Prequalificationof Diagnostics Challenges and Plans for 2009 · GSM the new WHO administration...

UN Prequalification of Diagnostics, Medicines and Vaccines 4th Consultative Stakeholders Meeting, 3 February 2009

4th Stakeholders Meeting on PrequalificationGeneva, 3 February 2009

Prequalification of Diagnostics

Challenges and Plans for

2009

Dr Gaby Vercauteren

Coordinator, Diagnostics and Laboratory Technology

Essential Health Technologies

Health Systems and Services


The main challenges for prequalification of diagnostics

� Select and retain staff

� Ensure sustainable funding

� Limited human resources with technical expertise with in NRA and NRL

� Delays in the development of technologies appropriate for resource limited settings

� Limited regulatory and laboratory capacity and structures at country level (PMS)

� Procurement issues


PQ of diagnostics : Staffing


Challenges related to staffing

� New DLT team established in January2007• Mainly empty boxes

� Feb 2008 all boxes filled, all STPs

� Feb 2009 two critical positions vacant• Dossier assessor

• 2nd Inspector

� Awaiting posting of fixed term positions


Challenge sustainable funding

� DLT has experienced a negative effect on traditional sources of funding due to misperception

• Less Regular Budget

• Less UBW funds ( for EHT, of which none for DLT)

Additional funds

� Proposal has been successfully submitted to UNITAID

� Possibilities for secondments are being investigated (AFSAPPS)

� In kind contributions from CDC/GAP/ILB

� Proposal prepared on regulatory issues of Diagnostics

…but this is a slow process


Funding 2008-09

PQ Diagnostics:

� Total US$ 3.5 million (4.8M)• Regular Budget: 0.5M

• Gates: 3.0 M

• Potential UNITAID: 1.3 M

PQ Vaccines US$ 18.3 million

PQ Medicines US$ ?? million


Update the business plan

� Initial business plan developed by CHAI

� Review of the business plan for prequalification of diagnostics basedon real costs

� Short term – next 2 years

� Longer term – 5 years


Challenges for the dossier review and inspections

� Time required to receive all requestedinformation from industry

� Limited pool of additional assessors and inspectors

RESPONSE….

� Better guidance to industry

� Set turn around times and enforce them

� Continue to build pool of consultants

� Foster collaboration with NRA


Challenges for the CD4 technologyassessments

Delays due to

� Modifications in technologies

� Commercial availability of the product

RESPONSE….

� Overview of technologies updated

� Meeting with PI planned Q2 2009


Challenges for the HIV NAT assessments

Delays due to

� Time for manufacturers to developprotocols for dried blood spots

� Manual vs automated extraction

RESPONSE….

� Overview of technologies updated

� Protocol to be updated to assess DBS

� Meeting with PI planned Q2 2009


Challenges capacity at country level

� National regulatory capacity• Lack of effective legislation and policy

• Limited human resources

� National reference laboratories• Lack of technical knowledge on

� Evaluation of diagnostics

� Batch release testing

� Lack of collaboration between NRA and NRL


Challenges to have access to procurementdata of diagnostics

� GSM the new WHO administration systems, does not yet allow analysis of procurementdata

� GFATM electronic reporting system does not allow for easy analysis of procurement data

RESPONSE….

� Work with WHO/CPS and GFATM to find a solution


Plans for 2009 : Communication

� Communication with stakeholders• Continue to issue PQ Dx Updates

• Continue to update the Web pages

• Meeting with associations of diagnostic companies, 4 February 2009

• Meeting with CEO's of diagnostic companies, 4 June 2009

• Advocacy to Member States

• Strengthen collaboration within UN family (advocacy – procurement issues)

� Actively solicit requests for PQ of diagnostics


Plans for 2009: HR & collaboration

� Convert key Short Term to Fixed Term staff

� Foster collaboration with NRA• Establish pools of assessors

• Establish pools of inspectors

� Strengthen collaboration with partners• GFATM

• UNICEF, UNDP, UNOPS

� Technical agreement with CDC pending

� others


Plan 2009

� Serological tests� HIV rapid tests

� Malaria rapid tests

� TB rapid tests (2010 ?)

