontrolled studies, groups of patients with special conditions (eg insufficiency renal). • Provide very important information for IPP and labeling in general. 1 Order SAS / 3470/2009, of December 16, by which the guidelines on post-authorization type studies are published Observatory for medicines for human use., December 25, 2009. 2 Ramirez R. and Soto N. Preclinical and Clinical Studies. Executive Directorate of Product Authorization and Establishments COFEPRIS Mexico THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 2 of 11 Phase III b: • Clinical studies that are performed after regulatory submission and related dossiers, but before Be approved and released. • Quality of life studies. Phase IV with intervention: • Trials conducted after drug launch • Provides additional efficacy and safety data • Different formulations, doses, duration of Tx, interactions with others, and comparisons. • Population groups (age, race, gender) • Critical to collect security data. • Controlled and uncontrolled studies, groups of patients with special conditions Critical or very serious deviations: procedures or practices that negatively affect rights, security or the well-being of the subjects or the quality and integrity of the data.3 Major or serious deviations: procedures or practices that could negatively affect rights, the safety or well-being of the subjects or the quality and integrity of the data.3 Minor deviations: procedures or practices that are not expected to negatively affect rights, the safety or well-being of the subjects or the quality and integrity of the data. 3 Amendment to the project: Written description of change (s) or formal clarification of a project4. Relevant Amendment: Those modifications of the protocol that may affect the safety of the subjects of study or of modifying the interpretation of the scientific evidence that supports the development of the study or are significant from any other point of view that affect the benefit / risk balance for the participating subjects5. Amendment Not relevant: All modifications to the protocol that do not affect the security of the subjects of studies, do not modify the interpretation of the scientific evidence that supports the development of essay and are not significant from any other point of view, which affect the balance benefit / risk for participating subjects.5 Sponsor2: Individual, company, institution or organization responsible for initiating, administering / controlling and / or Fund a clinical study. This function can be performed by a corporation or agency outside the institution or by the researcher or hospital institution. 4. GUIDELINES FOR THE INITIAL PRESENTATION OF RESEARCH PROTOCOLS FOR THEIR EVALUATION According to Resolution 2378 of 2008 and 3823 of 1997, sponsors have the obligation to submit for approval by the Invima (Directorate of Medicines and Biological Products) the protocols of research with medicines carried out in Colombia between Phase I and Phase IV (with intervention) which are evaluated by the Clinical Research Group. Phase research protocols Observational IV (Observational studies) do not have to be submitted for approval by the Invima. 3 Classification and analysis of the GCP inspection findings of GCP inspections conducted at the request of the CHMP (Inspection reports to EMA 2000-2012). European Medicines Agency. 01 December 2014. INS / GCP / 46309/2012 4 Resolution 2378 of 2008 5 Directive 2001/20 / EC of the European Parliament and of the Council of April 4, 2001; Article 10; Item a) - Address of Medicines and Biological Products THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 3 of 11 Therefore the documents must be submitted to the Clinical Research Group of the Directorate of Medicines and Biological Products of the Invima, complying with the requirements specified in the Presentation Format and Evaluation of Research Protocols ASS-RSA-FM055. This submission must be in accordance with the provisions of the Presentation and Evaluation Format of the Research ASS-RSA-FM055 and Checklist format for receiving documents related to ASS-RSA-FM046 research protocols and the others that they relate to. The decision of the evaluation of the protocol (approval or not), will be notified to the sponsor by means of a administrative act Likewise, a list of the Research Protocols can be found on the Invima website Clinic submitted to the Clinical Research Group, which is updated monthly. Note: The extension of a study is considered as a new research protocol, so it must be submitted as such. EVALUATION OF THE PROTOCOL BY THE ETHICS COMMITTEE: Before submitting a new clinical study to Invima, it must be evaluated by a Committee (s) of Research Ethics attached to the certification in Good Clinical Practices of a Research Center. This evaluation must be completed in “PART II: INFORMATION ABOUT THE PROTOCOL OF RESEARCH TO BE DILIGENCED BY THE RESEARCH ETHICS COMMITTEE (CEI) ” found in the Presentation and Evaluation Format of Research Protocols ASS-RSA-FM055, which should be the signature and seal of the committee. The matters to be evaluated must be recorded in the official documents that the Committee has defined within its statutes or manuals and these may be subject to further evaluation. Principal Investigator (IP): The evaluation of the Principal Investigator will be carried out from the submission of the Research protocol to Invima and will be carried out based on what is established in the regulations in force and the Guide for the presentation of the amendments, new centers, new researchers and consents informed of research protocols ASS-RSA-GU031 Research Protocol: Evaluation of