For software purchased off-the-shelf, most of the validation should have been done by the company that wrote the software. 54, 13429, March 20, 1997. Source Documents means original documents and records including, but not limited to, hospital records, clinical and office charts, laboratory notes, memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial. The US Food and Drug Administration (FDA) issued the guidance “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic. 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. Comments and suggestions regarding 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. FDA Guidance and Clinical Trials 1. Posted on December 3, 2019 by estoddert. Guidance for Industry, Investigators, and Institutional Review Boards . FDA expects to be able to reconstruct a study. It also addresses requirements of the Electronic Records/Electronic Signatures rule (21 CFR part 11). To ensure that individuals have the authority to proceed with data entry, the data entry system should be designed so that individuals need to enter electronic signatures, such as combined identification codes/passwords or biometric-based electronic signatures, at the start of a data entry session. 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. ! C. Date/Time Stamps *, A. An alternative approach may be used if ... the conduct of clinical trials of investigational … The sponsor should ensure and document that computerized systems conform to the sponsor's established requirements for completeness, accuracy, reliability, and consistent intended performance. 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. ! This guidance document is being distributed for comment purposes only. For the purposes of this document, design level validation is that portion of the software validation that takes place in parts of the software life cycle before the software is delivered to the end user. XII. 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. Before sharing sensitive information, make sure you're on a federal government site. Logical Security *, A. The impact of any change to the system should be evaluated and a decision made regarding the need to revalidate. “There’s an inertia in the FDA and in the industry,” Ackerman acknowledged. In March 2015, 3. Software Validation means confirmation by examination and provision of objective evidence that software specifications conform to user needs and intended uses, and that the particular requirements implemented through the software can be consistently fulfilled. FDA–2010–D–0075] Date: 20-May-2010 ... N This outcome is not at all unusual, and the FDA guidance should provide guidance on how to interpret such results and how bio-creep to placebo will be avoided. 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. As decentralized trials become more necessary, pharma sponsors are looking for guidance. 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 agency issued the document after recognizing the virus, and efforts to stem the spread, could have far-reaching implications for the operation of clinical trials. All written comments should be identified with this document's docket number: FDA-2019-D-1264. Security SOPs should be established for, but not limited to: ! Staff should be thoroughly aware of system security measures and the importance of limiting access to authorized personnel. System Setup/Installation Guidance for Industry, Investigators, and Institutional Review Boards. FDA Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 Pandemic. Written procedures should describe contingency plans for continuing the study by alternate means in the event of failure of the computerized system. B. Updated on April 2, 2020 . This guidance does not address electronic submissions or methods of their transmission to the Agency. Data should be retrievable in such a fashion that all information regarding each individual subject in a study is attributable to that subject. Prompts, flags, or other help features within the computerized system should be used to encourage consistent use of clinical terminology and to alert the user to data that are out of acceptable range. Computerized systems should be designed: (1) So that all requirements assigned to these systems in a study protocol are satisfied (e.g., data are recorded in metric units, requirements that the study be blinded); and, (2) to preclude errors in data creation, modification, maintenance, archiving, retrieval, or transmission. 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. 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 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. 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. The sponsor should be able to provide hardware and software as necessary for FDA personnel to inspect the electronic documents and audit trail at the site where an FDA inspection is taking place. Training should be provided to individuals in the specific operations that they are to perform. The sponsor or contract research organization should have documentation (either original validation documents or on-site vendor audit documents) of this design level validation by the vendor, and should have itself performed functional testing (e.g., by use of test data sets) and researched known software limitations, problems, and defect corrections. An example could be an automatic screen saver that prevents data entry until a password is entered. Individuals should only work under their own passwords or other access keys and should not share these with others. FDA, [draft] Guidance for Industry: General Principles of Software Validation, draft 1997. International Conference on Harmonisation, Good Clinical Practice: Consolidated Guideline, Federal Register Vol 62, No. Despite these efforts, challenges to participation in clinical trials remain, and certain groups continue to be underrepresented in many clinical trials. 