prequalification of vaccines for un supply, facilitation ... · dr. nora dellepiane, scientist...

Dr. Nora Dellepiane, Scientist WHO/IVB/QSS 31 March 2010

Prequalification of vaccines for UN supply, facilitation of registration of prequalified

vaccines

by Dr. Nora Dellepiane

Les Pensières 29-31 March, 2010

Dr. Nora Dellepiane, Scientist WHO/IVB/QSS 6 January 2009


Outline of presentationOutline of presentation

� Conceptual description of the WHO prequalification procedure� Purpose

� Principles

� Procedure

� Its added value

� Pre-conditions for submission

� Assurance of Quality of UN supplied vaccines

� Procedure for expedited review of PQd vaccines� Scope and conditions

� Criteria for use

� Requirements

� Outcome and timeframes


PURPOSE OF THE PQ PROCEDUREPURPOSE OF THE PQ PROCEDUREPURPOSE OF THE PQ PROCEDURE

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 meet WHO recommendations and are suitable for the target population, at the recommended schedules with appropriate concomitant products and meet the needs of the programmeEnsure continuing compliance with specifications and established standards of quality


PRINCIPLESPRINCIPLES

GMP

Reliance on NRAof exporting country

Meeting WHO requirementsand tender specs

Consistency of finalproduct characteristics

Clinical data


PRINCIPLES (cont)PRINCIPLES (cont)

Reliance on the NRA of the exporting country

� NRA must be functional as a result of evaluation against the WHO assessment tool

� Functionality status needs to be sustained

� Vaccine needs to be licensed by the NRA

� Continued regulatory oversight by NRA is required as well as communication with WHO about potential problems with the vaccine


• Vaccine is licensed by the responsible NRA (Scientific opinion by EMA accepted)

• WHO guidelines/recommendations available

• Listed in the vaccine priority list (low priority vaccines may be postponed)

Pre-conditions for submissionPre-conditions for submission


PROCEDUREPROCEDURE

� Scientific and technical review of a Summary dossier (Product Summary File)

� Testing of final product characteristics

� Consultation with NRA of exporting country

� Audit of manufacturing facilities (jointly with NRA)


ADDED VALUE OF THE PQ PROCEDUREADDED VALUE OF THE PQ PROCEDUREADDED VALUE OF THE PQ PROCEDURE

What is different in the PQ procedure from the Marketing Authorization evaluation?

� Vaccine meets WHO requirements and tender specifications

� Relevance of the clinical data to the target population

� Immunization schedules and dosage compatible with those used in National Immunization Programmes

� Feasibility of co-administration with other vaccines

� Stability profile: Cold chain requirements/ suitability for use under field conditions, type of VVM to be used


ADDED VALUE OF THE PQ PROCEDURE (cont)

ADDED VALUE OF THE PQ PROCEDURE ADDED VALUE OF THE PQ PROCEDURE (cont)(cont)

What is different in the PQ procedure from the Marketing Authorization evaluation?

� Packaging: Volume of cold space required

� Suitability of presentation/primary packaging

� Multidose vial policy applicable or not

� Adequacy of information on labels for vials and boxes and package inserts: all relevant information is stated, insert reflecting product characteristics and do not contradict model inserts and WHO policies. Availability in all required languages

� Shipping boxes validated


Assurance of Quality of UN supplied vaccines

Assurance of Quality of UN supplied vaccines

Validation assessed---Shipping boxes

AlwaysSometimesConsistency testing

Compliance with WHO standard

Compliance with National standard

GMP

Critical: vials and AD syringesHighly flexiblePresentation

Assessed---Applicability of multidosevial policy

Suitability for developing countries + VVM

Suitability for exporting country

Stability profile & shelf life

Relevance to schedules used in UN country settings

Relevance to schedules used in exporting country

Schedule, co-administration

Review focused on data relevant to UN target population

Review focused on data relevant to population in producing country

Clinical data

---Exhaustive reviewNon-clinical data

Review of summary information

Exhaustive reviewChemico pharmaceutical and biological

WHO prequalification procedure

Exporting Country NRAAspects considered


Resources/ expertise required to carry out a MA evaluation

Resources/ expertise required to carry out a MA evaluation

� Multidisciplinary team of scientists including� experts in vaccinology, microbiology, infectious diseases, immunology, epidemiology, toxicology, pharmacology, biostatistics and clinical trial design.