the aspects that imply the technical quality of the clinical study, as well as its subsequent development at the research site. Among the minimum aspects to evaluate are: • The study will be conducted according to the ethical principles set forth in the Helsinki Declaration, the guidelines of Good Clinical Practice and regulatory requirements (Resolution 8430 of 1993 and Resolution 2378 of 2008 or current applicable standards) • The realization of the Research Protocol is justified according to the available knowledge • The risks in relation to the benefits, for the subject of study and for society, have been the sufficiently compared. • It has a theoretical foundation. • There is a fundamental objective. • The protocol design is adequate. • The statistical design is adequate. • There is a plan for analyzing the results. • The inclusion and exclusion criteria are adequately specified. • The protocol is reproducible. • If placebo is used, its use is justified. • Supportive therapy is used. • Concomitant treatment is specified. • A washing period is necessary. • The allocation of treatment to research subjects is appropriate. THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 4 of 11 • The main endpoint variable is objective and clinically relevant. • The criteria for evaluating the response have valid methods. • The failure criteria are specified. • It is allowed to replace losses. • All study information will be recorded so that it can be reported, interpreted and verified. precise way. • The data collection tool is adequate. • There is a format where adverse events are recorded. • The method of notification of the adverse event to the sponsor is specified. • Medical attention will be guaranteed to study subjects in case of an adverse event related to the study medication. • The patient care mechanism is specified, if an adverse event associated with the product occurs, while accessing the policy. • It has a contractual and extra contractual policy for adverse events associated and attributable to the product of investigation. • Procedures that guarantee the quality of each aspect of the project will be sufficiently and correctly implemented. study According to the Phase of the clinical study to be submitted, in addition to the above, attention should be paid to: Phase I: • Complete pre-clinical information (review of the pre-clinical information available in the manual of the researcher). • Adequate target population. • Sample size suitable for the study. Phase II: • Complete pre-clinical information (review of the pre-clinical information available in the manual of the researcher) • Adequate target population • Sample size suitable for the study • Safety and tolerability of the research drug in humans. • Complete pharmacokinetic information of the research drug in humans. Phase III • Complete pre-clinical information (review of the pre-clinical information available in the manual of the researcher) • Adequate target population • Sample size suitable for the study • Justified information of the investigational medicine regarding safety and efficacy in preliminary phases (phase I and phase II) • Updated information on the investigator's manual, regarding the research medication. Researcher's Manual: This document must contain all the information available from previous clinical studies (phase I, II, III as the case may be) on safety data of the molecule under investigation as toxicity, teratogenicity, pharmacodynamics, pharmacokinetics, physical and chemical properties, interactions with medications and / or food, side effects and adverse reactions, making clear the possible risks that can occur during the study. In addition, the investigator's manual must contain information Reliable from previous pre-clinical studies that justify the use of the molecule in humans. Informed Consent (ICF): The ethics committee should evaluate aspects such as materials and methods that are going to be used to obtain informed consent to the subjects participating in the clinical study, such as the THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 5 of 11 budgeted time for the taking of informed consent, which contemplates the pertinent information to bias-free research, which explains the coverage of the attention of adverse events, the possible risks and expected benefits, completely voluntary participation and which can be abandoned in any time of the study without the participant having a negative effect on health care, others alternative treatments when applicable, the schedule, number of visits and laboratory tests that will be made to the participant, the budget for food and transportation when applicable, the availability of an insurance policy in case of compensation or compensation, and the management of the data confidentiality, among others. The document must have a clear, legible letter with adequate information for the sociocultural level at the place of application, it must not be extensive, unambiguous and everything referred to in Resolution 8430 of 1993. It should be taken into account that the participation of minors It must follow the guidelines established in the mentioned resolution or in current sanitary norms. Likewise, informed consent must be evaluated for genetic samples, in which the sponsor specifies how these samples are going to be used, the time in which the destruction and the handling of the Confidentiality of this information. Take into account the guidelines for informed consents established in the Guide for the presentation of amendments, new centers, new researchers and informed consents of research protocols ASS-RSA-GU031 Amendments to the protocol (If applicable): When the modifications are relevant, that is to say that they affect the security of the participant or modify the design, statistical treatment and / or interpretation of the tests in the protocol, they should evaluate these characteristics in such a way that the integrity of Participating subjects It is important to consider that a relevant amendment may have the following Features: Changes in the safety and integrity of test subjects, change in criteria of inclusion and exclusion, extension of the window period, change in protocol design, statistical analysis, sample size, changes related to the drug, change in procedures, modification of efficacy and safety parameters, or those characteristics that the Ethics Committee considers in investigation. Take into account the guidelines for informed consents established in the Guide for the presentation of amendments, new centers, new researchers and informed consent of research protocols ASS-RSA-GU031 5. MAXIMUM EVALUATION TIME The clinical research protocol evaluation process is in charge of the Clinical Research Group of the Directorate of Medicines and Biological Products of Invima, with a maximum time of two (2) months to give response to the interested party NOTE: For the Clinical Research Protocols of impact on Public Health, the prioritization in its evaluation. 6. GUIDELINES FOR THE FOLLOW-UP OF RESEARCH PROTOCOLS The monitoring of research protocols is done in two different ways like this: 6.1 Evaluation of the documents related to the research protocol that must be submitted to the Invima: The documents referenced below must be submitted to the Clinical Research Group of the Directorate of Medicines and Biological Products, who will evaluate and analyze the approval or not of said documents: • Protocol amendment, new centers, new investigators and informed consents: You must complete the Format for the presentation of amendments, new centers, new researchers and informed consent of research protocols ASS-RSA-FM047, according to the Guide for the THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 6 of 11 presentation of the amendments, new centers, new researchers and informed consents of research protocols ASS-RSA-GU031 • Stability Studies: The Format for the presentation of studies of stability of investigational drugs ASS-RSA-FM088 according to the Guide for the presentation of stability studies of research drugs ASS-RSA-GU055 • New requests for Import of Supplies and Export of Biological Samples: fill out the presentation and evaluation format for new import requests for supplies for ASS-RSA-FM052 research protocols and Presentation and evaluation format for new export applications of biological samples for research protocols ASS-RSA-FM053 according to the Guide for presentation of new requests for import of supplies and export of biological samples for protocols ASS-RSA-GU036 • Modifications to the Investigator Manual: The Presentation and Evaluation Format of modifications to the ASS-RSA-FM054 researcher's manual according to the Presentation Guide and Evaluation of modifications to the researcher's manual ASS-RSA-GU037. • Annual Report: The Annual Report of Research Projects FormatASS-RSA-FM063 must be completed in accordance to the Guide for the Diligenciamiento of the Annual Format of Projects of Investigation ASS-RSA-GU041 • Protocol Closure: The format for notification of closure of clinical studies (protocols) must be completed. ASS-RSA-FM049 according to the Guide for notification of closure of clinical studies (protocols) ASS-RSA- GU033 6.2 Monitoring of research protocols: It will be carried out through visits to research centers that are developing the monitoring protocol. In this type of visits the status of a clinical study is verified in a research center, where the selection process, informed consent, management of the data (collection, registration and transcription), the management of the investigational medication, the current documentation approved by the Invima, the necessary documentation for the development of the clinical study and the monitoring of the protocol by the research ethics committee, among other things. Follow-up visits to the research protocol are made each time the Invima consider necessary and without prior notice. These visits are made in accordance with the provisions of paragraph 1, Article 4 of Resolution 2378 of 2008. Below are some guidelines for conducting a clinical study protocol within a Center for Research, which can be evaluated in follow-up visits. • The development of a clinical study in the country cannot begin until a concept of approval by Invima. • The research center must have a manual where all aspects are contemplated general operations about the investigation procedure. This manual must be approved by the representative legal of the institution and be aligned to its quality management system. In addition, a manual of functions and / or responsibilities of the research team and have documented the policy of conflicts of interest and confidentiality policy. • Each institution has the responsibility of verifying by means of a documented procedure, the supports of the Resumes of researchers and other members of the research team, including validation of the Information from undergraduate and graduate studies. • The clinical study must be conducted in accordance with current regulations and as defined by the Ethics Committee in Research, therefore should have the right amount of human resources, infrastructure and technical tools. • The medical history must be unified, according to Resolution 1995 of 1999; is the document source par excellence