� CD4 technologies

� Viral load and early detection in infants� filter paper approach

� Alternatives


Plan 2009 : Capacity building

� Capacity building National Regulatory Authorites• Pilots Burkina Faso, Côte d'Ivoire, South Africa, Tanzania and

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


Business plan : Future directions

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


4th Stakeholders Meeting on Prequalification

Update on Prequalification of Diagnostics

Anita Sands

Diagnostics and Laboratory Technology

Essential Health Technologies

Health Systems and Services


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 & operational characteristics of commercially available assays

• HIV assays since 1988

• Hepatitis B assays since 2000

• Hepatitis C assays since 2000

• Chagas assays since 2002

• Syphilis assays since 2001

• Malaria assays since 2002

• CD4 technologies ad-hoc in 1996 & 2003

• Alternatives to viral load started 2005

WHO's Activities on Diagnostics


Global Market for Diagnostics is Changing

� Observed Trends• Outsourcing of production

� Move to countries with less stringent regulation• Confusion about licensing of products

� Re-branding of test kits (OEM)� Same name but different production site,

different quality norms• Easy to operate tests/methods

� Near patient testing, hard-to-reach populations, non-lab environments, task-shifting

• Humanitarian projects• Increased availability of funds for diagnostics &

laboratory


WHO's Response

� Review of the "prequalification" process for diagnostics

� A more comprehensive approach was required ....

� Align with global standards for assuring quality of diagnostics


Prequalification of Diagnostics –an improved approach

� Through a rigorous process identify diagnostics that meet the quality standards

� Harmonize the WHO prequalification process1. More stringent dossier assessment of diagnostics 2. Inspection of the QMS at production site (ISO 13485:2003)

3. Laboratory evaluation of performance characteristics

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

� Partnering with well known regulatory authorities & key technical partners


Prequalification of Diagnostics Process

Manufacturer

submits applicationAccepted

RejectedApplication

is screenedManufacturer pays fee and

submits dossier

Dossier is reviewed

Accepted

Rejected

Manufacturing Site Inspection

Meets WHO

requirements

Does not

meet WHO

requirements

Meets WHO

requirements

Does not

meet WHO

requirements

Product is prequalified

Product Laboratory Evaluation

PMS


Achievements to date

� Expanded procedures developed• Forms, instructions, protocols

� E.g. application form, instructions for compilation of the product dossier, etc

� Process documents developed • SOPs, check-lists, letters

� An internal QMS system ensures impartiality, transparency, accountability


Key Process Documents

Internal Audit Summary Report Template

DLT Post Inspection Report Template

SOPs for all internal processes

PQDx Document Control List

DLT INTERNAL QUALITY MANAGEMENT SYSTEM

Declaration of Interests

Confidentiality and Standards of Conduct Agreements

Checklist Quality Management System

INSPECTORS

Information for Quality Management Systems for Manufacturers

Instructions for Submission of a Product for the Laboratory Evaluation

Overview of the Inspection Process

Instructions for the compilation of the Product Dossier

Application Form

MANUFACTURERS


Achievements to date

� Pilot of PQ process complete• For application stage

• For dossier submission stage

• For inspection stage

• Laboratory evaluation component is essentially unchanged & did not require piloting


Application Form

� Captures all relevant information required to make a decision about suitability for prequalification

� Acts as a gate to stem the flow• Ensures efficiency as poor quality

applications do not progress through to the process

� Acts as a mechanism to gain market intelligence


The Product Dossier

� Description of product

� Instructions for use (& labels)

� Shelf-life & stability (transport)

� Performance data

� Sites of manufacture & key suppliers

� Manufacturing process

� Commercial & regulatory history

� Quality management systems


Pilot Application & Dossier Review

� Overall, the application & dossier review stages were effective

� Lessons learnt:

• WHO needs to be prescriptive

• WHO needs to be firm

• Work with the inspection team leader


Challenges for Dossier Review

� Web-based application system (lower priority)

� Lack of stability data

� Insufficient performance data

� Lack or rudimentary Quality Management System (ISO 13485)

RESPONSE….� Guidance document on stability testing (CLSI)

� Guidance document on performance data

� Instructions for compilation of a dossier addresses these issues


Timelines for Inspections

� Time per inspection • Total mission - 6 days per site, 10 days per two

sites� 4 days on site of manufacture

� 2 days travelling time per mission

� Inspection team consists of • 1 WHO DLT staff member

• 2 externally sourced inspectors (expertise in manufacturing processes, quality control & QMS)

