1. A catalyst for Quality Local Production – factors for success
WHO Prequalification
A catalyst for Quality Local Production – factors for success
Africa Pharma Conference 2019
Johannesburg, South Africa
Deus Mubangizi
PQT Coordinator
4 – 5 June 2019

2. Outline of the presentation
Purpose and status of national regulation and impact on access
WHO PQ – responding to the need for access to quality assured health products
PQ scope, procedures, workflow and pipeline
PQ timelines, challenges and response measures
Noted challenges to manufacturers and proposed solutions
Benefits of PQ
WHO-PQT: Looking to the future
Take home messages

3. Purpose of regulation: Promoting and protecting public health
                                     
Promoting Health: Access
Protecting Health: Market Control

4. 1 2 3 4 WHO GBT Performance Maturity Levels ISO 9004
Continual improvement emphasized
No formal approach
Reactive approach
Stable formal system approach
WHO GBT
Some elements of regulatory system exist
Evolving national regulatory system
that partially performs essential regulatory functions
Stable, well-functioning and integrated regulatory system
Regulatory system operating at advanced level of performance and continuous improvement
Can ensure the quality of products if rely on ML 3/ ML 4 regulatory systems
Target of WHA
Resolution 67.20
Advanced and well resourced regulatory systems
100
Countries 44
Countries 50
Countries
74%
26%
12/08/2019 4

5. Status of National Regulatory Systems by Maturity Levels (ML) 194 WHO Member States
Facts
51% have limited capacity to perform core regulatory functions
Applicants face a landscape of disparate regulations, frequent delays and limited transparency
Implications
Access to quality assured and safe medicines and vaccines in countries at ML 1 & 2
high risk of SF medical products
Cost of inefficient regulatory systems drives up prices
Regulators less prepared for public health emergencies

6. Background
WHO responded to the need of procurement agencies and WHO Member States for quality-assured health products, by creating and applying quality-assurance mechanisms
Vaccines
Medicines
Diagnostics
Vector Control
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 in response to MDGs
PQ beginning:
2001
Origin:
Substandard performance of HIV assays in sub-Saharan Africa
Response:
HIV Test Kit Evaluation Programme (1988)
For initiation & monitoring Tx
PQ beginning:
2010
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

7. Prequalification decision Expression of interest (EOI)
Prequalification workflow
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
NRA functionality
Programmatic suitability
Lab evaluation
Dossier submission
Screening
Assessment
Inspection
capa
Follow-up inspection
Prequalification decision
Expression of interest (EOI)
Maintenance and monitoring
Collaborative registration
Routine inspections
Special inspections
Handling complaints
Variations
Annual reports
Requalification
Follow-up
NOC
Inspection closing letter
Letter of prequalification
Web listing
Public reports (WHOPAR, WHOPIR)

8. ANTI-TUBERCULOSIS MEDICINES (last updated 29 April 2019)
ANTI-TUBERCULOSIS MEDICINES (last updated 29 April 2019)
1. Single ingredient first-line anti-tuberculosis medicines
Number of individual FPPs prequalified
Number of individual FPPs under assessment
Ethambutol (E), coated tablet/capsule 200 mg
Ethambutol (E), coated tablet/capsule 275 mg
Ethambutol, coated tablet/ capsule 400 mg 4
Isoniazid, tablet /capsule 300 mg 5
Pyrazinamide (Z), film coated tablet/capsule 250 mg
Pyrazinamide, tablet/capsule 400 mg 3
Pyrazinamide, tablet/capsule 500 mg
Rifampicin, capsule 150 mg 2
Rifampicin, capsule 300 mg 1
Rifabutin, capsule 150 mg
Rifapentin, tablets 150 mg
Streptomycin, powder for injection 1g (vial) *  1
Streptomycin, powder for injection 0.75 g (vial) *