and must record all data related to the medical act, the application of inclusion and exclusion criteria, acceptance of informed consent and allocation procedure random of THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 7 of 11 Participating subjects There should not be a parallel medical history within the own file of the investigation study. A copy of the medical record may be included but this must be constantly updated. and be consistent with the original medical history. • The clinical study must have source documents that allow verifying the information Registered to the sponsor through the Data Collection Notebook (Case Report Forms - CRF). • The inclusion of participating subjects should be done according to the research protocol, maintaining the confidentiality • All medical decisions must be in charge of a medical professional with scientific competence adequate care. • Any document delivered to the participating subject, such as recruitment announcements, clinical study material among others, they must have been previously evaluated according to the confidentiality parameters and Well-being with the subject. • Informed consent and / or informed consent, regardless of type (general, genetic, etc.), must be reviewed and approved by the Research Ethics Committee, must comply with current regulations and must be applied only by the IP or IS, who fully knows the clinical research protocol and the specialty of the same. On the other hand it must be done in a suitable place for reading, where the possible participant subject I can read it calmly without time pressures. This must be signed, accepted and understood by part of the participant before starting any procedure and must be supported in the document main source that is the medical history. • In order to fully guarantee the understanding of informed consent by the participants, mechanisms should be sought to assess the ability to understand and be Documented supported. • It should be clarified that in the case that the participating subject is a minor, it must be apply informed consent according to current regulations and consent informed to the responsible adult. Research Team: This is responsible for carrying out the development of the clinical study protocol in the research center, led by the principal investigator and made up of health professionals according to the characteristics of Each study The minimum members that it must contain are: • Principal investigator (IP): He is responsible for the research protocol he assumes, so both is responsible for the entire research team, who may delegate functions according to The suitability of each professional. You must have full knowledge of the protocol, methodology, background, driving, file and all aspects that have to do with the clinical research study and therefore has the ability to support an audit or monitoring visit. • Secondary researcher (IS): Is the person in which the researcher delegates specific clinical or clinical functions. procedure in the research study. It may be one or more secondary researchers. • Research coordinator: The research coordinator must be a professional in the area of ​​health, delegate to handle the administrative aspects of the study. You must have the experience and suitability in research evaluated and defined by the research ethics committee. You can carry out several studies of according to their technical and labor capacity, however the number of clinical studies should be considered and patients in charge to avoid overreaching their burden. • Pharmaceutical chemist: Is the person responsible for all product handling of research (medications and supplies), from receipt, storage, accounting, dispensing and return and / or destruction. On the other hand it is a support for the analysis of the Adverse Events that are presented and to perform Pharmaceutical care activities THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 8 of 11 • Bacteriologist (a): Is the person responsible for taking, packing, shipping, conservation and Sample processing required by the clinical studies protocol. The research team must have designed a work plan that includes the functions and times that must comply with the processes carried out in each of the protocols under its responsibility, These same functions must be registered in the format of responsibilities (log responsability) of each study. The work plan is subject to verification in follow-up visits to protocols and to the Certification in Good Clinical Practices by Invima. On the other hand the Principal Investigator As leader of the research team, you should review and monitor the processes performed by each member. Every member of the research team must be trained in Good Clinical Practices through a face-to-face course or virtual, which must include training in national regulations in force in research, before come into contact with the research subject. The research team must have constant training according to the needs it deems relevant in the investigation process (BPC) or the protocols that are being carried out. The research team must guarantee the adherence of the participating subject to the research protocol, through of different internally created procedures. These procedures must be previously approved by the committee of ethics Ethical Regulations: The Ethics Committee must have a procedure for receiving, evaluating, analyzing, socializing, monitoring the decisions and approvals made regarding research protocols. The Research Center cannot initiate a clinical study protocol without its approval. initially by its ethics committee and it has the approval of the Invima. It