who prequalification of in-vitro diagnostics, medicines ... · “pqtm’s mission is to work in...

WHO PREQUALIFICATION TEAM

01 - 05 October 2018

WHO Prequalification of in-vitro diagnostics,

medicines, vaccines and vector control products

WHO Prequalification – contributing to access to

quality assured products and regulatory

harmonization

Deus Mubangizi

PQT Coordinator

[email protected]

WHO Technical Briefing Seminar Essential

Medicines and Health Products

Geneva, Switzerland

mailto:[email protected]


Outline of the presentation – PQ and its contribution to MDGs, SDG and 13th GPW – Organisation structure & procedures of PQT – PQ Transparency: Website and guidance documents Key numbers, product pipeline

– Updates on: New SRA definition New funding model and KPIs New PQT IT solution Collaborative registration procedure and harmonization

activities – WHO-PQT: Looking to the future – Take home messages

WHO PREQUALIFICATION PROGRAMME

3 • WHO-PQ contributed to the Millennium Development Goals (MDGs):

• Eight international development goals that 192 United Nations member states and at least 23 international organizations have agreed to achieve by the year 2015

4. Reduce child mortality

5. Improve maternal Health

6. Combat HIV/AIDs, Malaria and other diseases


4

WHO responded to the need of procurement agencies and WHO

Member States for quality-assured health products, by creating

and applying quality-assurance mechanisms

Diagnostics Vaccines Medicines

Origin:

Substandard

performance of

HIV assays in sub-

Saharan Africa

Response:

HIV Test Kit

Evaluation

Programme (1988)

PQ beginning:

2010

Origin:

Request by

UNICEF and

PAHO to

evaluate

quality, safety

and efficacy of

vaccines in the

context of

national

immunization

programmes

PQ beginning:

1987

Origin:

Request by

WHO MS to

assess the

quality, safety

and efficacy of

low-cost and

new FDCs

HIV/AIDS

generic

medicines

PQ beginning:

2001

Vector Control

Origin:

WHOPES set up in

1960 for evaluation

of pesticides for

public health. In

2015, WHO initiated

reforms to foster

innovation, improve

efficiency, assure

quality and align

with other PQ

programmes

PQ beginning:

2017


WHO-PQ contributes to the achievement of

Sustainable Development Goals (SDGs) http://www.un.org/sustainabledevelopment/sustainable-development-goals/

http://www.un.org/sustainabledevelopment/sustainable-development-goals/







6

WHO-PQ by making safe quality priority health products available

through efficient and scientifically solid assessment contributes to

achieving SDGs and UHC. SDG 3 targets by 2030 include:

reduce the global maternal mortality

end preventable deaths of newborns and children under 5 years of

age,

end the epidemics of AIDS, tuberculosis, malaria and neglected

tropical diseases and combat hepatitis, water-borne diseases and

other communicable diseases

ensure universal access to sexual and reproductive health-care

services, including for family planning

Achieve universal health coverage, including access to quality

essential health-care services and access to safe, effective, quality

and affordable essential medicines and vaccines for all

Support the research and development of vaccines and medicines for

the communicable and noncommunicable diseases that primarily

affect developing countries and provide access to medicines for all

Background

WHO PREQUALIFICATION TEAM 7

Key Themes of WHO’s 13th

General Programme of Work

2019-2023 Mission Promote Health - Keep the World Safe - Serve the Vulnerable

Strategic Priorities

Health Coverage: 1 billion more people with health coverage

Health Emergencies: 1 billion more people made safer

Health Priorities: 1 billion lives improved

Strategic Shifts

Set up

global

leadership

Focus

global

public

goods

on

impact

Drive impact in every country

Policy dialogue Strategic support

Technical assistance

Service delivery

Fragile health system Mature health system


8

PQ will contribute to the 13th General Programme of Work

(GPW 2019-2023) “The Organization will continue to support the availability of quality-assured

generic products for procurement by global agencies and countries through

the WHO prequalification Programme, which will evolve to meet the

changing health needs of countries.”

PQ through the EUAL will contribute to:

“ensure that populations affected by emergencies have rapid access to essential

life-saving health services.”

