3rd WHO Prequalification Stakeholders Meeting :Diagnostics 3rd Stakeholders Meeting on Prequalification Geneva, 4th February 2008 Update and Future Directions

3rd WHO Prequalification Stakeholders Meeting :Diagnostics

3rd Stakeholders Meeting on Prequalification Geneva, 4th February 2008

Update and Future Directions of Prequalification of Diagnostics

Dr Gaby VercauterenCoordinator, Diagnostics and Laboratory Technology

Essential Health TechnologiesHealth Systems and Services


The aim of prequalification of diagnostics

To promote and facilitate access to safe and appropriate diagnostic technologies of good quality in an equitable manner.


Assessment of the performance and operational characteristics of test kits • HIV tests since 1988• Hepatitis B tests since 2000• Hepatitis C test kits since 2000• Chagas tests since 2002• Syphilis tests since 2001• Malaria tests since 2002.• CD4 technologies ad hoc in 1996 and 2003• Alternatives to viral load started 2005

Provide technical information on various diagnostics

WHO's Diagnostics activities


Global market for diagnostics is changing

Trends Outsourcing of production

Move to countries with less stringent regulations

Confusion about licensing of products Re-branding of test kits (OEM) Same name, but different production site, different quality norms

Easy to operate tests/methodsNear patient testing, hard to reach populations, non lab environments, tasks shifting

Humanitarian projects- initiative from companies Availability of funds for diagnostics


WHO's response

Review of the prequalification process for diagnostics

As a more comprehensive approach was required ...

Align with global standards for assuring quality of diagnostics


Prequalification of Diagnostics – New approach

Through a rigorous process identify diagnostics that meet the quality standards

Harmonize the WHO prequalification process 1. More stringent dossier assessment of diagnostics 2. Inspection of the QMS at production site (ISO 13485/GMP)3. Laboratory assessment of performance characteristics

4. Building capacity at country level (NRA and NRLs) and establishing post-market surveillance for priority diagnostics

Partnering with well known regulatory authorities and with key technical partners


PQ strategic plan

Objective 1: increase number of diagnostics reviewed each year

by expanding technical managerial and administrative capacity, and by improving efficiency of the PQ process

Objective 2a : Create and/or refine norms and standards for

prequalifying diagnosticsObjective 2b: Prequalify diagnostics


PQ strategic plan

Objective 2c: Increase country capacity to effectively regulate

diagnostics and diagnostics manufacturers to submit products for prequalification

Objective 3 : Ensure financial sustainability of UN Prequalfication

programme after project completion


Priority Diagnostics

HIV Malaria TB Ongoing and new diagnostic markers


WHO - ensuring improved access, quality & appropriate use of Diagnostics

WHO departments and teams

Essential Health Technologies, (EHT)• Diagnostics and Laboratory technology; (DLT)

HIV department (HIV) Stop TB, (STB)

• TB strategy and operations (TBS) UNDP/World Bank/WHO special Programme for Research and

Training in Tropical Diseases, (TDR) • Product Development and Evaluation, (PDE)

Global Malaria Programme,(GMP), SCM WPRO : Malaria, other vector borne diseases; (MVP)

Key priority for 2007-2012Prequalification of Diagnostics


Achievements 2007

New team in place Expanded procedures developed

• Forms-instructions-protocols Process documents developed

• SOP – check lists- letters Quality Management System applied Communication strategy


Achievements 2008 start new process

Applications and dossier assessments, inspections, lab evaluations, HIV, malaria diagnostics

Plan and organize field sites VL and CD4 tests Increase communication to key stakeholders

and industry about PQ


Achievements 2007

Diagnostics and Laboratory Technology

New team established in January 2007

…. But


Department of Essential Health Technologies

M s Irm a VelazquezTechnical O fficer (P4 )

M rs D ivina M aram baAdm inistrative Assistant (G 6)

M s K ittie Rasm ussenAssistant to D irector (G 5)

VacantPool Secretary (G 4 )

Dr Selm a Kham ass iM edical O fficer, Safe Injection (P4 )

Dr Noryati Abu Am in (P /4)M edical O fficer (P4 )

Dr Saloney Nazee r (STP/4 against )M edical O fficer (P4 )

M s Jan Fordham (STP/4 against)Technical O fficer (P4 )

M rs Evelyn Jiguet (G 6 against )Assistant to Coordinator (G 5 )

M s Leslie Angeles (STG /4 )Secretary, G 4

Vacant STP/4Technical O fficer, B loo d cold chain

Short-term Professional Pos t

Dr Neelam DhingraCoordinator, BTS* (P5 )