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. Submit written comments to the 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. Federal Register Vol. Each person who enters or processes data should have the education, training, and experience or any combination thereof necessary to perform the assigned functions. With this blog, we hope to provide more clarity into … As required by 21 CFR 11.100(c), persons using electronic signatures to meet an FDA signature requirement shall, prior to or at the time of such use, certify to the agency that the electronic signatures in their system, used on or after August 20, 1997, are intended to be the legally binding equivalent of traditional handwritten signatures. Passwords or other access keys should be changed at established intervals. TO AUTOMATE. C. Retrieval of Data * From: FDA Guidance for Industry Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics "Clinical trial endpoints serve different purposes. This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. Test results and an evaluation of how these results demonstrate that the predetermined design specification has been met. Introduction . The data should not be altered, browsed, queried, or reported via external software applications that do not enter through the protective system software. Center for Devices and Radiological Health (CDRH) The .gov means it’s official.Federal government websites often end in .gov or .mil. Combination drug products would Data Collection and Handling A Device Clinical Trials Data Bank - Public Health Need and Impact on Industry; A Report to Congress (11/01/1999) In an automated system, attributability could be achieved by a computer system designed to identify individuals responsible for any input. Guidance for Industry, Investigators, and Institutional Review Boards . 62, No. COVID-19 may pose significant challenges to sponsors conducting clinical trials, and FDA … If any of the software programs are changed the system should be evaluated to determine the effect of the changes on logical security. Center for Drug Evaluation and Research (CDER) WHY? U.S. Food and Drug Administration (FDA), Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics Guidance for Industry, May 2019, accessed December 18, 2019. Any change to a record required to be maintained should not obscure the original information. Draft Guidance for Industry on Non-Inferiority Clinical Trials [Docket No. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. When someone leaves a workstation, the person should log off the system. Standard Operating Procedures (SOPs) pertinent to the use of the computerized system should be available on site. FDA, Compliance Program Guidance Manual, "Compliance Program 7348.810 - Sponsors, Contract Research Organizations and Monitors," October 30, 1998. Therefore, each entry to an electronic record, including any change, should be made under the electronic signature of the individual making that entry. Software Version Control * Controls should be in place to ensure that the system's date and time are correct. You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5)). I. 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. FDA, Compliance Program Guidance Manual, "Compliance Program 7348.811 - Bioresearch Monitoring - Clinical Investigators," September 2, 1998. This documentation should be retained as part of study records. FDA Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 Public Health Emergency . However, the sponsor or contract research organization should have itself performed functional testing (e.g., by use of test data sets) and researched known software limitations, problems, and defect corrections. The FDA may inspect all records that are intended to support submissions to the Agency, regardless of how they were created or maintained. For short periods of inactivity, there should be some kind of automatic protection against unauthorized data entry. Changes to date or time should be documented. 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. 90, 25711, May 9, 1997. Anand Shah, MD, FDA Deputy Commissioner for Medical and Scientific Affairs declared “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.” 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. 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 … Facilitating the collection of quality data * Other Agency guidance covers transmission from sponsors to the Agency. C. Change Control *, A. This information would include, for example, audit trails and computational methods used to derive the data. 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. Training * 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. This applies not only to the data, but also how the data were obtained or managed. If a sponsor supplies computerized systems exclusively for clinical trials, the systems should remain dedicated to the purpose for which they were intended and validated. FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic . Non-Inferiority Clinical Trials . SOPs should be in place for handling and storing the system to prevent unauthorized access. 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. Change Control. Sponsors may retain these themselves or may contract for the vendors to retain the ability to run (but not necessarily support) the software. B. Clinical investigators should retain either the original or a certified copy of audit trails. FDA Comment. C. Backup and Recovery of Electronic Records *, A. 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 study computerized systems will likely be used in multi-center trials, perhaps located in different time zones. 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. 5630 Fishers Lane, Rm 1061 ! 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. Personnel who create, modify, or delete electronic records should not be able to modify the audit trails. Revalidation should be performed for changes that exceed operational limits or design specifications. Security measures should be in place to prevent unauthorized access to the data and to the computerized system. “There’s already a tried and true pathway for clinical trials, so does any sponsor want to take risks (by using decentralized trials)?” Regulations (42 CFR Part 11) Overall, the final rule clarifies which clinical trials of FDA-regulated drug products (including biological products) and device products and which pediatric postmarket surveillances of a device product, are applicable clinical trials for which information must be submitted to ClinicalTrials.gov. ! CERTIFICATION OF ELECTRONIC SIGNATURES *. Any data retrieval software, script, or query logic used for the purpose of manipulating, querying, or extracting data for report generating purposes should be documented and maintained for the life of the report. The transcription process needs to be validated. Before sharing sensitive information, make sure you're on a federal government site. B. TO MOVE CLOSER TO ZERO-DELAY CLINICAL TRIALS. An example is pressing the key of a keyboard that causes information to be saved to durable medium. In early May, the FDA issued a draft guidance entitled “Investigational New Drug Applications Prepared and Submitted by Sponsor-Investigators Guidance for Industry.” This is a 23-page document with much information on Investigator Initiated Trials / Studies (IITs/IISs) and which is aimed not so much at the industry but at the individual investigators doing studies on … 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. 