“Ensure that populations affected by health emergencies have access to

essential life-saving health services and public health interventions;”

PQ will contribute to the Heath priorities:

Women, children and adolescent health

Reduce maternal deaths (maternal mortality ratio) by 50% (RH)

Reduce the rate of under-five child deaths by 30% (D, Vx, Dx)

Increase degree to which contraceptive demand is satisfied through modern

methods by 10% (RH)

Increase coverage of cervical cancer vaccine by 40 percentage points (SBP)


9

PQ will contribute to the 13thGPW Heath priorities…

HIV, Tuberculosis, malaria, hepatitis, neglected tropical

diseases, antimicrobial resistance and polio At least 1 million fewer new HIV infections per year

Reduce deaths from tuberculosis by 50%

Reduce malaria deaths by 50%

Prevent half a million deaths per year from hepatitis B and C virus related

liver disease

Eliminate at least one neglected tropical disease in 35 countries

Eradicate polio: zero cases of poliomyelitis caused by wild poliovirus or

circulating vaccine-derived poliovirus

Increase coverage of treatment for multidrug- and rifampicin-resistant

tuberculosis to 80% of estimated incidence

Noncommunicable diseases (NCDs), mental health, substance use, road

traffic injuries

Reduce prevalence of raised blood pressure by 20%


10

PQ already designed to fit in the 13th GPW strategic shifts

Step global leadership:

PQ has been recognised as a stamp of quality and a point of reference

for QA for UN, International, regional and national procurement

Drive impact in every country:

Programmatic suitability built in Vx PQ

Focus on EID and RDTs for use in resource limited settings

Collaborative procedure, harmonization and capacity building

Placing countries at the centre:

“PQTm’s mission is to work in close cooperation with national regulatory

agencies and partner organizations to make quality priority medicines available for

those who urgently need them. This is achieved through assessment and inspection

activities, building national capacity for manufacture, regulation and monitoring

of medicines, and working with regulators to register those medicines

quickly.” https://extranet.who.int/prequal/content/overview-history-mission

Each bimonthly assessment session in CPH attracts ≥50 experts from

across the globe, ≥35 from LMICs and ≥15 from well resourced NRMAs –

best impact on capacity building and promoting convergence

https://extranet.who.int/prequal/content/overview-history-mission







Outline of the presentation – PQ and its contribution to MDGs, SDG and 13th GPW – Organisation structure & procedures of PQT – Transparency: Website and guidance documents Key numbers, product pipeline




Structure of the Prequalification Team

Prequalification Team

Vaccines Assessment

Medicines Assessment

Diagnostics Assessment

Inspections Vector control

Coordinator’s office


Product eligibility: Based on WHO Member States needs, WHO disease programmes set eligibility

criteria and determine priorities for prequalification

Diagnostics

In vitro diagnostics (IVD) & male

circumcision device (MCD)

Medicines Finished pharmaceutical

product (FPP), active pharm ingredient (API), quality control lab (QCL)

Vaccines

Vaccines (Vx), Immunization device

(ImD) & cold chain equipment (CCE)

Vector Control

VC Products (VCP) (VCPs: FPPs & APIs)

Larvicides Long-lasting

insecticidal nets Indoor residual

spraying products Space spraying

products

24 priority diseases, covering vaccines required for routine immunization

Eligibility criteria for evaluation includes NRA functionality & programmatic suitability

HIV/AIDS Malaria Tuberculosis Diarrhoea Influenza Reproductive

Health Neglected tropical

diseases (NTDs)

HIV/AIDS Hep B Hep C HPV Malaria G6PD Cholera Syphilis

80 IVD 2 MCD 312FPP 129 API

44 QCL

148 Vx (327 Vx*)

400 ImDs/CCE

71 VCP

(Cumulative numbers of PQed products: August 2018)

Hep B Hep C

NEW: as of Jan 2017

Vx*: covering all dosage forms 13


14

For each type of product, prequalification includes a comprehensive dossier

assessment and a manufacturing site inspection, as well as other product-

specific elements of evaluation

Prequalification workflow

NRA functionality

Programmatic suitability

Lab

evaluation

Dossier

submission

Screening

Assessment Inspection

CAPA

Follow-up

inspection

CAPA

Prequalification decision

Pre-submission

form

Maintenance and monitoring Collaborative registration

Routine inspections Special inspections Handling complaints

Variations Annual reports Requalification

Inspection closing letter Letter of prequalification Web listing Public reports (WHOPAR, WHOPIR)

