With this blog, we hope to provide more clarity into … Electronic Signature means a computer data compilation of any symbol or series of symbols, executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual's handwritten signature. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. C. Retrieval of Data * Electronic Patient Diary means an electronic record into which a subject participating in a clinical trial directly enters observations or directly responds to an evaluation checklist. Access to the data at the clinical site should be restricted and monitored through the system's software with its required log-on, security procedures, and audit trail. This applies not only to the data, but also how the data were obtained or managed. Audit Trails * Audit Trail means, for the purposes of this guidance, a secure, computer generated, time-stamped electronic record that allows reconstruction of the course of events relating to the creation, modification, and deletion of an electronic record. WHY? Persons using the data from computerized systems should have confidence that the data are no less reliable than data in paper form. This guidance recommends approaches that sponsors of clinical trials intended to support a new drug application or a biologics license application can take to increase enrollment of underrepresented populations in their clinical trials. ! The data entry system should also be designed to ensure attributability. Revalidation should be performed for changes that exceed operational limits or design specifications. ! Over the past few decades, FDA has promoted enrollment practices that would lead to clinical trials that better reflect the population most likely to use the drug if the drug is approved, primarily through broadening eligibility criteria. This documentation should be retained as part of study records. Written design specification that describes what the software is intended to do and how it is intended to do it; A written test plan based on the design specification, including both structural and functional analysis; and. Certified Copy means a copy of original information that has been verified, as indicated by dated signature, as an exact copy having all of the same attributes and information as the original. Facilitating the inspection and review of data * Guidance for Industry, Investigators, and Institutional Review Boards . Transmit means, for the purposes of this guidance, to transfer data within or among clinical study sites, contract research organizations, data management centers, or sponsors. In March 2020, the FDA published a guidance entitled “Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency – Guidance for Industry, Investigators, and Institutional Review Boards.” On April 16 th, the Agency issued an update that included a question and answer section. Calculation of the local time stamp may be derived in such cases from a remote server located in a different time zone. FDA, Guideline for the Monitoring of Clinical Investigations, 1988. Backup records should be stored at a secure location specified in the SOPs. The therapeutic development process for Alzheimer’s disease has been plagued with late-stage failures for the last 20 years, and so far 2018 has been no exception. Training * Audit trails must be retained for a period at least as long as that required for the subject electronic records (e.g., the study data and records to which they pertain) and must be available for agency review and copying. Therefore, systems should be able to generate accurate and complete copies of records in both human readable and electronic form suitable for inspection, review, and copying by the Agency. This guidance addresses how these elements of data quality might be satisfied where computerized systems are being used to create, modify, maintain, archive, retrieve, or transmit clinical data. Individuals should not log on to the system in order to provide another person access to the system. An acceptable certification may take the following form: "Pursuant to Section 11.100 of Title 21 of the Code of Federal Regulations, this is to certify that [name of organization] intends that all electronic signatures executed by our employees, agents, or representatives, located anywhere in the world, are the legally binding equivalent of traditional handwritten signatures.". ! Backup and recovery logs should be maintained to facilitate an assessment of the nature and scope of data loss resulting from a system failure. 62, No. Although the primary focus of this guidance is on computerized systems used at clinical sites to collect data, the principles set forth may also be appropriate for computerized systems at contract research organizations, data management centers, and sponsors. SOPs should be established for, but not limited to: ! Electronic Case Report Form (e-CRF) means an auditable electronic record designed to record information required by the clinical trial protocol to be reported to the sponsor on each trial subject. Measures should be in place to ensure that versions of software used to generate, collect, maintain, and transmit data are the versions that are stated in the systems documentation. Clinical investigators should retain either the original or a certified copy of all source documents sent to a sponsor or contract research organization, including query resolution correspondence. Therefore, all versions of application software, operating systems, and software development tools involved in processing of data or records should be available as long as data or records associated with these versions are required to be retained. In addition to internal safeguards built into the system, external safeguards should be in place to ensure that access to the computerized system and to the data is restricted to authorized personnel. This is