Fatim Cham-Jallow

Joining Hands Against HIV www.muwrp.org

QUALITY LABORATORY SYSTEMS AND VACCINE TRIALS – THE MAKERERE UNIVERSITY WALTER REED PROJECT (MUWRP) LABORATORY

Fatim Cham-Jallow, PhD Laboratory Director Makerere University Walter Reed Project/Henry F Jackson Foundation For the Advancement of Military Medicine (HJF) Mulago, Kampala Uganda

PRESENTATION OUTLINE

1. Overview of The Makerere University Walter Reed Project (MUWRP )

2. Overview of the MUWRP College of American Pathology (CAP) accredited laboratory

3. Implementation of Quality Management Systems (QMS) and Accreditation

4. Relevance of safety lab tests for vaccine trials

5. Human Resource Capacity Development - The past , Present and Future for vaccine Trials







MAKERERE UNIVERSITY WALTER REED PROJECT (MUWRP)

• US Military HIV Research Program (MHRP) activities in Uganda began in 1999 in collaboration with the Rakai Project.

• Makerere University Walter Reed Project (MUWRP) established in 2002 is a Ugandan registered not for profit entity and one of several MHRP sites

• A collaboration between Makerere University and Henry M. Jackson Foundation (HJF).

• Primary purpose of MUWRP was infrastructure development for HIV vaccine testing capacity.

• Involved in PEPFAR related research and surveillance activities (Influenza , Ebola/Marburg, Sepsis etc)

MUWRP SITES

• Kampala District

Main Facility – Plot 42 Nakasero Road

Laboratory – Makerere University School of Medicine Mulago Campus

Influenza Research Laboratory (Animal) – COVAB

Influenza Research Laboratory (Human) – UVRI

• Kayunga , Mukono, Buvuma District - PEPFAR – Comprehensive HIV prevention, care and treatment program for adults and

paediatrics

– Orphans and Vulnerable Children (OVC) program

– PMTCT

– HRH Field laboratory

Clinic at Ntenjeru Health Center III

• Buikwe Districts – Medical Male Circumcision

MUWRP VACCINE AND RESEARCH ACTIVITIES – PAST AND PRESENT

• RV 156 – Phase I Vaccine Trial (VRC DNA)

• RV 164 – Normal Reference Values

• RV 173 – Cohort Development (Kayunga)

• RV-172 – Phase I/II Vaccine Trial (VRC DNA/ADV)

• RV247 – Ebola/Marburg Vaccine Trial

• RV 283 – Follow-up of RV 156A and RV 172

• RV 281 – Ebola Survivors

• RV231 – Surveillance of influenza and influenza-like viruses in humans, animals and migratory birds

• RV 262 – Phase I HIV Vaccine DNA/MVA

• RV-217 – HIV-1 Prevalence, Incidence, Cohort Retention, Host Genetics and Viral Diversity in High Risk cohorts in East Africa and Thailand (CSW, MSM)

• RV 329 - African Cohort Study (AFRICOS) – Observational Study

• RV 422 - Evaluate the safety, tolerability and immunogenicity of the EBOLA chimpanzee adenovirus vector vaccines in healthy adults

MUWRP VACCINE AND RESEARCH ACTIVITIES –FUTURE

• HIV Vaccine Trials

– RV 403 : Safety and Immunogenicity of Sanofi Pasteur Live Recombinant ALVAC-HIV (vCP1521) and Global Solutions for Infectious Diseases (GSID) gp120 B/E (AIDSVAX® B/E).

– Crucell / Johnson and Johnson

• RV 419: Characterization of Immunity and Viral Reservoir in HIV Positive and HIV Negative Adults in East Africa

• RV 398: Intervention trial - Safety and Virologic effect of VRC01







MUWRP LABORATORY

• A research, clinical and training Lab accredited by College of

American Pathologists (CAP) since June 2005

• Reaccreditation every two years latest in June 2013

• Biennial audits by NIH Division of AIDS conducted by FHI 360

• Providing support to MHRP sponsored Vaccine and Prevention Clinical Trials

• Providing support for external collaborators – fee for service contracts

EXTERNAL COLLABORATORS

• Infectious Disease Institute

• Fred Hutchinson Uganda Cancer Research Institute

• Makerere University - John Hopkins University

• Makerere University - University of California San Francisco

• Michigan State University

• University of Washington

• University of Colorado

• University of Minnesota

• Elizabeth Glaser Pediatric AIDS Foundation

• Bill and Melinda Gates

• NICHD

• NIH

• Crucell /Johnson and Johnson

• GSK

LABORATORY STAFF – 24 FTE

Lab has 6 units • Diagnostics • Flow Cytometry • Specimen Processing/Safety • Data • QA/QC • Research and Training

CLINICAL LAB CAPABILITY

• Serology (HIV, Hep B , Hep C , HSV, TB QFT, Syphilis, Troponin )