Follow-up NOC


WHO-PQm process

Expression of Interest

Acceptable

Additional information and data

Corrective actions

Compliance

Assessment Inspections

Prequalification

Maintenance and monitoring Collaborative registration

Product dossier SMF FPP: GMP

API: GMP CRO/BE: GCP/GLP

Closing letter WHOPIR

Routine inspections Special inspections Handling complaints

Follow-up NOC

Variations Requalification


WHO-PQT-Rx: Inspection Timelines

• First inspection: 6 months from dossier acceptance for assessment or from site confirming it is ready for inspection.

• Notification: 1 – 2 months before inspection.

• Onsite days: 3 – 5 days based on scope and complexity.

• Report: 30 days from last date of inspection.

• CAPAs: 30 days from receipt of report (max 2 rounds, comprehensive, soft and not hard copies)

• Closing of inspection: 6 months from inspection.

• Follow-up inspection: 6 months from inspection

• Routine inspection: – Due date 1 – 3 years from the previous inspection (risk based) – Actual ± 3 months from due date.


17

Inspections – Team and scope

• Team: qualified and experienced inspectors

• WHO representative (qualified inspector)

• Inspector from well-established inspectorate (Pharmaceutical

Inspection Cooperation Scheme countries – PIC/S)

• National inspector/s invited to be part and observe the inspection

• Observer from recipient/developing countries (nominated by

NMRA of the country)

• Scope

• Compliance with guidelines: GMP for API and FPP sites, GCP

for CROs, GLP for FPP/API factory QCL, CRO-BAL, NQCL,

IQCL

• Data integrity verification – data manipulation, falsification,

(validation, stability, clinical, bioanalytical)

2. Prequalification process


USP BP

Ph. Eur. Ph. Int.

International norms, standards and guidelines used in PQT inspection activities to ensure wide applicability

Other guidelines e.g. ICH, ISO

http://www.who.int/prequal/assessment_inspect/info_inspection.htm#2

http://apps.who.int/prequal/assessment_inspect/info_inspection.htm

http://apps.who.int/prequal/assessment_inspect/info_inspection.htm


Prequalification Programme: Use of Inspection

reports from other NMRAs

Inspectorates whose reports are recognized:

√ PICS member inspectorates

√ EU (EDQM + EMA)

√ USFDA – now also member of PICS

What GMP evidence to submit:

– SMF – Up-to-date

– Inspection report - conducted NMT 2 years

• + CAPAs to deficiencies + final conclusion

– Product Quality Review – not more than 1 year old

Review of the report:

scope covered the specific FPP or API

Is comprehensive and supports the final outcome.

PQP reserves the right to inspect the FPP/API manufacturer – as long as product is active in WHO-PQP.

on-going GMP compliance will be confirmed by WHO


Risk-based approach in:

definition and classification of deficiencies

• Deficiencies are descriptions of non-compliance with GMP requirements.

• A distinction is made between deficiencies as a result of: - – a defective system or,

– failure to comply with the system.

• Deficiencies may be classified as: – Critical Observation – potential risk harm to the user

– Major Observation – major deviation from GMP/GCP

– Minor or Other Observation – minor deviation from GMP


21 Risk-based approach in:

Conclusion following an inspection

• When there are "other" observations only: – considered to be operating at an acceptable level of compliance with

WHO GMP.

– The manufacturer is expected to provide CAPAs.

– CAPAs are evaluation and followed up during the next routine inspection.

• When the are "other" and a few "major" observations: – compliance with WHO GMP is made after the CAPAs have been

assessed.

– CAPAs for majors to include documented evidence of completion.

– CAPAs paper evaluated ± an on-site follow up inspection.

• When there are "critical" or several "major" observations:

– considered to be operating at an unacceptable level of compliance with WHO GMP guidelines.

