Introduction to Good Clinical Laboratory Practices (GCLP) Version 5.0, August 2012 Goal of GCLP: To ensure accurate laboratory testing results. GCLP Training: 3 day course; comprehensive GCLP training including advanced modules for Quality Management and Verification of Performance Specifications. A certificate will be issued only to those who have completed all the required training. An Electronic Registration System will be used to ensure participation of all attendees for the 3 days of training. Introduction and welcome: Introduce and acknowledge representatives from DAIDS, course trainers, and representatives from other organizations in attendances.

Didactic Presentation Activities and Discussion Workshop Approach Objectives Didactic Presentation Course objectives will be reviewed for each module followed by didactic presentation, as well as training activities and opportunities for group discussion. Ask if there are any questions and facilitate discussion. Activities and Discussion 2

DAIDS GCLP Standards Booklet Workshop Materials DAIDS GCLP Standards Booklet Module Handouts Reference Materials ARS Key Pads 3

Audience Response System (ARS) Respond to Questions Change an Answer Responses are Anonymous Question cue is a on preceding slide Ensure remote is on by pressing and holding the “On/Off” button Please leave remotes on the tables Choose your answer Send or change your answer Before moving on to the course objectives, let us introduce and review the use of the Audience Response System (ARS). The ARS system will be used to test your understanding of the modules and training provided. (Facilitator to review ARS system). To respond to questions: The answer choices will appear on the remote screen. Use up and down arrows to scroll to an answer choice, then press the button in the top right corner to “Send” your answer. Be sure to choose the answer on the keypad that corresponds to the answer on the screen. A checkmark and x in parentheses will appear in the bottom center of the remote screen indicating that the response was submitted. Refer attendees to ARS quick reference card on table for additional information and visual. Remind participants that all responses are confidential. A blue star will be in the top right corner of slides preceding a question. Participants should ensure that their remotes are on by pressing and holding the On/Off button. Please leave remotes on tables after each session.

Audience Response System (ARS) (con’t) Good Documentation Practices include following the principles of: Electronic Record Management “ALCOA” Electronic Signatures Choose your answer Send or change your answer Let’s test out using the ARS/Quizdom system. The question is: Good Documentation Practices include following the principles of: Electronic record management “ALCOA” Electronic signatures The correct answer is: B. “ALCOA” which stands for Attributable, Legible, Contemporaneous, Original and Accurate. We’ll review this later today. Show the participants results slide from Quizdom.

Audience Response System (ARS) (con’t) Name one of the words that is applied within the acronym “ALCOA.” Choose your answer Send or change your answer Let’s test out using the ARS/Quizdom system. The question is: Name one of the words that is applied within the acronym “ALCOA” Now type in your answer Show the participants results slide from Quizdom. The correct answer may include any of the following: Attributable, Legible, Contemporaneous, Original, and Accurate.

Survey What position do you hold in your facility? Laboratory Technician QA/QC Coordinator Laboratory Manager Laboratory Director Other (laboratory) Other (nonlaboratory) Let’s test out using the ARS/Quizdom system. The survey question is: “What position do you hold in your facility?” Enter the applicable letter corresponding to your position. If your position is not represented here, enter “E” or “F”. Review overall responses.

Survey (con’t) How many years of research experience do you have? None < 1 1 – 5 6 – 10 >10 Here is another survey question. Please enter the letter that corresponds with the number of years experience you have in research. Review overall responses.