is considered the beginning of a clinical study, when the first research subject is included at the time of pre-selection. It is the responsibility of the Research Center to submit for approval of the Research Ethics Committee any changes made in the research study and report any deviation that occurs during the Conduction of the study. The ethics committee has the obligation to receive the information, analyze it and To issue a concept, all these processes must be documented in the archives of the ethics committee. For that matter of the deviations should be defined whether or not it affects the research subject and generate corrective measures or depending on the severity of an improvement plan, which must be verified by the ethics committee in audit or other monitoring mechanism. As established by the research ethics committee and the Invima, the research center must make periodic, annual and final reports of each protocol in clinical research, which must be submitted to the Ethics Committee and the sponsor to consolidate it and send a final report of the study to Invima. The researcher must have available for review all records, correspondences, budget and other documents submitted and approved by the Ethics Committee, which may be subject to audit by the competent authorities and by the Ethics Committee when required. The ethics committee must verify that the policy is in force, which covers the adverse events of the study, compensation in case of death and you must also verify the accessibility of said policy, you must also verify the processes for the attention of the adverse events of the participating subjects, while accessing The insurance policy. Note: The Ethics Committee is the highest authority at the research site, however the principal investigator You can use the resource to inform the Invima of any observations or inconsistencies generated from the ethics committee in its approvals according to current regulations. Adverse events: THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 9 of 11 Adverse events that are generated in the development of clinical research protocols should be reported in according to the regulations in force to the sponsor and / or regulatory agency in the corresponding formats according to the Guide for the completion of the adverse event report formats in ASS-RSA- research protocols GU057. On the other hand these must be registered in the adverse event report formats of the protocol of corresponding investigation. The principal investigator according to his knowledge, criteria, competence and experience within the Research study and / or with the support of the research team professionals should determine the causality of the adverse event. In the same way, within the analysis carried out by the ethics committee, you can qualify to the adverse event differently. The research center must have established the processes / activities that should be carried out in case that an adverse event occurs in order to ensure timely and adequate medical attention to the subjects participants. Research Product: The handling of the research product must be under the responsibility of a qualified professional (Pharmaceutical Chemist), according to what is established for the management of a Pharmaceutical Service in the regulations National in force. Among its processes / activities is the reception, storage, accounting, informed dispensation, destruction and / or return of the research product, among many others that according to their knowledge and capabilities can develop. All of the above must be documented and have records implemented that allow make traceability As for the dispensing of investigational drugs, an agile, safe, reliable and useful process must be created for the medication request, which must be supported by the information or assignment given by the Interactive Voice Response System (IVRS). With this information the Pharmaceutical Chemist must deliver to the participating subject the investigational medication and inform in a clear and common vocabulary the use and storage of the medication, it is say, among other things, transport conditions, storage conditions and taking times; this in order to avoid or reduce the risk of drug interaction with concomitant medication. Therefore it is responsibility within the dispensation generate information mechanisms to ensure that the subject has complete information and adequate management of the investigational medication, such as through brochures, which should be previously evaluated and approved by the Research Ethics Committee. During the storage process, the Pharmaceutical Chemist is responsible for monitoring the conditions of Storage of research products, is also responsible for ensuring the control of dates of expiration of these products to avoid expiring expired medications to research subjects. In accordance with the provisions of Colombian regulations for the management of expired medication or with Obvious problems in terms of quality or that by prior authorization of the sponsor must be removed, must There is a separate and identified storage area. With respect to the return and / or destruction of the investigational drug, a implemented process in which records of this activity are kept. In cases that are returned the medicine to the sponsor or sent to another institution for its destruction, is the responsibility of the Center of investigation require a copy of this process, which should rest in the file where control of the medicine guaranteeing the management of the inventory of the product under investigation in a clear and reliable way. For the latter case, databases