– Another inspection will be required


• Website: https://extranet.who.int/prequal/

• Email: [email protected]

| WHO Prequalification of Medicines 23 Further information

https://extranet.who.int/prequal/

mailto:[email protected]


24


25

Through the prequalification process, WHO has made available

numerous quality-assured products to WHO Member State markets

At the close of August 2018, PQT’s list of prequalified products included:

Key numbers

Medicines

412 FPPs 129 APIs

44 QCLs

Diagnostics

81 IVDs 2 MCDs

Vaccines

148 Vx 400 ImDs

Vector control

71


1. Oral hormonal contraceptives #FPPs PQ’d #FPPs under assessment

Ethinylestradiol + desogestrel, tablet 30 micrograms +150 micrograms

4 2

Ethinylestradiol + levonorgestrel, tablet 30 micrograms + 150 micrograms

8 2

Levonorgestrel, tablet 30 micrograms 2 -

Levonorgestrel, tablet 750 micrograms (pack of two) 3 1

Levonorgestrel, tablet 1.5 mg (pack of one) 3 2

Norethisterone, tablet 350 micrograms 2 -

Norgestrel, tablet 75 micrograms - -

Lynestrenol, tablet 500mcg 1 -

https://extranet.who.int/prequal/key-resources/documents/summary-fpps-and-apis-invited-prequalification
















http://www.who.int/diagnostics_laboratory/pq_status/en/




Expert Review Panel (ERP)

• ERP established in April 2009 by GF and WHO.

• Objective: To review the potential risk/benefit for FPPs not yet WHO-prequalified or SRA-authorized, for the purpose of providing information to aid procurement decisions

• ERP risk categories developed by WHO/RHT.

• ERP is coordinated by the WHO/RHT as a service to interested procurers

• ERP reviews are done by experienced regulatory professionals

• Procurer responsible for all communications with manufacturers and procurement decision.


29

WHO prequalification serves as a guarantee of good quality for

health products, is a reference in terms of internal technical

expertise and has the power to convene external expertise

Benefits for stakeholders

Access to quality-assured products, adapted to their specific needs

Accurate prevention, diagnosis, and treatment

Patients

List of prequalified products

Increased availability of quality-assured products

Monitoring quality of prequalified products

Healthy market: diversity and affordability of products

Donors, procurers and UN agencies

Reduced burden for regulatory approval

Increased regulatory capacity & harmonization of regulatory practices in WHO MS

Implementation of specifically developed and road-tested international guidelines

Access to quality-assured products

WHO Member States & NRAs


30

WHO prequalification serves as a guarantee of good quality for

health products, is a reference in terms of internal technical

expertise and has the power to convene external expertise

Benefits for stakeholders

Access to donor-sponsored tenders

Faster regulatory approval

Timely assessment of variations and changes

International quality-assured product status (improved image)

Recognition of GMP status, beyond prequalified products

Increased capacity in quality management systems

Target Product Profiles

Harmonization of regulatory practices within WHO Member States

Reduced operating and manufacturing costs

Manufacturers

International recognition of prequalified QCLs

Technical assistance and scientific advice

QC labs


New SRA definition

Recommendations from the 52nd ECSPP

• That the term “stringent regulatory authority (SRA)” be replaced by

“WHO-Listed Authority”.

• That those NRAs currently identified as “SRAs” in accordance with the

current interim definition be regarded as WHO-Listed Authorities.

• That the designation of additional NRAs as WHO-Listed Authorities

should be based on an assessment against the Global Benchmarking

Tool (GBT), as well as successful completion of an agreed and

transparent confidence-building process.

• That a procedure for listing be developed accordingly through the usual

public consultation process.”

-Draft WHO Global Benchmarking Tool (GBT) version VI was published

comments in January 2018 to end of February. The comments are currently

under consideration


New Funding Structure for PQ • Objectives:

– ensure the financial sustainability of WHO’s PQ

– to make PQ better equipped to address current global quality challenges,

– to lay the ground for strengthening and expanding services provided, and

– to improve financial predictability and transparency

• Fees structure:

– Designed to ensure equity among manufacturers

– modelled on the practice of NRAs around the world,

• Fees principles and structure:

– product nature: active pharmaceutical ingredient (API) or finished pharmaceutical product (FPP);

– type of assessment: full or abridged assessment of new application, or assessment of major variation;

– an annual maintenance fee tailored to whether the initial assessment was full or abridged.

Diagnostics Model went live on 1 August 2018

New application

full assessment

New application

abridged assessment

Annual fee Change

assessment fee

5,000 + 12,000 8,000 4,000 3,000


PQT – revised fee model - When are fees payable?

