This document outlines the Division of Acquired Immunodeficiency Syndrome (DAIDS) laboratory-related requirements and deliverables for non-US laboratories.
Laboratories should be conducting operations in accordance with Good Clinical Laboratory Practices (GCLP). GCLP embraces both the research/pre-clinical and clinical aspects of Good Laboratory Practices (GLP). Complying with GCLP is an ongoing process that is central to optimal clinical research laboratory operations. DAIDS will monitor the progress toward GCLP compliance through annual audits and/or site visits. GCLP compliance will ensure that consistent, reproducible, auditable, and reliable laboratory results that support clinical trials will be produced in an environment conducive to study reconstruction.
The NIH/NIAID/DAIDS guidelines for GCLP standards (PDF) document is provided to clearly define the standards that encompass GCLP to include applicable portions of 21 Code of Federal Regulations (CFR) part 58, or GLP, and 42 CFR part 493, or Clinical Laboratory Improvement Amendment (CLIA) rules. Due to the ambiguity of some parts of these regulations, these GCLP standards also include guidance from accrediting bodies such as the College of American Pathologists and South African National Accreditation System.
These GCLP standards should be applied to all laboratories performing testing that supports a clinical trial funded and/or sponsored by the DAIDS. Institutions must also meet sponsor-specific requirements as outlined in the Sponsor Statement section of the GCLP standards document.
In addition, accreditation by College of American Pathologists (CAP) or an equivalent in-country accrediting body that meets ISO 15189:2007 Standards is highly recommended.
1.1. CD4 Testing
CD4 determinations must be done using standard flow cytometric measurements, and consideration should be given to the Centers for Disease Control and Prevention (CDC) guidelines that describe dual-platform technology – Morbidity and Mortality Weekly Report (MMWR) 1997;46 (No. RR-2), or single-platform technology - MMWR 2003; 52(RR-02).
The CD4 laboratory must successfully participate in the CD4 proficiency testing program administered by the United Kingdom National External Quality Assessment Service (UKNEQAS) and must be responsive to the trouble-shooting and assistance efforts by the DAIDS Immunology Quality Assessment (IQA) contract. see Information about the UKNEQAS CD4 PT program. Proficiency testing (PT) samples are sent every two months, beginning in January. The CD4 laboratory will have to pass at least one round of PT before testing study subjects. Particular DAIDS-funded Networks (e.g. HPTN) may have more stringent requirements. Enrollment in this program will have to be requested from DAIDS. The cost of participation may be borne by DAIDS or may have to be included in the grant application. Please contact Daniella Livnat at 301-435-3775 or email to discuss.
There is no fee for receiving assistance from the DAIDS IQA. Laboratories are responsible for the cost of test kits/reagents used to test the proficiency panels and these too should be taken into account when preparing the budget for conducting the trial.
1.2. HIV Virology
The use of FDA-approved methods is strongly encouraged. See the Consensus virological methods. Laboratories performing HIV viral load tests, HIV DNA PCR and HIV genotypic drug resistance testing must participate in the DAIDS Virology Quality Assessment (VQA) program.
To request enrollment in VQA PT program(s), please contact Joe Fitzgibbon at 301-451-2738. For HIV viral load certification, the laboratory is required to successfully complete testing of an initial panel of 20 coded samples and two subsequent five-sample panels. The process of achieving certification takes at least five months.
For laboratories performing testing for DAIDS-sponsored studies, there is no fee for participating in the VQA program. However, laboratories are responsible for the cost of shipping the panels from the VQA to the laboratory, and for test kits/reagents used to test the proficiency panels. These costs should be taken into account when preparing the budget for conducting the trial.
1.3. Other tests
Different providers of EQA surveys send samples at different frequencies. Most CAP surveys are sent three times a year. The laboratory will have to successfully pass at least one round of EQA for each clinical trial analyte and satisfy all other network specific requirements before starting the trial. EQA results from safety, eligibility, and diagnostic tests will be reviewed by the DAIDS contractors and/or network lab managers. The laboratory will also receive assistance and instructions for corrective actions from DAIDS contractors and/or network lab managers/
The cost of participation in EQA programs (buying, shipping and testing PT panels) may be borne by DAIDS or may have to be included in the grant application. Please contact Daniella Livnat at 301-435-3775 or email to discuss.
2.1. Research Use Only (RUO)
RUO assays, such as Enzyme-Linked Immunosorbent Spot (ELISPOT) and Intracellular Cytokine Staining (ICS), are intended to be used for performing basic scientific research, are not considered to be effective diagnostic tools and must be appropriately labeled “for Research Use Only, Not for use in diagnostic procedures”. External quality assurance should be applied to such tests. If existing EQA surveys are not available, a suitable form of alternative proficiency assessments should be devised and proposed to DAIDS for approval. Results from these assays are not to be used for making clinical decisions. See Information on EQA programs provided for RUO assays.
