WHO Prequalification of Diagnostics, Medicines and Vaccines - 3rd Consultative Stakeholders Meeting

WHO prequalification of vaccines and vaccine delivery devices Drs. Umit Kartoglu and Nora DellepianeWHO HQ, Geneva- 4 February 2008

Vaccines prequalification- Purpose

A service provided to UN purchasing agencies.

Provide Independent opinion/ advice on the quality, safety and efficacy of vaccines for purchase

Ensure that candidate vaccines are suitable for the target population and meet the needs of the programme

Ensure continuing compliance with specifications and established standards of quality

Vaccines prequalification-Principles

GMP

Reliance on NRA

Meeting WHO requirements and tender specs

Consistency of final product characteristics

Clinical data

Vaccines prequalification- Reliance on NRA

The responsible National Regulatory Authority (usually that of the producing country) is independent and functional:

Meets all the critical indicators required for prequalification purposes following a WHO independent assessment

The status of the NRA is reassessed at regular intervals

Vaccine source

UN agency

UN agency

Direct Procurement

Direct Procurement

ProductionProduction

Functionsassured by NRA of producing country and WHO PQ system

Functionsassured by NRA of producing country and WHO PQ system

Fuctions assuredby NRA of producing

country

Fuctions assuredby NRA of producing

country

Regulatory functions depending on vaccine source

Licensing

Access to laboratoryRegulatory inspections

Lot release

AEFI monitoring

Regulation System

Regulatory functions

Authorization of clinical trials

Vaccines prequalification- Required regulatory oversight

L

Lot to lot release

Inspections at regularIntervals.Inform WHO of seriousGMP deviations

Post-marketing surveillancefor safety and efficacyInform WHO in case of reportsof serious AEFI

Regulatory Actions:Inform WHO in case of withdrawalsor recalls of lots and licensesuspensions

Critical for Critical for countries:countries:

allows to ensure quality of actual

lots received

Vaccines prequalification- Evaluation procedure

• Review of quality data• Review of efficacy and safety data

with focus on data relevant for the target population in the recommended schedules

• Production consistency at commercial scale• Compliance with GMP• Compliance with WHO recommendations • Compliance with UN tender specifications• Programmatically suitable presentation

Vaccines Prequalification- Impact of the project

World Health Organization, HTP/V&B/ATT. LBelgharbi

Number of countriesTotal = 193 countries

84

65

44

UN agency Procuring Producing

NRA andManufacturerstrengthened

Seal of qualityRequirement for

procurement

Assured QualityReplacing country'sRegulatory oversight

Vaccines Prequalification- Features

Pre- evaluation meetings with mfgs and NRAs 3 deadlines for submissions, joint reviews 12 months evaluation (time taken by manufacturer

excluded) Clock stop system Increased portfolio of vaccines Prioritization system defined by UN agencies PQ status valid for 2 to 5 years Information published on WHO website (updated

monthly)

Vaccine PQ- Evaluations and Reassessments

0

5

10

15

20

25

30

35

40

45

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

vaccineapplications

reassessments

Vaccines PQ- Addressing the challenges

Provision for fast-track procedure in case of emergency vaccines (six months)

Addressing seasonal and pre-pandemic influenza vaccines (expedited procedure)

Provision for parallel evaluation with NRA for high priority vaccines

Increased human resources Guidance documents produced Strengthening quality assurance system

SOPs Quality database Testing database Collaboration with EDM and EHT for development of

common database for monitoring submissions

Vaccines PQ- The way forward

Sustainability of the process: risk based approach:

High risk: products from manufacturers with limited/no experience with the PQ process/ the product in question, and/or the NRA is borderline with respect to functionalityMedium risk: manufacturer with or more prequalified vaccines and experience with product in question, or manufacturer is new to the system but supported by a JV with a with a well established mfg and NRA is functional.Low risk: Manufacturer is well established, more than one product prequalified, and may or may not have experience with product in question but has good research and development infrastructure. NRA is functional.