• Screening, application/evaluation fee, inspection fee:

– Payment should be made within 15 days of receipt of the invoice from WHO

– Application/evaluation (including variation) fee for medicines invoiced after the application has been successfully screened and accepted for assessment

– Screening, application and inspection fees for vaccines are invoiced before start of activity

• The annual fee:

– for medicines and APIs is fixed, whereas for vaccines the annual levy is linked to sales from PQ’d vaccines (PQ enabled sales).

– The annual fee is invoiced by the 1 October each year for all products that have been present on the list of prequalified APIs, FPPs or vaccines for 12 months or greater as of the 1 September of that year. Payment of the annual fee should be made before 30 November of the calendar year in which the invoice was issued.


• Certain products with low commercial value will be eligible for reduced fees or a waiver of the fees*.

– This is to ensure that fees to do not become an impediment

to access.

– Equally, waiver should not compromise the objectives of

equity (based on actual sales and profits) and contribution

to the financial sustainability of related PQ activities.

• A reduced annual fee or waiver of the annual fee will be

granted following an application.

*https://extranet.who.int/prequal/sites/default/files/documents/PQ_Fees_Annex_092017.pdf

Principles for reduced and waivers of annual fees for

medicines manufacturers

http://who.int/medicines/news/finance-arrangements-prequal-med/en/


1. A reduced annual fee or waiver of the annual

fee will be granted following an application.

2. This information will be reviewed to inform the decision on the reduction/waiver request, putting into consideration:

• supply security (need plus availability of alternative sources)

plus

• equity and fairness to all players – based on actual sales and profit.

37

Criteria for granting reduced fees and waivers


New PQ funding model: Updates

• There has been good response to the new

funding model and fee structure

• There is no apparent impact on the number of

applications received.

• There were some products withdrawn but these

were mainly related to changes in the treatment

guideline and EOI and hence reduced demand.

• Reduction or waiver of annual fees have been

granted where this was deemed justified.


40

2014 2015 2016 2017

FPP Received* 66 56 65 52

FPP accepted for assessment 65 49 63 50

APIs Received* 23 26 24 22

APIs accepted for assessment 23 24 23 22

0

10

20

30

40

50

60

70

No

of

app

licat

ion

s

Trends in application submitted to PQ


Reasons for introducing new performance metrics

Increased transparency for manufacturers and other

stakeholders following the introduction of the new fee model

Advantages of those new performance indicators

Following up the progress of applications throughout the PQ

pipeline (as opposed to only measuring timeline at the end of the

PQ assessment)

Monitoring performance of the different components of the PQ

assessment

Measuring performance of processes controlled by WHO PQ

(limited external influence on performance)

- Reasons & Advantages -

41

* https://extranet.who.int/prequal/content/key-performance-indicators-who-prequalification

Key performance Indicators (KPIs)*

https://extranet.who.int/prequal/content/key-performance-indicators-who-prequalification












Key performance Indicators (KPIs)

42

Time to prequalification (from acceptance for assessment to prequalification) for applications accepted after 1 January 2015, 2016 for APIs

100 Number of products PQed - -

110 Median WHO PQ time - N/A

111 Median manufacturer PQ time - N/A

112 Median total PQ time - N/A

KPI 1% of products prequalified at or below target WHO

PQ time

70%

(30% for

APIs)

Full assessment:

270 calendar days, 350 calendar days for IVDs PQed

without the alternative laboratory mechanism

Abridged assessment:

100 calendar days, 180 calendar days for IVDs PQed

without the alternative laboratory mechanism

Annual PQ cohort (products prequalified in a calendar year)

Time to ‘screening first action’

200 Number of PQ applications submitted - -

210 Number of ‘screening first actions’ - -

KPI 2% of 'screening first actions' taken at or below

target time80% 30 calendar days

Submission cohort (PQ applications submitted for PQ assessment in a calendar year)


Key performance Indicators (KPIs)

43

Time to 'first action’

300 Number of PQ applications accepted - -

310 Number of ‘dossier first actions’ - -

KPI 3.1% of ‘dossier first actions’ taken at or below target

time80%

90 calendar days, 120 calendar days for FPPs & APIs

(due to fixed assessment sessions)