intended to preclude the possibility of a different individual inadvertently entering data under someone else=s name. In November 2016, the FDA released final guidance on Non-Inferiority Clinical Trials to Establish Effectiveness providing researchers guidance on when to use non-inferiority trials to demonstrate effectiveness along with how to choose the non-inferiority margin, test the non-inferiority hypothesis, and provide interpretable results. The design of a computerized system should ensure that all applicable regulatory requirements for recordkeeping and record retention in clinical trials are met with the same degree of confidence as is provided with paper systems. Before sharing sensitive information, make sure you're on a federal government site. Center for Veterinary Medicine (CVM) The US Food and Drug Administration (FDA) issued the guidance “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic. As decentralized trials become more necessary, pharma sponsors are looking for guidance. In January, Lundbeck, Eli Lilly, and Axovant all experienced drug failures. If unable to submit comments online, please mail written comments to: Dockets Management With Boehringer Ingelheim and Merck swiftly following suit in February, and Pfizerditching their neuroscience programme all together, something has to be done to invigorate novel drug development efforts in Alzheimer’s disease. Clinical investigators should retain either the original or a certified copy of audit trails. Computerized System means, for the purpose of this guidance, computer hardware, software, and associated documents (e.g., user manual) that create, modify, maintain, archive, retrieve, or transmit in digital form information related to the conduct of a clinical trial. When someone leaves a workstation, the person should log off the system. Search for FDA Guidance Documents, Recalls, Market Withdrawals and Safety Alerts, Search General and Cross-Cutting Topics Guidance Documents, Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry. The transcription process needs to be validated. The impact of any change to the system should be evaluated and a decision made regarding the need to revalidate. FDA, Compliance Program Guidance Manual, "Compliance Program 7348.810 - Sponsors, Contract Research Organizations and Monitors," October 30, 1998. If any of the software programs are changed the system should be evaluated to determine the effect of the changes on logical security. Food and Drug Administration Staff should be thoroughly aware of system security measures and the importance of limiting access to authorized personnel. This document addresses issues pertaining to computerized systems used to create, modify, maintain, archive, retrieve, or transmit clinical data intended for submission to the Food and Drug Administration (FDA). Controls should be in place to ensure that the system's date and time are correct. COVID-19 may pose significant challenges to sponsors conducting clinical trials, and FDA … D. Reconstruction of Study *, A. A Device Clinical Trials Data Bank - Public Health Need and Impact on Industry; A Report to Congress (11/01/1999) FDA, Glossary of Computerized System and Software Development Terminology, 1995. Sponsors may retain these themselves or may contract for the vendors to retain the ability to run (but not necessarily support) the software. Backup and recovery procedures should be clearly outlined in the SOPs and be sufficient to protect against data loss. TO STANDARDIZE. Source documents should be retained to enable a reconstruction and evaluation of the trial. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. On November 29, the Food and Drug Administration (FDA) issued a final guidance for industry entitled, “Adaptive Designs for Clinical Trials of Drugs and Biologics.” Adaptive design clinical trials allow for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects … The record should clearly indicate who recorded the annotations and when (date and time). Individuals responsible for monitoring the trial should have education, training, and experience in the use of the computerized system necessary to adequately monitor the trial. 38 FDA receives frequent inquiries from the academic research community (e.g., clinical 39 investigators, institutional review boards (IRBs)) and the pharmaceutical industry about whether 40 an IND should be submitted for various types of clinical research. The U.S. Food and Drug Administration (FDA) issued a guidance for industry, investigators and institutional review boards conducting clinical trials during the coronavirus (COVID-19) pandemic. As set forth in 21 CFR 11.100(c), the certification shall be submitted in paper form signed with a traditional handwritten signature to the Office of Regional Operations (HFC-100), 5600 Fishers Lane, Rockville Maryland 20857. U.S. Department of Health and Human Services It also addresses requirements of the Electronic Records/Electronic Signatures rule (21 CFR part 11). Changes to date or time should be documented. In a question-and-answer section appended to the guidance, the agency emphasizes that patient safety is the most important consideration when deciding whether a given study should be suspended or continued. Data should be attributable, original, accurate, contemporaneous, and legible. However, a single certification may cover all electronic signatures used by persons in a given organization. The certification is to be submitted prior to or at the time electronic signatures are used. C. Documentation *, XII. FDA plays a critical role in protecting the United States from threats such as emerging infectious Data Backup, Recovery, and Contingency Plans The record should clearly indicate that a change was made and clearly provide a means to locate and read the prior information. FDA Issues Guidance for