� Inspectors trained in Good Manufacturing and good Laboratory Practices

� Testing capacity: facilities, equipment, infrastructure, consistent quality of reagents, materials, Quality Systems in place. Conditions to achieve validated/reliable testing methods. Testing requires a minimum number of tests to be conducted yearly in order to maintain expertise and reliability of test results.


Required functions according tovaccine source


Clinical oversight

Producing country

Direct purchase

UN agency supply

Regulatory Inspections

TestsLot release

PMSMAA & licensing

Vaccine Source R

egu

latory S

ystem

Exporting country + WHO-PQ

Exporting Country




Clinical oversight

Producing country

Regulatory Inspections

TestsLot release

PMSMAA & licensing

Vaccine Source

Resources and expertise required to secure all functions

Reg

ulato

ry System

Responsibility for domestic supply and eventual exports

No other authority can replace any of the functions


Countries procuring vaccines through UN agencies

Countries procuring vaccines through UN agencies

Post Marketing Surveillance system requires

� experts in vaccinology, microbiology, infectious diseases, immunology, epidemiology, toxicology, pharmacology, biostatistics and clinical trial design.

� AEFI reporting system in place

� Ability to perform case investigation

� Regulatory/Quality evaluation

� Communication strategyBUT: Product already licensed by functional NRA and assessed by WHO

Resources and expertise neededNo other country can replace this functionWHO can help to certain extent

Therefore Marketing AuthorizationProcess can be simplified,expedited

WHO offers to countries a procedure to expedite the

review process of imported prequalified vaccines with view to granting a MA

MA evaluation requires


Countries procuring vaccines directlyCountries procuring vaccines directly

Access to qualified laboratory when needed is enough

Needs to be done based on critical review of SLP Expertise and resources required

Same concepts as for UN procuring apply

TESTINGLOT RELEASEMAAPMS

These countries can also benefit from theuse of an expedited procedure forreview of imported PQd vaccines


Procedure for expedited review of imported prequalified vaccines for use in national immunization programmes. WHO/IVB/07.08

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


Procedure for expedited review of PQd vaccinesSCOPE AND CONDITIONS

Procedure for expedited review of PQd vaccinesSCOPE AND CONDITIONS

� Intended for countries that source their vaccines through UN agencies, or who use the WHO prequalification as a basis for selection of vaccines for purchase

� It provides guidance on how NRAs of such countries can expedite the regulatory review for such products.

� Applies to vaccines used in National Immunization Programmes

� Not intended to affect in any way post-approval activities in place in these countries

� Countries intending to use the procedure should ensure that their national regulations contain provisions to allow to shorten the normal regulatory approval process.


Criteria for useCriteria for use

Scenario 1

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

Scenario 2

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


Requirements for licensing vaccines from PQ sourcesRequirements for licensing vaccines from PQ sources

1. Same as in scenario 12. Same as in scenario 13. Same as in scenario 14. Same as in scenario 1in addition to

ensure consistency with national tender specifications if different

5. Same as in scenario 16. Same as in scenario 17. Same as in scenario 18. Same as in scenario 1

Scenario 1

1. Check prequalification status2. Request product samples, product

inserts, NRA lot release certificates from the country of origin, a list of countries where the product is licensed and marketed, and summary lot protocols of three final lots.

3. Visual inspection of samples4. Review summary lot protocols

(check specifications), labels, boxes and inserts against WHO model. Ensure presence of VVM

5. Prepare report of compliance (non-compliance)

6. If compliant, issue Certificate of Approval

7. Inform manufacturer and WHO8. If novel vaccine with limited clinical

data, review of clinical data may be needed

Scenario 2


Outcome and timeframes for expedited review procedureOutcome and timeframes for expedited review procedure

1. Waiver of fees from countries is requested

2. Total timeframe for evaluation should not exceed 30 days unless clinical data need to be reviewed, in which case timeframe is extended to 120 days

3. If info submitted by manufacturer is not complete, clock is halted awaiting Completion.

4. Inform WHO that the procedure is being adopted. WHO will keep NRA informed of updates regarding PQ status.

5. Countries should not stop use of PQ vaccines not yet registered in the country

1. Same as in scenario 12. Same as in scenario 1. If country

has testing capabilities and vaccine samples will be tested as part of the registration process, 90 days instead of 30 will be the timeframe for completion of procedure, except when clinical data need to be reviewed (120 days)

3. Same as in scenario 14. Same as in scenario 1;5. Same as in scenario 16. Same as in scenario 1

Scenario 1 Scenario 2

prequalification of vaccines for un supply, facilitation ... · dr. nora dellepiane, scientist...

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