Technical O ffice r

Dr Anne B adrichan iScientis t

Inspection s

Technical O ffice r

Project O fficer

Technical O ffice r

Technical O fficer ,

M rs Julia M iraillet, 80 %Team Assistant,

M s Katthy AparicioSecretary

Vacan tSecretary (G 4)

Technical O ffice r

Dr G aby Vercautere nCoordina tor, DLT *

Vacan tTechnical O ffic er, Consultan t

M rs G udrun IngolfsdottirAssistant to Coordinator (G 5 )

M r B jorn Fahlgren (STP/4 against )Technical O ffic er (Vacant P4 )

Vacant P 5Coordina tor D IM *

Dr M een a Cheria nM edical O fficer (P4 )

M rs F iona ConstableAssistant to Coordinator (G 5 )

M rs Chris Faivre-P ierret (STG /4, 50) M rs Anita Korinsek (STG /3, 50% )

Secretary, G 4

M s M ar Carm onaTechnical O fficer (P2 )

Dr Luc Noe lCoordinator CPR* (P5 )

Dr S teffen G rothD irector (D1 )

* BTS Blood Transfusion Safety CPR Clinical Procedures DIM Diagnostic Imaging and Medical Devices DLT Diagnostics and Laboratory Technology

*


PQ of diagnostics : Staffing

2006 2007J F M A M J J A S O N D J F M A M J J A S O N D

WHO Funds

Project manager G Vercauteren

Technical Officer M Perez Gonzales

Technical Officer P Ghimere

B&M GF Funds

Inspection scientist 1 J Twell

Inspection scientist 2 A Saffari

Scientists HIV assays A Janssen (75%)

A Sands P3

Scientist for CD4 A Badrichani/ W Urasa

Communications officer D Dimancesco

G5 Assistant J Miraillet (80%)

G4 Assistant K Aparicio/C Doucelin (80%)

WHO Funds Consultant work B&M GF Funds


Prequalification project management team

Diagnostics-Medicines and Vaccines• Bi-monthly meetings

1 day meeting reviewed the 3 PQ processes:• Similarities• Differences• Opportunities for efficiency (web-based

applications, tracking, etc)

Malaria diagnostics working group • Regular meetings• Improved collaboration


The communication strategy Communications mapping and analysis Annual stakeholders meeting Annual prequalification report Prequalification web pages (FAQs) Communications specific for target audiences

• Manufacturers• Donors • NRA - NRL• Users• Buyers


Key Messages

Different elements of the case will be emphasized according to the different target audiences.

Prequalification of diagnostics:

• facilitates the procurement of appropriate, quality diagnostics at reasonable cost for resource limited countries by UN and other agencies involved in procurement

• reduces expenditure of human and financial resources on poor-quality, ineffective diagnostic technologies

• contributes to the scaling-up of prevention and treatment programs, slowing of drug resistance and treatment failures

• Empowers people at risk and/or infected with HIV/AIDS or malaria by assuring that the patient receives an appropriate diagnosis and consequently optimal treatment.


Manufacturers

Objectives

To increase awareness and maintain manufacturers' interest in submitting products for PQ and to encourage manufacturers to prepare PQ submissions adequately.

To urge manufacturers to focus on producing priority diagnostics, appropriate for resource-limited settings and to cater to both paediatric and adult populations.

To encourage compliance with GMS.

To encourage manufacturers to ensure adequate product maintenance and customer service locally.

Messages

PQ enables product to be included in UN Bulk Purchasing Scheme and reinforces global image of quality diagnostic.

Adequate submissions result in timely PQ.

Products that are not appropriate for resource limited countries or that are not considered priority will not be eligible for PQ.

Compliance with GMS is necessary for PQ.

PQ, in addition to local customer service will help to establish the diagnostic product in the market.


Donors

Objectives To urge donors to

contribute to the purchase of not only medicines, but also diagnostics.

To maintain and increase financial support for diagnostics PQ.

Messages Prevention and

treatment scale-up initiatives rely on access to quality, affordable diagnostics.

The purchase of prequalified diagnostics is cost efficient spending of public funds.

The purchase of prequalified diagnostics should be a requirement.