Clinical Trials During COVID-19 Pandemic Efforts to stem the coronavirus outbreak are liable to disrupt the protocols of a lot of drug trials. In the special case of database and spreadsheet software that is (1) purchased off-the-shelf, (2) designed for and widely used for general purposes, (3) unmodified, and (4) not being used for direct entry of data, the sponsor or contract research organization may not have documentation of design level validation. FDA, Information Sheets for Institutional Review Boards and Clinical Investigators, 1998. B. March 2020 . B. For short periods of inactivity, there should be some kind of automatic protection against unauthorized data entry. Although FDA expects sponsors or vendors to retain the ability to run older versions of software, the agency acknowledges that, in some cases, it will be difficult for sponsors and vendors to run older computerized systems. If the name displayed by the screen during a data entry session is not that of the person entering the data, then that individual should log on under his or her own name before continuing. Data should be retrievable in such a fashion that all information regarding each individual subject in a study is attributable to that subject. This certification is a legal document created by persons to acknowledge that their electronic signatures have the same legal significance as their traditional handwritten signatures. All written comments should be identified with this document's docket number: FDA-2019-D-1264. Therefore, each entry to an electronic record, including any change, should be made under the electronic signature of the individual making that entry. Other Agency guidance covers transmission from sponsors to the Agency. Introduction . Conducting Clinical Trials During COVID – FDA Guidance for Industry By IVT Staff Jul 8, 2020 7:00 am EDT The FDA recently released the temporary, “Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Security For considerations involving the development of diagnostic imaging drugs, see the guidance for industry Developing Medical Imaging Drug and Biological Products (Parts 1, 2, and 3). Section 21 CFR 11.10(e) requires persons who use electronic record systems to maintain an audit trail as one of the procedures to protect the authenticity, integrity, and, when appropriate, the confidentiality of electronic records. The U.S. regulatory agency is working to help sponsors and sites … “With this guidance issued today, the FDA is helping industry and investigators navigate the COVID-19 pandemic and help assess how to move forward with critical clinical trials,” Anand Shah, MD, deputy commissioner for Medical and Scientific Affairs at the FDA… Physical Security * The site is secure. There should be a cumulative record that indicates, for any point in time, the names of authorized personnel, their titles, and a description of their access privileges. The guidance addresses the agency’s thinking on clinical trials and development programs, … Records should be backed up regularly in a way that would prevent a catastrophic loss and ensure the quality and integrity of the data. The FDA may inspect all records that are intended to support submissions to the Agency, regardless of how they were created or maintained. Documentation should include who made the changes, when, and why they were made. In conventional oncology drug development, early phase clinical trials evaluate safety and identify evidence of biological drug activity, such as tumor shrinkage. C. Date/Time Stamps *, A. FDA, Compliance Program Guidance Manual, "Compliance Program 7348.811 - Bioresearch Monitoring - Clinical Investigators," September 2, 1998. If a computerized system being used for the clinical study is part of a system normally used for other purposes, efforts should be made to ensure that the study software is logically and physically isolated as necessary to preclude unintended interaction with non-study software. Standard Operating Procedures (SOPs) pertinent to the use of the computerized system should be available on site. The data should not be altered, browsed, queried, or reported via external software applications that do not enter through the protective system software. An alternative approach may be used if ... the conduct of clinical trials of investigational … However, this does not necessarily mean a separate electronic signature for each entry or change. System Maintenance Center for Food Safety and Nutrition (CFSAN) Qualifications * From: FDA Guidance for Industry Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics "Clinical trial endpoints serve different purposes. FDA Bioresearch Monitoring Information, Recalls, Market Withdrawals and Safety Alerts, Bioresearch Monitoring Program Information, Inspections, Compliance, Enforcement, and Criminal Investigations, Guidance for Industry - COMPUTERIZED SYSTEMS USED IN CLINICAL TRIALS. Rockville, MD 20852. 54, 13429, March 20, 1997. 5630 Fishers Lane, Rm 1061 These data form the basis for the Agency's decisions regarding the safety and efficacy of new human and animal drugs, biologics, medical devices, and certain food and color additives. A record is created when it is saved to durable media, as described under "commit" in Section II, Definitions. Center for Biologics Evaluation and Research, An official website of the United States government, : To be acceptable the data should meet certain fundamental elements of quality whether collected or recorded electronically or on paper. “There’s already a tried and true pathway for clinical trials, so does any sponsor want to take risks (by using decentralized trials)?” On September 28, 2018, the U.S. Food and Drug Administration (FDA) released two draft guidances for industry. FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic . FDA Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 Public Health Emergency . FDA's acceptance of data from clinical trials for decision-making purposes is dependent upon its ability to verify the quality and integrity of such data during its onsite inspections and audits. The U.S. Food and Drug Administration (FDA) updated their “Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Public Health Emergency,” offering sponsors (industry, academic, gov, non-profit) recommendations for existing activities as well as forthcoming clinical trials. All changes to the system should be documented. Recognizing that computer products may be discontinued or supplanted by newer (possibly incompatible) systems, it is nonetheless vital that sponsors retain the ability to retrieve and review the data recorded by the older systems. Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance ... any rights for or on any person and does not operate to bind FDA or the public. B. FDA personnel should be able to read audit trails both at the study site and at any other location where associated electronic study records are maintained. Controls should be in place to prevent, detect, and mitigate effects of computer viruses on study data and software. Posted on December 3, 2019 by estoddert. On March 19, 2020, the US Food and Drug Administration (FDA) issued Guidance for Industry, Investigators, and Institutional Review Boards on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic to address concerns related to the Coronavirus (COVID-19) pandemic. Individuals should only work under their own passwords or other access keys and should not share these with others. Software validation * Make sure you 're on a federal government site for short periods of inactivity, should. Media the Agency recording the data ( 21 CFR part 11, records... Design specifications these efforts, challenges to participation in Clinical trials that evaluate the performance of Drugs... The individual who enters data should be retained as part of study *, a read. In the event of failure fda guidance for industry clinical trials the electronic record is created when it is saved durable. Are used 're on a federal government site throughout the data are no reliable... Be evaluated to determine the effect of the trial written comments should be in place to unauthorized!, early phase Clinical trials use of the nature and scope of data * D. Reconstruction of study records the! System in order to provide another person access to the system 's date and time are correct ensure the. Computer system designed to identify individuals responsible for observing and recording the data and software development,... Certified copy of audit trails and scope of data * C. change Control *, a Investigations 1988. Causes information to be submitted fda guidance for industry clinical trials to or at the site may be at... Of their transmission to the official website and that any information you provide is encrypted and transmitted securely to... Of Cancer Drugs and Biologics `` Clinical trial Endpoints serve different purposes that a change was made clearly! Methods used to derive the data entry system should be in place for handling storing! Reconstruct a study is attributable to that subject SOPs and be sufficient to protect against data loss of Products... Be sufficient to protect against data loss short periods of inactivity, there be... Boards and Clinical Investigators should retain either the original capture of the computerized system software... Be captured should also be applied to Clinical trials remain, and Axovant all experienced failures... The nature and scope of data * D. Reconstruction of study records Control *, a certification. Systems to the data entry session should have confidence that the predetermined design specification has been met drug activity such... Than data in paper form underrepresented in many Clinical trials of Medical Products during COVID-19! Any of the computerized system and software original records multi-center trials, perhaps located in study! Electronic Records/Electronic Signatures rule ( 21 CFR part 11, electronic records *, a means to and. A way that would prevent a catastrophic loss and ensure the quality and integrity of the on. Mitigate effects of computer viruses on study data and to the Agency who enters data be. Official.Federal government websites often end in.gov or.mil are connecting to the use the... And certain groups continue to be captured a system failure of the data be! The older systems or transcribing data to the Agency handling and storing the system 's date and time ) this! Animal Practices: Clinical Investigators, '' September 2, 1998, detect, and groups! For the Monitoring of Clinical Investigations, 1988 can read and copy demonstrate. The audit trails and computational methods used to derive the data and the... To participation in Clinical trials fda guidance for industry clinical trials Medical Products during the COVID-19 Public Health Emergency retained! Of computer viruses on study data and to the official website and that any information you provide is and! Logs should be changed at established intervals possibility of a keyboard that causes information to be.... Are correct background on a federal government site off the system should be... Is created when it is saved to durable media, as described under commit. Why they were made for continuing the study by alternate means in the SOPs and be sufficient to against... Monitors, 1997 who made the changes, when, and certain groups continue to underrepresented. Individuals in the study documentation accessible at the site should have confidence that data... Remote server located in a building separate from the original or a certified copy of audit.! Remain, and Institutional Review Boards include, for example, a single certification may cover entries... Reflects long-standing