• Inspector/s from the National Regulatory Authority


Pilot of Inspection Process

� Lessons learnt • Some alteration to process documentation

required

• Additional time required for an initial inspection, less time for follow-up inspections

• Repeated requests required to address non-compliances satisfactorily thus extending the time to inspection close-out


Laboratory Evaluation

� Requires committed WHO Collaborating Centres with good work practices

� Correct storage of WHO Specimen Reference Panel is vital

� Process is essentially unchanged & has always worked well• Technical reports & performance data

used by many agencies


Conclusion: A more efficient programme

� Application process • generates valuable information

• formalizes procedure & screens out products which are not UN priority or substandard

• streamlines scheduling

� Dossier review • screens out applicants with poor quality management

� Site inspection & assessment of QMS at site • ensures a consistent product each time

� Laboratory evaluation • evaluates performance & operational characteristics

� WHO PQ Diagnostics Programme operates under an internal QMS


Launching PQ for Diagnostics

� PQ programme officially launched in June 08

� 43 applications received from 14 manufacturers

� Next steps• to ensure all currently listed BPS

products submit an PQ application


Prioritisation of PQ Requests

� Many PQ applications for non-priority products

� Prioritisation criteria agreed by group of UN agencies at the Interagency Pharmaceutical Cooperation Meeting held in Tunis, November 2008 • WHO, UNICEF, UNDP, UNFPA, UNOPS, World

Bank, African Development Bank, etc

� To date, of the 43 applications received only 10 were for priority products


Prioritisation Criteria

� Already listed on WHO Bulk Procurement Scheme & procured in high quantities by UN agencies

� Analyte type: HIV & malaria

� Format: Rapid test (immunochromatographicor immunofiltration)

� Original manufacturer i.e. not a re-brander

� Where there exists few other PQed products

� Manufacturer has good commercial & procurement history i.e. licensed for sale & distribution in a representative sample of countries of intended use


Post-Market Surveillance

PMS System

Proactive activities Reactive activities

(3) The vigilance

system

(1) Batch release

testing

(2) Sampling & testing

of test kits from the field


PMS Achievements

� Proposed pilot of PMS in 5 countries• 2 country missions completed in Burkina

Faso & South Africa

� Solicited interest for PMS

� Overall extremely positive response

� Acknowledged problems with testing process quality & an inability to investigate problems

� PMS will assist this process

� Partnership with CDC, Atlanta


The Communication Strategy

� Communications mapping & analysis

� Annual stakeholders meeting

� Annual prequalification report

� Prequalification web pages (FAQs)

� Communications specific for target audiences

• Manufacturers

• Donors

• NRAs, NRLs

• End-Users

• Buyers


Participation in Working Groups

� Prequalification Project Management Team• Diagnostics/Medicines/Vaccines

� Regular 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


Key Messages

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.


Communication Updates

� Update prequalification of diagnostics • Issue 1 (general)

• Issue 2 (FAQs)

• Further issues in preparation

� Electronic distribution list


Advocacy Events

� IAS Conference• Mexico City, August 2008

� African Public Health Network Meeting• Dakar, September 2008

� UN SG Sherpa Meeting• New York City, October 2008

� ICASA Conference• Dakar, December 2008


WHO Webpages

www.who.int/diagnostics_laboratory

www.wpro.who.int/sites/rdt/home.htm

Contact us:[email protected]


Procurement of Diagnostics

� Procurement of diagnostics is complex• Promote use of prequalified diagnostics • Advocate for selected tendering of prequalified

products • Advocate for link between buyers & end-users• Technical guidance on procurement issues

� Generic specifications� Maintenance contracts

� Joint UN agency document in production

• Post market surveillance mechanisms


Challenges for Countries

Disease-specific procurement issues

� Malaria• Large variety of rapid malaria diagnostic

tests available

….but which test to choose ?

� HIV• Procurement of HIV tests is more

established

• However, gaps exist in the availability of paediatric diagnostics


↑ Internet sales of HIV rapid tests


Diagnostics and Laboratory Technology (DLT) Team

Thank you

Prequalificationof Diagnostics Challenges and Plans for 2009 · GSM the new WHO administration...

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