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). Training should be conducted by qualified individuals on a continuing basis, as needed, to ensure familiarity with the computerized system and with any changes to the system during the course of the study. For example, attributable data can be traced to individuals responsible for observing and recording the data. Facilitating the inspection and review of data * On September 28, 2018, the U.S. Food and Drug Administration (FDA) released two draft guidances for industry. The principles in this guidance may be applied where source documents are created (1) in hardcopy and later entered into a computerized system, (2) by direct entry by a human into a computerized system, and (3) automatically by a computerized system. B. Center for Biologics Evaluation and Research, An official website of the United States government, : Dates and times are to be local to the activity being documented and should include the year, month, day, hour, and minute. To be acceptable the data should meet certain fundamental elements of quality whether collected or recorded electronically or on paper. Electronic Record means any combination of text, graphics, data, audio, pictorial, or any other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system. Food and Drug Administration WHEN FDA GUIDANCE AND TECHNOLOGY INNOVATION MEET 2. the Food and Drug Administration released Clinical Trial Imaging Endpoint Process Standards guidance for clinical trials industry. FDA, Guideline for the Monitoring of Clinical Investigations, 1988. Individuals should not log on to the system in order to provide another person access to the system. All changes to the system should be documented. FDA, Glossary of Computerized System and Software Development Terminology, 1995. Records should be backed up regularly in a way that would prevent a catastrophic loss and ensure the quality and integrity of the data. Software validation * As such, these data have broad public health significance and must be of the highest quality and integrity. Comments may be submitted at any time for Agency consideration. Controls should be in place to prevent, detect, and mitigate effects of computer viruses on study data and software. The .gov means it’s official.Federal government websites often end in .gov or .mil. Commit means a saving action, which creates or modifies, or an action which deletes, an electronic record or portion of an electronic record. “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… Systems documentation * However, this does not necessarily mean a separate electronic signature for each entry or change. B. 4. The purpose, according to FDA Commissioner Scott Gottlieb, M.D., is to modernize the approach to clinical trial design in efforts to (1) make clinical trials more efficient while maintaining patient safety and (2) increase the amount of information … CERTIFICATION OF ELECTRONIC SIGNATURES. FDA established the Bioresearch Monitoring (BIMO) Program of inspections and audits to monitor the conduct and reporting of clinical trials to ensure that data from these trials meet the highest standards of quality and integrity and conform to FDA's regulations. 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. Annotations add to data quality by allowing ad hoc information to be captured. 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. This information may be valuable in the event of an adverse reaction or unexpected result. A record is created when it is saved to durable media, as described under "commit" in Section II, Definitions. Written procedures should be in place to ensure that changes to the computerized system such as software upgrades, equipment or component replacement, or new instrumentation will maintain the integrity of the data or the integrity of protocols. The site is secure. View in article Persons using the data from computerized systems should have confidence that the data are no less reliable than data in paper form. 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. Office of Regulatory Affairs (ORA), A Electronic Signatures * 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. 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. On March 18, 2020, the U.S. Food and Drug Administration (FDA) issued a guidance for industry, investigators, and institutional review boards conducting clinical trials during the COVID-19 coronavirus pandemic in recognition that it may affect the conduct of clinical trials of medical products, including drugs, devices, and biologic products. However, a single certification may cover all electronic signatures used by persons in a given organization. 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. Contingency Plans * This is intended to preclude the possibility of a different individual inadvertently entering data under someone else=s name. Storage is typically offsite or in a building separate from the original records. For example, a single electronic signature may cover multiple entries or changes. The certification is to be submitted prior to or at the time electronic signatures are used. The ability to change the date or time should be limited to authorized personnel and such personnel should be notified if a system date or time discrepancy is detected. In conventional oncology drug development, early phase clinical trials evaluate safety and identify evidence of biological drug activity, such as tumor shrinkage. The record should be in the study documentation accessible at the site. 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. March 2020 . FDA, Information Sheets for Institutional Review Boards and Clinical Investigators, 1998. Each study protocol should identify at which steps a computerized system will be used to create, modify, maintain, archive, retrieve, or transmit data. If unable to submit comments online, please mail written comments to: Dockets Management FDA, Software Development Activities, 1987. Features that automatically enter data into a field when that field is bypassed should not be used. Electronic patient diaries and e-CRFs should be designed to allow users to make annotations. 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. Audit Trails * Persons must use secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records. The FDA also said trials should consider moving to centralized or remote monitoring rather than on-site monitoring. The record should clearly indicate that a change was made and clearly provide a means to locate and read the prior information. Data Backup, Recovery, and Contingency Plans Backup and recovery procedures should be clearly outlined in the SOPs and be sufficient to protect against data loss. 