320 Number of ‘inspection first actions’ - -

KPI 3.2% of ‘inspection first actions’ taken at or below


330 Number of 'laboratory first actions’ - -

KPI 3.3% of 'laboratory first actions’ taken at or below


Assessment cohort (PQ applications accepted for PQ assessment in a calendar year)

Time to ‘post-PQ change first action’

400 Number of post-PQ change applications assessed - -

410 Number of ‘post-PQ change first actions’ - -

KPI 4% of 'post-PQ change first actions' taken at or

below target time80%

APIMF|major (minor) amendment: 90 (60) calendar days

APIMF|immediate notification: 45 calendar days

FPP|major (minor) variation: 90 (60) calendar days

FPP|immediate notification: 45 calendar days

IVD|reportable change: 90 calendar days

Vx|major variation, type A: 90 calendar days

Change cohort (post-PQ change applications accepted for change assessment in a calendar year)


Time to prequalification of medicines (FPPs, median,

full assessment) 2010-2017

0

100

200

300

400

500

600

700

800

900

1000

2010 2011 2012 2013 2014 2015 2016 2017

WHO time Company time Total time to PQ

270 days


285

147

203

131 122

162

238

194

544

289

488

246

307

263

467

276

0

100

200

300

400

500

2010 2011 2012 2013 2014 2015 2016 2017

DA

YS

YEARS

Time to Vaccines Prequalification

WHO average time Total time to PQ

270 days


PQ measures to reduce manufacturer time, and total

time to prequalification - PQ provides advice at any stage before, or after submission (F2F-meetings,

TC, e-mails, specific pre-submission meetings) – PQ is accessible.

- Pre-submission meetings now mandatory for all new applicants

- Strict response timelines for manufacturers introduced – 30, 60 or 90 days

depending on the deficiencies

- Common Deficiencies in FPP Dossiers – additional guidance to manufacturers

- Feb 2018

- 1st PQ Quality workshop for manufacturers held in July 2018

- PQ develops product-specific guidance, on an ongoing basis, e.g. BE study

design, Q&As (ZnSO4, MgSO4, RH products, HVAC, TSS, TGS, etc.).

- PQ reviews final draft BE study protocols, before study start.

- PQ does an in-depth screening of dossiers, to ensure that dossiers are

complete before start of full assessment. This feedback is provided to the

applicant. The screening checklist is on the PQ website.

- Model dossier in CTD format to guide applicants (2016) and for IVDs

- Alternative lab performance evaluation

- Expansion of the expert pool – annual clearance


• Fast track to prequalification = Good quality dossier

at submission + prompt, complete, good-quality

responses to PQ’s questions, throughout the

process.


Universally accepted comparator:

enables one BE study to be conducted for use across countries

enables such generic products to be interchangeable.

Lists for comparator products for each treatment area

available on PQTm website which is updated regularly https://extranet.who.int/prequal/key-resources/documents/application-reference-scaled-criteria-auc-bioequivalence-studies-conducted

Not all products listed in PQ Expressions of Interest

(EOIs) will have comparators indicated on these lists

For example, some dispersible products do not have

comparable references so conventional product may have

to be used as comparator

If a comparator is not listed, consult PQTm

Comparator products

https://extranet.who.int/prequal/key-resources/documents/application-reference-scaled-criteria-auc-bioequivalence-studies-conducted



















A regulatory authority that is

a member of ICH prior to 23 October 2015, namely: the US

Food and Drug Administration, the European Commission

and the Ministry of Health, Labour and Welfare of Japan also

represented by the Pharmaceuticals and Medical Devices

Agency; or

an ICH observer prior to 23 October 2015, namely: the

European Free Trade Association, as represented by

Swissmedic and Health Canada; or

a regulatory authority associated with an ICH member

through a legally-binding, mutual recognition agreement prior

to 23 October 2015, namely: Australia, Iceland, Liechtenstein

and Norway.

Comparator products:

Where can they be purchased?