Objectives Explain what GCLP is and why it is important List GCLP standards List the key entities involved in ensuring GCLP Explain the role that audits play in ensuring GCLP

Pre-Assessment Question #1 Good Clinical Laboratory Practices are important for which of the following reasons? To ensure accurate laboratory testing results To allow for reconstruction of the study To define the performance of specific laboratory functions A and B only A, B and C Remember to pick the best answer. The correct answer is: D. “A and B only”

Pre-Assessment Question #2 According to GCLP, accurate documentation is important for which of the following reasons? To allow for reconstruction of a study To ensure that data are reliable, and accurately recorded To explain why, how, and by whom an activity was performed All of the above Remember to pick the best answer. The correct answer is: D. “All of the above”

Pre-Assessment Question #3 Which organization generates action plan documents after international audits and supports Corrective Action and Preventive Action (CAPA), External Quality Assurance (EQA) / Proficiency Testing (PT)? DAIDS Patient Safety Monitoring in International Laboratories (SMILE) DAIDS Clinical Laboratory Oversight Team (DCLOT) CRSS Remember to pick the best answer. The correct answer is: B. “SMILE”

Pre-Assessment Question #4 Site monitors ensure compliance to GCLP standards by conducting __________________. Site visits Data entry Laboratory audits A and B only A and C only None of the above Remember to pick the best answer. The correct answer is: E. “A and C only”

Laboratory Oversight Relationships DAIDS DCLOT SMILE CRSS FHI WESTAT DCLOT and SMILE -generate action plan documents after audits; -SMILE supports CAPA, EQA/PT. Clinical Operations Clinical Support Review the workflow diagram/information flow slide. - Oversee Laboratory Audits LABORATORIES & REPOSITORIES

DAIDS Guidelines for GCLP Standards Outlines the minimal requirements clinical research laboratories should follow Encompass elements of: GLP (21CFR Part 58), CLIA (42CFR Part 493), and Guidance from ISO and CAP Deployed globally Compliance is an ongoing process Monitoring of compliance by the DAIDS through site visits and laboratory audits Overview of DAIDS Guidelines for GCLP Standards This is an appendix to DAIDS Policy on “Requirements for DAIDS funded and /or Sponsored Laboratories in Clinical Trials.” DAIDS Guidelines for GCLP Standards outlines the minimal requirements for clinical laboratories to ensure data generated is accurate and reliable. DAIDS GCLP standards encompass applicable portions of: Good Laboratory Practices (GLP) (GCLP, 21CFR Part 58), and The Clinical Laboratory Improvement Amendments (CLIA, 42CFR Part 493); as well as, Additional guidance from: the College of American Pathologists (CAP) and the International Organization for Standardization (ISO). DAIDS GCLP standards are deployed globally. The “GCLP Standards” document is translated in 6 languages (Spanish, Portuguese, Chinese (Mandarin), Thai, Khmer and French) Compliance is monitored through annual laboratory audits.

GCLP Standards Provide for… And ensure that… Sufficiently trained, experienced, and competent staff Appropriate and adequate facilities Optimal functioning equipment Adequate reagents and materials Relevant standard operating procedures (SOPs) that are approved and in place for use by laboratory personnel And ensure that… Analytical Plans exist Quality Assurance and Quality Control programs are in place Specimen integrity is maintained

Why GCLP? To ensure quality, reliability, and integrity of study data To ensure comparability of study data To allow for reconstruction of the study Why GCLP? GCLP is the cornerstone of all laboratory-based activities in any organization. A large amount of safety and efficacy data required for clinical trials are laboratory results. Reliable and accurately reported data is critical to the safety and well-being of research participants during trials, and to the public if products are marketed for use following the trials. Everyone in the laboratory plays a role in ensuring GCLP and quality laboratory results. GCLP allows for reconstruction of the study: Years later there is a need to understand what happened within a study. Documentation practices must be such that results can be traced back to WHO performed WHAT practices for WHICH study participant and WHEN. Sponsor and regulatory investigators need to be able to verify the accuracy of data through monitoring visits and regulatory inspections. GCLP standards have been deployed to various centers around the world. Implementing these standards ensure uniformity across all laboratories performing clinical studies. To achieve uniformity of the performance of specific functions across all laboratories worldwide 17

Elements of GCLP Organization and Personnel Safety Facilities and Equipment Verification of Performance Specifications Laboratory Information Systems (LIS) Testing Facilities Operation Test and Control Articles Records and Reports Specimen Management and Tracking Quality Management These are the elements of GCLP, and the course will review these within individual modules. Review the list. Expand on the following topics: LIS – i.e., LIMS, review policies for which these systems need to comply. Testing Facilities Operation – how we document procedures within the laboratory (SOPs, etc.)