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Cu

rren

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pro

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lighter

Lig

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re*

*Strict compliance with post-marketing commitments and close FU of functionality of NRA

Building on vaccine PQ system to expedite MAA process in receiving countries

Countries require that only licensed vaccines be used

Manufacturers are asked to submit dossiers and pay fees

Licensing timelines may be very long Expertise for review not always available Confidentiality not always guaranteed Use of vaccine in country sometimes delayed

pending evaluation

Procedure for expedited approval of prequalified vaccines used in NIP

Intent of the procedure:

To comply with national regulations and international standards.

To continue to provide timely access to vaccines that meet standards of assured quality.

To enable countries to put more emphasis on post marketing surveillance system (AEFI).

Focuses on regulatory approval process and does not affect any post-approval activities in place.

Procedure for Expedited Approval of Prequalified Vaccines used in NIP

Scenario 1: Countries sourcing from UN agencies

For an expedited approval of WHO-prequalified vaccines that are sourced from UN procurement agency.

Scenario 2: Countries procuring directly

For an expedited approval of WHO-prequalified vaccines that are procured directly.

Provides guidance as to how NRAs of these countries can build on the processes in place for the WHO prequalificationto expedite the granting of regulatory approval for such products

Proposed implementation plan- SEARO 2008

Review national regulations, procurement process, vaccine import procedures, and any other processes as required.

Adapt and adopt guidelines as part of national regulatory process applied to vaccines for use in NIP.

Ensure smooth transition period. Encourage manufacturers to start the process. Receive applications from manufacturers Review applications and notify WHO & the manufacturer

(with copy to UN procurement agency if relevant). Add product information to national approved drug list. Encourage other manufacturers and repeat the process until

all pre-qualified vaccines (suppliers) receive expedited regulatory approval.

WHO website link to PQ and expedited approval procedures

http://www.who.int/immunization standards/vaccine_quality/pq_suppliers/en/index.html

Performance, Quality and Safety (PQS)Background- The interested parties

WHO: takes the duty to specify and verify cold chain and other products for immunization.

UN procurement agencies: are products fit for purpose?

Client countries: what’s the performance of the product, and where should it be used?

Industry: a fair basis for tendering and investing in development.

PQS Background- Product Information Sheets (PIS)

-Collaboration between UNICEF Supply Division and WHO

-Performance specifications and test procedures for

immunization-related products, including cold chain equipment.

-Main information for buyers of products used in NIP

-Conform products listed -Last PIS eddition 2000

PQS- Product categories

E01 > Cold rooms, freezer rooms and related equipment. E02 > Transport (guidance only – includes refrigerated

vehicles) E03 > Refrigerators and freezers, including solar (PV)

systems. E04 and E11 > Cold boxes, vaccine carriers and

biological specimen carriers. E05 > Ice packs E06 > Temperature monitoring devices. E08 and E13 > Single-use injection devices (AD syringes

for immunization and curative services). E10 > Waste management equipment.

PQS- Procedures

PQS works on a cost-recovery basis.

SOPs that detail the procedure (writing/amending specs, product review and disqualification,

test laboratory accreditation)

Product evaluation: Compliance with an ISO standard.

All pre-qualified products subject to annual review.

All product data sheets and guidelines web-based.

http://www.who.int/immunization_standards/vaccine_quality/pqs/en/index.html

PQS- Organizational Structure

Field MonitoringWorking Group

EHT

WHO Geneva

QAC TSC

UNICEFCopenhagen

SpecificationWorking Groups

PQSSecretariat

PQS Steering Group

Technicalspecialists

Testinglabs

Industryreps

External consultees

SIGNe-forum

Standardsbodies

output

dialogue

Key

institutional link

PQSdatabase

verificationprotocols

performancespecs

IVB/QSS

TechNet21e-forum

MoHs &end users

PATH

Approveddocuments

feedbackreports

Annual reviewreports

PQS- Enpoint

PQS website

Companyregister

Laboratoryregister

PQS Secretariat

PQS database

End users

Documentmanagement

Productregister

User feedback

Functions:- Browse current catalogue- Download PDF catalogue- Print PDF catalogue- Do criteria searches- Browse on-line guides- Submit product feedback

Public realm

Private realm

Functions:- Maintain registers- Manage correspondence- Generate catalogue updates- Manage user feedback- Traceability- Institutional memory