• Trichomonas Vaginalis – POC Test

• Molecular Diagnostics ( PCR, APTIMA (HIV , GC/CT) )

• Immune Monitoring

– HIV Viral Load

– Immunophenotyping (CD4/CD8 enumeration)

• Hematology (CBC+ differentials - automated and manual)

• Coagulation – PT /APTT

• Parasitology - Malaria

• Clinical Chemistry

• Serum/Urine Pregnancy Testing

• Urinanalysis – Dipstick

RESEARCH LAB CAPABILITY

• Peripheral Blood Mononuclear Cell (PBMC) processing and cryopreservation

• Serum and plasma processing

• Mucosal Sample Processing and storage : CVL, semen, CSF, tonsil biopsy, saliva etc

• Cellular Immunogenicity

- Intracellular Cytokine staining

- T-cell immune activation

• Neutralizing Antibody

• Shipment of samples according to IATA guidelines

REPOSITORY

• Long term storage of research samples

– - 86°C Freezers : 524, 880 vials

– Liquid Nitrogen Freezers : 305,000 vials

• In house production of Liquid Nitrogen

– Two operational plants

322 liters capacity

222 liters capacity

• Back-up power supply

– 2 Generators

– Inverter systems

• Real time alert system for all temperature sensitive equipment







BENEFITS OF LABORATORY ACCREDITATION

• Provision of laboratory services with the highest level of quality

• Assures results are internationally comparable and acceptable

• Ensures standardized lab practices

• Confidence to use lab reports in clinical decisions

• Enhances staff confidence and reduces turn over

• Cost savings and elimination of waste

• Assures value for money to funders/clients

• Ensure lab is prepared for Vaccine or Biomedical /Intervention trials

according to GCLP standards

IMPLEMENTATION OF QUALITY MANAGEMENT SYSTEMS (QMS) AND ACCREDITATION

1. GAP analysis : Self Inspections and External Audits

2. Apply for accreditation – CAP/SANAS/ISO 15189 etc

3. Creation of quality system unit involved with:

• SOP Development

• Quality Systems Implementation

• Training and Competency assessments

4. Participate in EQA Programs for all tests: CAP, UKNEQAS,

BIORAD, VQA, EQAPOL

IMPLEMENTATION OF QUALITY MANAGEMENT SYSTEMS (QMS) AND ACCREDITATION

5. Inter-laboratory comparisons

6. Equipment and Assay validation prior to

implementation

7. Establishment of quality control ranges – Hematology,

Coagulation, Flow Cytometry, Chemistry and Viral load

8. Determination of Normal reference ranges

9. Establishing acceptable values for lot-to-lot testing of

kits and reagents

ESSENTIAL ELEMENTS FOR MANAGING AN ACCREDITED LABORATORY

• Strengthening of an independent QA /QC unit

• Development and continuous review of Standard Operating Procedures (SOPs) , quality assurance and safety guidelines

• Regular meetings : – Weekly Head of section meetings

– Bimonthly section meetings

– Bimonthly meeting with lab QA/QC unit and supervisors

– Bimonthly Heads of department meetings

– Monthly Continuous Quality Improvement (CQI) Meetings

– Quarterly Executive management meetings

– Biennial lab retreats


• Monitoring key performance indicators

– Corrective and Preventive Action (CAPA):Protocol /SOP deviations

– Turn- Around-Time (TAT)

– Levy – Jennings Charts (LJs) / Westgard Rules

– PBMC indicators : Viabilities , Yields and recovery etc

– Equipment - Operations and Service contracts

• Complaint resolution

– Regular Client feedback - Biennial client surveys

– Regular inventories and reports to clients


• Personnel Development

– Training and Competency assessments

– Annual Staff appraisals and performance based increment • Annual practicing licenses renewals

• Annual review of job description and CVs

– On the job training – lab rotations, GCLP, CAP, CMEs, Journal clubs, webinars, conferences, etc

• External Quality Assurance (EQA)

– Comply with accreditation standards and guidelines

– EQA Participation • Evidence of EQA report Review

• Investigations and corrective actions







RELEVANCE OF SAFETY LAB TESTS FOR VACCINE TRIALS

WHAT ARE SAFETY LAB TESTS ?

• Clinical Chemistry and Hematological values pertinent in

evaluation of safety profile of an Investigation product (IP)

• Consists of currently known parameters that are or may be

potentially impacted by the IP

• Establishes Vaccine Safety and Tolerability

• General: LFTs, RFTs, CBC

• Specific: Cardiac markers for MVA vector vaccines or PT/ PTT for

Ebola/Marburg vaccines

PRE-STUDY REQUIREMENTS

1. Review Protocol schedule of events (SOE) and Develop

Lab SOPs

2. Verify all tests in the protocol are in the lab tests menu

or validate new tests as necessary

3. Discuss with regulatory and clinic to ensure tube types

and number per SOE and lab test requirements

4. Establish normal reportable ranges for all safety labs

PRE-STUDY REQUIREMENTS

5. Establish an efficient sample collection /transport system

6. Establish key performance indicators for all test processes

7. Develop lab job aids – flow charts , tube requirements and

tests per visit

8. Training of lab staff on protocol

RELEVANCE OF SAFETY LAB TESTS FOR VACCINE TRIALS

Safety Labs performed @:

1. Screening: To determine eligibility

2. Baseline: Immediately pre-administration

3. Further protocol-specified time points: Prior to

each vaccination

SCREENING TESTS AS PER PROTOCOL ELIGIBILITY

• HIV Testing : A robust algorithm to screen out acute HIV

infections

• Pregnancy : Urine /Serum

• Troponin : Cardiac marker

• Coagulation tests : PT/APTT

• Hematology (CBC) & other

• Clinical Chemistry (LFTs/RFTs)

FURTHER TIME-POINT SAFETY LABS

• Established by Protocol

• Identical evaluations as baseline

• Identification of changes from baseline

SAFETY LAB MUST-DO’S

• Determine applicable normal reference range (local or “international”)

• Establish a rejection criteria for samples and TATs for tests

• Establish mechanism for prompt Critical Value notification (phone and email)

• Develop an algorithm to identify HIV Vaccine Induced seropositivity (VISP) vs. HIV Infection

• Establish reporting mechanisms to prevent un-blinding of study

participants /clinicians

SAFETY LAB MUST-DO’S

• Grade 3/ 4 safety labs without clinical signs and symptoms require verification

• Essential to stick to lab SOPs – Blood draw order & instructions – Time to delivery – Storage temp – Bench time

• Timely communication with PI/ Regulatory Office/ Clinic – Protocol deviations – Changes in procedure

• Data Clarification • Documentation (memos)







CENTER OF EXCELLENCE FOR RESEARCH

GOALS:

1. Formulate hypotheses that seek to provide answers to questions of

public health importance in Uganda and Africa.

2. Design competitive research proposals in response to grant calls

3. Collaborate with other grant applicants with expertise in a

particular field

4. Provide a synergistic hub for other grant awardees (National and

International) to execute their research and implement new assays

e.g. IRID, BMF

MUWRP RESEARCH UNIT

• Submission of proposals in response to grant calls

• Access to HINARI and Internet

• Career guidance and mentorship for staff and MU students

• Guide staff/students to prepare publications, abstracts, thesis

proposals and presentations

• Encourage participation of staff in Meetings/Conferences

• Encourage collaborations with national , sub-regional and

international scientists /bodies

• Bi weekly Research meetings

CENTRE OF EXCELLENCE FOR TRAINING

• College of American Pathologists accredited Lab - 10 years

• Model for laboratory Quality Management Systems (QMS)

• Well trained staff in different specialties of laboratory science

• Equipped premises facilitated to serve as a training center for:

– Clinical labs

– Diagnostics

– Cellular and Humoral Immunology

– Molecular biology

– PBMC processing and cryopreservation

• Support Staff Career advancement and short term placements

CAPACITY BUILDING 2006 – PRESENT

• Support MSc and Phd Students – Tuition , flexible work schedules and Thesis

research projects

• In house laboratory rotations

• Presentations at National and International Conferences

• Lunch Time seminars/ Webinars : Grant writing , career advice , lab budgeting,

GCLP, Safety , lab quality and compliance

• Internships for MU students

Degrees Status

Completed Ongoing

M.Sc 11* 4

PhD 1

CAPACITY BUILDING 2006 – PRESENT

• Training in international labs through Research Grants/ fellowships/

MHRP Lab network

• Guest Lectures at MU and other organizations

• Access to CAP competency assessment training program

• Journal Clubs and Continuous Medical Education (CMEs)

• Technology Transfer to other MHRP sites

• Support QMS strengthening of National Public Health and private

lab

BENEFITS OF A SUSTAINALBLE RESEARCH AND TRAINING PROGRAM

A. Income generation for the lab through resource mobilization and

competition for grants leading to increase in compensation for

staff

B. Laboratory/Research Staff are involved and confident to :

1. Initiate and establish collaborations with national and international scientist to

develop research questions of mutual interest

2. Contribute to publications and presentation of data generated from internal

and external protocols .

BENEFITS OF A SUSTAINALBLE RESEARCH AND TRAINING PROGRAM

C. Build and maintain a pool of well trained Ugandan research

scientists that can:

1. Provide advice to junior/young scientists interested in pursuing careers in

research and/or laboratory system strengthening

2. Work with MSc and PhD students to design research projects and serve as

mentors

3. Contribute to training and mentorship of lab professionals in Uganda and

Africa to help eliminate the brain drain of African scientist

ACKNOWLEDGEMENTS

• Meeting organizers

• Vaccine and Clinical Trial volunteers

• MUWRP Management

• MUWRP Lab

• MUWRP Clinic

• MUWRP Regulatory

• MHRP Team

• HJF

QUESTIONS

Documents

Fatim Cham-Jallow