Biowaivers In vitro approaches for demonstrating safety and

efficacy of products in lieu of conducting in vivo bioequivalence studies

Biopharmaceutics Classification System (BCS) –

based biowaivers Suitable for products containing eligible APIs Abbreviated submission if API is on the eligibility list

Additional strengths biowaivers Suitable for additional strengths in a product line when

one of the strengths has shown in vivo bioequivalence

to the comparator


BCS-based Biowaivers

eligible APIs

Medicines for HIV/AIDS and

related diseases Abacavir sulfate (Class III)

Emtricitabine (Class I)

Fluconazole Polymorphs II & III (Class I)

Lamivudine (Class III)

Stavudine (Class I)

Zidovudine (Class I)

Neglected Tropical Disease

medicines

Diethylcarbamazine (Class III)*

Anti-tuberculosis medicines Ethambutol (Class III)

Isoniazid (Class III)

Levofloxacin (Class I)

Linezolid (Class I)

Moxifloxacin HCl (Class I)

Ofloxacin (Class I)

Pyrazinamide (Class III)


BCS-based Biowaivers Do not use classifications provided in 2006 WHO

TRS 937, Annex 8 ECSPP overseeing the development of a new

biowaiver classification list Living document

Information on equilibrium solubility experiments Appendix 2 of WHO TRS 1003, Annex 6 (2017)

Document with more technical detail under

development by ECSPP


PQ of Vector Control Products: Progress

56

PQT-VC Prequalification

Established Single Point of Entry to WHO Data requirements determined and under review 125+ manufacturers meetings Operations manual developed 89 product applications for conversion received in PQ 71 products prequalified 7 new products applications under review 1 active ingredient under re-evaluation Website developed and information posted, e.g.: guidance, process, meetings Communication strategy under development, including Website re-design

PQT-VC Stakeholders Meeting with procurement

agencies Manufacturers meetings Conferences and WHO

organised meetings

PQT-VC Assessors Group SOPs for evaluation process,

documentation development and decision making

2nd Assessors Group meeting held in Arusha, Tanzania

3rd Assessors meeting planned for 26-30 November


• New PQT IT solution for all PQT streams is under

development

• Medicines platform will be launched Q1/Q2 2019

• Applicants will upload all their submissions to the IT

platform

• Applicants will need to create accounts to be verified

before submission

• Communication will be done using system communicator.

• System will allow applicant to monitor progress of their

applications.

• eCTD software under investigation

57

New IT platform


Regional harmonization initiatives

ASEAN SIAHR Project

PANDRH African Vaccine Regulators Forum (AVAREF)

African Medicines Regulatory Harmonization Project (AMRH)


59

The collaborative procedure enables NRAs to accelerate the

registration of prequalified products so that they can enter local

markets more quickly

Collaborative procedure

Procedure in

development

Ongoing discussions

with NRAs

Diagnostics

WHO PQ shares the reports that served as the basis for the prequalification

decision, so that NRAs do not conduct assessment and inspections

National registration based on PQT evaluation

Started in 2012

As of February 2018:

31 countries

participating

299 registrations in

more than 20

countries for over73

different products

Medicines

Procedure published

in 2007, harmonized

for medicines and

vaccines as of 2014

In 2015:

Adopted by expert

committee (ECBS)

Vaccines

Pri

ncip

les


Participating NMRAs

1. Armenia 2. Botswana 3. Burkina Faso 4. Burundi 5. Cameroon 6. *Caribbean Community (CARICOM) 7. Cameroon 8. Cote d'Ivoire 9. Dem. Rep. Congo 10. Eritrea 11. Ethiopia 12. Georgia 13. Ghana 14. Kenya 15. Kyrgyzstan 16. Lao PDR * CARICOM Member States: Antigua and Barbuda, Bahamas, Belize, Dominica, Grenada, Haiti, Jamaica, Montserrat, Saint Lucia, St. Kitts and Nevis, St Vincent and the Grenadines, Suriname and Trinidad and Tobago Associate Member States: Anguilla, Bermuda, British Virgin Islands, Cayman Islands and Turks and Caicos Islands

17. Madagascar 18. Malawi 19. Mali 20. Mozambique 21. Namibia 22. Nigeria 23. Pakistan 24. Philippines 25. Senegal 26. Sierra Leone 27. South Africa 28. Sri Lanka 29. Tanzania 30. Thailand 31. Uganda 32. Ukraine 33. Zambia 34. Zanzibar 35. Zimbabwe

As at 16 May 2018


• Voluntary

• Product and registration dossier

in countries are 'the same' as

prequalified by WHO.