Documentation Maintenance of prompt, accurate, and complete records “If it is not documented, it never happened!” Why, how, when, and by whom was the test performed Documentation is extremely important to validate the data used in clinical trials. “If it is not documented it never happened!” Documentation is necessary to: Ensure all results and procedures are documented (e.g., maintain analyzers, QC testing, resolving issues/problems, CAPA, etc.). Be able to explain why an activity was performed, how it was performed, by whom, when …etc. “Write down what you do, do what is written down!”

A L C O ttributable egible ontemporaneous riginal ccurate Study Data FDA expects data acquired during a clinical study to be: A L C O ttributable egible ontemporaneous riginal ccurate FDA expects clinical laboratory data to comply with ALCOA. A- who recorded the data; which laboratory? L- data needs to be legible to ensure that it can be accurately interpreted by others; use of pencils/white-out not allowed. C- record data in real time (i.e., recording refrigerator temperature); must be recorded when it is done. O- do not forge data. A- ensure data is recorded as accurately as possible (i.e., filling in temperatures for the whole month).

Compliance to GCLP standards will ensure that data reported is: Consistent Reproducible Auditable Produced in an environment conducive to study reconstruction

Additional Training Resources DAIDS Learning Management System (DLMS): https://daidslms.plateau.com/learning/user/login.do Laboratory Curriculum GCLP Online Review Courses Quality Management Curriculum CAPA for Laboratory Staff FSTRF Training Laboratory Data Management System (LDMS) Courses Comprehensive GCLP Workshop

DAIDS Laboratory Audits General Laboratory Audit Central Laboratory Audit Histology Audit Types of Audits PBMC Laboratory Audit Repository Audit TB Laboratory Audit

DAIDS-Sponsored Programs GCLP Standards GCLP Training GCLP Audits 24

Skill Check A DAIDS audit has just been announced in your laboratory. How should your laboratory respond? The QA/QC Coordinator should sign and predate all temperature charts that were not reviewed the previous year Send all staff without complete personnel records on forced vacation Embrace the audit and use the opportunity to improve your systems Move all equipment without documented maintenance out of the laboratory and bring it back as soon as the auditor has left None of the above Remember to pick the best answer. Answer: C. “Embrace the audit and use the opportunity to improve your systems”

Teamwork Teamwork is the ability to work together toward a common vision—the ability to direct individual accomplishments toward organizational objectives. It is the fuel that allows common people to attain uncommon results. Andrew Carnegie

Post-Assessment Question #1 Good Clinical Laboratory Practices are important for which of the following reasons: To ensure accurate laboratory testing results To allow for reconstruction of the study To define the performance of specific laboratory functions A and B only A, B and C Remember to pick the best answer. Correct answer: D. “A and B only”

Post-Assessment Question #2 According to GCLP, accurate documentation is important for which of the following reasons? To allow for reconstruction of a study To ensure that data are reliable, and accurately recorded To explain why, how, and by whom an activity was performed All of the above Remember to pick the best answer. The correct answer is: D. “All of the above”

Post-Assessment Question #3 Which organization generates action plan documents after international audits and supports CAPA, EQA/PT? DAIDS SMILE DCLOT CRSS Remember to pick the best answer. The correct answer is: B. “SMILE”

Post-Assessment Question #4 Site monitors ensure compliance to GCLP standards by conducting __________________. Site visits Data entry Laboratory audits A and B only A and C only None of the above Remember to pick the best answer. The correct answer is: E. “A and C only”

Wrap Up