2.2. Investigational Use Only
Endpoint tests, such as new non-FDA approved pharmacological and virological assays do not require an investigational devise exemption (IDE) submission to the FDA. These are classified as investigational use only (IUO) tests while clinical studies are being done to evaluate their performance. Results from these tests are not intended to be used for the diagnosis, treatment or management of patients without confirmation by other medically established procedures. IRB review (21 CFR part 56) and human subjects regulations (21 CFR parts 50) apply.
If shipments of specimens are to occur, they must be done according to the most current International Air Transport Association (IATA) shipping regulations.
If the laboratory plans to use a Laboratory Information Management System (LIMS) or a Laboratory Data Management System (LDMS), the elements of 21 CFR Part 11 compliance should be taken into consideration.
The lab QMP describes the laboratory’s approach to management of quality and study-participant safety by providing guidance for the operation of a laboratory. It must monitor, assess, and correct problems identified in pre-analytical, analytical and post analytical aspects of all lab operations.
All laboratories performing testing that supports a clinical trial funded and/or sponsored by the DAIDS must have a documented QMP that describes the overall quality management program of the laboratory. For additional please refer to guidance in preparing and implementing a QMP (PDF).
The QMP should describe the following: the laboratory’s plan to ensure overall quality and patient safety, corrective action and preventive action (CAPA) activities, risk assessment activities, QC and EQA activities, monitoring of key indicators and continuous improvement plans. For information on required elements that must be included in the QMP please refer to the Lab Quality Management Checklist (Word).
The cost of the workshop is free, however all attendees are responsible for their own travel, hotel, and per diem expenses through their network or group affiliations. Training materials for each participant will be provided. Translated materials in other languages will be provided upon request.
A certificate of participation is provided to participants that attend the full three-day workshop. See information on up-coming DAIDS-sponsored GCLP training workshops.
After an audit, performed by DAIDS or PPD, an audit report will be distributed to the laboratory. The laboratory is responsible for working with DAIDS or its contractor, SMILE, to resolve the audit report findings. These audit report findings must be adequately addressed by the laboratory to maintain a satisfactory performance standard.
For the types of audits performed and the report resolution process please refer to the GCLP Lab Audit Information Document (PDF).
Please email for inquiries about the DAIDS-sponsored GCLP audit and report resolution processes.
For information on guidelines for conducting a validation study refer to the GCLP standards/guidelines document (PDF).
9.1. For requirements described in Section 1.0 above, please include the following in the Comprehensive Laboratory Plan:
9.1.1. Proof of laboratory accreditation/certification if available
9.1.2. A spreadsheet that lists all the tests that will be done for the trial, all the laboratories in which these tests will be done, and the external QA providers and PT surveys that will be used to monitor each test. The template is provided for your convenience as an example of how this information can be provided see Protocol Analyte List Template (Excel). You may modify this as appropriate
9.1.3. Normal ranges for tests or a plan to obtain normal ranges by testing specimens from the local population
9.1.4. Master list of all the laboratory’s SOPs
9.1.5. A copy of the index of the laboratory’s QMP
9.2. For requirements described in Section 2.0 above, please include the following in the Comprehensive Laboratory Plan:
9.2.1. A list of the RUO and or IUO tests
9.2.2. Test SOPs in a format that includes information about test principle, specimen requirements, reagents, supplies and equipment, procedure, calculations, quality control, procedural notes and references
9.2.3. Complete identifying information for the laboratories indicated in 9.1.2 above (e.g. name of lab, geographical location, telephone number, email address)
9.2.4. A description of the external PT measures undertaken for each test in each laboratory
9.2.5. Documentation of the ability of staff to proficiently perform proposed tests
9.2.6. A copy of the index of the laboratory’s QMP
9.3. For requirements described in Section 3.0 above, please include the following in the Comprehensive Laboratory Plan:
9.3.1. The study-specific Specimen Management Plan
9.3.2. Proof of training in IATA shipping regulations (certification) if specimen shipments are planned for the trial
9.4. For requirements described in Section 4.0 above, please include the following in the Comprehensive Laboratory Plan:
9.4.1. The study-specific laboratory data management plan
9.4.2. A description of the testing that was done to ensure that data flow smoothly and maintain integrity from the point of acquisition to the study database
9.4.3. Proof of 21 CFR Part 11 compliance if available
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Last Updated May 04, 2009