• Shared confidential information

to support NRA decision making

in exchange for accelerated

registration process

• 'Harmonized product status' is

monitored and maintained

KEY Principles of WHO PQ Collaborative Registration Procedure

WHO PREQUALIFICATION PROGRAMME 62

Manufacturer informs PQP about national submission

and

gives consent with information sharing

Participating NMRA confirms its interest to

participate in procedure for specific product

PQP shares with participating NMRA

outcomes of assessment and inspections

Participating NMRA reviews WHO PQP outcomes,

decides within 90 days decides upon the national

registration and informs PQP about its decision

Steps of the procedure: registration

PQ product is submitted for national registration

to NMRA participating in the procedure

NMRA is informed about the interest to follow PQP


WHO PQ CRP: Documents shared

Assessment reports (All reports generated through the review process)

Inspections reports (API, FPP and CROs)

WHO Quality Information Summary (QIS)

NB: This information is useful for NRA for marketing authorisations


What has been achieved through CRP: as of February 2018

299 registrations

Median = 85 days

35 plus countries

manufacturer

WHO

NRA

Before CRP – 2 months to 10 years

Days

Target


WHO-PQT: Looking to the future

– Continue the assessment of current scope of products by PQT at HQ – Rx,

VCP, Vx and Dx.

– Complete the transition from WHOPES to PQ-VCP and streamline

procedures

– Gradually expand scope of PQ to cover products, e.g. on the EML through: • setting up criteria for prioritisation and gradual scope expansion

• NCDs: BTP/SBP pilot launched, under discussion (Diabetes/Insulin, Hypertension, other cancer medical products)

• IVDs for Cholera, TB, NCDs, NTDs/Dengue, measles, Rubella, etc. Consultation scheduled for Q42018

– Gradually expand the mechanisms for PQ through:

• Expanding the abridged assessment of products approved by WHO Listed

Authorities as defined from time to time. • Reliance on regional-network-joint-assessments that have been quality assured by PQ with cooperation from RSS -

medicines.

– Strengthen mechanisms to evaluate new products developed with special focus on LMICs and emergencies – including cooperation with EU Art58, Swiss medic MAPGHP.

– Expand risk based approaches like ERP, ERPD, EUAL and other mechanisms for Snake anti-venoms, Rabies vaccine, RSV, DAT, other products on the EML.


To summarise, WHO Prequalification:

• Current scope: IVDs, MCDs, FPPs, APIs, QCLs, vaccines, immunization devices, VCPs and VCIs

• Contributes to achieving SDGs and UHC

facilitates access to quality assured priority health products

• Role recognized by WHO 13th General Programme of Work (2019 – 2013):

The Organization will continue to support the availability of quality-assured generic products for procurement by global agencies and countries through the WHO prequalification programme, which will evolve to meet the changing health needs of countries.

• Already designed to fit in the WHO 13th GPW strategic shifts:

Step up global leadership - recognized as a stamp of quality

Drive impact in every country and placing countries at the centre:

Doing it with NMRAs – best impact on capacity building and promoting convergence

Programmatic suitability of vaccines

Focus on IVDs - POC, EID and RDTs - for use in resource limited settings


Take home messages

PQ responded to needs of members states and contributed to

objectives and targets of MDGs and SDGs

The WHO 13th GPW (2019 – 2013) recognises continued

need for PQ which will evolve

PQ has been recognized as a stamp of quality and a point of

reference for QA for UN, International, regional and national

procurement

PQ has been instrumental in building national capacity for the

manufacture, regulation and monitoring of medicines –

promoting harmonization and convergence

PQ has put in place measures to improve sustainability and

transparency

PQ is evolving and adapting to the needs of the time and

future


Contacts 69

Diagnostics

Irena Prat

[email protected]

Medicines

Matthias Stahl

[email protected]

Vaccines

Carmen

Rodriguez Hernandez

[email protected]

Inspections

Johanna Gouws

[email protected]

Technical assistance &

laboratories

Rutendo Kuwana

[email protected]

Prequalification team

Deus Mubangizi

PQT Coordinator

[email protected]

Vector control

Marion Law

[email protected]