may be developed where at least the following are specified fields: medication identification code, expiration date, lot number, date received in the center, date of dispensation, data of the research subject, date of return of medications to center (if applicable) and return date to the sponsor or CRO (Contract Research Organization) (if applicable). THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 10 of 11 It is important to remember that it is the responsibility of the Principal Investigator and / or the Pharmaceutical Chemist to carry out follow up to treatment adherence. Coordination of clinical studies Within the institution there must be a specific site where the administrative part of the research study, which must have the infrastructure, space, technical capacity and human resources competent, according to the number, complexity and difficulty of the research studies carried out out in the IPS. This site must keep the privacy, confidentiality and security required by the Good Clinical Practices, therefore it cannot be shared with another area of ​​the Research Center. The research file must contain the minimum documents set forth in Resolution 2378 of 2008, must be in a suitable space according to the number of studies carried out in the institution, which guarantees the custody and integrity of the documents. This must be separated from the care area and from any other administrative area of ​​the institution including the research area, but at scope of the research team, finally it must be locked up so that confidentiality is kept Own study. In the case of closed studies you must have a defined space. Its storage will be at least two (2) years after approval of the marketing application or until at least two years have elapsed since the formal suspension of the clinical development of the research product. SPONSOR: He has the responsibility of training the research team in the initial monitoring of The following topics: Research Protocol, Good Clinical Practices, National Regulation, Management of the research product, CRF, randomization, deviation management and reporting of adverse events, among others. The sponsor must notify Invima only the deviations that occurred during the development of the clinical study classified as critical or very serious and major or serious, using the Format notification of deviations in Clinical Trials ASS-RSA-FM101. These deviations must be notified to the mail invimabpc@invima.gov.co in a maximum time of 15 working days since the Sponsor / CRO has knowledge. There must be a contractual agreement between the sponsor and the institution / researcher, which must be signed by the legal representative of each of the parties. The document must include aspects such as: term of contract, budget and method of payment, responsibilities of the parties, confidentiality, insurance or compensation, conflict of interest, measures or penalties in case of non-compliance, retention time of the archive, among others. Likewise, the agreements made between other parties involved for the development of the clinical study they must be in writing, between the institution and contracted services such as the ethics committee, laboratory clinical or other services. It is the responsibility of the Sponsor to submit any changes made in the study of Invima to the approval of the Invima investigation. 7. ANNEXES • Format of Presentation and Evaluation of Research Protocols ASS-RSA-FM055 Guide for the presentation of research protocols ASS-RSA-GU030 Format Checklist for receiving documents related to research protocols ASS- RSA-FM046 • Format for the presentation of amendments, new centers, new researchers and informed consents of ASS-RSA-FM047 research protocols Guide for the presentation of amendments, new centers, new researchers and informed consents of research protocols ASS-RSA-GU031 THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos HEALTH INSURANCE SANITARY RECORDS AND ASSOCIATED PROCEDURES GUIDE FOR THE EVALUATION AND MONITORING OF RESEARCH PROTOCOLS Code: ASS-RSA-GU039 Version: 03 Issue Date: 06/07/2018 Page 11 of 11 • Format for Notification of Closure of Clinical Studies (Protocols) ASS-RSA-FM049 Guide for Notification of Closure of Clinical Studies (Protocols) ASS-RSA-GU033 • Format for Presentation and Evaluation of New Requests for Importing Supplies for Research protocols ASS-RSA-FM052 Presentation and Evaluation Format for New Applications for the Export of Biological Samples for ASS-RSA-FM053 Research protocols Guide for the Presentation of New Requests for Importing Supplies and Exporting Samples Biological for research protocols ASS-RSA-GU036 • Format Annual Report of Research Projects ASS-RSA-FM063 Guide for the completion of the annual research project format ASS-RSA-GU041 • Presentation format and evaluation of modifications to the ASS-RSA-FM054 researcher's manual Guide for the Presentation and Evaluation of Modifications to the ASS-RSA-GU037 Investigator Manual • Format for the presentation of studies of drug stability in research ASS-RSA-FM088 Guide for the Presentation of Research Stability Studies in Research ASS-RSA-GU055 • Guide for Research Ethics Committees ASS-RSA-GU040 • Guide for Medicines and Clinical Research Supplies ASS-RSA-GU045 • Guide for the completion of the adverse event report formats in research protocols ASS- RSA-GU057 • Format deviation notification in clinical trials ASS-RSA-FM101 • List of research protocols developed by the institution (IPS): active and closed studies ASS-AYC- FM046 THIS PRINTED DOCUMENT IS AN UNCONTROLLED COPY To view the controlled document, go to https://www.invima.gov.co/procesos