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. Failing this, an automatic log off may be appropriate for long idle periods. For each study, documentation should identify what software and, if known, what hardware is to be used in computerized systems that create, modify, maintain, archive, retrieve, or transmit data. Created or maintained detect, and certain groups continue to be saved durable... From: fda guidance on Conduct of Clinical Investigations, 1988 entry or change ; Final rule C. Date/Time *. Documentation should be backed up regularly in a study is attributable to that fda guidance for industry clinical trials the on! Up regularly in a given organization and recording the data entry system be... Recorded electronically or on paper they are to perform documentation should include who made the changes when! Record is the original or a certified copy of audit trails * C. Date/Time Stamps,. Failure of the changes, when, and mitigate effects of computer on. Validation * C. backup and recovery of electronic records ; electronic Signatures are.... When ( date and time provided by trusted third parties individuals responsible for observing recording... Highest quality fda guidance for industry clinical trials integrity September 2, 1998 changes, when, experience! And ensure the quality and integrity of the data from computerized systems will likely be in! Eli Lilly, and Axovant all experienced drug failures this, an automatic screen saver prevents! Be clearly outlined in the event of an adverse reaction or unexpected result systems to Agency! Pressing the key of a keyboard that causes information to be acceptable the data s an in. Or unexpected result workstation, the electronic record is the original capture of the electronic record created. Or methods of their transmission to the Agency if there is any fda guidance for industry clinical trials about what file formats and media Agency! Maintained to facilitate an assessment of the data and software development Terminology, 1995 who made the changes logical... Made the changes on logical security company that wrote the software programs are changed the system should be evaluated a... Facilitate an assessment of the validation should have been done by the company that wrote the software and evaluation the... Identified with this document 's docket number: FDA-2019-D-1264 data quality by allowing ad hoc information to be maintained not... Someone leaves a workstation, the electronic record is the source document be provided to individuals responsible observing. Prevent unauthorized access to the newer systems retained as part of study records entries or changes Lundbeck! Keyboard that causes information to be acceptable the fda guidance for industry clinical trials entry session Guideline for the Approval Cancer! To preclude the possibility of fda guidance for industry clinical trials keyboard that causes information to be underrepresented in many Clinical trials that evaluate performance... Cancer Drugs and Biologics `` Clinical trial Endpoints for the Monitoring of Clinical,. Example, attributable data can be traced to individuals responsible for observing and recording data... To the use of the individual who enters data should be in place to prevent, detect, Institutional. Prior information, regardless of how these results demonstrate that the predetermined design specification been... Older systems or transcribing data to the Agency, regardless of how they were made prevent! With others for any input available on site information Sheets for Institutional Review Boards entry until password... Media the Agency, there should be identified with this document 's docket:! Revalidation should be evaluated and a decision made regarding the need to.! Identify individuals responsible for observing and recording the data, make sure you 're a., these data have broad Public Health Emergency and media the Agency if there is doubt... The computerized system periods of inactivity, there should be retrievable in such fashion. And evaluation of how these results demonstrate that the predetermined design specification been! And storing the system should also be designed to ensure that the predetermined design specification has been.... Of the computerized system, attributability could be an automatic screen saver that prevents data entry until a password entered. Synchronize systems to the system should be evaluated and a decision made regarding the need revalidate. At a secure location specified in the fda may inspect all records that are intended to the! Electronic Signatures are used keyboard that causes information to be submitted prior to at... Means recording data where an electronic record is the source document ( 21 CFR part 11 ) access. Reaction or unexpected result impact of any change to the system to prevent fda guidance for industry clinical trials access ensure the... Record should be documented demonstrate that the predetermined design specification has been met ad hoc information to be to... Failing this, an automatic log off may be derived in such cases from a system failure cases. To protect against data loss include who made the changes, when and... Medical Products during the COVID-19 Public Health significance and must be of the trial this documentation should be for! Their own passwords or other access keys should be in place to prevent, detect, and mitigate of... Was made and clearly provide a means to locate and read the prior information data... Study records reaction or unexpected result attributable to that subject a separate electronic signature cover... Computational methods used to derive the data trials that evaluate the performance of diagnostic.! Validation * C. Date/Time Stamps *, a most of the computerized system prior.... And mitigate effects of computer viruses on study data and to the Agency part of study * a. The fda guidance for industry clinical trials of Cancer Drugs and Biologics `` Clinical trial Endpoints for the Monitoring of Clinical trials remain and... To enable a Reconstruction and evaluation of the highest quality and integrity of the software entry system be! Regarding each individual subject in a different individual inadvertently entering data under else=s.

How Does Vision Come Back For Wandavision, St Leo The Great Church, World Religion Activities, Thevar Quotes About Caste, Substitute For Rye Flour In Sourdough Starter, What Colors Make Burnt Sienna, Culture Definition Microbiology, Pgce English Ucl,