9. Median times to PQ for FPPs- Full assessment route
270 days

10. PQ’s response to long manufacturer’s time
Measures to try to reduce manufacturer time to prequalification
Pre-submission meetings – Now mandatory for all new applicants – since late Gaps in QOS-PD discussed.
Strict response timelines for manufacturers introduced – 30, 60 or 90 days depending on the deficiencies – since late 2017
Common Deficiencies in Finished Pharmaceutical Product (FPP) Dossiers – additional guidance to manufacturers - Feb 2018
Annual PQ Quality workshop for manufacturers - 1st in July 2018 an 2nd in July 2019 in Copenhagen, Denmark
Model product dossier published to guide new applicants
Specific guidance on Bioequivalence Studies – list of guidance continuously updated
PQ review of manufacturer BE protocols before studies – always strongly recommended

11. Fast track to prequalification=
prompt, complete, good-quality responses to PQ’s questions, throughout the process.
Good quality dossier at submission +

12. Challenges and suggested solutions
Limited R&D
Inadequate pharmaceutical development
Inadequate products and process knowledge
Challenge addressing deviations and changes
Challenge in sourcing and evaluation of raw materials
Sourcing from brokers and distributors
Batch to batch variations
Inherent quality gaps built in the product
Inadequate BE studies
Poor design of BE studies
Poor choice of comparator
Poor GCP compliance
Inadequate QMS/maintenance culture
Deteriorating premises and equipment
QMS not kept up-to-date
Build R&D Capacity
Partner with academia and research institutions
Technology transfer
Sourcing of raw materials
Use prequalified APIs/CEPs
Strategic partnerships
Joint vendor audits
Pooling orders
BE studies
Pre-approved protocols
Use PQ listed comparators
Build CRO capacity
QMS/maintenance culture
Preventive maintenance
Develop a quality culture

13. Benefits for stakeholders
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
Patients
Access to quality-assured products, adapted to their specific needs
Accurate prevention, diagnosis, and treatment
WHO Member States & NRAs
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
Donors, procurers and UN agencies
List of prequalified products
Increased availability of quality-assured products
Monitoring quality of prequalified products
Healthy market: diversity and affordability of products

14. Benefits for stakeholders
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
Manufacturers
Access to donor-sponsored tenders and MPP licences
Faster regulatory approval – using CRP
Timely assessment of variations and changes
PQ of APIs - Sources of quality APIs
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
QC labs
International recognition of prequalified QCLs
Technical assistance and scientific advice

15. WHO-PQT: Looking to the future
Continue to assess and facilitate access to quality assured health products.
Gradually expand scope of PQ to cover more products on the EML through:
setting up criteria for prioritisation and gradual scope expansion
NCDs (Cancer/SBP pilot, Diabetes/Insulin, Hypertension, etc.)
IVDs for Cholera, TB, NCDs, NTDs/Dengue
Gradually expand the mechanisms for PQ through:
Expand the abridged assessment of products approved by WHO Listed Authorities assessed using the GBT.
Reliance on quality assured regional-network-joint-assessments.
Expand mechanisms to evaluate new products developed with special focus on LMICs and emergencies (EU Art.58, Swiss EUL)
Expand risk based approaches like ERP, ERPD and other mechanisms - Snake anti-venoms and other products on the EML.

16. Take home messages WHO Prequalification:
Contributes to access and achieving SDGs and UHC
facilitates access to quality assured priority health products
Role recognized by WHO 13th General Programme of Work: :
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.
Has been instrumental in building national capacity for the manufacture, regulation and monitoring of medicines – promoting harmonization and convergence
Stepped up global leadership:
PQ has been recognized as a stamp of quality and a point of reference for QA for UN, International, regional and national procurement
WHO Expert Committee on Specifications, Oct 2010

17. Prequalification team
Deus Mubangizi
PQT Coordinator
Diagnostics
Irena Prat
Medicines
Matthias Stahl
Vaccines
Carmen Rodriguez Hernandez
Vector control
Marion Law
Inspections
Johanna Gouws
Technical assistance & laboratories
Rutendo Kuwana
Collaborative registration procedure
Luther Gwaza
Dankie