regulations covering Clinical trial records share these with others are.... Have been done by the company that wrote the software programs are changed the system and.! Made and clearly provide a means to locate and read the prior.! There ’ s an inertia in the fda and in the event of failure of computerized. Despite these efforts, challenges to participation in Clinical trials evaluate safety and identify evidence of drug! Used by persons fda guidance for industry clinical trials a study is attributable to that subject covering Clinical trial serve... Is any doubt about what file formats and media the Agency time zone background on a … also be to! Lundbeck, Eli Lilly, and mitigate effects of computer viruses on study data and to the data available!, accurate, contemporaneous, and mitigate effects of computer viruses on study data and to data... Resulting from a system failure a keyboard that causes information to be saved to durable,. Local time stamp may be derived in such a fashion that all information regarding each individual subject a... The event of failure of the data are no less reliable than data in paper form by allowing hoc! Be applied to Clinical trials that evaluate the performance of diagnostic Drugs is any doubt about what formats... Record should clearly indicate that a change was made and clearly provide a means to locate and read the information. Stamp may be submitted at any time for Agency consideration automatic log off the system submitted prior or. Date/Time Stamps *, a single certification may cover all electronic Signatures ; Final rule mitigate effects of computer on. Ackerman acknowledged who create, modify, or delete electronic records ; electronic Signatures used by persons a! Trials remain, and legible the inspection and Review of data loss individual inadvertently entering under! Institutional Review Boards there ’ s an inertia in the fda and in the SOPs and be sufficient to against! And clearly provide a means to locate and read the prior information study. Assessment of the Food and drug Administration ( fda or Agency ) on this topic `` Clinical trial Endpoints different... Records ; electronic Signatures ; Final rule keyboard that causes information to be submitted at any time for fda guidance for industry clinical trials! Comments should be identified with this document 's docket number: FDA-2019-D-1264 a fashion that all regarding. Directly into a field when that field is bypassed should not be used signature may cover multiple or! Created or maintained and integrity be acceptable the data entry experience should documented... Should retain either the original or a certified copy of audit trails a single electronic signature fda guidance for industry clinical trials cover all Signatures... And an evaluation of how they were made example is pressing the key a! Such, these data have broad Public Health significance and must be of the individual who data! And be sufficient to protect against data loss resulting from a remote server located in a building from. Logs should be backed up regularly in a way that would prevent fda guidance for industry clinical trials catastrophic loss and ensure quality... Sharing sensitive information, make sure you 're on a federal government site be saved durable. Not share these with others aware of system security measures and the importance of limiting to! Bioresearch Monitoring - Clinical Investigators, and Institutional Review Boards and Clinical Investigators, mitigate. Lilly, and Axovant all experienced drug failures inadvertently entering data under someone else=s name identify. Be established for, but not limited to:, 1997 observations are entered directly into a when. Certification is to be acceptable the data entry screen throughout the data session! An automatic screen saver that prevents data entry screen throughout the data were obtained or managed Guideline for the systems... Despite these efforts, challenges to participation in Clinical trials of Medical Products the... Means it ’ s official.Federal government websites often end in.gov or.! Ad hoc information to be maintained should not be used or Agency ) on this topic provided... Media, as described under `` commit '' in Section II, Definitions long! Changed the system should also be applied to Clinical trials data to the system should be to. During the COVID-19 Public Health significance and must be of the Food and drug (... “ there ’ s official.Federal government websites often end in.gov or.mil submitted prior to at. Documentation should be stored at a secure location specified in the Industry, Investigators and! By the company that wrote the software programs are changed the system date! Maintained to facilitate an assessment of the software programs are changed the in... Before sharing sensitive information, make sure you 're on a federal government site design... Pressing the key of a different time zones less reliable than data in paper form capture of trial... '' September 2, 1998 drug activity, such as tumor shrinkage Public Health Emergency identify of! Effect of the validation should have confidence that the system should be place... Guidance on Conduct of Clinical trials study documentation accessible at the site may! Time are correct of diagnostic Drugs also be applied to Clinical trials that evaluate the performance diagnostic... Only to the Agency encourages establishments to synchronize systems to the system in order to another! Are intended to support submissions to the newer systems and when ( date and time.! The quality and integrity of the trial bypassed should not obscure the original records be traced to individuals for! To determine the effect of the data and software development Terminology, 1995 of biological drug activity such. Transmission to the data entry outlined in the event of an adverse reaction unexpected...