Diagnostics Procurement Issues

Promote use of pre-qualified diagnostics Advocate for selected tendering of pre-

qualified products Advocate for link buyers and users Technical guidance on procurement

issues• Generic specifications• Maintenance contracts

Post-market surveillance mechanisms


Communication Updates

Update prequalification of diagnostics • Issue 1 (general)• Issues 2- 8 ( topics

identified, issues in preparation)

AIDS conference; Mexico 3-8 August 2008• Organize briefing

session


WHO webpages

www.who.int/diagnostics_laboratory


Prequalification of Diagnostics Process

Manufacturer submits application

Application is screened

Rejected

Accepted Manufacurer pays fee and submits dossier

Rejected

Accepted

Dossier is reviewed

Laboratory Evaluation Manufacturing Site Inspection

Does not meet WHO requirements

Meets WHO requirements

Meets WHO requirements

Does not meet WHO requirements

Product is prequalified (eligible to tender with UN)

Review of all information


Achievements 2007: Key Process DocumentsMANUFACTURERS

Application Form

Instructions for the compilation of the Product Dossier

Overview of the Inspection Process

Instructions for Submission of a Product for the Laboratory Evaluation

Information for Quality Management Systems for Manufacturers

INSPECTORS

Checklist Quality Management System

Confidentiality and Standards of Conduct Agreements

Declaration of Interests

DLT INTERNAL QUALITY MANAGEMENT SYSTEM

PQDx Document Control List

SOPs for all internal processes

DLT Post Inspection Report Template

Internal Audit Summary Report Template


Challenges for the dossier review

Web based application system (lower priority)

Lack of stability data Insufficient performance data Lack or rudimentory Quality Managment

System ( ISO 13485)

RESPONSE…. Guidance document on stability testing (CLSI) Guidance document on performance data Instructions for compilation of a dossier

address these issues (organize some sessions)


Terminology

What is a Quality Management System? 'The system should ensure consistency and improvement

of working practices, which in turn should provide products and services that meet customer's requirements.

ISO 9000 series is the most commonly used international standard that provides a framework for an effective quality management system.'


International Organization for Standardizationwho uses ISO 13485?

US FDA Quality System (FDA 21 CFR Part 820) regulation now 'harmonized' with ISO 9001 and ISO 13485 (minor variations) European Union Therapeutic Goods Administration (TGA ) Australia Health Care Canada Global Harminization Task Force (GHTF)

• Australia-Canada-EU-Japan-USA Asian Harmonization Working Party (AHWP)

• 16 Asian countries, including China, Korea, …• Alliance with GHTF


Quality Management of the project

Continual Improvement ofThe Quality Management System

Resource management

Analysis of feedback

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Management responsibility

Prequalification Assessment


Achievements 2007

Quality Management Explained policies, processes and procedures

required for planning and execution of the prequalification assessment

integrates WHO processes and applies a process approach

enables DLT to identify, measure, control and improve the prequalification processes that will lead to improved performance


Challenges for Countries and for the PQ Dx programme

Procurement Issues Malaria

• Large variety of rapid malaria diagnostic tests available, … but which test to choose ?

HIV• Procurement HIV tests more established• Gaps in availability of pediatric

diagnostics


Potential inspections in 2008

Priority for diagnostics currently procured by UN (Web buy list)

• 32 HIV tests (20 rapid, 7 EIA and 5 confirmatory)

• 53 Malaria tests (53 rapid) Additional 7 manufacturers are of

interest Rapid tests have priority 40 sites manufacture rapid tests


Inspections (site visits only) 2008

Time per inspection mission:• 3 days on site of manufacture +2 days

travelling time per mission• 5 days:1 site – 1 product, 6 days: 1 site- 2

products, 9 days: 2 sites – 2 products

Inspection team consists of • One WHO DLT staff member• 2 externally sourced inspectors • Inspector/s from the National Regulatory

Authority


Priority setting for laboratory assessment of diagnostics

• Serological tests• HIV rapid tests• Malaria rapid tests• TB rapid tests (2009 …) • HIV incidence tests

• CD4 technologies

• Viral load and early detection in infants

• filter paper approach

• Alternatives


Conclusion: A more efficient programme Application process

• Generates valuable information• formalizes procedure and screens out products which

are not UN priority or substandard• streamlines scheduling

Dossier review• screens out applicants with poor quality management

Assessment of QMS of production of diagnostics through site inspection• ensures a consistent product each time

Laboratory evaluation • (operational characteristics and performance)

PQ Diagnostics Programme operates under an internal QMS


Capacity building

Capacity building National Regulatory Authorites• Pilots South Africa, China • Generic regulations• Strengthened national capacity for inspections

Capacity building National Reference Laboratories • Performance assessments• Batch release testing

Pilot Post-market surveillance • QA programmes for users• Tools to record problems

Guidance on Procurement and supply management• Selection of diagnostics • Tendering processes GFATM, UN agencies, key players


Update the business plan

Review of the business plan for prequalfication of diagnostics based on real costs

Short term – next 2 years Longer term


Future directions

Expand range of diagnostics• TB• STI's – HPV tests• HIV incidence tests

Capacity building • NRA • NRL

Guidance to address found weaknesses Expand Post market surveillance

Guidance on Procurement and supply management• Selection of diagnostics • Tendering processes GFATM, UN agencies, key players


Diagnostics and Laboratory Technology (DLT) Team

Thank you